Title of Invention	METHODS AND COMPOSITIONS FOR TREATING AMYLOID-RELATED DISEASES
Abstract	This invention relates to compounds of Formula I as defined in the description; pharmaceutical composition comprising the same for treating or preventing amyloid-related disease.

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METHODS AND COMPOSITIONS FOR TREATING AMYLOID-RELATED DISEASES Related Applications This application claims priority to U.S. Patent Application No. 10/ , , filed June 18,2004 (identified by Attorney Docket No. NBI-162A), U.S. Patent Application No. 10/ filed June 18,2004 (identified by Attorney Docket No. NBM62B), U.S. Provisional Patent Application No. 60/512,047, filed October 17, 2003, and U.S. Provisional Patent Application No. 60/480,906, filed June 23, 2003, all entitled Methods and Compositions for Treating Amyloid-Related Diseases. This application is also related to U.S. Provisional Patent Application No. 60/512,017, filed October 17,2003, U.S. Provisional Patent Application No. 60/480,918, filed June 23,2003, and U.S. Patent Application No. 10/ , , filed June 18,2004 (identified by Attorney Docket No. NBM49), all entitled Methods for Treating Protein Aggregation Disorders. This application is related to U.S. Provisional Patent Application No. 60/512,116, filed October 17,2003, U.S. Provisional Patent Application No. 60/480,984, filed June 23,2003, and U.S. application 10/ , , filed June 18, 2004 (identified by Attorney Docket No. NBI-152), all entitled Pharmaceutical Formulations of Amyloid-Inhibiting Compounds. This appplication is related to U.S. Provisional Patent Application No, 60/436,379, filed December 24,2002, U.S. Provisional Patent Application No. 60/482,214, filed June 23 2003, entitled Combination Therapyfor the Treatment of . Alzmer's Diseaye,U.S.Patent ApplicationNo. 10/746,138, filed December 24,2003, International Patent Application No. PCT/CA2003/002011, and U.S. Patent Application No. 10/ , , filed June 18,2004 (identified by NBI-154CP), entitled Therapeutic Formulations for the Treatment of Beta-Amyloid Related Diseases. This application is related to U.S. Provisional Patent Application No. 60/512,135, filed October 17,2003, U.S. Provisional Patent Application No. 60/482,058, filed June 23,2003, both entitled Synthetic Process for Preparing Compounds for Treating Amyloidosis, and U.S. Patent Application No. 10/ , filed June 18,2004 (identified by Attomey Docket No. NBI-156), entitled Improved Pharmaceutical Drug Candidates and Method for Preparation Thereof This application is related to U.S. Provisional Patent Application Serial No. 60/512,018, filed on October 17,2003 and U.S. Provisional Patent Application Serial No. 60/480,928, filed on June 23,2003, and U.S. application 10/ . filed June 18, 2004 (identified by Attorney Docket No. NBM63), all entitled Methods and Compositions for Treating Amyloid- and Epileptogenesis-Associated Diseases, This application is also related to Method for Treating Amyloidosis, U.S. Patent Application No. 08/463,548, now U.S. Pat No. 5,972,328. The entire contents of each of these patent applications and patents are hereby expressly incorporated herein by reference including without limitation the specification, claims, and abstract, as well as any figures, tables, or drawings thereof Background Amyloidosis refers to a pathological condition characterized by the presence of amyloid fibrils. Amyloid is a generic tenn referring to a group of diverse but specific protein deposits (intracellular or extracellular) which are seen in a number of different diseases. Though diverse in their occurrence, all amyloid deposits have common morphologic properties, stain with specific dyes (e.g.^ Congo red), and have a characteristic red-green birefrngent appearance in polarized light after staining. They also share common ultrastructural features and conamon X-ray diffraction and infrared spectra. Amyloid-related diseases can either be restricted to one organ or spread to several organs. The first instance is referred to as "localized amyloidosis" while the second is referred to as "systemic amyloidosis." Some amyloid diseases can be idiopathic, but most of these diseases appear as a complication of a previously existing disorder. For example, primary amyloidosis (AL amyloid) can appear without any other pathology or can follow plasma cell dyscrasia or multiple myeloma. Secondary amyloidosis is usually seen associated with chronic infection (such as tuberculosis) or chronic inflammation (such as rheunmatoid arthritis). A familial form of secondary amyloidosis is also seen in other types of familial amyloidosis, e.g.. Familial Mediterranean Fever (FMF). This familial type of amyloidosis is genetically inherited and is found in specific population groups. In both primary and secondary amyloidosis, deposits are found in several organs and are thus considered systemic amyloid diseases. "Localized amyloidoses" are those that tend to involve a single organ system. 'Different amyloids are also characterized by the type of protein present in the deposit For example, neurodegenerative diseases such as scrapie, bovine spongiform encephalitis, Creutzfeldt-Jakob disease, and the like are charactoized by the appearance and accumulation of a protease-resistant form of a prion protein (referred to as AScr or PrP-27) in the central nervous system. Similarly, Alzheuner's disease, another neurodegenerative disorder, is characterized by neuritic plaques and neurofibrillary tangles. In this case, the amyloid plaques found in the parenchyma and the blood vessel is formed by the deposition of fibrillar Ap amyloid protein. Other diseases such as adult-onset diabetes (type II diabetes) are characterized by the localized accumulation of amyloid fibrils in the pancreas. Once these amyloids have formed, there is no known, widely accepted therapy or treatment which significantly dissolves amyloid deposits in situ, prevents fiirther amyloid deposition or prevents the initiation of amyloid deposition. Each amyloidogenic protein has the ability to undergo a conformational change and to organize into β-sheets and form insoluble fibrils which may be deposited extracellularly or intracellularly. Each amyloidogenic protein, although different in amino acid sequence, has the same property of forming fibrils and binding to other elements such as proteoglycan, amyloid P and complement component. Moreover, each amyloidogenic protein has amino acid sequences which, although different, show similarities such as regions with the ability to bind to the glycosaminoglycan (GAG) portion of proteoglycan (referred to as the GAG binding site) as well as other regions which promote β-sheet formation. Proteoglycans are macromolecules of various sizes and structures that are districuted almost everywhere in the body. They can be found in the intracellular compartment, on the surface of cells, and as part of the extracellular matrix. The basic structure of all proteoglycans is comprised of a core protein and at least one, but fi-equently more, polysaccharide chains (GAGs) attached to the core protein. Many different GAGs have been discovered including chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin, and hyaluronan. In specific cases, amyloid fibrils, once deposited, can become toxic to the surrounding cells. For example, the Ap fibrils organized as senile plaques have been shown to be associated with dead neuronal cells, dystrophic neurites, astrocytosis, and microgliosis in patients with Alzheimer's disease. When tested in vitro, oligomeric (soluble) as well as fibrillar Ap peptide was shown to be capable of triggering an activation process of microglia (brain macrophages), which would explain the presence of microgliosis and brain inflammation found in the brain of patients with Alzheimer's disease. Both oligomeric and fibrillar Aβ peptide can also induce neuronal cell death in vitro. See, e.g., MP Lambert, et al, Proc Natl Acad. Sci. USA 95, 6448-53 (1998). In another type of amyloidosis seen in patients with type II diabetes, the amyloidogenic protein LAPP, when organized in oligomeric forms or in fibrils, has been shown to induce P-islet cell toxicity in vitro. Hence, appearance of lAPP fibrils in the pancreas of type 11 diabetic patients contributes to the loss of the β islet cells (Langerhans) and organ dysfunction which can lead to insulinemiua. Another type of amyloidosis is related to P2 microglobulin and is found in long-ter, hemodialysis patients. Patients undergoing long term hemodialysis will develop β2-microglobulin fibrils in the carpal tunnel and in the collagen rich tissues in several joints. This causes severe pains, joint stiffness and swelling. Amyloidosis is also characteristic of Alzheimer's disease. Alzheimer's disease is a devastating disease of the brain that results in progressive memory loss leading to dementia, physical disability, and death over a relatively long period of time. With the aging populations in developed countries, the number of Alzheimer's patients is reaching epidemic proportions. People suffering from Alzheimer's disease develop a progressive dementia in adulthood, accompanied by three main structural changes in the brain: diffuse loss of neurons in multiple parts of the brain; accumulation of intracellular protein deposits termed neurofibrillary tangles; and accumulation of extracellular protein deposits termed amyloid or senile plaques, surrounded by misshapen nerve terminals (dystrophic neurites) and activated microglia (microgliosis and astrocytosis). A main constituent of these amyloid plaques is the amyloid-p peptide (Ap), a 39-43 amino-acid protein that is produced through cleavage of the β-amyloid precursor protein (APP). Extensive research has been conducted on the relevance of Ap deposits in Alzheimer's disease, see, e.g., Selkoe, Trends in Cell Biology 8,447-453 (1998). Ap naturally arises from the metabolic processing of the amyloid precursor protein ("APP") in the endoplasmic reticulum ("ER")the Golgi apparatus, or the endosomal-lysosomal pathway, and most is normally secreted as a 40 ("Aβ1-40") or 42 ("Aβ1-42") amino acid peptide (Selkoe, AnniL Rev. Cell Biol 10, 373-403 (1994)). A role for Ap as a primary cause for Alzheimer's disease is supported by the presence of extracellular Ap deposits in senile plaques of Alzheimer's disease, the increased production of Ap in cells harboring mutant Alzheimer's disease associated genes, eg., amyloid precursor protein, presenilin I and presenilin II; and the toxicity of extracellular soluble (oligomOTc) or fibrillar Ap to cells in culture. See e,g,, Ga^ais, Eur. Biopharm. Review 40-42 (Autumn 2001); May, DDT 6,459-62 (2001). Although symptomatic treatments exist for Alzheimer's disease, this disease cannot be prevented or cured at this time, Alzheuner's disease is characterized by diffuse and neuritic plaques, cerebral angiopathy, and neurofibrillary tangles. Plaque and blood vessel amyloid is believed to be formed by the deposition of insoluble Ap amyloid protein, which may be described as diffuse or fibrillary. Both soluble oligomeric Ap and fibrillar Aβ are also believed to be neurotoxic and inflammatory. Another type of amyloidosis is cerebral amyloid angiopathy (CAA). CAA is the specific deposition of amyloid-p fibrils in the walls of leptomingeal and cortical arteries, arterioles and veins. It is commonly associated with Alzheimer's disease, Down's syndrome and normal aging, as well as with a variety of familial conditions related to stroke or dementia {see Frangione et al. Amyloid: J. Protein Folding Disord. 8, Suppl 1, 36-42 (2001)). Presently available therapies for treatment of P-amyloid diseases are almost entirely symptomatic, providing only temporary or partial clinical benefit Although some pharmaceutical agents have been described that offer partial symptomatic relief, no comprehensive pharmacological therapy is currently available for the prevention or treatment of, for example, Alzheimer's disease. Summary of The Invention The present invention relates to the use of certain compounds in the treatment of amyloid-related diseases. In particular, the invention relates to a method of treating or preventing an amyloid-related disease in a subject comprising administering to the subject a therapeutic amount of a compound of the invention. The invention also pertains to each of the novel compounds of the invention as described herein. Among the compounds for use in the invention are those according to the following Formulae, such that, when administered, amyloid fibril formation, organ specific dysfunction (e.g., neurodegeneration), or cellular toxicity is reduced or inhibited In one embodiment, the invention pertains, at least in part to compounds of Formula I: Wherein: R1 is a substituted or unsubstituted cycloalkyl, heterocyclic, aryl, arylcycloalkyl, bicyclic or tricyclic ring, a bicyclic or tricyclic fused ring group, or a substituted or unsubstituted C2-C10 alkyl group; R is selected from a group consisting of hydrogen, alkyl, mecaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, and benzoimidazolyl; X+ is hydrogen, a cationic group, or an ester-forming group (i,a, as in a prodrug, which are described elsewhere herein); and each of L1 and L2 is independently a substituted or unsubstituted C1-C5 alkyl group or absent, or a pharmaceutically acceptable salt thereof provided that when R1 is alkyl, L1 is absent In another embodiment, the invention pertains, at least in part to compounds of Formula 11: wherein: R1 is a substituted or unsubstituted cyclic, bicyclic, tricyclic, or benzoheterocyclic group or a substituted or unsubstituted C2-C10 alkyl group; R is hydrogen, alkyl, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, benzoimidazolyl, or linked to R1 to fonn a heterocycle; X+ is hydrogen, a cationic group, or an ester fomiing moiety; m is O or l; n is 1,2, 3, or 4; L is substituted or unsubstituted C1-C3 alkyl group or absent, or a pharmaceutically acceptable salt thereof. provided that when R1 is alkyl, L is absent In yet another embodiment, the invention pertains, at least in part to compounds of Formula HE: A is nitrogen or oxygen; R11 is hydrogen, salt-forming cation, ester forming group, -KCH2)x-H5, or when A is nitrogen, A and R11 taken together may be the residue of a natural or unnatural amino acid or a salt or ester thereof; Q is hydrogen, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl; and pharmaceutically acceptable salts and esters thereof. provided that said compound is not 3-(4-phenyl-1, 2,3, 6-tetrahydro-l-pyridyl)-l-propanesulfonic acid. In yet another embodiment, the invention pertains at least in part to compounds of Formula IV: A is nitrogen or oxygen; R11 is hydrogen, salt-forming cation, ester forming group, —(CH2)x"-Q, or when A is nitrogen, A and R11 taken together may be the residue of a natural or unnatural amino acid or a salt or ester thereof; benzoimidazolyl; xisO, 1,2, 3,or 4; n is 0,1,2,3,4,5,6,7, 8,9, or 10; aa is a natural or unnatural amino acid residue; m isO, 1,2, of 3; R14 is hydrogen or protecting group; R15 is hydrogen, alkyl or aryl, and phannaceutically acceptable salts and prodrugs thereof. In another embodiment, the invention includes compounds of the Formula VI: R11 is hydrogen, salt-forming cation, ester forming group, —(CH2)x"-Q, or when A is nitrogen, A and R11 taken together may be the residue of a natural or unnatural amino acid or a salt or ester thereof; Q is hydrogen, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl; x is O, 1,2,3, or 4; R19 is hydrogen, alkyl or aryl; is oxygen, sulfur, or nitrogen; Y is carbon, nitrogen, or oxygen; In another embodiment, the invention includes compounds of Formula VH: In one embodiment, the compounds disclosed herein prevent or inhibit amyloid protein assembly into insoluble fibrils which, in vivo, are deposited in various organs, or it favors clearance of pre-formed deposits or slows deposition in patients already having deposits. In another embodiment, the compound may also prevent the amyloid protein, in its soluble, oligomeric form or in its fibrillar form, from binding or adhering to a cell surface and causing cell damage or toxicity. In yet another embodiment, the compound may block amyloid-induced cellular toxicity or macrophage activation. In another embodiment, the compound may block amyloid-induced neurotoxicity or microglial activation. In another embodiment, the compound protects cells from amyloid induced cytotoxicity of B-islet cells. In another embodiment, the compound may enhance clearance from a specific organ, e.g., the brain or it decreases concentration of the amyloid protein in such a way that amyloid fibril formation is prevented in the targeted organ. The compounds of the invention may be administered therapeutically or prophylactically to treat diseases associated with amyloid fibril formation, aggregation or deposition The compounds of the invention may act to ameliorate the course of an amyloid related disease using any of the following mechanisms (this list is meant to be illustrative and not limiting); slowing the rate of amyloid fibril formation or deposition; lessening the degree of amyloid deposition; inhibiting, reducing, or preventing amyloid fibril formation; inhibiting neurodegeneration or cellular toxicity induced by amyloid; inhibiting amyloid induced inflammation; enhancing the clearance of amyloid; or favoring the degradation of amyloid protein prior to its organization in fibrils. The compounds of the invention may be administered therapeutically or prophlactically to treat diseases associated with amyloid-p fibril formation, aggregation or deposition. The compounds of the invention may act to ameliorate the course of an amyloid-p related disease using any of the following mechanisms (this list is meant to be illustrative and not limiting): slowing the rate of amyloid-p fibril formatibn or deposition; lessening the degree of amyloid-p deposition; inhibiting, reducing, or preventing amyloid-P fibril formation; inhibiting neurodegeneration or cellular toxicity induced by amyloid-P; inhibiting amyloid-P induced inflammation; enhancing the clearance of amyloid-P firom the brain; or favoring the degradation of amyloid-P protein prior to its organization in fibrils. Therapeutic compounds of the invention may be effective in controlling amyioid-p deposition either following their entry into the brain (following penetration of the blood brain barrier) or from the periphery. When acting firom the periphery, a conpound may alter the equilibrium of Aβ between the brain and the plasma so as to favor the exit of A)3 from the brain. It may also increase the catabolism of neuronal Aβ and change the rate of exit from the brain An increase in the exit of Aβ firom the brain would result in a decrease in Aβ brain and cerebral spinal fluid (CSF) concentration and therefore favor a decrease in Aβ deposition. Alternatively, compounds that penetrate the brain could control deposition by acting directly on brain Aβ eg., by maintaining it in a non-fibrillar form, favoring its clearance firom the brain, or by slowing down APP processing. These compounds could also prevent Ap in the brain fi-om interacting with the cell surface and therefore prevent neurotoxicity, neurodegeneration or inflammation. They may also decrease Aβ production by activated microglia. The compounds may also increase degradation by macrophages or neuronal cells. In one embodiment, the method is used to treat Alzheimer's disease (e.g., sporadic, familia, or early AD). The method can also be used prophylactically or therapeutically to treat other clinical occurrences of amyloid-p deposition, such as in Down's syndrome individuals and in patients with cerebral amyloid angiopathy ("CAA") or hereditary cerebral hemorrhage. In another embodiment, the method is used to treat mild cognitive impairment Mild Cognitive Impairment ("MCT") is a condition characterized by a state of mild but measurable impairment in thinking skills, which is not necessarily associated with the presence of dementia. MCI frequently, but not necessarily, precedes Alzheimer's disease. Additionally, abnormal accumulation of APP and of amyloid-β protein in muscle fibers has been implicated in the pathology of sporadic inclusion body myositis (IBM) (Askanas, et al., Proc. NatL Acad. ScL USA 93,1314-1319 (1996); Askanas, et al, Current Opinion in Rheumatology 7,486-496 (1995)). Accordingly, the compounds of the invention can be used prophylactically or therapeutically in the treatment of disorders in which amyloid-beta protein is abnormally deposited at non-neurological locations, such as treatment of IBM by delivery of the compounds to muscle fibers. Additionally, it has been shown that Ap is associated with abnormal extracellular deposits, known as drusen, that accumulate along the basal surface of the retinal pigmented epithelium in individuals with age-related macular degeneration (AMD). AMD is a cause of irreversible vision loss in older individuals. It is believed that Aβ deposition could be an important component of the local inflammatory events that contribute to atrophy of the retinal pigmented epithelium, drusen biogenesis, and the pathogenesis of AMD (Johnson, et al, Proc. Natl. Acad. Sci. USA 99(18), 11830-5 (2002)). The present invention therefore relates to the use of compounds of Formulae I, n, in, IV, V, VI, Vn, or otherwise described herein in the prevention or treatment of amyloid-related diseases, including, inter alia, Alzheimer's disease, cerebral amyloid angiopathy, mild cognitive impairment, inclusion body myositis, Down's syndrome, macular degeneration, as well as other types of amyloidosis like lAPP- related amyloidosis (e.g., diabetes), primary (AL) amyloidosis, secondary (AA) amyloidosis and β2 microglobulin-related (dialysis-related) amyloidosis. In Type II diabetes related amyloidosis (lAPP), the amyloidogenic protein lAPP induces p-islet cell toxicity when organized in oligomeric forms or in fibrils. Hence, appearance of lAPP fibrils in the pancreas of type 11 diabetic patients contributes to the loss of the p islet cells (Langerthans) and organ dysfunction which leads to insulinemia. Primary amyloidosis (AL amyloid) is usually found associated with plasma cell dyscrasia and multiple myeloma. It can also be found as an idiopathic disease. Secondary (AA) amyloidosis is usually seen associated with chronic infection (such as tuberculosis) or chronic inflammation (such as rheumatoid arthritis). A familial fonn of secondary amyloidosis is also seen in Familial Mediterranean Fever (FMF). β2 microglobulin-related (dialysis-related) amyloidosis is found in long-term hemodialysis patients. Patients undergoing long term hemodialysis will develop β2-microglobulin fibrils in the carpal tunnel and in the collagen rich tissues in several joints. This causes severe pains, joint stiffness and swelling. These deposits are due to the inability to maintain low levels of β2M in plasma of dialyzed patients. Increased plasma concentrations of β2M protein will induce structural changes and may lead to the deposition of modified β2M as insoluble fibrils in the joints. Detailed Description of The Invention The present invention relates to the use of compounds of Formulae I, n, HI, IV, V, VI, Vn, or compounds otherwise described herein in the treatment of amyloid-related diseases. For convenience, some definitions of terms referred to herein are set forth below. Amyloid-Related Diseases AA (Reactive) Amyloidosis Generally, AA amyloidosis is a manifestation of a number of diseases that provoke a sustained acute phase response. Such diseases include chronic inflammatory disorders, chronic local or systemic microbial infections, and malignant neoplasms. The most common form of reactive or secondary (AA) amyloidosis is seen as the result of long-standing inflammatory conditions. For example, patients with Rheumatoid Arthritis or Familial Mediterranean Fever (which is a genetic disease) can develop AA amyloidosis. The terms "AA amyloidosis" and "secondary (AA) amyloidosis" are used interchangeably. AA fibrils are generally composed of 8,000 Dalton fragments (AA peptide or protein) formed by proteolytic cleavage of serum amyloid A protein (ApoS AA), a circulating apolipoprotein which is mainly synthesized in hepatocytes in response to such cytokines as IL-1, IL-6 and TNF. Once secreted, ApoSAA is complexed with HDL. Deposition of AA fibrils can be widespread in the body, with a preference for parenchymal organs. The kidneys are usually a deposition site, and the liver and the spleen may also be affected. Deposition is also seen in the heart, gastrointestinal tract, and the skirt Underlying diseases which can lead to the development of AA amyloidosis include, but are not limited to inflammatory diseases, such as rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondylitis, psoriasis, psoriatic arthropathy, Reiter-'s syndrome. Adult Still's disease, Behcet's syndrome, and Crohn's disease. AA deposits are also produced as a result of chronic microbial infections, such as leprosy, tuberculosis, bronchiectasis, decubitus ulcers, chronic pyelonephritis, osteomyelitis, and Whipple's disease. Certain malignant neoplasms can also result in AA fibril amyloid deposits. These include such conditions as Hodgkin's lymphoma, renal carcinoma, carcinomas of gut, lung and urogenital tract, basal cell carcinoma, and hairy cell leukemia. Other underlying conditions that may be associated with AA amyloidosis are Castleman's disease and Schnitzler's syndrome. AL Amyloidoses (Primary Amyloidosis) AL amyloid deposition is generally associated with almost any dyscrasia of the B lymphocyte lineage, ranging firom malignancy of plasma cells (multiple myeloma) to benign monoclonal gammopathy. At times, the presence of amyloid deposits may be a primary indicator of the underlying dyscrasia. AL amyloidosis is also described in detail in Current Drug Targets, 2004, J 159-171. Fibrils of AL amyloid deposits are composed of monoclonal immunoglobulin light chains or fragments thereof. More specifically, the fragments are derived from the N-terminal region of the light chain (kappa or lambda) and contain all or part of the variable (VL) domain thereof. Deposits gneerally occur in the mesenchymal tissues, causing peripheral and autonomic neuropathy, carpal tunnel syndrome, macroglossia, restrictive cardiomyopathy, arthropathy of large joints, immune dyscrasias, myelomas, as well as occult dyscrasias. However, it should be noted that almost any tissue, particularly visceral organs such as the kidney, liver, spleen and heart, may be involved. Hereditary Systemic Amyloidoses There are many forms of hereditary systemic amyloidoses. Although they are relatively rare conditions, adult onset of symptoms and their inheritance patterns (usually autosomal dominant) lead to persistence of such disorders in the general population. Generally, the syndromes are attributable to point mutations in the precursor protein leading to production of variant amyioidogenic peptides or proteins. Table 1 summarizes thr fibril composition of exemplary forms of these disorders. Data derived from Tan SY, Pepys MB. Amyloidosis, Histopathologyy 25(5), 403-414 (Nov 1994), WHO/IUIS Nomenclature Subcommittee, Nomenclature of Amyloid and Amyloidosis. Bulletin of the WorldHealfliOrganisationl993;71:10508; and Mwlinic^a/., Clin Chem Lab Med 2001; 39(11): 1065-75. The data provided in Table 1 are exemplary and are not intended to limit the scope of the invention. For example, more than 40 separate point mutations in the transthyretin gene have been described, all of which give rise to clinically similar fonns of familial amyloid polynem-opathy. In general, any hereditary amyloid disorder can also occur sporadically, and both hereditary and sporadic forms of a disease present with the same characteristics with regard to amyloid. For example, the most prevalent form of secondary AA amyloidosis occurs sporadicallyy, e.g. as a result of ongoing inflammation, and is not associated with Familial Mediterranean Fever. Thus general discussion relating to hereditary amyloid disorders below can also be applied to sporadic amyloidoses. Transthyretin (TTR) is a 14 kiloDalton protein that is also sometimes referred to as prealbumin. It is produced by the liver and choroid plexus, and it functions in transporting thyroid hormones and vitamin A. At least 50 variant forms of the protein, each characterized by a single amino acid change, are responsible for various forms of familial amyloid polyneuropathy. For example, substitution of proline for leucine at position 55 results in a particularly progressive form of neuropathy; substitution of methionine for leucine at position 111 resulted in a severe cardiopathy in Danish patients. Amyloid deposits isolated from heart tissue of patients with systemic amyloidosis have revealed that the deposits are composed of a heterogeneous mixture of TTR and fragments thereof, collectively referred to as ATTR, the full length sequences of which have been characterized. ATTR fibril components can be extracted from such plaques and their structure and sequence determined according to the methods known in the art (e.g,, Gustavsson, A., et ah. Laboratory Invest. 73: 703-708,1995; Kametani, F., et al., Biochem. Biophys, Res. Commun, 125: 622-628. 1984; Pras, M., et al, PNAS 80: 539-42,1983). Persons having point mutations in the molecule apolipoprotein Al (e.g., Gly->Arg26; Trp->Arg50; Leu->Arg60) exhibit a form of amyloidosis ("Ostertag type") characterized by deposits of the protein apolipoprotein AI or fragments thereof (AApoAI). These patients have low levels of high density lipoprotein (HDL) and preset with a peripheral neuropathy or renal failure. A mutation in the alpha chain of the enzyme lysozyme (e.g., Ile->Thr56 or Asp->His57) is the basis of another form of Ostertag-type non-neuropathic hereditary amyloid reported in English, families. Here, fibrils of the mutant lysozyme protein (Alys) are deposited, and patients generally exhibit impaired renal function. This protein, unlike most of the fibril-forming proteins described herein, is usually present in whole (unfragmented) form (Benson, M.D., et al CIBA Fdn. Symp. 199:104-131, 1996). Comparison of amyloidogenic to non-amyloidogenic light chains has revealed that the fonner can include replacements or substitutions that appear to destabilize the folding of the protein and promote aggregation, AL and LCDD have been distinguished from other amyloid diseases due to their relatively small population monoclonal light chains, which are manufactured by neoplastic expansion of an antibody-producing B cell. AL aggregates typically are well-ordered fibrils of lambda chains. LCDD aggregates are relatively amorphous aggregations of both kappa and lambda chains, with a majority being kappa, in some cases KIV. Bellotti et al., JOURNAL OF STRUCTURAL BIOLOGY 13:280-89 (2000), Comparison of amyloidogenic and non-amyloidogmic heavy chains in patients having AH amyloidosis has revealed missing and/or altered components. Eulitz et ai, PROC NATL ACAD Sci USA 87:6542-46 (1990) (pathogenic heavy chain characterized by significantly lower molecular mass than non-amyloidogenic heavy chains); and Solomon et al AM JHEMAT 45(2) 171-6 (1994) (amyloidogenic heavy chain characterized as consisting solely of the VH-D portion of the non-amyloidogenic heavy chain). Accordingly, potential methods of detecting and monitoring treatment of subjects having or at risk of having AL, LCDD, AH, and the like, include but are not limited to immunoassaying plasma or urine for the presence or depressed deposition of amyloidogenic light or heavy chains, e.g., amyloid \ amyloid K, amyloid KIV, amyloid 7, or amyloid 7I. Brain Amyloidosis The most firequent type of amyloid in the brain is composed primarily of Ap peptide fibrils, resulting in dementia associated with sporadic (non-hereditary) Alzheimer's disease. In fact, the incidence of sporadic Alzheimer's disease greatly exceeds forms shown to be hereditary. Nevertheless, fibril peptides forming plaques are very similar in both types. Brain amyloidosis includes those diseases, conditions, pathologies, and other abnormalities of the structure or function of the brain, including components thereof in which the causative agent is amyloid. The area of the brain affected in an amyloid-related disease may be the stroma including the vasculature or the parenchyma including functional or anatomical regions, or neurons themselves. A subject need not have received a definitive diagnosis of a specifically recognized amyloid-related disease. The term "amyloid related disease" includes brain amyloidosis. the predominant form produced, 5-7% of total Aβ exists as AP42 (Cappai et al. Int. J. Biochem. Cell Biol 31. 885-89 (1999)). As used herein, the terms "β amyloid," "amyloid-p," and the like refer to amyloid β proteins or peptides, amyloid p precursor protems or peptides, intermediates, and modifications and fragments thereof mxless otherwise specifically indicated. In particular, "Aβ" refers to any peptide produced by proteolytic processing of the APP gene product, especially peptides which are associated with amyloid pathologies. Gelsolin is a calcium binding protein that binds to fragments and actin filaments. Mutations at position 187 {e.g., Asp->Asn; Asp->Tyr) of the protein result in a form of hereditary systemic amyloidosis, usually found in patients from Finland, as well as persons of Dutch or Japanese origin. In afflicted individuals, fibrils formed from gelsolin fragments (Agel), usually consist of amino acids 173-243 (68 kDa carboxyterminal fragment) and are deposited in blood vessels and basement membranes, resulting in corneal dystrophy and cranial neuropathy which progresses to peripheral neuropathy, dystrophic skin changes and deposition in other organs. (Kangas, H,, et ai Human MoL Genet 5(9): 1237-1243,1996). Other mutated proteins, such as mutant alpha chain of fibrinogen (AfibA) and mutant cystatin C (Acys) also form fibrils and produce characteristic hereditary disorders. AfibA fibrils form deposits characteristic of a nonneuropathic hereditary amyloid with renal disease; Acys deposits are characteristic of a hereditary cerebral amyloid angiopathy reported in Iceland (Isselbacher, Harrison's Principles of Internal Medicine, McGraw-IEll, San Francisco, 1995; Benson, et al). In at least some cases, patients with cerebral amyloid angiopathy (CAA) have been shown to have amyloid fibrils containing a non-mutant form of cystatin C in conjunction with amyloid beta protein (Nagai, A., et al Molec. Chem. NeuropathoL 33: 63-78,1998). Certain forms of prion disease are now considered to be heritable, accounting for up to 15% of cases, which were previously thought to be predominanfly infectious in nature. (Baldwin, etal, in Research Advances in Alzheimer's Disease and Related Disorders, John Wiley and Sons, New York, 1995). In hereditary and sporadic prion disorders, patients develop plaques composed of abnormal isofonns of the nomial prion protein (PrPsc). A predominant mutant isoform, PrPsc, also referred to as AScr, differs from the normal cellular protein in its resistance to protease degradation, insolubility after detergent extraction, deposition in secondary lysosomes, post-translational synthesis, and high β-pleated sheet content. Genetic linkage has been established for at least five mutations resulting in Creutzfeldt-Jacob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). (Baldwin, supra) Methods for extracting fibril peptides from scrapie fibrils, determining sequences and making such ppetides are known in the art (e.g., Beekes, M., et al J. Gen. Virol. 76:2567-76,1995). For example, one form of GSS has been linked to a PrP mutation at codon 102, while telencephalic GSS segregates with a mutation at codon 117. Mutations at codons 198 and 217 result in a form of GSS in which neuritic plaques characteristic of Alzheimer's disease contain PrP instead of Aβ peptide. Certain forms of familial CID have been associated with mutations at codons 200 and 210; mutations at codons 129 and 178 have been found in both familial CJD and FFL (Baldwin, supra). Cerebral Amyloidosis Local deposition of amyloid is common in the brain, particularly in elderly individuals. The most frequent type of amyloid in the brain is composed primarily of Aβ peptide fibrils, resulting in dementia or sporadic (non-hereditary) Alzheimer's disease, The most common occurrences of cerebral amyloidosis are sporadic and not familial For example, the incidence of sporadic Alzheimer's disease and sporadic CAA greatly exceeds the incidence of familial AD and CAA. Moreover, sporadic and familial forms of the disease cannot be distinguished from each other (they differ only in the presence or absence of an inherited genetic mutation); for example, the clinical symptoms and the amyloid plaques formed in both sporadic and familial AD are very similar, if not identical. Cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the walls of leptomingeal and cortical arteries, arterioles and veins. It is commonly associated with Alzheimer's disease, Down's syndrome and normal agmg, as well as with a variety of familial conditions related to stroke or dementia (see Frangione et al. Amyloid: J. Protein Foldmg Disord. 8, Suppl. 1,36-42 (2001)). CAA can occur sporadically or be hereditary. Senile Systemic Amyloidosis Amyloid deposition, either systemic or focal, increases with age. For example, fibrils of wild type transthyretin (TTR) are commonly found in the heart tissue of elderly individuals. These may be asymptomatic, clinically silent, or may result in heart failure. Asymptomatic fibrillar focal deposits may also occur in the brain (Aβ), corpora amylacea of the prostate (02 microglobulin), joints and seminal vesicles. Dialysis-related Amyloidosis (DRA) result from the aggregation of the islet amyloid polypeptide (lAPP) or amylin, which is a 37 amino acid peptide, derived from a larger precursor peptide, called pro-IAPP. lAPP is co-secreted with insulin in response to β-cell secretagogues. This pathological feature is not associated with insulin-dependent (Type I) diabetes and is a unifying characteristic for the heterogeneous clinical phenotypes diagnosed as NIDDM (Type II diabetes). Longitudinal studies in cats and immunocytochemical investigations in monkeys have shown that a progressive increase in islet amyloid is associated with a dramatic decrease in the population of insulin-secreting p-cells and increased severity of the disease. More recently, transgenic studies have strengthened the relationship between lAPP plaque fonnation and p-cell apoptosis and dysfunction, indicating that amyloid dq>osition is a principal factor in increasing severity of Type n diabetes. and cause death or dysfunction of the cells. This may occur even when the cells are fix)m a healthy donor and the patient receiving the transplant does not have a disease that is characterized by the presence of fibrils. For example, compounds of the present invention may also be used in preparing tissues or cells for transplantation according to the methods described in International Patent Application (PCX) number- WO 01/003680. The compounds of the invention may also stabilize the ratio of the concentrations of Pro-IAPP/IAPP, pro-Insulin/Insulin and C-peptide levels. In addition, as biological markers of efficacy, the results of the different tests, such as the arginine-insulin secretion test, the glucose tolerance test, insulin tolerance and sensitivity tests, could all be used as markers of reduced β-cell mass and/or accumulation of amyloid deposits. Such class of drugs could be used together with other drugs targeting insulin resistance, hq)atic glucose production, and insulin secretion. Such compoimds might prevent insulin thCT^y by preserving P-cell fimction and be applicable to preserving islet transplants. Hormone-derived Amyloidoses Endocrine organs may harbor amyloid deposits, particularly in aged individuals. Hormone-secreting tumors may also contain hormone-derived amyloid plaques, the fibrils of which are made up of polypeptide hormones such as calcitonin (medullary carcinoma of the thyroid), and atrial natriuretic peptide (isolated atrial amyloidosis). Sequences and structures of these proteins are well known in the art. Miscellaneous Amyloidoses There are a variety of other forms of amyloid disease that are normally manifest as localized deposits of amyloid. In general, these diseases are probably the result of the localized production or lack of catabolism of specific fibril precursors or a predisposition of a particular tissue (such as the joint) for fibril depotion. Examples of such idiopathic position include nodular AL amyloid, cutaneous amyloid, endocrine amyloid, and tumor-related amyloid Other amyloid related diseases include those described in Table 1, such as failial amyloid polyneuropathy (FAP), seni systemic amyloidosis, Tenosynovium, familial amyloidosis, Ostertag-type, non-neuropathic amyloidosis, cranial neuropathy, hereditary cerebral hemorrhage, familial dementia, chronic dialysis, familial Creutzfeldt-Jakob disease; Gerstmarm-Straussler-Scheinker syndrome, hereditary spongiform encephalopathies, prion diseases, familial Mediterranean fever, Muckle-Well's syndrome, nepropaty, deafnss, urticaria, limb pain, cardiomyopathy, cutaneous deposits, multiple myeloma, benign monoclonal gammopathy, maccoglobulinaemia, myeloma associated amyloidosis, medullary carcinomas of the thyroid, isolated atrial amyloid, and diabetes. The compoundsf the invention may be administered therapeutically or prophylactically to treat diseases associated with amyloid fibril formation, aggregation or dsposition, regardless of the clinical setting. The compounds of the invention may act to ameliorate the course of an amyloid related disease using any of the following mechanisms, such as, for example but not limited to: slowing the rate of amyloid fibril formation or deposition; lessening the degree of amyloid deposition; inhibiting, reducing, or preventing amyloid fibril formation; inhibiting amyloid induced inflammation; enhancing the clearance of amyloid firom, for example, the brain; or protecting cells from amyloid induced (oligomers or fibrillar) toxicity. In an embodiment, the compounds of the invention maybe administered therapeutically or prophylactically to treat diseases associated with amyloid-β fibril formation, aggregation or depositioon The compounds of the invention may act to ameliorate the course of an amyloid-p related disease using any of the following mechanisms (this list is meant to be illustrative and not limiting): slowing the rate of amyloid-p fibril formation or deposition lessening the degree of amyloid-β deposition; inhibiting, reducing, or preventing amyloid-p fibril formation; inhibiting neurodegeneration or cellular toxicity induced by amyloid-p; inhibiting amyloid-p induced inflammation; enhancing the clearance of amyloid-P from the brain; or favoring greater catabolism of Aβ, In a preferred embodiment, the method is used to treat Alzheimer's disease (e.g., sporadic or familial AD). The method can also be used prophylactically or therapeutically to treat other clinical occurrences of amyloid-β deposition, such as in Down's syndrome individuals and in patients with cerebral amyloid angiopathy ("CAA"), hereditary cerebral hemorrhage, or early Alzheimer's disease. In another embodiment, the method is used to treat mild cognitive impairment. Mild Cognitive Impairment ("MCT") is a condition characterized by a state of mild but measurable impairment in thinking skills, which is not necessarily associated with the presence of dementia, MCI frequently, but not necessarily, precedes Alzheimer's disease. Additionally, abnormal accumulation of APP and of amyloid-p protein in muscle fibers has been implicated in the pathology of sporadic inclusion body myositis (IBM) (Askanas, V., et al (1996) Proc. Natl Acad, Set USA 93:1314-1319; Askanas, V. et al (1995) Current Opinion in Rheumatology 7:486-496), Accordingly, the compounds of the invention can be used prophylactically or therapeutically in the treatment of disorders in which amyloid-beta protein is abnormally deposited at non-neurological locations, such as treatment of IBM by delivery of the compounds to muscle fibers. amyloidosis, e.g., Alzheimer's disease, Down's syndrome or cerebral amyloid angiopathy. These compounds can also improve quality of daily living in these subjects. The therapeutic compounds of the invention may treat amyloidosis related to type II diabetes by, for example, stabilizing glycemia, preventing or reducing the loss of β cell mass, reducing or preventing hyperglycemia due to loss of β cell mass, and modulating (e.g., increasing or stabilizing) insulin production. The compounds of the invention may also stabilize the ratio of the concentrations of pro-IAPP/IAPP, The thCTapeutic compounds of the invention may treat AA (secondary) amyloidosis and/or AL (primary) amyloidosis, by stabilizing renal fimction, decreasing proteinuria, increasing creatinine clearance (e.g., by at least 50% or greats: or by at least 100% or greater), by leading to remission of chronic diarrhea or weight gain (e.g., 10% or greater), or by reducing serun creatinine. Visceral amyloid content as determined, e.g., by SAP scintigraphy may also be reduced. Compounds of the Invention The present invention relates, at least in part, to the use of certain chemical compounds (and pharmaceutical formulations thereof) in the prevention or treatment of amyloid-related diseases, including, inter alia, Alzheimer's disease, cerebral amyloid angiopathy, inclusion body myositis, Down's syndrome, diabetes related amyloidosis, hemodialysis-related amyloidosis (β2M), primary amyloidosis (e.g., λ or K chain-related), familial amyloid polyneuropathy (FAP), senile systemic amyloidosis, familial amyloidosis, Ostertag-type non-neuropathic amyloidosis, cranial neuropathy, hereditary cerebral hemorrhage, familial dementia, chronic dialysis, familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, hereditary spongiform encephalopathies, prion diseases, familial Mediterranean fever, Muckle-Well's syndrome, nephropathy, dea&ess, urticaria, limb pain, cardiomyopathy, cutaneous deposits, multiple myeloma, benign monoclonal gammopathy, maccoglobulinaemia, myeloma associated amyloidosis, medullary carcinomas of the thyroid, and isolated atrial amyloid. The chemical stmctures herein are drawn according to the conventional standards known in the art Thus, where an atom, such as a carbon atom, as drawn appears to have an unsatisfied valency, then that valency is assumed to be satisfied by a hydrogen atom even though that hydrogen atom is not necessarily explicitly drawn. The structures of some of the compounds of this invention include stereogenic carbon atoms. It is to be understood that isomers arising from such asymmetry (e.g., all enantiomers and diastereomers) are included within the scope of this invention unless indicated otherwise. That is, unless otherwise stipulated, any chiral carbon center may be of either (R) or (S)-stereochemistry. Such isomers can be obtained in substantially pure form by classical separation techniques and by stereochemically-controlled synthesis. Furthennore, alkenes can include either the E- or Z- geometry, where appropriate. In addition, the compounds of the present invention may exist in unsolvated as well as solvated forms with acceptable solvents such as water, TEIF, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the group) bonded to a leaving group; however, an electrophile may also be an unsaturated group, such as an aldehyde, ketone, ester, or conjugated (α,β-unsaturated) analog thereof which upon reaction with a nucleophile forms an adduct The term "leaving group" generally refers to a group that is readily displaced and substituted by a nucleophile (e.g., an amine, a thiol, an alcohol, or cyanide). Such leaving groups are well known and include carboxylates, 7V-hydroxysuccinimide ("NHS*'), N-hydroxybenzotriazole, a halogen (fluorine, chlorine, bromine, or iodine), alkoxides, and thioalkoxides, A variety of sulfur-based leaving groups are routinely α-naphthyldipheylmethyl, 9-anthrylmethyl, 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethyIbeiizyi, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-mtrobenzyl, 4-nitrobenzyI, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, 4-cyanobenzyldiphenylmethyl, or bis(2-nitrophenyl)methyl groups. In certain embodiments, a straight-chain or branched-chain alkyl group may have 30 or fewer carbon atoms in its backbone, e,g,, C1-C30 for straight-chain or C3-C30 for branched-chain- In certain embodiments, a straight-chain or branched-chain alkyl group may have 20 or fewer carbon atoms in its backbone, e,g., C1-C20 for straight-chain or C3-C20 for branched-chain, and more preferably 18 or fewer. Likewise, prefored cycloalkyl groups have from 4-10 carbon atoms in their ring structure, and more preferably have 4-7 carbon atoms in the ring structure. The term "lower alkyl" refers to alkyl groups having from 1 to 6 carbons in the chain, and to cycloalkyl groups having from 3 to 6 carbons in the ring structure. rings that are not aromatic so as to form a polycycle (e.g., tetralin). An "arylene" group is a divalent analog of an aryl group. Aryl groups can also be fixsed or bridged with alicyclic or heterocyclic rings which are not aromatic so as to fonn a polycycle (e.g, tetralin). Some typical aryi groups include substituted or unsubstituted 5- and 6-membered single-ring groups. In another aspect, each Ar group may be selected from the group consisting of substituted or unsubstituted phenyl, pyrrolyl, furyl, fluenyl, thiazolyl, isothiaozolyi, imidazolyi, triazolyl, tetrazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyridinyl, pyrazinyl, pyridazinyl, and pyrimidinyl groups. Further examples include substituted or unsubstituted phenyl, l-naphthyl, 2-naphthyl, biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imida2olyl, pyrazinyi, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5- The term "alkoxyl as used herein means an alkyl group havmg an oxygen atom attached thereto. Representative alkoxy groups include groups having 1 to about 12 carbon atoms, preferably 1 to about 6 carbon atoms, e.g., methoxy, ethoxy, propoxy, tert-butoxy and the like. Examples of alkoxy groups include methoxy, ethoxy, isopropyloxy, propoxy, butoxy, and pentoxy groups. The alkoxy groups can be substituted with groups such as alkenyi, alkynyl, halogen, hydroxyl, alkylcaibonyloxy, arylcarbonyioxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato. cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino, and aIkylarylamino), acylamino (including aIkylcarbonylamino, aryicarbonylamino. laurate, borate, benzoate, lactate, citrate, maleate, fumarate, succinate, tartrate, naphthylate mesylate, glucoheptonate, or lactobionate. Compounds containing a cationic group covalently bonded to an aniomc group may be referred to as an "internal salt." It will be understood that "substitution" or "substituted with" includes the implicit proviso that such substitution is in accordance with the permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transfonnation such as by rearrangement, cyclization, elimination, etc. As used herein, the tenn "substituted" is , meant to include all pemiissible substituents of organic compounds, In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromadc and nonaromatic substituents of organic compounds. The permissible substituents can be one or more. In one embodiment. the invention perains to compounds of Fonnula I: wherein: R3 is a substituted or unsubstituted cycloalkyl, heterocyclic, aryl, alylcycloalkyl, bicyclic or tricyclic ring, a bicyclic or tricyclic fused ring group, or a substituted or unsubstituted C2-C10 alkyl group; R2 is selected from a group consisting of hydrogen, alkyl, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, thiazolzl, triazolyl, imidazolyl, benzothiazolyl, and benzoimidazolyl; embodiments, R1 may also be substituted with a thioether moiety. Examples of thioethers iuclude S-Me, S-Et, etc. In certain embodiments, the alkyl R1 moiety is substituted with both an aryi or a thioether moiety and an amido moiety. In other embodiments, the alkyl R1 moiety may be substituted with both a thioether and a In certain embodiments, R^ is cyclopropyl or cyclohexyL In certain embodiments, the cyclopropyl or cyclohexyl group is subsituted with, an ether group or an alkyl group. In certain further embodiments, the ether group is a benzyl ether group. In another embodiment, wherein R1 is alkyl, it is substituted with groups such as phenyl, or hydroxy. In other embodiments, the compound of the invention is selected from the group consisting of: and phannaceutically acceptable salts, esters, and prodrugs thereof. In another embodiment, the invention patains to compounds of Fonnula III wherein: A is nitrogen or oxygen; R11 is hydrogen, salt-forming cation, ester forming group, —(CH2)x-Q or when A is nitrogen, A and R11 taken togethier may be the residue of a natural or unnatural amino acid or a salt or ester thereof Q is hydrogen, thiazolyl, triazolyl, imidazolyl, benzothiazolyi, or benzoimidazolyl; X is 0,1,2,3, or 4; n is 0,1,2,3,4,5,6,7,8,9, or 10; In another embodiment, R11 is a salt-fonning cation. Examples of salt forming cations include pharmaceutically acceptable salts described herein as well as lithium, sodium, potassium, magnesium, calcium, barium, zinc, iron, and ammonium. In another embodiment, R11 is an ester-forming group. An ester-forming group includes groups which when bound form an esto-- Examples of such groups include substituted or unsubstituted alkyl, aryl, alkenyl, alkynyl, or cycloalkyl. In another embodiment, A is In another further embodiment, R11 and A taken together are a natural or unnatural amino acid residue or a pharmaceotically acceptable salt or ester thereot Examples of amino acid residues include esters and salts of phenylalanine and leucine. halogen, hydroxyl, alkyl, alkoxyl, halogenated alkyi, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, cyano, thiazol)d, triazolyi, inridazolyl, tetrazolyi, benzothiazolyl, and benzoimidazolyl, and phannacenticafly acceptable salts and esters thereof. including D forms, and a- and β-amino add dervatives. It is noted that certain amino acids, e.g., hydroxyproline, that are classified as a non-natural amino acid herein, may be found in nature within a certain organism or a particular protein. Amino acids with many different protecting groups approprite for immediate use in the solid phase synthesis of peptides are commercially available, In addition to the twenty most common naturally occurring armno acids, the following examples of non-natural amino acids and amino acid derivatives maybe used according to the invention (common abbreviations in parentheses): β-alanine 03-ALA), 'γ-aminobutyric acid (GABA), 2-aminobutyric acid (2-Abu), α;β-dehydro-2-aminobutyiic acid (8-AU), l-aminocyclopropane-l-carboxylic acid (ACPC), aminoisobutyric acid (Aib), 2-amino-thiazoline-4-carboxyiic acid, 5-aminovaleric add (5-Ava), 6-aminohexanoic acid (6-Ahx), 8-aminooctanoic acid (8-Aoc), 11-amino-undecanoic acid (11-Aun), 12-aminododecanoic acid (12-Ado), 2-aminobenzioic acid (2-Ab2), 3-aminobenzoic acid and pharmaceutically acceptable salts, estas, and prodrugs therof. In another embodiment, the invention pertains, at least in part, to compounds of Formula VI; R23 is hydrogen, alkyl, amino, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, thiazolyl, triazolyl, tetrazolyl, imidazolyi, benzothiazolyl, or benzoimidazolyl, or absent if Y is nitrogen or oxygen; or phannaceutically acceptable salts thereof. In another embodiment, R11 is a salt-forming nation. Examples of salt forming cations include pharmaceutically acceptable salts described herein as well as lithium, sodium, potassium, magnesium, calcium, barium, zinc, iron, and ammonium. In a further embodiment, the salt is a sodium salt In a further, embodiment, A is oxygen. In another embodiment, Y1 is oxygen or sulfur, and R22 is absent In another embodiment, Y2 is oxygen and R is absent Examples of R include benzyl, aryl (e.g., phenyl), alkyl, cycloalkyl (e.g., adamantyl), etc. In other embodiment, Y2 is nitrogen and R21 is hydrogen. In other embodiment, R21 is benzyl. In another further embodment, R and R are linked to form a pyridyl ring. In another embodiment, Y1 is sulfur. Examples of compounds of the invention, include methoxy, ethoxy, etc. In certain embodiments, two or more R258 substituents can be linked to form a fused ring (e.g., to form a methylendioxyphenyl moiety). Examples of compounds of the invention include: The invention pertains to both salt forms and acid/base forms of the compounds of the invention. For example, the invention pertains not only to the particular salt fonns of compounds shown herein as salts, but also the invention includes other pharmaceutically acceptable salts, and the acid and/or base fonn of the compound. The invention also pertains to salt forms of compounds shown herein. Compounds of the invention are also shown in Table 2 below. It should be noted that in the above table and throughout the application when an atom is shown without hydrogens, but hydrogens are required or chemically necessary to form a stable compound, hydrogens should be inferred to be part of the compound. In one embodiment, the invention does not pertain to the compounds described in WO 00/64420 and WO 96/28187. In this embodiment, the invention does not pertain to methods of using the compounds described m WO 00/64420 and WO 96/28187 for the treatment of diseases or disorders described therein, In a further embodiment, the invention pertains to methods of using the conpounds described in WO 00/64420 and WO 96/28187 for methods described in this application, which are not described in WO 00/64420 and WO 96/28187. Both of WO 00/64420 and WO 96/28187 are incorporated by reference herein in their entirety. In another embodiment, the invention pertains to methods of the invention which use and pharmaceutical compositions comprising, the compounds of Table 2A- In another embodiment, the compounds of the invention do not include the compounds of Table 2 A. It should be understood that the use of any of the compounds described herem or in the applications identified in "The Related Applications" Section is within the scope of the present invention and is intended to be encompassed by the pres^it invention and each of the applications are expressly incorporated herein at least for these purposes, and are furthermore expressly incorporated for all other purposes. Subjects and Patient Povulations The term "subject"' includes living organisms in which amyloidosis can occur, or which are susceptible to amyloid diseases, 6-g., Alzheimer's disease, Down's syndrbmej CAA, dialysis-related (βM) amyloidosis, secondary (AA) amyloidosis, primary (AL) amyloidosis, hereditary amyloidosis, diabetes, etc. Examples of subjects include humans, chickens, ducks, peking ducks, geese, monkeys, deer, cows, rabbits, sheep, goats, dogs, cats, mice, rats, and transgenic species thereof. Administration of the compositions of the present invention to a subject to be treated can be carried out using known procedures, at dosages and for periods of time effective to modulate amyloid aggregation or amyloid-induced toxicity in the subject as further described herein. An effective amount of the therapeutic compoound necessary to achieve a therpeutic effect may vary according to factors such as the amount of amyloid already deposited at the clinical site in the subject, the age, sex, and weight of the subject, and the ability of the therapeutic compound to modulate amyloid aggregation in the subject Dosage regimens can be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. In certain embodiments of the invention, the subject is in need of treatment by the methods of the invention, and is selected for treatment based on this need. A subject in need of treatment is art-recognized, and includes subjects that have been identified as having a disease or disorder related to amyloid-deposition or amyloidosis, has a symptom of such a disease or disorder, or is at risk of such a disease or disorder, and would be expected, based on diagnosis, e-g., medical diagnosis, to benefit from treatment (e.g., curing, healing, preventing, alleviating, relieving, altering, remedying, ameliorating, improving, or affecting the disease or disorder, the symptom of the disease or disorder, or the risk of the disease or disorder). In an exemplary aspect of the invention, the subject is a human. For example, the subject may be a human over 30 years old, human over 40 years old, a human over 50 years old, a human over 60 years old, a human ova- 70 years old, a human over 80 years old, a human over 85 years old, a human ova: 90 years old, or a human over 95 years old. The subject may be a female human, including a postmenopausal female human, who may be on hormone (estrogen) replacement therapy. The subject may also be a male human. In another embodiment, the subject is under 40 years old. Several genotypes are believed to predispose a subject to Alzheimer's disease. These include the genotypes such as presenilin-1, presenilm-2, and amyloid precursor protein (APP) missense mutations associated with familial Alzheimer's disease, and α-2-macroglobulin and LRP-1 genotypes, which are thought to increase the risk of acquiring sporadic (late-onset) Alzheimer's disease. E-van Uden, et al, X Neurosci: 22(21), 9298-304 (2002); JJ.Goto, et al, J. Mol. Neurosci 19(1-2), 37-41 (2002). Another genetic risk factor for the development of Alzherimer's disease are variants of ApoE, the gane that encodes apolipoprotein E (particulariy the apoEA genotype), a constituent of the low-density lipoprotein particle. WJ Strittmatter, et al, Annl Rev, Neurosci. 19,53-77 (1996). The molecular mechanisms by whihc the varioxis ApoE alleles alter the likelihood of developing Alzheimer's disease are unknown, however the role of ApoE in cholesterol metabolism is consistent with the growing body of evidence linking cholesterol metabolism to Alzheimer's disease. For example, chronic use of cholesterol-lowering dmgs such as statms has recently been associated with a lower incidence of Alzheimer's disease, and cholesterol-lowering dmgs have been shown to reduce pathology in APP transgenic mice. These and other studies suggest that cholesterol may affect APP processing. ApoE4 has been suggested to alto: Ap trafficking (in and out of the brain), and fevor retention of Ap in the brain. ApoE4 has also been suggested to favor APP processing toward Ap formation. Environmental factors have been proposed as predisposing a subject to Alzheimer's disease, including exposure to aluminum, although the epidemiological evidence is ambiguous. In addition, prior infection by certain viral or bacterial agents may predispose a subject to Alzheimer's disease, including the herpes simplex virus and chlamydia pneumoniae. Finally, other predisposing factors for Alzheimer's disease can include risk factors for cardiovascular or cerebrovascular disease, including cigarette smoking, hypertension and diabetes. "At risk for Alzheimer's disease" also encompasses any other predisposing factors not listed above or as yet identified and includes an increased risk for Alzheimer's disease caused by head injury, medications, diet, or lifestyle. In still a further embodiment, the subject is shown to be at risk by a diagnostic brain imaging technique, for example, one thazt measures brain activity, plaque deposition, or brain atrophy. In still a fiirther embodiment, the subject is shown to be at risk by a cognitive test such as Clinical Dementia Rating ("CDR"), Alzeimer's Disease Assessment Scale-Cognition ("ADAS-Cog"), or Mini-Mental Stale Examination ("MMSE"). The subject may exhibit a below average score on a cognitive test, as compared to a historical control of similar age and educational background. The subject may also exhibit a about 22, below about 20, below about 18, below about 16, below about 14, below about 12, below about 10, below about 8, below about 6, bdow about 4, below about 2, or below about 1. Another means to evaluate cognition, particularly Alzherimer's disease, is the Alzheimer's Disease Assessment Scale (ADAS-Cog), or a variation tenned the By using the methods of the present invention, the levels of amyloid β peptides in a subject's plasma or cerebrospinal fluid (CSF) can be reduced from levels prior to treatment from about 10 to about 100 percent, or even about 50 to about 100 percent In an alternative embodiment, the subject can have an elevated level of amyloid Aβ 4o and Aβ 42 peptide in the blood and CSF prior to treatment, according to the present The pharmaceutical compositions of the invention may act to ameliorate the course of an amyloid-related disease using any of the following mechanisms (this list is meant to be illustrative and not limiting): slowing the rate of amyloid fibril formation or deposition; lessening the degree of amyloid deposition; inhibiting, reducing, or preventing amyloid fibril formation; inhibiting neurodegeneration or cellular toxicity induced by amyloid; inhibiting amyloid induced inflammation; enhancing the clearance of amyloid from the brain; enhancing degradation of Aβ in the brain; or favoring clearance of amyloid protein prior to its organization in fibrils. "Modulation" of amyloid deposition includes both inhibition, as defined above, and enhancement of amyloid deposition or fibril formation. The term "modulating" is intended, therefore, to encompass prevention or stopping of amyloid formation or accumulation, inhibition or slowing down of further amyloid formation or accumulation in a subject with ongoing amyloidosis, e.g, already having amyloid deposition, and reducing or reversing of amyloid formation or accumulation in a subject with ongoing amyloidosis; and enhancing amyloid deposition, eg:, increasing the rate or amount of amyloid deposition in vivo or in vitro. Amyloid-enhancing compounds may be useful in animal models of amyloidosis, for example, to make possible the development of amyloid deposits in animals in a shorter periodof time or to increase amyloid deposits over a selected period of time. Amyloid-enhacing compounds may be useful in screening assays for compounds which inhibit amyloidosis in vivo, for example, in animal models, cellular assays and in vutro assays for amyloidosis. Such compounds may be used, for example, to provide faster or more sensitive assays for compounds. successfully treat a subject's dementia by slowing the rate of or lessening the extent of cognitive decline. In one embodiment, the term "treating" includes maintaining a subject's CDR rating at its base line ratmg or at 0. In anotha- embodiment, the term treating includes decreasing a subject's CDR rating by about 0.25 or more, about 0.5 or more, about 1.0 or more, about 1.5 or more, about 2.0 or more, about 2,5 OR more, or about 3.0 or more. In another embodiment, the term "treating" also includes reducing the rate of the increase of a subject's CDR rating as compared to histcrical controls. In another embodiment, the term includes reducing the rate of increase of a subject's CDR rating by about 5% or more, about 10% or more, about 20% or more, about 25% or more, about 30% or more, about 40% or more, about 50% or more about 60% or more, about 70% or more, about 80% or more, about 90% or more, or about 100%, of the increase of the historical or untreated controls. In another embodiment, the term "treating" also includes maintaining a subject's score on the MMSE. The term "treating" includes increasing a subject's MMSE score by about 1, about 2, about 3, about 4, about 5, about 7.5, about 10, about 12.5, about 15, about 17-5, about 20, or about 25 pomts. The term also includes reducing the rate of the decrease of a subject's MMSE score as compared to historical controls. In another embodiment, the term includes reducing the rate of decrease of a subject's MMSE score by about 5% or less, about 10% or less, about 20% or less, about 25% or less, about 30% or less, about 40% or less, about 50% or less, about 60% or less, about 70% or less, about 80% or less, about 90% or less or about 100% or less, of the decrease of the historical or untreated controls. In yet another embodiment, the term "treating" includes maintaining a subject's score on the ADAS-Cog. The term "treating" includes deceasing a subject's ADAS-Cog score by about 1 point or greater, by about 2 points or greato:, by about 3 points or greats, by about 4 points or greater, by about 5 points or greater, by about 7,5 points or greater, by about 10 pomts or greater, by about 12.5 points or greater, by about 15 points or greater, by about 17.5 points or greater, by about 20 pomts or greater, or by about 25 points or greater. The term also includes reducing the rate of the increase of a subject's ADAS-Cog score as compared to historical controls. In anotho: embodiment, the term includes reducmg the rate of increase of a subject's ADAS-Cog score by about 5% or more, about 10% or more, about 20% or more, about 25% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, about 70% or more, about 80% or more, about 90% or more or about 100% of the increase of the historical or untreated controls. deposition is not reached), Furthennore, the cxnnpounds described herein may inhibit or reduce an interaction between amyloid and a cell surface constituent, for example, a glycosaminoglycan or proteoglycan constituent of a basement membrane, whereby inhibiting or reducing this interaction produces the obsoved neuroprotective and cell-protective effects. For example, the compound may also prevent an amyloid peptide from binding or adhering to a cell surface, a process which is known to cause cell damage or toxicity. Similarly, the compound may block amyloid-induced cellular toxicity or microglial activation or amyloid-induced neurotoxicity, or inhibit amyloid induced inflammation. The compound may also reduce the rate or amount of amylooid aggregation, fibril formation, or deposition, or tbe compound lessens the degree of amyloid deposition. The foregoing mechanisms of action should not be construed as limiting the scope of the invention inasmuch as the invention may be practiced without such information. amyloid angiopathy is known to be associated with cerebral hemorrhage (or hermorhagic stroke). The invention also relates to a method for modulating, e.g., minimizing, amyloid-associated damage to cells, comprising the step of administering a compound capable of reducing the concentration of amyloid (e.g,, AL amyloid protein (λ or k-chain The present invention also provides a method for modulating amyloid-associated damage to cells, comprising the step of administering a compound capable of reducing the concentration of Aβ, or enable of mlmimizing the interaction of Ap (soluble oligomeric or fibrillary) with the cell surface, such that said amyloid-associated damage to cells is modulated. In certain aspects of the invention, the methods for modulating amyloid-associated damage to cells comprise a step of administering a compound enable of reducing the concentration of A|i or redudng the interaction of Ap with a cell surface. In accordance with the present invention, there is further provided a method for preventing cell death in a subject, said method comprising administering to a subject a therapeutically effective amount of a compound capable of preventing Aβ-mediated events that lead, directly or indirectly, to cell death. The present invention also provides a method for modulating amyloid-associated damage to cells, comprising the step of administering a compound capable of reducing membrane" refers to an extracellular matrix comprising glycoproteins and proteoglycans, including laminin, collagen type IV, fibronectin, perlecan, agrin, dermatan sulfate, and heparan sulfate proteoglycan (HSPG). In one embodiment, amyloid deposition is inhibited by interfering with an interaction between an amyloidogenic protein and a sulfated glycosaminoglycan such as HSPG, dermatan detennined by reading the absorbance. The fraction of test compound bound can then be calculated by comparing the amount remaining in the supernatants of incubations with Aβ to the amount remaining in control incubations which do not contain Aβ fibers. Thioflavin T and Congo Red, both of which are known to bind to Aβ fibers, may be included in each assay run as positive controls. Before assaying, test compounds can be diluted to 40 µM,which would be twice the concentration in the final test and then scanned using the Hewlett Packard 8453 UV/VIS spectrohoto,meter to detennine if the absorbance is sufficient for detection. In one embodiment, a subject's score on the MMSE is maintained. Alternatively, the subject's score on the MMSE may be increased by about 1, about 2, about 3, about 4, about 5, about 7.5, about 10, about 12.5, about 15, about 17.5, about 20, or about 25 points. In another alternative, the rate of the decrease of a subject's MMSE score as compared to historical controls is reduced. For example, the rate of the decrease of a subject's MMSE score may be reduced by about 5% or more, about 10% or more, about 20% or more, about 25% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, about 70% or more, about 80% or more, about 90% or more, or about 100% or more of the decrease of the historical or untreated Furthermore, the invention pertains to any novel chemical compound described herein. That is, the invention relates to novel compounds, and novel methods of their use as described herein, which are within the scope of fee Formulae disclosed herein, and which are not disclosed in the cited Patents and Patent Applications. Synthesis of Compounds of the Invention In general, the compounds of the present invention may be prepared by fee mefeods illustrated in fee general reaction schemes as, for example, described below, or by modifications feereof, using readily available starting materials, reagents and conventional synfeesis procedures. In feese reactions, it is also possible to make use of variants which are in feemselves known, but are not mentioned here. Functional and structural equivalents of fee compounds described herein and which have fee same general properties, wherein one or more simple variations of substitments are made which do not adversely affect fee essential nature or fee utility of the compound are also included. The compounds of fee present invention may be readily prepared in accordance wife fee synfeesis schemes and protocols described herein, as illustrated in fee specific procedures provided However, feose skilled in fee art will recogmze that ofeer synfeetic pafeways for forming fee compoimds of this invention may be used, and feat fee following is provided merely by way of example, and is not limiting to fee present The compounds of the invention may be supplied in a solution with an appropriate solvent or in a solvent-free fonn {e,g., lyophilized). In another aspect of the invention, the compounds and buffers necessary for carrying out fee methods of the invention may be packaged as a kit, optionlly including a container. The kit may be commercially used for treating or preventing amyloid- related disease according to the methods described herein and may include instructions for use in a method of the invention. Additional kit components may include acids, bases, buffering agents, inorganic salts, solvents, antioxidants, preservatives, or metal chelators. The additional The agents of the invention may be supplied in a solution with an appropriate solvent or in a solvent-free form (e.g., iyophilized). In another aspect of the invention, the agents and buffers necessary for carrying out the methods of the invention may be packaged as a kit The kit may be commercially used according to the methods described herein and may include instructions for use in a method of the invention. Additional kit components may include acids, bases, buffering agents, inorganic salts, solvents, antioxidants, preservatives, or metal chelators. The additional kit components are present as pure compositions, or as aqueous or organic solutions that incorporate one or more maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, fhimerosal, and the like. In many cases, isotonic agents are included, for example, sugars, sodium chloride, or polyalcohols such as mannitol and sorbitol, in the compositioa Prolonged absorption of the injectable compositions can be brougiht about by including in the composition an agent which delays absorption, for example, aluminum monostearate or gelatin. vehicle. The specification for the dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the therepeutic agent and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such a therapeutic agent for the treatment of amyloid dqposition in subjects. The present invention therefore includes pharmaceutical formulations comprising the agents of the Formulae described herein, including phannaceutically acceptable salts thereof, in phannaceutically acceptable vehicles for aerosol, oral and parenteral administration- Also, the present invention includes such agents, or salts thereof, which have been lyophilized and which may be reconstituted to form pharmaceutically acceptable formulations for administration, as by intravenous, intramuscular, or subcutaneous injection. Administration may also be intradermal or transdermal. Pharmaceutical compositions may also be coated by conventional methods, typically with pH or time-dependent coatings, such that the subject agent is released in the gastrointestinal tract in the vicmity of the desired topical application, or at various times to extend the desired action. Such dosage forms typically include, but are not limited to, one or more of cellulose acetate phthalate, polyinyiacetate phthalate, hydroxypropyi methyl cellulose phthalate, ethyl cellulose, waxes, and shellac. Other compositions useful for attaining systemic delivary of the subject agents include sublingual, buccal and nasal dosage forms. Such compositions typically comprise one or more of soluble filler substances such as sucrose, sorbitol and mannitol; and binders such as acacia, microcrystalline cellulose, carboxymethyi cellulose and hydroxypropyi methyl cellulose. Glidants, lubncants, sweeteners, colorants, antioxidants and flavoring agents disclosed above may also be included. The compositions of this invention can also be administered topically to a subject, e.g., by the direct laying on or spreading of the composition on the epidermal or epithelial tissue of the subject, or transderaially via a "patch". Such compositions include, for example, lotions, creams, solutions, gels and solids. These topical compositions may comprise an effective amount, usually at least about 0.1%, or even from about 1% to about 5%, of an agent of the inventioa Suitable carriers for topical administration typically remain in place on the skin as a continuous film, and resist being removed by perspiration or immersion in water. Generally, the carrier is organic in nature and capable of having dispersed or dissolved therein the therapeutic agent The carrier may include pharmaceutically acceptable emolients, emulsifiers, thickening agents, solvents and the like. In one embodiment, active agents are administered at a therapeutically effective dosage sufficient to inhibit amyloid deposition in a subject A "therapeutically effective" dosage inhibits amyloid deposition by, for example, at least about 20%, or by at least about 40%, or even by at least about 60%, or by at least about 80% relative to untreated subjects. In the case of an Alzheimer's subject, a "therapeutically effective" dosage stabilizes cognitive function or prevents a further decrease in cognitive function (i.e., preventing, slowing, or stopping disease progression). The present invention accordingly provides therapeutic drugs. By "therapeutic" or "drug" is meant an agent having a beneficial ameliorative or prophylactic effect on a q)ecific disease or condition in a living human or non-human animal. In the case of AA or AL amyloidosis, the agent may improve or stabilize specific organ function. As an example, renal function may be stabilized or improved by 10% or greater, 20% or greater, 30% or greater, 40% or greats, 50% or greater, 60% or greater, 70% or greater, 80% or greater, or by greater than 90%. In the case of lAPP, the agent may maintain or increase β-islet cell function, as determined by insulin concentration or the Pro-IAPP/IAPP ratio, In a further embodiment, the Pro-IAPP/IAPP ratio is increased by about 10% or greater, about 20% or greater, about 30% or greater, about 40% or greater, or by about 50%, In a further embodiment, the ratio is increased up to 50%. In addition, a therapeutically effective amount of the agent may be effective to improve glycemia or insulin levels. In another embodiment, the active agents are administeredat a therapeutically effective dosage sufficient to treat AA (secondary) amyloidosis and/or AL (primary) amyloidosis, by stabilizing renal function, decreasing proteinuria, increasing creatinine clearance (e.g., by at least 50% or greater or by at least 100% or greater), remission of chronic diarrhea, or by weight gain (e.g., 10% or greater). In addition, the agents may be administered at a therapeutically effective dosage sufficient to improve nephrotic syndrome. Furthemore, active agents may be administered at a therepeutically effective dosage sufficient to decrease deposition in a subject of amyloid protein, eg., Aβ40 or Aβ42. A therapeutically effective dosage decreases amyloid deposition by, for example, at least about 15%, or by at least about 40%, or even by at least 60%, or at least by about 80% relative to untreated subjects. ■ In another embodiment, active agents are administered at a theraputically effective dosage sufficient to increase or enhance amyloid protein, eg., Aβ40 or Aβ42, in the blood, CSF, or plasma of a subject. A therapeutically effective dosage increases the concentration by, for example, at least about 15%, or by at least about 40%, or even by at least 60%, or at least by about 80% relative to untreated subjects. In yet another embodiment, active agents are administered at a therapeutically effective dosage sufficient to maintain a subject's CDR rating at its base line rating or at 0. In another embodiment, the active agents are administered at a therapeutically effective dosage sufficient to decrease a subject's CDR rating by about 0.25 or more, about 0.5 or more, about 1.0 or more, about 1.5 or more, about 2.0 or more, about 2.5 or more, or about 3.0 or more. In another embodiment, the active agents are administered at a therapeutically effective dosage sufficient to reduce the rate of the increase of a subject's CDR rating as compared to historical or untreated controls. In another embodiment, the therapeutically effective dosage is sufficient to reduce the rate of increase of a subject's CDR rating (relative to untreated subjects) by about 5% or greater, about 10% or greater, about 20% or greats, about 25% or greater, about 30% or greater, about 40% or greater, about 50% or greater, about 60% or greater, about 70% or greater, about 80% or greater, about 90% or greats or about 100% or greater. In yet another embodiment, active agents are administered at a therapeutically effective dosage sufficient to maintain a subject's score on the MMSE. In another embodiment, the active agents are administered at a therapeutically effective dosage sufficient to increase a subject's MMSE score by about 1, about 2, about 3, about 4, about 5, about 7,5, about 10, about 12.5, about 15, about 17 .5, about 20, or about 25 points. In another embodiment, the active agents are administered at a therapeutically effective dosage sufficient to reduce the rate of the decrease of a subject's MMSE score as compared to historical controls. In another embodiment, the therapeutically effective dosage is sufficient to reduce the rate of decrease of a subject's MMSE score may be about 5% or less, about 10% or less, about 20% or less, about 25% or less, about 30% or less, about 40% or less, about 50% or less, about 60% or less, about 70% or less, about 80% or less, about 90% or less or about 100% or less, of the decrease of the historical or untreated controls. In yet another embodiment, active agaits are administered at a therapeutically effective dosage sufficient to maintain a subject's score on the ADAS-Cog. In another embodiment, the active agents are administered at a therapeutically effective dosage sufficient to decrease a subject's ADAS-Cog score by about 2 points or greats, by about 3 points or greater, by about 4 points or greater, by about 5 points or greater, by about 7.5 points or greater, by about 10 points or greater, by about 12,5 points or greater, by about 15 points or greater, by about 17.5 points or greater, by about 20 points or greater, or by about 25 points or greater. In another embodiment, the active agents are administered at a therapeutically effective dosage sufficient to reduce the rate of the increase of a subject's ADAS-Cog scores as compared to historical or untreated controls. In another embodiment, the therapeutically effective dosage is sufficient to reduce the rate of increase of a subject's ADAS-Cog scores (relative to untreated subjects) by about 5% or greater, about 10% or greater, about 20% or greater, about 25% or greater, about 30% or greater, about 40% or greater, about 50% or greater, about 60% or greater, about 70% or greater, about 80% or greater, about 90% or greats or about 100% or greater. In another embodiment, active agents are administered at a therapeutically effective dosage sufficient to decrease the ratio of Aβ42:Aβ40 in the CSF or plasma of a subject by about 15% or more, about 20% or more, about 25% or more, about 30% or more, about 35% or more, about 40% or more, about 45% or more, or about 50% or more. In another embodiment, active agents are administered at a therapeutically effective dosage sufficient to lower levels of Aβ in the CSF or plasma of a subject by about 15% or more, about 25% or more, about 35% or more, about 45% or more, about 55% or more, about 75% or more, or about 95% or more. Toxicity and therapeutic efficacy of such agents can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e,g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and can be axpressed as tbe ratio LD50/ED50, and usually a larger therapeutic index is more efficacious. While agents that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such agents to the site of affected tissue in order to minimize potential damage to unaffected cells and, thereby, reduce side effects. It is understood that appropriate doses depaid upon a number of factors within the ken of the ordinarily skilled physician, veterinarian, or researcii«. The dose(s) of the small molecule will vary, for example, depending upon tbe identity, size, and condition of the subject or sample being treated, further depending upon the route by which the composition is to be administered, if applicable, and the effect which the practitioner desires the small molecule to have upon the subject Exemplary doses include milligram or microgram amounts of the small molecule per kilogram of subject or sample weight (e.g., about 1 microgram per kilogram to about 500 milligrams per kilogram, about 100 micrograms per kilogram to about 5 milligrams per kilogram, or about 1 microgram per kilogram to about 50 micrograms per kilogram). It is furthemore understood that appropriate doses depend upon the potency. Such appropriate doses may be determined using the assays described herein. When one or more of these compounds is to be administered to an animal (e.g., a human), a physician, veterinarian, or researcher may, for example, prescribe a relatively low dose at first, subsequently increasing the dose until an appropriate response is obtained In addition, it is understood that the specific dose level for any particular animal subject will depend upon a variety of factors including the activity of the specific agent employed, the age, body weight, general health, gender, and diet of the subject, the time of administration, the route of administration, the rate of excretion, and any drug combination. The ability of an agent to inhibit amyloid deposition can be evaluated in an animal model system that may be predictive of efficacy in inhibiting amyloid deposition in human diseases, such as a transgenic mouse expressing human APP or other relevant animal models where Aβ deposition is seen or for example in an animal model of AA amyloidosis. Likewise, the ability of an agent to prevent or reduce cognitive impairment in a model system may be indicative of efficacy in humans. Altermiatively, the ability of an agent can be evaluated by examining the ability of the agent to inhibit amyloid fibril formation in vitro, e.g., using a fibrillogenesis assay such as that described herein, including a ThT, CD, or EM assay. Also the binding of an agent to amyloid fibrils may be measured using a MS assay as described herein The ability of the agent to protect cells from amyloid induced toxicity is determined in vitro using biochemical assays to determine percent cell death induced by amyloid protein. The ability of an agent to modulate renal function may also be evaluated in an appropriate animal model system- The therapeutic agent of the invention may be also be administered ex vivo to inhibit amyloid deposition or treat certain amyloid-related diseases, such as β2M amyloidosis and other amyloidoses related to dialysis. Ex vivo administration of the therapeutic agents of the invention can be accomplished by contacting a body fluid (e.g., blood, plasma, etc.) with a therapeutic compound of the invention such that the therapeutic compound is capable of performing its intended function and administering the body fluid to the subject. The therapeutic compound of the invention may perform its function ex vivo (e.g., dialysis filter), in vivo (e.g., administered with the body fluid), or both For example, a therapeutic compound of the invention may be used to reduce plasma β2M levels and/or maintain β2M in its soluble form ex vivo, in vivo, or both. Blood-Brain Barrier Regardless of the particular mechanism by which the compound exerts its biological effects, the compound prevents or treats amyloid-related diseases, such as for example Alzheimer's disease, CAA, diabetes related amyloidosis, AL amyloidosis, Down's syndrome, or JS2M amyloidosis. The compound may reverse or favor deposition of amyloid or the compound may favor plaque clearance or slow deposition. For example, the compoimd may decrease the amyloid concentration in the brain of a subject versus an untreated subject. The compound may penetrate into the brain by crossing the blood-brain barrier ("BBB") to exert its biological effect The compound may maintain soluble amyloid in a non-fibrillar form, or alternatively, the compound may increase the rate of clearance of soluble amyloid from the brain of a subject versus an xmtreated subject The compound may also increase the rate of degradation of Aβ in the brain prior to organization into fibrils. A compound may also act in the periphery, causing a change in the equilibrium of the amyloid protein concentration in the two conmpartments (i.e., systemic vs, central), in which case a compoimd may not be required to penetrate the brain to decrease the concentration of Aβ in the brain (a "sink' effect). Agents of the invention that exert their physiological effect in vivo in the brain may be more useful if they gain access to target cells in the brain. Non-limiting examples of brain cells are neurons, glial cells (astrocytes, oligodendrocytes, microglia), cerebrovascular cells (muscle cells, endothelial cells), and cells that comprise the meninges. The blood brain barrier ("BBB") typically restricts access to brain cells by acting as a physical and functional blockade that separates the brain parenchyma from the systemic circulation (see, e.g,, Pardridge, et al,l Neurovirol 5(6), 556-69 (1999); Rubin, et al, Rev, Neurosci. 22,11-28 (1999)). Circulating molecules are normally able to gain access to brain cells via one of two processes: lipid-mediated transport through the BBB by free diffusion, or active (or catalyzed) transport. The agents of the invention may be formulated to improve distribution in vivo, for example as powdered or liquid tablet or solution for oral administration or as a nasal spray, nose drops, a gel or ointment, through a tube or catheter, by syringe, by packtail, by pledget, or by submucosal infusion. For example, the blood-brain barrier (BBB) excludes many highly hydrophilic agents. To ensure that the more hydrophilic therapeutic agents of the invention cross the BBB, they may be formulated, for example, in liposomes. For methods of manufacturing liposomes, see, e.g., U.S. Pat. Nos. 4,522,811; 5,374,548; and 5,399,331. The liposomes may comprise one or more moieties which are selectively transported into specific cells or organs ("targeting moieties" or "targeting groups" or "transporting vectors"), thus providing targeted drug delivery {see, eg., V.V. Ranade J, Clin. Pharmacol 29,685 (1989)). Likewise, the agents may be linked to targeting groups that facilitate penetration of the blood brain barrier. In one embodiment, the method of the present invention employs a naturally occurring polyamine linked to an agent that is a small molecule and is useful for inhibiting e.g-, Aβ deposition. To facilitate transport of agents of the invention across the BBB, they may be coupled to a BBB transport vector (for review of BBB transport vectors and mechanisms, see, Bickel, et al. Adv. Drug Delivery Review 46,247-79 (2001)), Exemplary transport vectors include cationized albumin or the OX26 monoclonal antibody to the transferrin receptor; these proteins undergo absorptive-mediated and receptor-mediated transcytosis through the BBB, respectively. Natural cell metabolites that may be used as targeting groups, include, inter alia, putrescine, spermidine, spermine, or DHA. Other exemplary targeting moieties include folate or biotin {see, e.g., U.S. Pat No. 5,416,016); mannosides (Umezawa, et ai, Biochem. Biophys. Res. . Commun. 153,1038 (1988)); antibodies (P.G. Bloeman,et al, FEBS Lett. 357,140 (1995); M. Owais, et ai, Antimicrob. Agents Chemother. 39,180 (1995)); surfactant protem A receptor (Briscoe, et al, Am J. Physiol 1233,134 (1995)); gpl20 (Schreier, et al, J. Biol Chem. 269,9090 (1994)); see also, K. Keinanen and M.L. LauVkanen, FEBSLett. 346,123 (1994); JJ. Killion and LJ. Fidler,Immunomethods 4,273 (1994), Examples of other BBB transport vectors that target receptor-mediated transport systems into the brain include factors such as insulin, insulih-like growth factors ("IGF-I," and '(IGF-IT'), angiotensin II, atrial and brain natriuretic peptide ("ANP," and "BNP"), interleukin I ("IL-1") and transferrin. Monoclonal antibodies to the receptors feat bind these factors may also be used as BBB transport vectors. BBB transport vectors targeting mechanisms for absorptive-mediated transcytosis include cationic moieties such as cationized LDL, albumin or horseradish peroxidase coupled with polylysine, cationized albumin or cationized immunoglobulins. Small basic oligopeptides such as the dynorphin analogue E-2078 and the ACTH analogue ebiratide may also cross the brain via absorptive-mediated transcytosis and are potential transport vectors. Other BBB transport vectors target systems for transporting nutrients into the brain. Examples of such BBB transport vectors include hexose moieties, eg., glucose and monocarboxylic acids, e.g., lactic acid and neutral amino acids, eg., phenylalanine and amines, e.g,, choline and basic amino acids, eg., arginine, nucleosides, eg., adenosine and purine bases, eg., adenine, and thyroid hormone, eg., triiodothyridine. Antibodies to the extracellular domain of nutrient transporters may also be used as transport vectors. Other possible vectors include angiotensin II and ANP, which may be involved in regulating BBB penneability. In some cases, the bond linking the therapeutic agent to the transport vector may be cleaved following transport into the brain in order to liberate the biologically active agent Exemplary linkers include disulfide bonds, ester-based linkages, thioether linkages, amide bonds, acid-labile linkages, and Schiff base linkages. Avidin/biotin linkers, in which avidin is covalently coupled to the BBB drug transport vector, may also be used. Avidin itself may be a drug transport vector, Transcytosis, including receptor-mediated transport of compositions across the blood brain barrier, may also be suitable for the agents of the invention. Transferrin receptor-mediated delivery is disclosed in U.S. Pat. Nos. 5,672,683; 5,383,988; 5,527,527; 5,977,307; and 6,015,555. Transferrin-mediated transport is also known. P-M. Friden, et al, Phannacol Exp. Ther. 278,1491-98 (1996); H.J. Lee, J. Phannacol Exp. Titer. 292,1048-52 (2000). EGF receptor-mediated delivery is disclosed in Y. Deguchi, et al, Bioconjug. Chem. 10,32-37 (1999), and transcytosis is described in A. Cerletti, et al, J. Dmg Target. 8,435-46 (2000). Insulin firagments have also been used as carriers for delivery across the blood brain barrier, M. Fukuta, et al, Phann. Res. 11.1681-88 (1994). Delivery of agents via a conjugate of neutral avidin and cationized human albumin has also been described, Y.S. Kang, et al, Pharm. Res. 1, 1257-64 (1994), Other modifications in order to enhance penetration of the agents of the invention across the blood brain barrier may be accomplished using methods and derivatives known in the art. For example, U.S. Pat. No, 6,024,977 discloses covalent polar lipid conjugates for targeting to brain and central nervous system. U.S. Pat No. 5,017,566 discloses cyclodextrin derivatives comprising inclusion complexes of lipoidal forms of dihydropyridine redox targeting moieties. U.S. Pat No. 5,023,252 discloses the use of phannaceutical compositions comprising a neurologically active drug and a compound for facilitating transport of the drug across the blood-brain barrier including a macrocyclic ester, diester, amide, diamide, amidine, diamidine, thioester, dithioester, thioamide, ketone or lactone. U.S. Pat No. 5,024,998 discloses parenteral solutions of aqueous-insoluble drugs with cyclodextrin derivatives. U.S. Pat. No. 5,039,794 discloses the use of a metastatic tumor-derived egress factor for facilitating the transport of compounds across the blood-brain barrier. U.S. Pat. No. 5,112,863 discloses the use of N-acyl amino acid derivatives as antipsychotic drugs for delivery across the blood-brain barrier. U.S. Pat No. 5,124,146 discloses a method for delivery of therapeutic agents across the blood-brain barrier at sites of increase permeability associated with brain lesions. U.S. Pat No. 5,153,179 discloses acylated glycerol and derivatives for use in a medicament for improved penetration of cell membranes. U.S. Pat No. 5,177,064 discloses the use of lipoidal phosphonate derivatives of nucleoside antiviral agents for delivery across the blood-brain barrier. U.S. Pat. No. 5,254,342 discloses receptor-mediated transcytosis of the blood-brain barrier using the transferrin receptor in combination with pharmaceutical compounds that enhance or accelerate this process. U.S. Pat No. 5,258,402 discloses treatment of epilepsy with imidate derivatives of anticonvulsive sulfamate. U.S. Pat No. 5,270,312 discloses substituted piperazines as central nervous system agents. U.S. Pat No. 5,284,876 discloses fatty acid conjugates of dopamine drugs. U.S. Pat No. 5,389,623 discloses the use of lipid dihydropyridine derivatives of anti-inflammatory steroids or steroid sex hormones for delivery across the blood-brain barrier. U.S. Pat No. 5,405,834 discloses prodrag derivatives of thyrotropin releasing hormone. U.S. Pat. No. 5,413,996 discloses acyloxyalkyl phosphonate conjugates of neurologically-active drags for anionic sequestration of such drags in brain tissue. U.S. Pat No. 5,434,137 discloses methods for the selective opening of abnormal brain tissue capillaries using bradykiin infused into the carotid artery. U.S. Pat No. 5,442,043 discloses a peptide conjugate between a peptide having a biological activity and incapable of crossing the blood-brain barrier and a peptide which exhibits no biological activity and is enable of passing the blood-brain barrier by receptor-mediated endocytosis. U.S. Pat No. 5,466,683 discloses water soluble analogues of an anticonvulsant for the treatment of epilepsy. U.S. Pat No. 5,525,727 discloses compositions for differential uptake and retention in brain tissue comprising a conjugate of a narcotic analgesic and agonists and antagonists thereof with a Upid form of dihydropyridine that forms a redox salt upon uptake across the blood-brain barrier that prevents partitioning back to the systemic circulation. Nitric oxide is a vasodilator of the peripheral vasculature in normal tissue of the body. Increasing generation of nitric oxide by nitric oxide synthase causes vasodilation without loss of blood pressure. The blood-pressure-independent increase in blood flow through brain tissue increases cerebral bioavailability of blood-bom compositions. This increase in nitric oxide may be stimulated by administering L-arginine. As nitric oxide is increased, cerebral blood flow is consequently increased, and drugs in the blood stream are carried along with the increased flow into brain tissue. Therefore, L-arginine may be used in the pharmaceutical compositions of the invention to enhance delivery of agents to brain tissue after introducing a pharmaceutical composition into the blood stream of the subject substantially contemporaneously with a blood flow enhancing amount of L-arginine, as described in WO 00/56328. Still further examples of modifications that enhance penetration of the blood brain barrier are described in Intemational (PCT) Application Publication Number WO 85/02342, which discloses a drug composition comprising a glycerolipid or derivative thereof. PCT Publication Number WO 089/11299 discloses a chemical conjugate of an antibody with an enzyme which is delivered specifically to a brain lesion site for activating a separately-administered neurologically-active prodmg. PCT Publication Number WO 91/04014 discloses methods for delivering therapeutic and diagnostic agents across the blood-brain barrier by encapsulating the drugs in liposomes targeted to brain tissue using transport-specific receptor ligands or antibodies. PCT Publication Number WO 91/04745 discloses transport across the blood-brain barrier using cell adhesion molecules and fragments thereof to increase the permeability of tight junctions in vascular endothelium. PCT Publication Number WO 91/14438 discloses the use of a modified, chimeric monoclonal antibody for facilitating transport of substances across the blood-brain barrier. PCT PubUcation Number WO 94/01131 discloses lipidized proteins, including antibodies. PCT PubUcation Number WO 94/03424 discloses the use of amino acid derivatives as dmg conjugates for faciUtating transport across the blood-brain barrier. PCT PubUcation Number WO 94/06450 discloses conjugates of neurologically-active dmgs with a dihydropyridine-type redox targeting moiety and comprising an amino acid Unkage and an aliphatic residue. PCT PubUcation Number WO 94/02178 discloses antibody-targeted Uposomes for deUvery across the blood-brain barrier, PCT PubUcation Number WO 95/07092 discloses the use of dmg-growth factor conjugates for deUvering drags across the blood-brain barrier. PCT PubUcation Number WO 96/00537 discloses polymeric microspheres as injectable drug-deUvery vehicles for deUvering bioactive agents to sites within the central nervous system. PCT PubUcation Number WO 96/04001 discloses omega-3-fatty acid conjugates of neurologically-active drags for brain tissue deUvery. PCT WO 96/22303 discloses fatty acid and glyceroUpid conjugates of neurologicaUy-active drags for brain tissue deUvery. In general, it is well within the ordinary skill in the art to prepare an ester, amide or hydrazide derivative of an agent of the invention, for example, from the corresponding carboxylic acid and a suitable reagent For instance, a carboxylic acid-containing compound, or a reactive equivalent thereof may be reacted with a hydroxyl-containing compound, or a reactive equivalent thereof, so as to provide the corresponding ester. See, e.g., "Comprehensive Organic Transformations," 2nd Ed., by RC. Larock, VCH Publishers John Wiley & Sons, Ltd. (199989); "March's Advanced Organic Chemistry," 5th Ed., by M.B. Smith and J. Marcli, John Wiley & Sons, Ltd. (2000). Prodrugs The present invention is also related to prodrugs of the agents of the Formulae disclosed herein. Prodrugs are agents which are converted in vivo to active forms {see, eg., R.B. Silverman, 1992, "The Organic Chemistry of Drug Design and Drug Action," Academic Press, Chp. 8). Prodrugs can be used to alter the biodistribution (e.g., to allow agents which would not typically enter the reactive site of the protease) or the pharmacokinetics for a particular agent For example, a caiboxylic acid group, can be esterified, e.g., with a methyl group or an ethyl group to yield an ester. When the ester is administered to a subject, the ester is cleaved, enzymatically or non-enzymatically, reductively, oxidatively, or hydrolytically, to reveal the amonic group. An anionic group can be esterified with moieties (eg., acyloxymethyl esters) "v^diich are cleaved to reveal an intermediate agent which subsequently decomposes to yield the active agent. The prodrug moieties maybe metabolized in vivo by esterases or by other mechanisms to carboxyUc acids. Examples of prodrugs and their uses are well known in the art {see, e.g,, Berge, et al, "Pharmaceutical Salts", J.Phann. Sci. 66,1-19 (1977)), The prodrugs can be prepared in situ during the final isolation and purification of the agents, or by separately reacting the purified agent in its free acid form with a suitable derivatizing agent Caiboxylic acids can be converted into esters via treatment with an alcohol in the presence of a catalyst Examples of cleavable caiboxylic acid prodrug moieties include substituted and unsubstituted, branched or unbranched lower alkyl ester moieties, (e.g;, ethyl esters, propyl esters, butyl esters, pentyl esters, cyclopentyl esters, hexyl esters, cyclohexyl esters), lower alkenyl esters, dilower alkyl-amino lower-alkyl esters {e,g., dimethylaminoethyl ester), acylamino lower alkyl esters, acyloxy lower alkyl esters (eg-, pivaloyloxymethyl ester), aryl esters (phenyl ester), aiyl-lower alkyl esters {e.g, benzyl ester), substituted (e.g., with methyl, halo, or methoxy substituents) aryl and aryl-ower alkyl esters, amides, lower-alkyl amides, dilower alkyl amides, and hydroxy amides. Pharmaceuticallv Acceptable Salts Certain embodiments of the present agents can contain a basic functional group, such as amino or alkylamino, and are, thus, capable of forming phaimaceutically acceptable salts with phaimaceutically acceptable acids. The term "pharmaceutically acceptable salts" in this respect, refers to the relatively non-toxic, inorganic and organic acid addition salts of agents of the present invention. These salts can be prepared in situ during the final isolation and purification of the agents of the invention, or by separately reacting a purified agent of the invention in its free base form with a suitable organic or inorganic acid, and isolating the salt thus formed, Representative salts include the hydrohalide (including hydrobromide and hydrochloride), sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napthylate, mesylate, glucoheptonate, lactobionate, 2-hydroxyethanesulfonate, and laurylsulphonate salts and the like. See, e.g., Berge et al, 'Pharmaceutical Salts", J. Pharm. Sci 66,1-19 (1977). In other cases, the agents of the present invention may contain one or more acidic functional groups and, thus, are capable of forming phaimaceutically acceptable salts with pharmaceutically acceptable bases. The term 'phaimaceutically acceptable salts" in these instances refers to the relatively non-toxic, inorganic and organic base addition salts of agents of the present invention. These salts can likewise be prepared in situ during the final isolation and purification of the agents, or by separately reacting the purified agent in its firee acid fonn with a suitable base, such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. 'Thannaceutically acceptable salts" also includes, for example, derivatives of agents modified by making acid or base salts thereof as described further below and elsewhere in the present application. Examples of pharmaceutically acceptable salts include mineral or organic acid salts of basic residues such as amines; and alkali or organic salts of acidic residues such as carboxylic acids. Pharmaceutically accaptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent agent formed, for example, from non-toxic inorganic or organic acids. Such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfarmic, phosphoric, and nitric acid; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, palmoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, silfanilic, 2-acetoxybenzoic, fumaric, tolueesulfonic, methanesulfonic, ethane disulfonic, oxalic, and isethionic acid, Pharmaceutically acceptable salts may be synthesized from the parent agent which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts may be prepared by reacting the free acid or base forms of these agents with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two. All acid, salt, base, and other ionic and non-ionic forms of the compounds described are included as compounds of the invention. For example, if a compound is shown as an acid herein, the salt forms of the compound are also included. Likewise, if a compound is shown as a salt, the acid and/or basic forms are also included. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents are considered to be within the scope of this invention and covered by the claims appended hereto. The contents of all references, issued patents, and published patent applications cited throughout this application are hereby incorporated by reference. The invention is further illustrated by the following examples, which should not be construed as further limiting. Examples Binding and Antifibnillosenic Assays The test compounds were synthesized and screened by mass spectrometry ("MS") assays, except for selected compoimds which were purchased from a commercial source. The MS assay gives data on the ability of compounds to bind to proteins, in this example, to β-amyloid and lAPP. In the MS assay for Ap40, samples were prepared as aqueous solutions (adding 20% ethanol if necessary to solubilize in water), 200 µM of a test compound and 20 µM of solubilized AP40, or 400 µM of a test compound and 40 µM of solubilized Ap40. The pH value of each sample was adjusted to 7.4 (±0,2) by addition of 0.1% aqueous sodium hydroxide. The solutions were then analyzed by electrospray ionization mass spectrometry using a Waters ZQ 4000 mass spectrometer. Samples were introduced by direct infusion at a flow-rate of 25 µlVmin within 2 hr. after sample preparation. The source temperature was kept at 70 °C and the cone voltage was 20 V for all the analysis. Data were processed using Masslynx 3.5 software. The MS assay gives data on the ability of compounds to bind to soluble Ap, whereas the ThT, EM and CD assays give data on inhibition of fibrillogenesis. The results from the assay for binding to Ap are summarized in Table 3. In Table 3, a blank box means that a value was not determined for that compound in that assay. The assay for lAPP was conducted under the same conditions except that 200 µM of test compound and 20 µM of solubilized lAPP were employed. The key below describes the codes used in Table 3 to quantify the binding based on the intensity of the absorption. Transgenic mice, TgCRNDS, expressing the human amyloid precursor protein (hAPP) develop a pathology resembling Alzheimer's disease. In particular, high levels of AP40 and Ap42 have been documented in the plasma and the brain of these animals at 8-9 weeks of age, followed by early accumulation of amyloid plaques similar to the senile plaques observed in AD patients. These animals also display progressive cognitive deficits that parallel the appearance of degbnerative changes. See, e.g., (Chishti, et al J. Biol Chem. 276,21562-70 (2001). The short term therapeutic effect of 19 compounds of the invention was studied. These compounds were administered over a 14 or 28 day period at the end of which the levels of Ap peptides in the plasma and brain of TgCRNDS animals were determined. Methods Male and female transgenic mice from the 3rd and 4th B6C3F1 generations were used in this example and given daily subcutaneous or oral administrations of one of a series of compounds for 14 or 28 days. The following abbreviations are used to designate these animals from the 3rd and 4th generation backcross in the present protocol: TgCRND8-2.B6C3Fl(N3); TgCRND8-2.B6C3Fl(N4). Baseline animals (Group 1) consisted of naive TgCRND8-2. B6C3F1(N3) at 11 ±1 weeks of age. These mice were used to detemine the Aβ levels in the plasma and brain of naive transgenic animals at the initiation of treatment Starting at 11 weeks of age (±1 week) animals received daily administration of their respective treatment for a period of 14 or 28 days (groups 2-21), at a dose of 250 mg/kg at 10 ml/kg or of vehicle only (water, group 2) or 1% methyl cellulose only (group 21). The route of administration was subcutaneous for water-soluble compounds and oral for compounds solubilized in methylcellulose 1% (MC 1%). At the end of the treatment periods, plasma and perfused brains were collected for quantification of Aβ levels. The mice used in this study were derived from a breeding colony at Institut Armand Frappier, and were well-acclimated to the animal facility environment prior to initiation of the study. Animals were assigned, according to age and gender, into the following experimental groups: Anunal Health Monitoring All animals were examined daily for signs of ill health when handled in the morning for their daily treatment and twice a day for mortality checks (once daily during weekends and holidays). Detailed examinations were performed on the treatment initiation, weekly during the study, and once before terminal procedures. More frequent observations were undertaken when considered appropriate. Death and all individual clinical signs were individually recorded. Individual body weights were recorded at randomization, once weekly during the study, and once before terminal procedures. Sample Collection At 11 ± 1 weeks of age for the Baseline group, and at the end of the treatment administration animals were sacrificed and samples collected. An approximate blood volume of 500 µl was collected £rom the orbital sinus and kept on ice until centrifugation at 4°C at a minimum speed of 3,000 rpm for 10 minutes. Plasma samples were immediately fix)zen and stored at -80 °C pending analysis. The brains were removed, frozen, and stored at -80°C awaiting analysis. Compounds were scored based on their ability to modulate levels of Ap peptides in the plasma and the cerebral soluble/insoluble levels in the brain. Levels of Aβ observed in the plasma and brain of treated animals were normalized using values from vehicle-treated (water) or methylcellulose-treated control groups and ranked according to the strength of the pharmacological effect Results are shown in Tables 3 to 11. Increases in the levels of Aβ peptides are indicated using " + " symbols, while decreases in the levels of Ap peptides are indicated using " - " symbols. The strongest effects are recorded as "-H-+" or " " while the weakest are shown as " + " or"-". Specifically, increases in the levels of Ap (relative to untreated control) of 20 to 39% are scored as "+"; increases of 40 to 69% are scored as **++"; and increases of 70% or highler are scored as "+ -f +", Deoreases in the levels of Ap of 5 to 19% are scored as "-"; decreases of 20 to 38% are scored as "- -"; and deoreases of 39% or more are scored as — . The data are presented in Tables 6-11. Treatment with these compounds after 14 and/or 28 days resulted in a significant change in the cerebral levels of AiS40 and/or Aβ342 (Tables 8-11). Furthermore, treatment with these compounds, for instance. Compound BX (3-(t-butyl)amino-l-propanesulfonic acid), resulted after 14 and 28 days (Tables 6-7) in a significant increase in the levels of Aβ peptides in the plasma. This suggests that some of diese compounds may act by a penpheral sink effect, sequestering Ap peptides in the plasma and thereby facilitating their clearance from the CNS as previously suggested for treatment by passive immunization using anti-Aβ monoclonal antibody m266 (DeMattos et al. Science 295(5563):2264-7), The tables show levels of Aβ peptides in the plasma and brain of TgCRND8 mice treated for 14 and 28 days with compounds of the invention. Tables 6A and 6C show the data from Pay 14 and Day 28 for the Plasma Vehicle group, respectively. Tables 6B and 7 show the data for the Plasma Methylcellulose group on Days 14 and 28, respectively. Tables 8 and 10 show the data on Days 14 and 28 for the Brain homogenate vehicle group, respectively. Tables 9 and 11 show the data for brain homogenate for the Methylcellulose group on Days 14 and 28, respectively. Effects Of Long Term Treatment In Adult Transgenic CRND8 Mice 0verexpressing BAPP Transgenic mice, TgCRND8, as those used in the short term treatment, overexpress a human APP gene with the Swedish and Indiana mutations leading to the production of high levels of the amyloid peptides and to the development of an early-onset, aggressive development of brain amyloidosis. The high levels of Aβ peptides and the relative overabundance of Aβ42 compared to KΒAQ are believed to be associated with the severe and early degenerative pathology observed. The pattern of amyloid deposition, presence of dystrophic neuritis, and cognitive deficit has been well documented in this transgenic mouse line. The levels of Aβ peptides in the brain of these mice increase dramatically as the animals age. While the total amyloid peptide levels increase from - 1.6 x 105 pg/g of brain to - 3.8 x 106 between 9 and 17 weeks of age. While the early deposition of amyloid in this model allows the rapid testing of compounds in a relatively short time frame, the aggressivity of this model and the high levels of Aβ peptides renders therapeutic assessment in the longer term a more difficult task. The long-term therapeutic effects of compounds of the present invention on cerbral amyloid deposition and β-amyloid (Aβ) levels in the plasma and in the brains of transgenic mice, TgCRNDS, expressing the human amyloid precursor protein (hAPP) was studied. These compounds were administered over an 8 or 16 week period at the end of which the levels of Aβ peptides in the plasma and brain of TgCRNDS animals were determined. The goal of this study was to evaluate the efficacy of the compounds at modulating the progression of the amyloidogenic process in the brain and in the plasma of a transgenic mouse model of Alzheimer's disease (AD) Methods The mice used in the study consisted of animals bearing one copy of the hAl*P gene (+/-) from the 2rd and 3rd generation progenies (No and N3) dcnved from backcrosses from TgCRNDS.FVB(N2)AJ(N3) with B6AF1/J hybrid anunals. N1 - TgCRND8.FVB(N2)AJ(N3) x B6AF1/J N2= TgCRND8.FVB(N2)AJ(N3).B6AFl/J(Ni) x H(.AFl/J N3 = TgCRND8.FVB(N2).AI(N3).B6AFl/J(N:;) B6AF1/J The following abbreviations are used to designate these animals in the preasent study: TgCRND8.B6AFl/J(N2); TgCRND8.B6AFl/J(N3)- Male and female traanspenic mice were given daily subcutaneous (compound BX) or oral (compounds BW and HZ) administrations of the appropriate compounds for 8 or 16 weeks. Baseline animals consisted of 9 ± 1 week old naive TgCRND8.B6AFl /J anunals from the 2" and 3rd generations. These mice were used to determine the extent oi cerebral amyloid deposits and A/3 levels in the plasma and brain of naive transgenic animals at the initiation of treatment. Starting at 9 weeks of age (±1 week) animals received daily administration of their respective treatment for a period of 8 or 16 weeks, at a dose of 30 or 1 ()() mg/ku al 10 ml/kg. The route of administration was subcutaneous for water-sohuble compounds (Compound BX) and oral for compounds solubilized in methylcelllulose 1% (MC I'/o) (Compounds BW and BZ). At the end of the treatment periods, plasma and perfused brains were collected for quantification of Aβ levels. Animal health was monitored, samples were collected and A/3 levels were measured as described above in the short term treatment study. Compounds were scored based on their ability to modulate levels of Aβ peptides in the plasma and the cerebral soluble/insoluble levels in the brain. Levels of Aβ observed in the plasma and brain of treated animals were compared to that of vehicle-treated (water) or methylcellulose' treated control groups and ranked according to the strength of the pharmacological effect. Results are shovvjn in Table 12. Increases in the levels of A/3 peptides are indicated using "+" symbols, while decreases in the levels of Aβ peptides are indicated using "-" symbols. The strongest effects are recorded as "+++" or'—" while the weakest are shown as "+" or "-". Specifically, increases in the levels of A/3 (relative to untreated control) of 5 to 14% are scored as "+"; increases of 15 to 29% are scored as "+4 "; mid increases ol :30)% or higher are scored as "+'-f +". Decreases in the levels of Aβ of 5 to 14% are scored as "-"; decreases of 15 to 29% are scored as "- -"; and decreases of 30%. or more arc scored as "—". Additionally, changes of 4% or less in either direction are scored as "O" Table 12 shows levels of A)3 peptides in the plasma and brain of TgCRND8 mice treated for 8 and 16 weeks with compounds of the invention. Treatment with these compounds after 8 and/or 16 weeks in many cases resulted in a change in the levels of Aβ4o and/or Aβ42 in the plasma and/or brain. For example, administration of compound BX generally resulted in a dramatic decrease m the amount of A/3 m the brain at both 8 and 16 weeks. Compound BW also resulted in a dramatic decrease in bram and plasma levels of Aβ at 8 weeks and plasma levels at 16 weeks. Additionally, preliminary histochemical experiments using ThioS staining of brain sections indicated that both the nmnber of plaques and the area occupied by the plaques were decreased in mice treated with 30 mg/kg of compound BX. EXAMPLE 11: Evaluation of Compounds Binding to NAC Peptide by Mass Spectrometry Recent findings have demonstrated that a high percentage of Alzheimer Disease (AD) patients also form Lewy bodies, most abundantly in the amygdala (Hamilton. 2000, Brain Pathol, 10:378; Mukaetova-Ladinska,et al. 2000. J Neuropathol Exp Neurol 59:408). Interestingly, the highly hydrophobic non-amyloid component (NAC) region of aα-synuclein has also been described as the second most abundant component of amyloid plaques in the brain of AD patients, after. Alpha-synuclein has been shown to form fibrils in vitro. Futhermore it binds to Ap and promotes its aggregation (Yoshimoto, et al. 1995, Proc Natl Acad Sci USA 92:9141). It was in fact originally identified as the precursor of the non-amyloid beta (Ap) component (NAD) of AD plaques (Ueda, et al 1993. Proc Natl Acad Sci USA 90:11282; Iwai. 2000. Biochem Biophys Acta 1502:95; Masliah, et al, 1996, Am J Pathol 148:201). NAC is a 35 amino acid long peptide with highly hydrophobic stretches which can self-aggregate and form fibrils in vitro. Moreover, these fibrils can efficiently seed the formation of Ap fibrils in vitro (Han, et al. 1995. Chem Biol.2: 163-169; Iwai, et al. 1995. Biochemistry 34:10139). It is in fact through its NAC domain that alpha-synuclein retains its fibrillogenic properties. Modulating the properties of NAC or targeting NAC with the compounds of the invention could therefore be a valid therapeutic avenue to inhibit the formation of protein aggregates and inclusions associated with alpha-synucleopathies, as well as the formation of aggregates between the beta-amyloid peptide and NAC of alpha-synuclein. The ability of the compounds of the present invention to bind to NAC peptide in aqueous solution was evaluated. The binding ability correlates to the intensities of the peptide-compound complex peaks observed by the Electrospray Mass Spectrum. Millipore distilled deionized water was used to prepare all aqueous solutions. For pH determination a Beckman 36 pH meter fitted with a Coming Semi-Micro Combination pH Electrode was employed. NAC (MW 3260.6 Da) at 20µM was first analyzed at pH 7,40 and the usual sodium clusters was observed at +2, +3 and +4 at m/z 1335.5,1116.7 and 843.4 respectively. The optimal cone voltage was determined to be 20V- Mass spectrometry- Mass spectrometric analysis was performed using a Waters ZQ 4000 mass spectrometer equipped with a Waters 2795 sample manager. MassLynx 4.0 (earlier by MassLynx 3.5) was used for data processing and analysis. Test compounds were mixed with disaggregated peptides in aqueous media (6.6% EtOH) at a 5:1 ratio (20 µM NAC: 100 µM of test compound or 40 µM NAC: 200 µM of test compound). The pH of the mixture was adjusted to 7.4 (±0.2) using 0.1% NaOH (3-5 µL). Periodically, NAC peptide solution at 20 µM or 40 µM was also prepared in the same fashion and run as control. The spectra were obtained by introducing the solutions to the electrospray source by direct infusion using a syringe pump at a flow rate of 25 µl/min, and scanning from 100 to 2100 Da in the positive mode. The scan time was 0.9 sec per scan with an inter-scan delay of 0.1 sec and the run time was 5 min for each sample. All the mass spectra were sum of 300 scans. The desolvation and source temperature was 70°C and the cone and capillary voltage were maintained at 20 V and 3.2 kV respectively. The total area under the peaks for the bound NAC-compound complex divided by total area under the peaks for unbound NAC was determined for each compound tested. The results are summarized in Table 13 below The present invention also relates to novel compounds and the synthesis thereof. Accordingly, the following examples are presented to illustrate how some of those compounds may be prepared. Synthesis of Compounds of the Invention Preparation of 3-isopropylamino-l-propanesulfonic acid (Compound CG) Isopropylamine (2.5 mL, 29 mmol) was added to a solution of 1,3-propane sultone (3.05g, 25 mmol) in a mixture of dichloromethane/ether (40 mL, 1:1). The mixture was heated at reflux for 3 hours. The reaction mixture was cooled to room temperatiure and hexane (10 mL) was added. The solid material was collected by filtration, rinsed with ether (10 mL), and dried in vacuo, Compound CG was obtained as a fine white powder (2.98g, 65.6% yield). m,p. 240-43 °C. 1HNMR(500MHz,D2O) 5 1.06 (d, J= 6.3 Hz, 6H), 1.86 (qt, > 7.6 Hz, 2H), 2.76 (t, J= 7.6 Hz, 2H), 3.14 (t, J-7.8 Hz, 2H), 3.13-3.21 (m, J= 6.6 Hz, IH). 13C NMR (125 MHz, D2O) 5 18.2,21.5,25.8,43.4,47.9, 50.8. Preparation of 3-cyclopropyIamino-l-propanesulfonic acid (Compound CI) Cyclopropylamine (3.7 mL, 52 mmol) was added to a solution of 1,3-propane sultone (6.9 g, 55.3 mmol) in THF (60 mL). The mixture was heated with an oil-bath at 42°C for 2 hours. Stirring was difficult and part of the solid formed a crust above the stirred mixture. The mixture was heated at reflux for 1 hoiu:, cooled to room temperature. The solid material was collected by filtration, dried in a vacuum oven for 2 hours at 60 °C (4,95 g). The solid was recrystallized in methanol/water (35mL/5 mL, v/v). The mixture was cooled in a fiidge then the solid was collected by filtration, rinsed with methanol (15 mL), air-dried for 15 minutes, and further dried in a vacuum oven at 60 C overnight Compound CI was obtained as long, fine, white needles (3.74g, 40 % yield). m.p. 234-236 °C. 1HNMR (500 MHz, D2O) 6 0.62-0.71 (m, 4H), 1.92 (qt, J= 7.6 Hz. 2H), 2.51-2.55 (m, J= 3.7 Hz, IH), 2.78 (d, /= 7.3 Hz, 2H), 3.09 (t, J= 7.8 Hz, 2H). 13C NMR. (125 MHz, D2O) 6 3.0,21.2,30.0,46.8,47.9. FT-IR (KBr) vmax 3051, 1570,1465,1039 Preparation of 3-cyclopentylamino-l-propanesulfonic acid (Compound CJ) Cyclopentylamine (3.95 mL, 40 mmol) was added to a solution of 1,3-propane sultone (5.5 g, 45 mmol) in THF (80 mL). The mixture was heated at reflux with an oil-bath for 4 hours. Stilting was difficult,some acetone and ethanol were added to restore stirring. The mixture was cooled to room temperature. The solid was collected by filtration, dried in a vacuum oven for 1 hour at 60 °C (5.47 g). The solid material was dissolved in methanol/water (35 mL/2.5 mL, v/v) at reflux. The mixture was cooled slowly to room temperature overnight, and further cooled in a Mdge. The product was collected by filtration, rinsed with methanol (15 mL), air-dried for 15 minutes, and further dried in a vacuum oven at 60 °C ovemight. The product. Compound CJ, was obtained as long fine white needles (4.79 g). A second crop was obtained from the combined crude and first recrystallization mother liquor (0.84 g). Both crops were pure and were combined, total 5.63 g, 68% yield. m.p. 280-82 °C. 1H NMR (500 MHz, D2O) 5 1.34-1.43 (m, 4H), 1.46-1.54 (m, 2H), 1.82-1.90 (m, 4H), 2,76 (7, /= 7.6 Hz, 2H), 2.95 (t, J= 7.8 Hz, 2H), 3.35 (qt, J= 12 Hz, IH). 13C NMR (125 MHz, D2O) 5 21.5,23.6, 29.3,45.1,47.9, 59.5. FT-IR(KBr) vmax 3558,3501,2972,1647,1587, 1466 Preparation of 3-cycloheptylammo-l-propanesalfonic acid (Compound CK) Cycloheptylamine (3.9 mL, 30 mmol) was added to a solution of 1,3-propane sultone (4.1 g, 33 mmol) in TEIF (65 mL). The mixture was heated at reflux for 5 hours with a heating mantle. The mixture was cooled to room temperature and the solid was collected by filtration, and then dried in a vacuum oven for 1 hour at 60 °C (6.21 g). The solid material was dissolved in methanol/water (30 mL/3 mL, v/v). The solution was cooled slowly to room temperature, and further cooled with an ice-bath. The solid product was collected by filtration, rinsed with methanol, air-dried for 15 mmutes, and further dried in a vacuum oven at 60 °C. Compound CK was obtamed as small white flakes (5.08 g, 72 % yield). m.p, 341-43 °C. ^H NMR (500 MHz, D2O) 5 1.21-1.42 (m, 8H), 1.45-1.51 (m, 2H), 1.79-1.89 (m, 4H), 2,76 (7, J= 13 Hz, 2H), 2.96 (t, J= 7.8 Hz, 2H),3.35(m,J=4.6Hz, IH).13CNMR(125MHz,D20)6 21.6,23.3,27.3,30.5,43.6, 48.0,59.6. FT-IR (KBr) vmax 2924,1615,1464,1243. Preparation of 3-benzyloxycarbonylamino-2-hydroxy-l-propanesulfonic acid, sodium salt (Compound AC) 3-Amino-2-hydroxy-l-propanesulfonic acid (15.51 g, 100 mmol) was dissolved in water (150 mL) with the help of 1 equivalent of NaOH (4.08 g). A solution of CBZ-OSuc (27.4 g, 110 mmol) in MeCN (300 mL) was added. After stirring for 4 hours at room temperature, the solvent was evaporated under reduced pressure. The wet cake (one equivalent in weight of water) was then suspended in acetone (400 mL) and heated under reflux for 20 minutes. The mixture was cooled to room temperature and the solid was collected by filtration, washed with acetone and dried overnight in then vacuum oven at 40 °C. Compound AC was obtained as a white fine solid (28.85 g, 87.6 mmol, 88%). The 1H and 13C NMR were consistent with the structure. Preparation of 4-benzyloxycarbouylamino-l-butanesulfonic acid, sodium salt (Compound AD) 4-Amino-l-butanesulfonic acid sodium salt (0.516 g, 2.95 mmol. was dissolved in water for a final concentration of 0.5 M (slightly yellow solution). A solution of CBZ-OSuc in CH3CN (2 M, 1.55 mL, 3.1 mmol, 1.05 eq.) was added. The reagent precipitated. A mixture of 1,4-dioxane and ethanol was added until ahnost all of the solid was dissolved. After 3.75 h, the solvent was evaporated under reduced pressure. The solid was dried in vacuo over the weekends. The solid was then suspended in acetone and heated under reflux for 30 minutes. The mixture was cooled to room temperature and the solid was collected by filtration, washed with acetone and dried overnight in vacuo. Compound AD was obtained as a white fine solid (0.7610 g, 2.32 mmol, 78%). The 1H NMR was consistent with the structure. Preparation of 3-benzyloxycarbonylamino-l-propanesulfonic acid sodium salt (Compound AE) 3-Ainino-l-propanesulfonic acid sodium salt (1.09 g, 6.76 mmol) was dissolved in water for a final concentration of 0.5 M. A solution of CBZ-OSuc in CH3CN (2 M, 3.55 mL, 7.1 mmol, 1.05 eq.) was added. The reagent precipitated. A mixture of 1,4-dioxane and ethanol was added until almost all the solid was dissolved. After 3.75 hours, the solvent was evaporated under reduced pressure. The solid was dried in vacuo over the weekends. The solid was then suspended in acetone and heated undo: reflux for 30 minutes. The mixture was cooled to room temperature and the solid was collected by filtration, washed with acetone and dried ovenii^t in vacuo. Compound AE was obtained as a white fine solid (1.58 g, 5.06 mmol, 75%). The 1H NMR was consistent with the structure. 90% pure (10% mol of homotaurine). A solution of (Boc)20 (800 mg, 3.5 mmol) in 1,4-dioxane (5 mL) was added to a cold (0 °C solution of di-L-Phe-Phe (1 g, 3.20 mmol) in 1,4-dioxane (6 mL) and IN NaOH (3.3 mL). The mixture was stirred at 0-5 °C for 2 hours. Another portion of (B0C)20 (100 mg) was added and the mixture was stirred for an additional 60 minutes at 0-5 °C then at room temperature for 30 minutes. The mixture was then evaporated to dryness. The solid was taken in a mixture of water / EtOAc and pH was adjusted to 2 with 2N HQ, The aqueous layer was extracted 3 times with EtOAc. The combined organic layers were dried with brine and the solvent was evaporated. Some solid was insoluble in a mixture of EtOAc / CHCI3: it was removed by filtration. The desired N-Boc-L-Phe-L-Phe 1 was obtained as a white foamy solid (913.7 mg, 2.215 mmol, 71% yield). Step 1: 3-azido-l-propanesulfomc acid sodium salt (5) A solution of 1,3-propane sultone 4 (6.12 g, 49.1 mmol) in acetone (30 mL) was added to a mixture of sodium azide (3.22 g, 49.1 mmol) in water / acetone (70 mL, 20 to 50). The clear solution was stirred at room temperature. The reaction was completed within 1 hour. The solvent was removed by evaporation under reduced pressure. The solid obtained was rinsed with hot ether (50 mL) and then with ether at room temperature (150 ml). The solid was then dried in the vacuum oven at 40 °C for overnight The title compound 5 was obtained as a white solid (8.69 g, 46.4 mmol, 95% yield). Step 2: 3-azido-l-propanesulfonvl chloride 3-Azidopropanesulfonic acid, sodium salt 5 (1.87 g, 10.0 mmol) was suspended in dry benzene (20 mL), and PCI5 (2.3 g, 10.5 mmol) was added to the suspension. The mixture was stirred at room temperature for 30 minutes, then at gentle reflux for about 1 hour. The benzene and P(0)C13 were removed by evaporation under reduced pressure. Benzene was added to the crude mixture and the solvent was removed again under reduced pressure. The residue was dried in vacuo. The dried residue was dissolved in dichloromethane (anhydrous, 15 mL) and cooled at -10 °C using an ice / acetone bath. step 3: 3-azido-l-propanesulfonic acid, isobutyl ester A solution of isobutanol (LOO mL, 10.8 nunol) and 2,6-lutidine (1.3 mL, 11.2 mmol) in dichloromethane (10 mL) was added slowly to the cold sulfonyl chloride solution. The mixture was stirred at -10 °C for 5 minutes then at room temperature for 2 hours. The reaction was quenched with water and dichloromethane was added to extract the product The organic layer was washed once with water, aqueous saturated NaHC03, brine, and then dried over magnesium sulfate. The solvent was removed by evaporation under reduced pressure and the residue was dried in vacuo. The remaining 2,6-lutidine hydrochloride was removed by washing the residue with ether. The resulting oil (1,78 g) was then applied on flash column (silica gel, EtOAc in Hexanes from 15% to 20%) to give afford the desired ester as an oil (790 mg, 35%). Step 4: 3-amino-l-propanesulfonic acid isobutyl ester A solution of isobutyl 3-azidopropanesulfonate (1.13 g, 5.11 mmol) in isobutanol (10 xnL) was added under H2, via a cannula, to a suspension of Pd/C (10%, 200 mg) in isobutanol (4 mL) which had been saturated with H2- The mixture was then stirred under H2 (40 psi) at room temperature overnight The solid was then removed by filtration. The filtrate was evaporated to dryness. And the residue was dried in vacuo. The title compound 2, homotaurine isobutyl ester, was obtained as brown oil (808.7 mg, 81%). Reaction of Component 1 with Component 2 HOBT (340 mg, 2.215 mmol) was added to a cold (0-5 °C) solution of iV-Boc-L-Phe-L-Phe 1 (913.7 mg, 2215 mmol) and homotaurine isobutyl ester 2 (423 mg, 2,21 mmol) in dichloromethane (anhydrous, 30 mL). After 5 minutels, a solution of 1-cyclohexyl-3-(2-morpholin9ethyl)carbodiimide metho---toluenesulfonate (982 mg, 2215 mmol) in dichloromethane (10 mL) was added dropwise. The solution was stirred overnight at room temperature. The mixture was diluted with dichloromethane (50 mL) and flie organic layer was washed sequentially with IN NaHS04, aqueous saturated NaHCO3, and brine, and dried over sodium sulfate. The solvent was removed by evaporation under reduced pressure. Three compounds in the mixture were shown on TLC, Since the impurities were less soluble in methanol, repeated treatment with methanol followed by filtration removed most of the impurities. Column chromatography on silica gel (2% MeOH in CHCI3) afforded the tripeptide 3 as amber glassy solid (156.1 mg, 12%). Preparation of L-Phe-L-Phe-homotaurine isobutyl ester Concentrated HCl (0.7 mL) was added to a cold (0 °C) solution of iV-Boc-L-Phe-L-Phe-homotaurine isobutyi ester (202 mg, 0.343 mmol) in methanol. The mixture was stirred at room temperature for 2 hours and then left standing in the refrigerator overnight The solvent was removed under reduced pressure and the residual solid was dried in vacuo to afford the L-Phe-L-Phe-homotaurine isobutyl ester as a white solid (171.8 mg, 95%). Preparation of L-Phe-LrPhe-homotaurine (Compound X) A solution of N--BOC-L-phenylalanine-N--hydroxusuccinimide ester (400 mg, 1.1 mmol) in a mixture of ethanol (6 mL) and 1,4-dioxane (4 mL) was added to a solution of L-Phe-Homotaurine (273 mg, 1.0 mmol) in IN NaOH (1.05 mL), water (3 mL) and ethanol (4 mL). The mixture was stirred at room temperature overnight The solvent was removed under reduced pressure and the solid (601.9 mg) was suspended in a mixture of acetone (8 mL) and isopropanol (0.2 mL) and stirred overnightat room temperature. The mixture was heated under refluxed for 30 minutes and then was cooled to room temperature. The white solid was collected by filtration, washed with ether, then dried in the vacuum oven for 45 minutes. The resulting solid (423.1 mg) was dissolved in a mixture of water/tert-butanol (7:3,5 mL) and treated with Amberlite IR-120 plus (washed, 15 g dry weight) for 2 minutes at room temperature. The resin was removed by filtration and washed 3 times with the mixed solvents of water and tert- butanol (10 mL). Concentrated HCl (4 mL) was added. The solvents were removed under reduced pressure, and the resulting solid was dried in vacuum. The compound was purified by recrystallization from a mixed solvent of THF and MeOH. The resultingsoildwas heated under reflux in methanol (about 3 mL) to remove the yellowish color. Thesoildwas dried in vacuo. Compound X was obtained as white solid (84.4 mg, 20%). The 1Hand 13C NMR were consistent with the structure. Preparation of N-(3-aminopropane-l-sulfoiiyI)-phenyIalanme, ethyl ester (Compound CL) The 3-chloropropane-l-sulfonyl chloride (10 mmol, 1.21 mL) was added drop wise to a cold (-10 °C) solution of L-phenylalanine ethyl ester (10 mmol, 2.3 g) and 4-methylmorpholine (20 mmol, 2.2 mL) in dichloromethane (30 mL). The mixture was stirred for 30 minutes at -10 °C and for 2 hours at room temperature. The mixture was diluted with dichloromethane (40 mL) and washed twice with water, once with brine, dried over sodium sulfate. Evaporation of the solvent under reduced pressure gave rise to almost pure 3-chloropropyl sulfonamide as a yellow-oil in quantitative yield. The 1H and 13C NMR were consistent with the structure. A mixture of the 3-chloropropyl sulfonamide (10 mmol), sodium azide (20 mmol) and a catalytic amount of BU4NI in DMF (40 ml) was heated at 60 °C for 24 hours. The mixture was diluted with ethyl acetate, washed with water three times, and once with brine, dried over sodium sulfate. Evaporation of the solvent gave rise to the azide as a brown-oil (3.0489 g, 8.96 mmol, 90%). The 1H and 13C NMR were consistent with the structure. The azide (2.70 g, 7,94 mmol) was stured under H2 (40 psi) with 10% Pd/C (348 mg) in ethanol (16 mL) at room temperature overnight The solid was removed by filtration OVER Celite, The filtrate was treated with TMSCl/EtOH in attempt to obtain a crystalline hydrochloride salt of the product The solvent was evaporated to give a thick residue (2.2 g, 6.27 mmol, 79%) that crystallized under none of the conditions tried. The crude hydrochloric acid salt was dissolved in dichloromethane and washed once with saturated sodium bicarbonate. The organic layer was recovered and dried over sodium sulfate. The solvent was removed by evaporation under reduced pressure. The residue was dissolved in methanol and treated with activated charcoal. The solid was removed by filtration over Celite and the filtrate was evaporated to dryness. The residue was dried in vacuo to afford a tan oil (1.3969 g, 56% from the azide). The 1Hand 13C NMR were consistent with the structure of Compound CL. Preparation of iV-Boc-L-Phe-(3-aminopropane-l-sulfonyl)-L-Phe, ethyl ester (Compound Y) A solution of iV-Z-BOC-L-PheN-hydroxysuccinimide ester (2.80 mmol, 1-01 g) in dichloromethane (12 mL) was added to a cold (0 °C) solution of 3-aminopropane-l-sulfonyl-L-Phe-OEt (2.66 mmol, 839 mg) in dichloromethane (10 mL). The mixture was stirred ovemight at room temperature. The mixture was diluted with dichloromethane, and washed with 2N HCl, aqueous saturated NaHCO3, and brine. The organic layer was dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was applied on flash column chromatography on silica gel (2% MeOH in CHCI3). A portion of the pure desired material (600 mg) was isolated. The remaining product was mixed with 40% of the succinimide. Some 3-aminopropanol (70 µL) was added to the mixture that was dissolved in dichloromethane (8 mL) and cooled to 0°C. The mixture was stirred for 1 hour at room temperature. The mixture was diluted with dichloromethane, and washed with 2N HCl, aqueous saturated NaHC03,brine. The organic layer was dried over magnesium sulfate and the solvent was removed under reduced pressure. The product was pueified by flash column chromatography on silica gel (2% MeOH in CHCI3). Another portion of the pure desired material (432,4 mg) was isolated along with the adduct of the succinimide and 3-aminopropanol (220.6 mg, 0.684 mmol). Compound Y was obtained as a white crystalline foamy solid (1030 mg, 1.83 mmol, 65%). The 1H and13C NMR were consistent with the structure. Preparation of L-Phe-(3-aminopropane-l-sulfonyl)-L-Phe, ethyl ester (Compound Z) Concentrated HCl (0.8 mL) was added to a cold (O°'^C) solution of the A'-Boc-L-Phe-(3-Aminopropane-l-Sulfonyl)-L-Phe, Ethyl Ester (197 mg, 0.350 mmol) in ethanol (8 mL). The mixture was cooled using an ice/water bath and stirred for 45 min and for 3 hours at room temperature. And the mixture was kept in freezer (-20 °C) over the weekend. The solvent was removed under reduced pressure. The residual ethanol was removed by coevq)oration 3 times with chloroform imder reduced pressure. The residue was dried in vacuo to give an off-white crystalline solid (175.3 mg) in quantitative yield. The 1Hand 13C NMR were consistent with the structure of Compound Z. Preparation of L-(N-Boc)-Phe-(3-aminopropane-l-sulfonyI)-L-Phe, sodium salt (Compound AA) One equivalent of IN NaOH (202 µL) was added to a solution of L-(N-Boc)-Phe-(3-aminopropane-l-sulfonyl)-L-Phe, ethyl ester (110 mg, 0.197 mmol) in methanol (2 mL). The mixture was stirred overnight at room temperature. A white suspension was observed after overnight stirring. MeOH (1 mL), water (1 mL) and IN NaOH (10 µL) were added. The mixture was stirred in a warm water bath for about 2 hours. The solvent methanol was removed under reduced pressure. The wet residue was then freeze-dried to give compound AA as a white powder in quantitative yield (110.2 mg). The 1Hand ^^C NMR were consistent with the structure. Preparation of L-Phe-(3-aminopropane-l-suIfony^Lr-Phe, methyl ester (Compound AB) The hydrolysis was done by the conventional LiOH/MeOH method. The product was purified by recrystallization from EtOAc and Hexanes. The L-(N-Boc)- Phe- (3-aminopropane-l-sulfonyl)-L-Phe-OH (203 mg, 0.382 mmol) was dissolved in methanol (4 mL) and the solution was cooled to 0 °C. Concentrated HQ (0.35 mL) was added and the mixture was stirred for 2 hours at 0 °C and for 2.5h at room temperature. The volatile solvents were removed under reduced pressure. The aqueous residue was freeze-dried to give the product as a white solid (171.4 mg). The NMR and MS showed to product to be a mixture of the free acid and the methyl ester. The MS showed also a strong association of the peptide. The dimer was the major species on the MS. The solid was dissolved into methanol and treated with HCl overnight at room temperature. The solvent was evaporated and the residue was dried in vacuo. The product was obtained as a white foamysoild(180.4 mg, 97%). The1'H and 13C NMR were consistent with the structure of compound AB. Preparation of 4-iodo-iV-(3-sulfopropyl)-L-phenylalanine amide (Compound CO) Thionyl chloride (8.2 mL, 112.5 mmol) was added to a cold MeOH (60 mL, in an ice-bath). The ice bath was removed and 4-iodo-L-phenylalanine (6.55 g, 22.4 mmol) was added to the mixture. The solution was stiired at reflux for 2h. The solvent was removed imder reduced pressure. The residual solid was dissolved in MeOH (40 mL) and the solution was poured into Et20 (300 mL). The solid was collected by filtration, washed with EtaO (2 x 50 mL) and dried in vacuo. The solid (1.96 g, 5.8 mmol) was dissolved in a minimum amount of water. To the solution was added aqueous NEI40H (28-30%, 15 mL). The reaction mixture was stirred at room temperature over weekend. The solvent was removed under reduced pressure and EtOAc(l 5 mL) was added. The mixture was heated under reflux. The hot solution was filtered. The filtrate was cooled to room temperature and was stored in the fridge. The solid was collected by filtration, washed with EtOAc, to give 4-iodophenylalanine amide. The amide (1.3 g, 4.4 mmol) was dissolved in 15 mL of 2-butanone with a few drops of DMF before 1,3-propane sultone (560 mg, 4.9 mmol) was added. The reaction mixture was stirred at reflux for 2 hours. The mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 20 mL) and dried in vacuo. The solid was suspended in MeOH (25 mL) and a small amount of water (1 mL). The suspension was stirred at reflux. The solid material was collected by filtration while the mixture was still hot. The solid was washed with hot MeOH (2x10 mL). Compound CO was obtained as a whitesoild(320 mg). Preparation of 3-[4-(4-flaorophenyI)-l,23,,6-tetrahydropyridin-l-yI]-l-propanesulfonic acid (Compound F) The 4-(4-fluorophenyl)-l,2,3,6-tetrahydropyridine hydrochloride (2,58 g, 14.5 mmol) was treated with IN NaOH (20 mL). The aqueous mixture was extracted with CH2CI2 (20 mL). The organic layer was separated and dried over MgSO4- The solvents w^e removed by evaporation under reduced pressure. To a solution of 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (1,96 g, 13.7 mmol) in acetone (30 mL) was added 1,3-propane sultone (1.74 g, 14.5 mmol). The mixture was stirred at reflux overnight Only a small amount of compound precipitated. The resulting suspension was cooled to room temperature with stirring and a larger amount ofsoildprecipitated. The suspension was heated with the addition of a small amount of MeOH until complete dissolution of the solid. The resulting solution was stirred at reflux for a few minutes and was cooled to room temperature with stirring. Thesoildwas collected by filtration, washed with MeOH and dried in vacuo. This allowed the isolation of compoxmd F, 1.33 g (32%). Preparation of 3-[4-(4-bromophenyI)-4-hydroxypiperidin-l-ylJ-l-propanesulfonic acid (Compound G) To a solution of 4-(4-bromophenyl)-4-piperidinol (2.51 g, 9.8 mmol) in MeOH (25 mL) was added 1,3-propane sultone (1.28 g, 10.7 mmol). The mixture was stirred at reflux for 2H Only a small amount of compound precipitated. The resulting suspension was cooled to room temperature with stirring and a solution of 50% MeOH/Acetone was added to precipitate a maximum of compound. Thesoildwas collected by filtration, washed with 50% MeOH/Acetone (2 x 25 mL) and dried in vacuo. This allowed the isolation of compound G, 2.11 g (57%). Preparation of 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yll-l-propanesulfomc acid (Compound H) To a solution of 4-(4-chlorophenyl)-4-piperidmol (2.5 g, 11.8 mmol) in acetone (25 mL) was added 1,3-propane sultone (1.56 g, 13.0 mmol). The mixture was stirred at reflux for 2h. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 20 mL) and dried in vacuo This allowed the isolation of compound H, 2.83 g (72%). Preparation of 3-(4-acetyl-4-phenylpiperidin-l-yr)-l-propanesulfonic acid (Compound I) 4-Acetyl-4-phenylpiperidine hydrochloride (3.32 g, 12.5 mmol) was treated with IN NaOH (20 mL). The aqueous mixture was extracted with CH2CI2 (20 mL). The organic layer was separated, dried over Na2S04, filtered, and the solvent was removed imder reduced pressure. To a solution of 4-acetylphenylpiperidine (1.83 g, 9.0 mmol) in acetone (22 ml.) was added 1,3-propane sultone (1.20 g, 10.0 mmol) . The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 20 mL) and dried in vacuo. This allowed the isolation of compound 1,2.65 g (90%). • Preparation of 3-[4-(4-chlorophenyr)-l>2,3,6-tetrahydropyridin-l-yI]-l- The 4-(4-chlorophenyl)-l,2,3,6-tetrahydropyridine hydrochloride (2.52 g, 10.9 mmol) was treated with IN NaOH (20 mL); and aqueous mixture was extracted with CH2CI2 (20 mL). The organic layer was separated, dried over Na2S04, and filtered. The solvent was removed under reduced pressure. To a solution of 4-(4-chlorophenyl)-l,2,3,6-tetrahydropyridine (2,07 g, 10.7 mmol) in acetone (25 mL) was added 1,3-propane sultone (1.41 g, 11.8 mmol). The mixture was stirred at reflux for 2h. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 20 mL) and dried in vacuo. The product was suspended in 50% MeOH/acetone (75 mL). The suspension was stirres at reflux for 5 minutes before 25 mL of cold acetone was added The solid material was filtered and washed with acetone (2 x 25 mL). This allowed the isolation of compound J, 1.48 g (44%). Preparation of 3-(4-phenylpiperazin-l-yI)-l-propanesulfonic acid (Compound K) To a solution of 1-phenylpiperazine (2.0 g, 1.9 mL, 12.3 mmol) in acetone (20 mL) was added l3-propane sultone (1.53 g, 12.9 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. This allowed the isolation of compound K, 3.04 g (87%). Preparation of 3-[4-(4-chlorophenyl)piperazin-l-yl]-l-propanesulfonic acid (Compound L) The l-(4-chlorophenyl)pipera2:ine dihydrochloride (2.5g, 9.3 mmol) was treated with IN NaOH (40 mL); and the aqueous mixture was extracted with CH2CI2 (40 mL). The organic layer was separated, dried over Na2S04, filtered and solvent was removed xmder reduced pressure. To a solution of l-(4-chlorophenyl)pipera2ine (L62 g, 8.2 mmol) in acetone (20 mL) was added 1,3-propane sultone (1.06 g, 8.6 mmol). The mixture was stirred at reflux for 2h. The reaction mixture was cooled'to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. This allowed the isolation of compound L, 2.11 g (81%). Preparation of 3-[4-(2-fluorophenyl)piperazin-l-yl]-l-propanesulfonic acid (Compound M) « To a solution of l-(2-fluorophenyl)piperazme (2.5 g, 2.2 mL, 13.9 mmol) in acetone (25 mL) was added 1,3-propane sultone (1.73 g, 14.6 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. This allowed the isolation of compound M, 3.56 g (85%). Preparation of 3-[4-(4-nitrophenyI)piperazin-l-yl]-l-propanesuIfonic acid (Compound N) To a solution of l-(4-mtrophenyl)piperazine (2.5S g, 12.1 mmol) in acetone (25 mL) was added 1,3-propane sultone (1.06 g, 8.6 mmol). The mixture was stirred at reflux for 2h. The reaction was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. This allowed the isolation of compound N, 2.85 g (71%). Preparation of 3-[4-(4-fluorophenyI)piperazin-l-yI]-l-propanesulfonic acid (Compound P) To a solution of l-(4-fluorophenyl)piperazine (2.0 g, 11.1 mmol) in acetone (20 mL) was added 1,3-propane sultone (1.46 g, 11.7 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. This allowed the isolation of compound P, 2.62 g (78%). Preparation of 3-(4-phenyl-l2,3,6-tetrahydropyridin-l-yl)propanoic acid (Compound Q) The 4-phenyl-l,2,3,6-tetrahydropyridine hydrochloride (L5 g, 7.8 mmol) suspended in 16 mL of CH2CI2. To this suspension was added triethylamine (2.1 mL, 15.3 mmol) followed by methyl 3-bromopropionate (1.0 mL, 9,2 mmol). The reaction was stirred at room temperature for 4h and at reflux for 2h. The reaction mixture was washed with water, IN HCl (2 x 20 mL), IN NaOH (2 x 20 mL) and Brine (1 x 20 mL). The organic layer was separated, dried over Na2S04, filtered; and solvent was removed under reduced pressure. To the crude product was added 2N NaOH (15 mL). The mixture was stirred at reflux for Ih. The reaction mixture was washed with CH2CI2 (3 x 20 mL) and neutralized with concentrated HCl. The aqueous solution was concentrated to dryness under reduced pressure, to give a solid residue. Sodium chloride in the residue was removed in the following way (three repeats): dissolving the residue in a minimum amount of water, treating the aqueous solution with acetone, removing the resultant sohd material by filtration, and concentrate the filtrate to dryness under reduced pressure. This allowed the isolation of compound Q (159.4 mg). Preparation of 3-dibenzylamino-l-propanesulfonic acid (Compound AV) To a solution of dibenzylamiae (9.8 mL, 50.8 mmol) in toluene (50 mL) was added 1,3-propane sultone (6.50'g, 53.3 mmol). The mixture was stirred at'reflux for 3h. A sticky paste was formed at the bottom of the flask. The reaction mixture was cooled to room temperature. The top layer was decanted; and the paste was partially dissolved in EtOAc with heating. The mixture was poured in a 10% EtOAc/Hexanes (200 mL). The mixture was heated and the paste was spread on the walls of the conical flask. The solvent was removed This process was repeated twice, MeOH (75 mL) was added to the paste. The mixture was heated until a white solid appeared. The solid was collected by filtration, washed with cold MeOH, and dried in vacuo, affording compound AV, 7.03 g (43%). Preparation of 3-(4-cyano-4-phenylpiperidin-l-yl)-l-propanesulfonic acid (Compound E) The 4-cyano-4-phenylpiperidine hydrochloride (2.0 g, 9.0 mmol) was treated with IN NaOH (20 mL) and the aqueous phase was extracted with CH2CI2 (20 mL). The organic layor was separated, dried over MgS04, filtered and solveat was removed under reduced pressure. To a solution of piperidine (1.43 g, 7.7 mmol) in acetone (20 mL) was added 13-propane sultone (1.02 g, 8.5 mmol). The mixture was stirred at reflux for 2h. The resulting suspension was cooled to room temperature. Thesoildwas collected by filtration, washed with acetone and dried in vacuo. Thesoildwas recrystallized from MeOH (and traces of water) to afford compound E, 800 mg (34%). Preparation of 3-(4-phe0yl-1,2,3,6-tetrahydropyridin-l-yl)butanoic acid hydrochloride (Compound R) The 4-phenyl-l,2,3,6-tetrahydropyridme hydrochloride (2.01 g, 10.2 mmol) was treated with IN NaOH (20 mL) and the aqueous phase wa extracted with CH2CI2 (20 mL). The organic layer was separated, dried over MgS04, filtered and solvent was removed under reduced pressure. The resulting 4-phenyl-1,,2,3,6-tetrahydropyridine (1.55 g, 9.7 mmol) was dissolved in 20 mL of 2-butanone. To this solution was added potassium carbonate (2.02 g, 14.6 mmol). The mixture was stirred 30 minutes at room temperature; ethyl 4-bromobutyrate (1.46 mL, 10.1 mmol) was added. The reaction mixture was stirred at reflux for 5 hours. After cooling to room temperature, inorganic salts were filtered. The solvent was evaporated under reduced pressure. The residue was dissolved in CH2CI2 (30 mL). The organic phase was washed with water (2 x 30 mL), 2N HCl (2 x 30 mL) and Brine (2 x 30 mL). The organic layer was dried with Na2S04, filtered, ev^K)rated under reduced pressure and dried in vacuo. This allowed the isolation of 1.55 g (58%) of the desired ester. The ester (5.7 mmol) was dissolved in 6N HCl (40 mL). The reaction mixture was stirred at room temperature for 5 hours and at reflux for 1 hour before it was cooled to room temperature. The reaction mixture was extracted with CH2CI2 (3 x 30 mL). The aqueous phase was evaporated under reduced pressure. The residue was dissolved in water (20 mL); and the aqueous solution was concentrated to dryness under" reduced pressure. The resultant material was fiither dried in vacuo, affording compound R, 973 mg(61%). Preparation of 3-piperonylamino-l-propanesulfonic acid (Compound AW) To a solution of piperonylamine (2.5 mL, 19.8 mmol) in acetone (30 mL) was added 1,3-propane sultone (2.52 g, 20.8 nunol). The mixture stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. The product was suspended in 90 % Acetone/MeOH (75 mL). The suspension was stirred at reflux for 30 sec, the solid was collected by filtration and dried in vacuo. This allowed the isolation of compound AW, 2.56 g (45%). Preparation of 3-(3,4,5-trimethoxybenzyl)amino-l-propanesulfonic acid (Compound AY) To a solution of 3,4,5-trimethoxybenzylamine (2.2 mL, 12,7 mmol) in 2-butanone (20 mL) was added 1,3-propane sultone (1.66 g, 13.3 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. The product was suspended in 90% Acetone/MeOH (75 mL). The suspension was stirred at reflux for 30 sec., the solid was collected by filtration, and dried in vacuo; ajSbrding compoimd AY, 2.61 g (64%), Preparation of 3-(2,3-dimethoxybenzyl)amino-l-propanesuifonic acid (Compound AZ) - To a solution of 2,3-dimethoxybenzylamine (2.2 mL, 15,0 mmol) in 2-butanone (20 mL) was added 1,3-propane sultone (1.97 g, 15.8 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. The crude product was suspended in 90% Acetone/MeOH (75 mL). The suspension was stirred at reflux for 30 seconds, the solid was collected by filtration, and dried in vacuo; affording compound AZ, 1.95 g (45%). Preparation of 3-(N-benzhydr3lcarbamyl)amino-l-propanesulfonic acid (Compound AF) The 3-amino-l-propanesulfonic acid (1.0 g, 7.2 mmol) was dissolved in 3N NaOH (370 mg, 9.4 mmol in 3 mL of water). After the solution was cooled to 0°C, diphenylmethyl isocyanate (1.4 mL, 7.2 mmol) was added. The reaction mixture was allowed to warm up to room temperature, stirred for 8h (r.t.), and followed by addition of 3N NaOH (3 mL). The reaction mixture was stirred for 18h. The pH of the reaction mixture was brought to 3 with 5N HCl. The solvent was evaporated under reduced pressure. EtOH (15 mL) was added and the mixture was stirred at reflux for 30 sec. The hot mixture was filtered. The filtrate was evaporated to dryness. This process was repeated 2 more times. The final product was dried in vacuo, affording compound AF, 837 mg (34%). Preparation of 3-(3,5-dimethoxybenzyI)amino-l-propanesulfonic acid (Confound BA) To a solution of 3,5-dimethoxybenzylamine (2.5 g, 15.0 mmol) m 2-butanone (22 mL) was added 1,3-propane sultone (1.95 g, 15.8 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL), and dried in vacuo. This allowed the isolation of compound BA, 2.89 g (67%). Preparation of 3-(2,4-dimethoxybenzyl)amino-l-propanesulfonic acid (Compound BB) The 2,4-dimethoxybenzylaimne hydrochloride (2.51g, 123 mmol) was txeatecl with IN NaOH (20 mL) and the aqueous phase was extracted with CH2CI2 (20 mL) The organic layer was separated, dried over MgS04, and filtered. Solvent was remcn ed under reduced pressure to give the amine (free base form). To a solution of 2,4-dimethoxybenzylainine (1.71 g, 10.3 mmol) in 2-butanone (15 inL) was added 1,3-propane sultone (1.31 g, 10.7 mmol). The mixture was stirre 1 a reflux for 2.5h. The reaction mixture was cooled to room temperature. The supen.; was decanted; and the paste was washed with acetone (2 x 30 mL), and dissolved in MeOH with heating. Acetone addition to the methanolic solution caused precipitated The solid material was collected by filtration, washed with acetone (2 x 25 mL), and dried in vacuo; affording compound BB, 1.14 g (38%). Preparation of 3-(phenylacetamido)-l-propanesulfonic acid, sodium salt (Compound AG) 3-amino-l-propanesulfonic acid (1.0 g, 7.2 mmol) was dissolved in solution of 3M NaOH (7.2 mL). The mixture was cooled to 0°C before phenylacetyl chloride (1.4 mL, 10.8 mmol) was added. The reaction mixture was allowed to warm up to room temperature and it was stirred for 22h. The solvent was evaporated under reduced pressure. The residue was suspended m 50% EtOH/Acetone. The mixture was stirred at reflux for 30 sec. The solid material was collected by filtration and dried in vacuo, i he product was recrystallized from 95 % EtOH/HiO and dried in vacuo, This allowed the isolation of compound AG, 880 mg (44%). Preparation of 3-(iV-benzylcarbamyl)amino-l-propanesulfonic acid, sodium salt (Compound AH) 3-amino-l-propanesulfonic acid (1.06 g, 7.7 mmol) was dissolved in 1.5N NaOH (5.3 mL). To this solution was added benzyl isocyanate (927 µL, 7.7 mmol). The reaction mixture was stirred at 70°C for 30 min, followed by addition to the mixture one-equivalent of benzyl isocyanate (927 µL, 7.7 mmol). The reaction mixture was stirred for 1hour. The solvent was evaporated under reduced pressure. The residue was suspended in hot acetone. The solid material was collected by filtration, washed with hot acetone, and dried in vacuo; affording compound AH, 2.07 g (92%). Preparation of 3-(N-n-dodecylcarbamyI)amino-l-propanesulfonic acid, sodium salt (Compound AJ) 3-amino-l-propanesulfonic acid (1.06 g, 7.7 mmol) was dissolved in 1.5N NaOH (5.3 mL). To this solution was added n-dodecyl isocyanate (1,7 mL, 7.7 rmnol). The reaction mixture was stirred at 70°C for 30min followed by addition to the mixture one-equivalent of n-dodecyl isocyanate (1.7 mL, 7.7 mmol). The reaction mixture was stirred for 1h. The solvent was removed under reduced pressure. The residual material was suspended in hot acetone. Thesoildmaterial was collected by filtration, washed with hot acetone, and dried in vacuo; affording compound AJ, 2.47g (86%). Preparation of 3-(N--l-adamantyicarbamyl)amino-l-propanesulfonic acid, sodium salt (Compound AK) 3-amino-l-propanesulfonic acid (1.06 g, 7.7 mmol) was dissolved in 1.5N NaOH (5.3 mL). To this solution was added 1-adamantyl isocyanate (1.36g 7.7 mmol) in hot EtOH (5 mL). The reaction mixture was stirred at 70°C for 30min followed by addition (to the mixture) of one-equivalent of 1-adamantyl isocyanate (1.37,7.7 mmol) in hot EtOH (5 mL). The reaction mixture was stirred for 1h, The solvent was removed under reduced pressure. The residue was suspended in hot acetone. The solid material was collected by filtration, washed with hot acetone, and dried in vacuo. The solid was recrystallized fi-om EtOH, affording compound AK, 519.4 mg (20%). Preparation of 3-[2-(4-isobutylphenyl)propanoyIJamino-l-propanesulfonic add, sodium salt (Compound AL) Thionyl chloride (1.6 mL, 21,1 mmol) was added to ibuprofen (1.02 g, 4.9 mmol). The reaction mixture was heated to reflux for 4h. The solvent was evaporated, dried in vacuo, giving corresponding acid chloride, 3-amino-l-propanesulfonic acid (308 mg, 2.2 mmol) was dissolved in 1.5N NaOH (3 mL). To this solution was added dropwise the acid chloride (500.8 mg, 4.4 mmol, prepared above). The reaction mixture was stirred at 70°C overnight. The solvent was removed under reduced pressure. The residue was suspended in acetone. The suspension was stirred at reflux for 30 seconds. The solid material was removed by filtration. Hie filtrate was evaporated to dryness under reduced pressure. The residual material was subjected to separation by flash chromatography (80% CH2Cl2/MeOH) This allowed the isolation of compound AL, 237 mg (14%). Preparation of 3-[(benzylamino)thiocarbonyI]amino-l-propanesulfonic acid, sodium salt (Compound AM) 3-amino-l-propanesulfonic acid (1.07 g, 7.7 mmol) was dissolved in 1.5N NaOH * (5.3 mL). To this solution was added benzyl isothiocyanate (1.02 mL, 7.7 mmol). The reaction mixture was stirred at 70°C for 0.5h; a second-equivalent of benzyl isocyauate (1.02 mL, 7.7 mmol) was added. The reaction mixture was stirred for 1h. The solvent was evaporated under reduced pressure. The residue was suspended m hot acetone. The solid material was collected by filtration, washed with hot acetone, and dried in vacuo. The residual material was recrystallized from MeOH (traces of water), affording compound AM, 1.00 g (42%). Preparation of 3-(3,4-dihydroxybenzyI)amiDO-l-propanesulfonic acid (Compound S) To a solution of 3,4-dimethoxybenzylamine {22 mL, 15.0 mmol) in 2-butanone (20 mL) was added 1,3-propane sultone (1.98 g, 15.8 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. The crude product was suspended in 75% Acetone/MeOH (75 mL). The suspension was stirred at reflux for 30 sec.; the solid material was collected by filtration, washed with acetone (2 x 25 mL), and dried in vacuo. The solid (1.94 g, 6.7 mmol) was dissolved hydrobromic acid (48%, 27 mL). The solution was .stirred at 100 °C for 4h. The solvent was removed under reduced pressure. The residue was dissolved in water (20 mL). The aqueous phase was washed with CH2CI2 (3 x 20 mL), and evaporated under educed pressure. Thesoildresidue was suspended in hot MeOH (75 mL). The suspension was stirred at reflux for 30 sec.; the sohd was collected by filtration, washed with 50% MeOH/acetone, and dried in vacuo. This allowed the isolation of compound S, 1.22 g (70%). Preparation of 4-(3-phenylpropyI)-l-suIfopropylpyridinium hydroxide, inner salt (CompoundC) To a solution of 4-(3-phenylpropyl)pyridine (14.5 mL, 76 mmol) in 2-butanone (150 mL) was added 1,3-propane sultone (10.0 g, 83.6 mmol). The mixture was stirred at reflux for 1.5h. Once the reaction mixture was cooled to room temperature, the precipitate was collected by filtration and washed with acetone. The solid material was recrystallized from EtOH (traces of Et2O), affording compound C, 15.8 g (66%). Preparation of 4-(3-phenylpropyI)-l-sulfopropyH,2,3,6-tetrahydropyridine (Compound D) 4-(3-phenylpropyl)-l-sulfopropylpyridine (10.7 g, 33.5 mmol) was dissolved in 60 mL of MeOR The solution was cooled to 0°C before sodium borohydride (2.55 g, 67.0 mmol) was added portionwise. The reaction mixture was stirred for 0.5 hour at room temperature. Water (10 mL) and concentrated HCl (5 mL) were successively added to the mixture. The inorganic material was removed by filtration. The filtrate was concentrated to dryness under reduced pressure and dried in vacuo. The resultant viscous residue was dissolved in MeOH (60 mL). The solution was stirred with Amberlite IR-120 ion exchange resin (8,3 g) for 15 min. The resin was removed by filtration and washed with MeOH, The filtrate and washing was combined and concentrated to dryness under reduced pressure. The residual material was recrystallized from water, affording compound D (8.05 g, 75%) as white crystals. Preparation of 3-ethylamino-l-propanesulfonic acid (Compound CV) Tetrahydrofuran (THF, 800 mL) was placed a 3 neck 2-L flask (equipped with a condenser) and cooled to 5°C with an ice-bath. To the cold THF was added aqueous ethylamine (70 wt. % solution in water, 85 mL, 1.07 mol), followed by addition of a cold solution of 1,3-propane sultone (25.08 g, 201 mmol) in THF (100 mL) over 24-min period. The mixture was stirred, while cooled with an ice-bath, for Ih. The ice-bath was removed and the mixture was stirred at room temperature overnight. It was then heated under reflux for 1h to distill off the ethylamine. The hot mixture was biphasic. Upon cooling, a solid crystallized at the bottom of the flask. Ether (400 mL) was added and the mixture was cooled to—20 °C. The supernatant was decanted. Methanol (about 120 mL) was added to the residue. The mixture was heated to reflux; and complete dissolution of the solid material was achieved. After the solution was cooled to room temperature, precipitates formed The mixture was cooled in an ice-bath; and the solid material was collected by filtration, rinsed with cold methanol and dried in vacuo (20.66 g, pure by NMR analysis). The solid material was recrystallized from methanol (100 mL). After the mixture was cooled using an ice-bath, the solid was collected by filtration, rinsed with cold methanol, and dried in a vacuum oven at 40°C. Compound CV was obtained as white fine needles (19.12 g, 57 %). The 1H and 13C NMR were consistent with the structure. The l-adamantanamine hydrochloride (80 g, 0.426 mol) was treated with NaOH (10%, 400 mL) in water. The aqueous mixture was extracted with dichloromethane (1 x 400 mL, 2 X 100 mL). The combined organic layers were washed with brine (50 mL) and dried over sodium sulfate (10 g). Solvent was removed under reduced pressure. The resulting white waxysoildwas co-evaporated with acetonitrile (50 mL). The wet solid was suspended in acetonitrile (200 mL). The suspension mixture was added dropwise over 20 min to a solution of 1,3-propane sultone (53 g, 0.426 mol) in acetonitrile (300 mL) and THF (200 mL). The thick mixture was stirred for 2 hours under reflux with a mechanical stirrer. The suspension was then cooled to 13 °C. The solid was collected by suction-filtration, rinsed with acetonitrile ( 2 x 100 mL) and ether (1 x 100 mL), air-dried for 30min, and further dried in vacuo at 60 °C ovemight (104.17g for crop 1). Another crop was collected from the filtrate and dried in vacuo in the same manner (3.39 g for crop 2). Both crops gave identical proton NMR spectrum. The two batches were combined for further purification. Thesoildwas suspended in methanol (720 mL) and the mixture was heated to reflux. Water (490 mL) was added dropwise over 45 min, while maintaining reflux. After complete dissolution of the solid, the solution was kept under reflux for 30 minute. The mixture.was left in the power-off heatmg mantle and allowed to cool slowly. After 90 min, the temperature reached 40 °C. The heating mantle was replaced by a thermostated water bath. The mixture was cooled to 5 °C and stirred overnight at this temperature. The white flaky solid was collected by filtration, rinsed with cold (0 °C) methanol (2 x 125 mL), air-dried for 60 minutes, and then dried in the vacuum oven at 60 °C overnight Conpound B W was obtained as a white flaky solid (white plates, 88.48 g, 76% yield for the first crop). The 1H NMR and MS were consistent with the stmcture. A second CTop (8.62 g) of compound BW was obtamed from the mother liquid The 1H NMR was identical to that of the first crop. This made the reaction a total yield of 83% from the hydrochloride. Preparation of 3-(2-norbomyI)amino-l-propanesulfonic acid (Compound BY) To a solution of 2-aminonorbomane (7.3 g, 65.7 mmol) in 2-butanone (50 mL) was added dropwise a solution of 1,3-propane sulfone (8.1 g, 65.7 mmol) in 2-butanone (10 mL). The mixture was stirred at 60 °C for Ih The suspension was cooled to room temperature. The solid material was collected by filtration and washed with ethanol (2 x 20 mL). The crude material was recrystallized from 95% EtOH to afford compound BY as a white crystallinesoild(8.2 g, 53% yield).. The 2-aminoadamantane hydrochloride (2 x 5g) was treated with NaOH in water. The aqueous mixture was extracted with dichloromethane. The organic layer was dried over magnesium sulfate. The solvent was removed under reduced pressure. The resulting white solid was dried 30 minutes at room temperature under vacuum. A solution of 1,3-propane sultone (7.4 g, 60 mmol) in THF was added to a solution of the free amine (7.98 g, 52 mmol) in THF (70 mL, total). The mixture was heated under reflux for 4h, cooled into an ice bath. The solid was collected by filtration, air-dried for 15 min., and further dried in vacuo (11.2g). Recrystallization was done with methanol/water (60 mL/35 mL). After cooled in a fiidge, the solid was collected by filtration, rinsed with methanol, dried in the vacuum oven at 60 °C overnight A white crystalline sandysoild(small plates, 10.45 g, 74% yield) was obtained. The 1H and 13C NMR were consistent with the structure of Compound BZ. To a solution of 3,4-dimethoxybenzylamino (2-2 mL, 15.0 mmol) in acetone (20 mL) was added 1,3-propane sidtone (1.97 g, 15.8mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL) and dried in vacuo. The crude product was suspended in 90 % acetone/MeOH (75 mL). The suspension was stirred at reflux for 30 sec., the solid material was collected by filtration, and dried in vacuo. Compound S (1.84 g, 43%) was isolated as a white solid. 1H NMR (D2O, 500 MHz) δ ppm 6.96 (m, 3H), 4.06 (s, 2H), 3.74 (s, 6H), 3.07 (t, IH, J= 7.8 Hz), 2.86 (t, IH, J= 7.8 Hz), 2.01 (m, 2H). 13C NMR (D20,125 MHz) 8 ppm 149.23,148.50, 123.63,123.37, 55.90,55.86,50.96,48.06,45.62,21.39. ES-MS 290 (M+1). To a solution of 1,2-diphenylethylaminne (2.49 g, 12.7 mmol) in 2-butanone (15 mL) was added 1,3-propane sultone (1.67 g, 13.3 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone(2x25mL),and diried in vacuo, to give compound ET:3.02 g(74%) 1H NMR (DMSO, 500 MHz) δ ppm 8.58 (s (broad), IH), 7.34 (m, 8H), 7.23 (t, 2H, J= 7.3 Hz), 4.32 (t, IH, J=7.8 Hz), 3.68 (d, 2H, J=7.3 Hz) 3.08 (t, 2H, J= 6.1 Hz), 2.57 (t, 2H, J= 7.3 Hz), 1,92 (m, 2H). 13C NMR (DMSO, 125 MHz) δ ppm 141.63,129.46,128.47,127.76, 50.85, 49.91,48.53,22.07. ES-MS 318 (M-1). To a solution oftert-butylamine (1.0 mL, 9.5 mmol) in tetrahydrofuran (15 mL) was added 2,4-butane sultone (1.33 g, 10.0 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid product was collected by filtration, washed with THF (2 x 20mL), and dried in vacuo; affording compound ES: 1HNMR (DMSO, 500 MHz) δ ppm 2.97 (t, 2H, J- 6.6 Hz), 2.62 (m, IH), 1.95 (m, 0.5H), 1.750 (m, 0.5H), 1.22 (s, 9H), 1.12 (d, 3H, 7= 6.8 Hz). 13C NMR (DMSO, 125 MHz) δ ppm 56.17,53.15,29.87,25.87,17,05. ES-MS 207 (M-1). Preparation of 4-(rer/-butylamino)-l-butanesulfonic acid (Compound ER) To a solution of tert-butylamine (1.0 mL, 9.5 mmol) in tetrahydrofuran (4 mL) was added 1,4-butane sultone (1.36 g, 10.0 mmol) at room temperature. The solution was stirred at reflux for 2 hours.. The reaction mixture was cooled to room temperature. The solid product was collected by filtration, washed with acetone (2 x 20 mL), and dried in vacuo; affording compound ER 690 mg, (34%); 1H NMR (D20,500 MHz) δ ppm 2.92 (t, 2H, J= 7.1 Hz), 2.82 (t, 2H, J= 7.1 Hz), 1.68 (m, 4H), 1.22 (s, 9H). 13C NMR (D20,125 MHz) δ ppm 57.07, 50.30,40.95,25,28,24.96,21.62, ES-MS 210 (M- 1). To a solution of l-ethylpropylamine (10.0 g, 115 mmol) in tetrahydrofuran (80 mL) was added a solution of 1,3-propane sultone (13.7 g, 110 mmol) in 20 mL of THF, The solution was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid product was collected by filtration, washed with acetone (2 x 50 mL), and dried in vacuo,, to afford compound DD (18.1, 80%): 1HNMR (D2O, 500 MHz) 6 ppm 3.08 (t, 2H, J= 7.3 Hz), 3.01 (m, IH), 2.87 (t, 2H,J=> 7.3 Hz) 2,00 (m, 2H), 1.59 (m, 4H), 0.82 (t, 6H, J= 7.3 Hz). 13C NMR (D20,125 MHz) δ ppm 60.87, 48.14, 43.68,21.81.21.60, 8.25. ES-MS 208 (M4). To a solution of tert-amylamine (2,0 g, 23.3 mmol) in tetrahydrofuran (15 mL) was added 1,3-propane sultone (2,76 g, 22.2 mmol). The solution was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid product was collected by filtration, washed with acetone (2 x 25 mL), and dried in vacuo, to afford compound DG (3.3 g, 73%): 1H NMR (D20,500 MHz) δ ppm 3.04 (t, 2H, J= 7.8 Hz), 2.89 (t, 2H, > 7.8 Hz), 2.87 (t, 2H, J=7.3 Hz), 1.97 (m, 2H), 1.55 (m, 2H), 1.18 (s, 6H), 0.82 (t, 6H, J= 7.3 Hz). 13C NMR (D20,125 MHz) δ ppm 60.42,48.17, 39.88, 30.81,22.23,21.98, 7.25. ES-MS 208 (M-1). Preparation of 3-(14-dimethyl-2-hydroxyethyl)amino-l-propanesulfonic acid (Compound DH) To a solution of 2-amino-2-methyH-propanol (2.0 g, 21.4 mmol) in tetrahydrofuran (15 mL) was added 1,3-propane sultone (2.66 g, 21.4 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The crude product was collected by filtration, washed with acetone (2 x 25 mL). The solid was suspended in EtOH (50 mL). The suspension was stirred at reflux for 5 minutes. The solid was collected by filtration and dried in a vacuum oven (50°C), affording compound DH (2.5 g, 58%): 1H NMR (D20,500 MHz) δ ppm 3.48 (s, 2H), 3.04 (t, 2H, J= 7.8 Hz), 2.90 (t, 2H, J= 7.3 Hz), 2.00 (m, 2H), 1.18 (s, 6H). 13C NMR (D20,125 MHz) δ ppm 64.88, 60.27,48.19,40.10,21.92,20.02. ES-MS 210 (M-1). Preparation of 3-(l-carboxy-l-methylethylamino)-l-propanesulfonic acid (Compound DI) To a cold (5°C) mixture of 2-aminoisobutyric acid (2.0 g, 19.4 mmol), NaOH (776 mg, 19.4 mmol) in 1,4-dioxane (10 mL) and water (4 mL) was added via syringe pump (over a 4-hour period), a solution 1,3-propane sultone (2.02 g, 16.2 mmol) in 1,4-dioxane (total: 4mL). The solution was stirred at room temperature for 2 hours before it was allowed to warm up to room temperature. The reaction mixture was stirred under these conditions overnight The solvent was evaporated under reduced pressure. The resultant solid material was recrystallized firom 5% water/EtOH The resultmg solid was dissolved in water; and the aqueous solution was passed though an ion exchange column (Dowex 50WX 8, lOOg, solvent: water). The solvent was evaporated under reduced pressure. The product was lyophilized to afford Compound DI (880 mg, 28%). 1H NMR (D2O, 500 MEIz) 5 ppm 3.00 (t, 2H, J=7.6 Hz), 2.91 (t, 2H, J= 7.3 Hz), 2.01 (m, 2H), 1.34 (s, 6H). 13C NMR (D20,125 MHz) δ ppm 176.93,63.89,48.13,42.04, 22,15,21.86. ES-MS 224 (M-1). Preparation of 3-[(lR,2S)-2-methyIcyclohexyIlainiao-l-propanesulfonic acid (Compound DJ) To a solution of 2-methylcyclohexylamine (98 % cis and trans isomers, 10.0 g, 88-3 mmol) in tetrahydrofuran (60 mL) was slowly added a solution of l,3-propane sultone (10.5 g, 84.1 mmol) in THF (20mL). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 50 mL). The solid was dissolved in 50% EtOH/water (200 mL); and solution was treated with Dowex 50WX8 resm (15 g). The suspension stirred at room temperature for 15 min. The resin was removed by filtration. The filtrate was concentrated to half of the original volume on a rotary evaporator. The solid product slowly crystallized. The product was collected by filtration, washed with acetone (2 x 50mL) and dried in a vacuum oven (50°C), to afford compound DJ (10.4 g, 53%): 1H NMR (D20,500 MHz) δ ppm 3,15 (m, IH), 3.03 (m, IH), 2,88 (t, 2H, J= 13 Hz), 2,76 (m, IH), 1.98 (m, 3H), L68 (m, 2H), 1.51 (m, 2H), 1.18 (m, 3H), 1,01 (m, IH), 0.92 (m, 3H). 13C NMR (D20,125 MHz) δ ppm 62.97, 48.16,42.72,34.77, 33.50,27.57,24.51,24.23,21.51,17,80. ES-MS 234 (M-1). Preparation of 3-(2,3-dimethylcycIohexyI)amino-l-propanesuIfonic acid (Compound DK) To a solution of 2,3-dimethylcyclohexylamine (10.0 g, 79.0 mmol) in tetrahydrofiiran (60 mL) was slowly added a solution of 1,3-propane sultone (93 g, 75.0 mmol) in THF (20 mL), The solution was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with THF (50 mL) and acetone (50 mL). The solid was dissolved in 25% EtOH/water (150 mL), and treated with Dowex 50WX8 resin (15 g). The suspension stirred at room temperature for 5 minutes. The resin was removed by filtration. The filtrate was concentrated to dryness under reduced pressure; and the solid residue was suspended in acetone (100 mL). The solid material was collected by filtration, and dried in vacuo; affording compound DK (7.4 g, 43%). 1H NMR (D2O, 500 MHz) δ ppm 3.29 (m, 0.5H), 3,09 (m, 2H), 2.88 (t, 2H, J=7.3 Hz), 2.80 (in, 0.5H), L99 (m, 3H), 1.40 (m, 7H), 0.81 (m, 6H3. 13C NMR (D20,125 MHz) δ ppm 62.85,61,56,59,88,58.22,48.26, 48.15,44.29, 43.84,43.59,42.65,42,01,41.03,37.34,36.12, 34.73,34.45, 33.88,33.64, 29.39,28.00,26.50,24.25,24.02, 23,64, 22.42,21.55,21.45,21.35,19.38,19.13,18.82, 18.40,14.38,13.39,4.59. ES-MS 248 (M-1). To a solution of neopentylamine (8.5 g, 98 mmol) in tetrahydrofuran (75 mL) was slowly added a solution of 1,3-propane sultone (11.5 g, 93 mmol) in THF (20 mL). The solution was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with acetone (2 x 50 mL). The solid was suspended in EtOH (150 mL). The suspension was stirred at reflux for 15 minutes. The solid product was collected by filtration, washed with acetone (2 x 50 mL), and dried in vacuo, to afford compound DL (13.3 g, 69%). 1H NMR (D20,500 MHz) δ ppm 3.09 (t, 2H, J= 73 Hz), 2,89 (t, 2H, J= 7.3 Hz), 2.78 (s, 2H), 2.04 (m, 2H), 0.901 (s,9H). 13CNMR(D20,125MHz)δppm 59.44,48.31,47.83,29.91,26.42, 21,06, ES-MS 208 (M-1). To a solution of cumylamine (10.5 g, 78 mmol) in tetrahydrofuran (75 mL) was slowly added a solution of 1,3-propane sultone (9.2 g, 74 mmol) in THF (20 mL). The mixture was stirred at reflux for 4h. The reaction mixture was cooled to room temperature. The solid was collected by filtration, and washed with THF (2 x 35 mL). The solid was suspended in EtOH (80 mL), The suspension was stirred at reflux for 15 minutes. The solid product was collected by filtration, washed with EtOH (35mL) and acetone (35 mL), The resulting solid was dried in vacuo, affording compound DM (5.6 g, 30%). 1HNMR (D20,500 MHz) δ ppm 7.41 (m, 5H), 2.74 (m, 4H), 1.88 (m, 2H), 1.66 (s, 6H). 13CNMR(D2O, 125 MHz) 6 ppm 138.36,129.44,129.41,126.52,61.56, 48.04,41.21,24.80,21,81. ES-MS 256 (M-1). To a solution of (R)-(+)-l-(4-methoxyphenyI)ethylamine (5.83 g, 38,6 mmol) in tetrahydrofuran (25 mL) was slowly added 1,3-propanesultone (4.56 g, 36.8 mmol). The solution was stirred at reflux for 4 hours. The reaction mixture was cooled to room temperature. The solid was collected by filtration, washed with THF (25 mL) and acetone (25 mL). The solid was suspended in EtOH (200 mL). The suspension was stirred at reflux for 15 min. The solid was collected by filtration, washed with cold EtOH (50 mL), and dried in a vacuum oven (50 °C), to afford compound FN (5.6 g, 56%). 1H NMR (D2O, 500 MHz) δ ppm 7.26 (d, 2H, J= 8.3 Hz), 6.90 (d, 2H, J= 8.3 Hz), 4.22 (m, IH), 3.68 (s, 3H), 2.92 (m, IH), 2.76 (m, 3H), 1.90 (m, 2H), 1.49 (d, 3H, J= 6.8 Hz). 13C NMR (D20,125 MHz) δ ppm 159.87,129.34,128.18,114.85, 57.99, 55.58,48.05,44.21,21.45,18.21. ES-MS 272 (M-1). To a solution of (R)-(-)-l-aminoindan (1,0 g, 7.5 mmol) in tetrahydrofuran (10 mL) was slowly added 1,3-propane sultone (890 mg, 7.1 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, and washed with THF (20 mL) and acetone (20 mL). The solid was suspended in 80% acetone/EtOH (40 mL). The suspension was stirred at reflux for 30 sec. The solid product was collected by filtration, washed with acetone (2 x 20 mL), and dried in vacuo, to afford compound DO (1.1 g, 61%). 1H NMR (D2O, 500 MHz) δ ppm 7.41 (d, IH, J=7.3 Hz), 7.30 (m, 2H), 7.24 (m, IH), 4.72 (m, IH), 3.14 (t, 2H, J= 7.8 Hz), 3.02 (m, IH), 2.88 (m, 3H), 2.43 (m, IH), 2.12 (m, IH), 2.01 (m, 2H). 13C NMR (D20,125 MHz) δ ppm 14538,136.39,130.31,127.20, 125.72,125.54, 62.98,48.10,43.93,29.84,28.62,21.64. [α]D= - 1.3 ° (c= 0.00515 in water). ES-MS 254 (M-1), Preparation of 3-(iV-tert-butyIcarbamyI)amino-l-propanesulfonic acid, sodium salt (Sodium Salt of Compound DP) 3-amino-l-propanesulfonic acid (2.0 g, 14.3 mmol) was dissolved in 1.6M NaOH (10 mL). To this solution was added tert-butyl isocyanate (1.1 g, 14.3 mmol). The reaction mixture was stirred at 70°C for Ih, followed by addition of one equivalent of tert-butyl isocyanate (1.1 g, 14.3 mmol). The reaction mixture was stirred for Ih. The solvent was evaporated under reduced pressure. The residue was suspended in EtOH (30 mL). The solid product was collected by filtration, washed with EtOH (20 mL) and acetone (20 mL). The resulting solid was dried in vacuo, to afford the sodium salt of compound DP (2.1 g, 66%). 1H NMR (D20,500 MHz) δ ppm 3.03 (t, 2H, J-= 6.6 Hz), 2.76 (t, 2H, J= 7.6 Hz), 1.72 (m, 2H), 1.12 (s, 9H). 13C NMR (D20,125 MHz) δ ppm 160.35, 50.26,48.74,38.31,28.86,25.24, ES-MS 280 (M+ Na). Preparation of 3'-(l,2-dimethyl-l-propyI)amino-l-propanesulfonic acid (Compound DQ) To a solution of 1,2-dimethylpropylamine (10.0 g, 115 mmol) in tetrahydrofuran (80 mL) was slowly added a solution of 1,3-propane sultone (13,7 g, 110 mmol) in THF (20mL). The solution was.stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid product was collected by filtration, washed with THF (50 mL) and EtOH (50 mL). The resulting solid was dried in vacuo, to afford compound DQ (17.5 g, 76%). 1H NMR (D2O, 500 MHz) δ ppm 3,07 (m, 3H), 2.88 (t, 2H, J= 7.3 Hz), 1.97 (m, 3H), 1.10 (d, 3H, J= 6.8 Hz), 0.85 (d, 3H, > 6.8 Hz), 0,81 (d, 3H, J= 6.8 Hz). 13C NMR (D20,125 MHz) δ ppm 59.79,48,19,44.18,29,72,21.51,18,44,15.02, 10.71. ES-MS 232 (M+Na). Preparation of 3-(4-methylcyclohexyl)amino-l-propanesulfonic acid (Compound DR) To a solution of 4-methylcyclohexylamine (97 % cis and trans isomers, 11,0 g, 97.4 mmol) in tetrahydrofuran (70 mL) was slowly added a solution of 1,3-propane sultone (1L5 g, 92.8 mmol) in TEBF (20mL). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with THF (50 mL) and acetone (50 mL). The solid was suspended EtOH. The suspension was stirred at room temperature for 5 minutes. The solid product was collected by filtration, washed with EtOH (50 mL), and dried in a vacuum oven (50°C), to afford compound DR (16.1 g, 75%). 1H NMR (D20,500 MHz) 8 ppm 3.08 (m, 2.5H), 2.93 (m, 0.5H), 2.87 (m, 2H), 1.99 (m, 4H), L64 (m, 3H), 1.47 (m, IH), 1.24 (m, 2H), 0.88 (m, IH), 0.78 (m, 3H). 13C NMR (D20,125 MHz) δ ppm 57.35,56.52,48.16,18.05,43.73,43.30, 32.45, 31.13,28.92,28.69,27.77,24.55,21.65, 21.53,21.20,18.38. ES-MS 236 (M+1). Preparation of 3-(2-methyl-l-butyl)amiDo-l-propanesulfonic acid (Compound DS) To a solution of (+A)-2-methylbutyiamine (10 g, 115 mmol) in tetrahydrofuran (80 mL) was slowly added a solution of l,3-propane sultone (13.5 g, 109 mmol) in THF (20mL), The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with * acetone (2 x 30 mL). The solid was suspended 95% Acetone/EtOH (200 mL). The suspension was stirred at room temperature for 5 minutes. The solid product was collected by filtration, and dried in a vacuum oven (50°C), to afford compound DS (17.6 g, 78%). 1H NMR (D2O, 500 MHz) 6 ppm 3.07 (t, 2H, J= 7.8 Hz), 2.93 (m, 3H), 2.76 (m, IH), 2.01 (m, 2H), 1.67 (m, IH), 1.30 (m, IH), 1.09 (m, IH), 0.81 (d, 3H, J= 6.8 Hz), 0.77 (t, 3H, >= 6.8 Hz). 13C NMR (D20,125 MHz) δ ppm 53.48,48.13,46.92, 31.96,26.38,21.29,16.11,10.19. ES-MS 210 (M+1). Preparation of 3-pivaloylamnio-l-propanesulfonic acid (Compound DT) 3-ainino-l-propanesulfonic acid (2.0 g, 14.4 mmol) was dissolved a NaOH (1.2 g, 30.2 mmol) solution in a mixture of 1,4-dioxane (5mL) and wateri[15 mL). The mixture was cooled to 0°C before pivaloyl chloride (2.8 mL, 2L6 mmol) in 1,4-dioxane (5 mL) was added dropwise. The reaction mixture was allowed to warm up to room temperature and it was stirred at 65 °C for 4h. The solvent was evaporated under reduced pressure. The resulting solid was dissolved in water (30 mL), and treated with Dowex 50WX8 resin. The suspension was stirred for 5 minutes and the resin was removed by filtration. The filtrate was evaporated xmder reduced pressure. The residual material was suspended in 20% EtOH/Acetone. The mixture was stirres at reflux for 30 seconds. The solid product was collected by filtration, and dried in vacuo, to afford compound DT (1.3 g, 41%). 1H NMR P2O, 500 MHz) δ ppm 3.16 (t, 2H, J= 6.8 Hz), 2.75 (t, 2H, J= 7.8 Hz), 1.78 (m, 2H), 1.1 (s, 9H).13C NMR P20,125 MHz) δ ppm 182.75,48,70, 38.57,38.18, 26.65,24.27. ES-MS 222 (M-1). Preparation of 3-(3,3,5-trimethylcyclohexyI)ammo]-l-propanesulfonic acid (Compound ED) To a solution of 3,3,5-trimethylcyclohexylamine (5.0 g, 35.4 mmol) in tetrahydrofuran (35 mL) was slowly added a solution of 1,3-propane sultone (4.17 g, 33.7 mmol)in THF- The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL). The solid was suspended 90 % Acetone/EtOH (100 mL) The suspension was stirred at room temperature for 5 min The solid product was collected by filtration, and dried in a vacuum oven (50°C), affording compound ED (5.9 g, 67%). 1H NMR (D2O, 500 MHz) δ ppm 3.20 (m, IH), 3,08 (m, 2H), 2,87 (t, 2H, J= 6.8 Hz), 1,96 (m, 3H), 1.60 (m, 2H), 1.29 (m, IH), 1.01 (m, IH), 0.84 (s, 3H), 0.73 (m, 8H). 13C NMR (D20,125 MHz) 6 ppm 54.98,48,06,46.51,43.28,40.96, 37.02,32.07, 3L23, 26.68,24.28,2L67,21.52. ES-MS 262 (M-1). Preparation of 3-(2-indanamino)-l-propanesulfonic acid (Compound EE) To a solution of 2-aminoindan (2.50 g, 18.8 mmol) in tetrahydrofuran (25 mL) was slowly added 1,3-propane sultone (2,24 g, 17.9 mmol). The mixture was stirred at reflux for 2.5h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL). The crude product was suspended in 90 % Acetone/EtOH (100 mL). The suspension was stirred at room temperature for 5 minutes. The solid product was collected by filtration, and dried in a vacuum oven (50°C), to afford compound EE (3.1 g, 67%), 1H NMR (DMSO, 500 MHz) 6 ppm 7.25 (m, 2H), 7.20 (m, 2H), 4.00 (m, IH), 330 (m, 2H), 3.13 (m, 2H), 3.02 (m, 2H), 2.64 (m, 2H), 1.96 (m, 2H). 13C NMR (DMSO, 125 MHz) δ ppm 130.98, 127.80,125.25, 57.70,49.24,45.87,36.32,22.66. ES-MS 254 (M-1). Preparation of 3-(4-biphenylamino)-l-propanesulfonic acid (Compound EF) To a solution of 4-ammobiphenyl (3.0 g, 17.8 mmol) in tetrahydrofuran (25 mL) was slowly added 1,3-propane sultone (2.11 g, 16.9 mmol). The solution was stirred at reflux for 3h. The reaction mixture was cooled to room temperature. The solid matreial was collected by filtration, washed with acetone (2 x 25 mL). The crude product was dissolved in a hot solution of 80% MeOH/HaO (120 mL). To this warm solution was added Dowex 50WX8 ion exchange resin (10 g). The hot suspension was stirred for 5 minutes and the resin was removed by. filtration. The filtrate was concentrated to dryness under reduced pressure. The residual solid was dried in a vacuum oven (50°C), affording compound EF (283 mg, 6%). 1H NMR (DMSO, 500 MHz) δ ppm 7.77 (d, 2H, J= 7.8 Hz), 7.66 (d, 2H, J= 7.8 Hz), 7.46 (m, 3H), 7.37 (m, IH), 3.44 (m, 2H), 2.68 (m, 2H), 1.98 (m, 2H). 13C NMR (DMSO, 125 MHz) δ ppm 139.74,129.69,128.74, 128.33,127.31,122.23,49.70, 22.93. ES-MS 290 (M-l). Preparation of 3-[(lR,2S)-2-hydroxy-l-(methoxymethyI)-2-phenylethyl]amino-l-propanesulfonic acid (Compound EG) To a solution of (liS',25)-2-amino-3-methoxy-l-phenyl-l-propanol (1.0 g, 5.5 mmol) in tetrahydrofuran (10 mL) was slowly added 1,3-propane sultone (662 mg, 53 mmol). The mixture was stirred at reflux for 2.5h. The reaction mixture was cooled to room temperature, The solid material was collected by filtration, washed with acetone (2 X 25 mL). The cmde product was suspended 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration and dried in a vacuum oven (50°C), to afford compound EG (1.0 g, 63%). 1H NMR (D2O, 500 MHz) δ ppm 7.32 (m, 5H), 4.77 (d, IH, J= 9.8 Hz), 3.53 (m, IH), 3.37 (m, 1H)326 (m, IH), 3.17 (m, 6H), 2.91 (t, 2H, J= 7.3 Hz), 2,07 (m, 2H). 13C NMR (D20,125 MHz) 5ppm 139.09,129.33,129.27,127.11,70.85,66.29,62.62,58.76,48.14,44.24, 21.47. [α]D= +42.6 ° (c= 0.00091 in water), ES-MS 302 (M-1). Preparation of 3-[(lR,2R,3R,5S)-l,2,6,6-tetramethyIbicyclo[3.1.1]hept-3-yllamino-1- propanesulfonic acid (Compound EH) To a solution of (lR,2R,3R,5S)-(-)-isopmocampheylamine (2.0 g, 13.0 mmol) in tetrahydrofuran (20 mL) was slowly added 1,3-propanesultone (1.56 g, 12.5 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid product was collected by filtration, washed with acetone (2 x 25 mL), and dried in a vacuum oven (50°C), to afford compound EH (2.7 g, 80%). 1H NMR (DMSO, 500 MHz) δ ppm 3.32 (m, 2H), 3.09 (d, 2H), 2.67 (m, 2H), 2.30 (m, 2H),' 1.96 (m, 4H), 1.75 (m, 2H), 1.18 (s, 3H), 1.11 (m, 4H), 0.90 (s, 3H). 13C NMR (DMSO, 125 MHz) 6 ppm 55.97, 50.11,47.55,45.86,41.15,40.91, 38.94, 32.81,31,61,27.96, 23.85,22.59,21.21, [αD= -17.2 ° (c= 0.00083 in water), ES-MS 274 (M-1). Preparation of 3-(2-methoxy-l-methylethyl)amino-l-propanesulfonic acid (Compound EI) To a solution of 2-amino-l-methoxypropane (5.0 g, 17.8 mmol) in tetrahydrofuran (25 mL) was slowly added 1,3-propane sultone (2.12 g, 17.0 mmol). The mixture was stirred at reflux for 4h. The reaction mixture was cooled to room temperature. The solid product was collected by filtration, washed with acetone,(2 x 25 mL), and dried in a vacuum oven (50°C), to afford compound EI (3.1 g, 86%). 1H NMR (P2O, 500 MHz) 8 ppm 3.53 (m, IH), 3.41 (m, 2H), 3.27 (s, 3H), 3.11 (m, 2H), 2.89 (t, 2H, J= 7.3 Hz), 2.00 (m, 2H), 1.18 (d, 3H, J= 5.9 Hz). 13C NMR (D20,125 MHz) δ ppm 71.73,58.80,53.79,48.08,43.55,21.52,12.79. ES-MS 210 (M-1). Preparation of 3-[(1R)-2-benzyH-hydroxyethyl]amino-l-propanesulfonic acid (Compound EJ) To a solution of (R)-(+)-2-amino-3-phenyH-propanol (1.0 g, 6.6 mmol) in tetrahydrofuran (10 mL) was slowly added 1,3-propane sultone (785 mg, 6.3 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL). The crude product was suspended 80% acetone/EtOH (100 mL). The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration, washed with acetone (2 x 25 mL), and dried in a vacuum oven (50°C), to afford compound EJ (890 mg, 52%). 1H NMR (DMSO, 500 MHz) δ ppm 8.58 (s (broad), IH), 7.26 (m, 5H), 5.30 (s (broad), IH), 3.53 (m, IH), 3.31 (m, 2H).3.14 (t, 2H), 2.98 (m, IH), 2-80 (m, IH), 2.62 (t, 2H), 1.98 (m, 2H). 13C NMR (DMSO, 125 MHz) δ ppm 137.31,130.00,129,26,127,49, 60.16, 57.78,49.90,45.34,33.78,22.49. [α]D= +9.7° (c=0.00118 in water). ES-MS272(M-1). Prepiaration of 3-[(15}-2-benzyl-1-hydroxyethyI]amnio-l-propanesulfonic acid (Compound EK) To a solution of (S)-(-)-2-amino-3-phenyl-l-propanol (2.0 g, 13.2 mmol) in tetrahydrofuran (20 mL) was slowly added 1,3-propane sultone (1.57 ,12.6 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL). The cmde product was suspended 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration, and dried in a vacuum oven (50°C), to afford compound EK (1.9 g,56%). 1H NMR (DMSO, 500 MHz) δ ppm 8.63 (s (broad), 1 H), 7.27 (m, 5H), 5.31 (s (broad), IH), 3.53 (m, IH), 3.25 (m, 2H).3.15 (t, 2H), 2.98 (m, IH), 2.80 (m, IH), 2.61 (t, 2H), 1.99 (m, 2H). 13C NMR (DMSO, 125 MHz) δ ppm 137.31,130.01,129,27,127.49, 60.18,57.77,49.88, 45.32,33.78, 22.49. [α]D= - 7.5 ° (c= 0.00118, H2O). ES-MS 272 (M-1). Preparation of 3-(N-methyl-N-tert-butylamino)-l-propanesulfomc acid (Compound EN) To a solution of N-methyl-butylamine (2.0 g, 22.9 mmol) in acetone (25 mL) was slowly added 1,3-propane sultone (2,72 g, 21,8 mmol). The mixture was stirred at reflux for 3h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL). The crude product was suspended in 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration, and dried in a vacuum oven (50°C), to afford compound EN (2.9 g, 65%). 1H NMR (DMSO, 500 MHz) δ ppm 9..40 (s (broad), IH), 3.45 (m, IH), 2.85 (m, IH), 2.59 (m, 5H), 1.99 (m, 2H), 1.28 (s, 9H). 13C NMR (DMSO, 125 MHz) δ ppm 63.23,51.12,49.73, 34.79,25.50,21.72. ES-MS 208 (M-1). Preparation of 3-[(lR,2S)-2-hydroxyindan-l-amino]-l-propanesuIfonic acid (Compound EO) To a solution of (1R,2S)-l-amino-2-mdanol (2.37 g, 15.9 mmol) in tetrahydrofuran (25 mL) was slowly added 1,3-propane sultone (1.89 g, 15.1 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, and washed with acetone (2 X 25 mL). The crude product was suspended in 80% acetone/ethanol (75 mL). The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration, and dried in a vacuum oven (50 °C), to afford the compound EO (2.7 g, 65%). 1H NMR (D2O, 500 MHz) δ ppm 7.36 (d, IH, J= 7.4 Hz), 7.24 (m, 3H), 4.70 (q, IH,J= 5.5 Hz ), 4.53 (d, IH, J= 5.4 Hz), 3.23 (t, 2H, J= 7.8 Hz), 3.10 (m, IH), 2.89 (m, 3H), (m, IH), 2.08 (m, 2H), 13CNMR(D20,125 MHz) δ ppm 141,60,134.30,130.53, 127.61,126.10,125,69,70,42,64.08,48.25,44.73, 38.33,21.50. [α]D= + 3.0 ° (c= 0.0018, water) ES-MS 272 (M+1). Preparation of 3-[(l.S)-l-(hydroxymethyl)-2-methyIpropyl]amino-l-propanesulfonic acid (Compound EP) To a solution of (S)-(-)-2-amino-3-methyH-butanol (2.50 g, 24.2 mmol) in tetrahydrofuran (35 mL) was slowly added 1,3-propane sultone (2.89 g, 23.0 mmol). The mixture was stirred at reflux for 3h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL). The cmde product was suspended in 80% acetone/ethanol (75 mL). The suspension was stirred at reflux for 30 secondes. The solid product was collected by filtration, and dried in a vacuum oven (50°C), to afford compound EP (2.9 g, 56%). 11HNMR (D20,500 MHz) δ ppm 3.78 (dd,lH), 3.62 (dd, IH), 3.13 (m, 2H), 2.90 (m, IH), 2.88 (t, 3H), 1.90 (m, 3H), 0.90 (d, 3H), 0.84 (d, 3H). 13C NMR (D20,125 MHz) δ ppm 64.74, 57.24,48.20,44.44,26.98,21.49,18.53,17.00. [ α]D= + 4.1 ° (c= 0.0017 in water), ES-MS 224 (M-1). Preparation of 3-[(1S)-l-carbamoyi-2-inethylpropyl]aniino-l-propanesulfonic acid (Compound EQ) L-valinamide hydrochloride (2.50 g, 16.4 mmol) was treated with a saturated solution of K2CO3 (75 mL). The mixture was extracted with EtOAc (3 x 75 mL). The organic extracts were combined, dried over Na2S04. The solid material was removed by filtration, and the filtrate was concentrated to dryness under reduced pressure. The residual material was dried in vacuo. To a solution of L-valinamide (1.57 g, 13.5 mmol) in tetrahydrofuran (20 mL) was slowly added 1,3-propane sultone (1.61 g, 12.9 mmol). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2 x 25 mL), The crude product was dissolved in water (60 mL) and treated with ion exchange resin Dowex Marathon C (strongly acidic, 15 g). The mixture was stirred for 15 minutes. The resin was removed by filtration. The filtrate was poured into EtOH (250 mL). The solid product, after the completion of the precipitation, was collected by filtration, and dried in vacuo, to afford compound EQ (1.6 g, 51%). 1H NMR (D20,500 MHz) δ ppm 3.63 (d, IH), 3.05 (m, 2H), 2.85 (m, 2H), 2.05 (m, 4H), 0.93 (d, 3H), 0.88 (d, 3H). 13C NMR (D20,125 MHz) δ ppm 170.24., 65.92,48.16,46.31,29.59,2L31,18.02,17.07. [a3i>= + 10.5 ° (c= 0.0027 in water), ES-MS 237 (M-1). Preparation of 3-isobutylammo-l-propanesulfonic acid (Compound CE) Isobutylamine (2.4 mL, 24 mmol) was added to a solution of 1,3-propaQe sultone (3.04g, 24.5 mmol) in 2-butanone (20 mL). The mixture was heated to reflux. After about 10 minutes, the mixture had turned into a lump. It was cooled to room temperature. Acetone was added and the lump was crushed. The solid was collected by filtration and dried in-vacuo (2,2 g). The white solid was suspended in ethanol (10 mL) and the mixture brought to reflux. A significant amoxmt of the solid dissolved. Water was added slowly until a clear pink solution was obtained. The solution was left at room temperature overnight The flask was placed in a fridge for 2 hours. The solid product was collected by filtration, rinsed with ethanol (5 mL), washed with ether (10 mL), and dried in-vacuo, Compound CE was obtained as long, fine white needles (1.87 g, 40 % yield), m-p. 255-57 °C. 1H NMR (500 MHz, D2O) 5 0.88 (d, J=6.8 Hz, 6H), 1.85-1,93 (m, J= 6.8 Hz, 1H), 2.03 (qt, J= 7.6 Hz, 2H), 2.80 (d, J= 7.3 Hz, 2H), 2.90 (t, J= 7.3 Hz, 2H),3.08(t,J=8.1Hz,2H), 13C NMR (125 MHz, D2O) 5 19.2,21.2,25.8,46.9,48.1,549 ES-MS 196 (M+1). FT-IR (KBr) Vmax 3566, 2973, 2021,1719. Preparation of 3-isoamyIamino-l-propanesulfonic acid (Compound CH) Isoamylamine (4 mL, 34.5 mmol) was added to a solution of 1,3-propane sultone (4.7g, 38 mmol) in 2-butanone (70 mL). The mixture was warmed to reflux. After 30 minutes, the mixture was too thick to stir. Acetone (15 mL) was added. The reflux was maintained for a total of 4 hours. The suspension was cooled at room temperature. The white solid was collected by filtration, rinsed with acetone (10 mL), then with ether (10 mL). Compound CH was obtained as a very Ught, fluffy white solid (4.48 g, 62 % yield). m.p. 220 °C: decomposed. 1H NMR (500 MHz, D2O) 5 0.65 (d, J= 6.3 Hz, 6H), 1,29 (q, J=- 7.7 Hz, 2H), 1.35-1.42 (m, J= 6.6 Hz, IH), 1.86 (qt, J= 7.6 Hz, 2H), 2.74 (t, > 7.3 Hz, 2H), 2.81 (t, J= 8.1 Hz, 2H), 2.93 (t, J= 7.8 Hz, 2H). 13C NMR (125 MHz, D2O) 5 21.3, 21.4,25.2,34.2,46.1,46.2,47.9 Preparation of 2-(tert-butyl)amino-1-ethanesulfonic Acid (Compound DU) A solution of 2-bromoethanesulfonic acid, sodium salt (42 g, 20 mmol) in water (total 12 mL) was added over 6 hours to a 42 °C solution of t-butyiamine (10 mL, 94 mmol) m a mixture of water (10 mL) and 1,4-dioxane (10 mL). The mixture was stirred at 42° for 18 hours. The mixture was then heated to 60 °C for 24h, By proton NMR, 30 % of elimination product (vinylsulfonic acid) was obsered. The mixture was concentrated to dryness and treated with ethanol at refluxing temperature. The solid material was collected (crop 1). The mother liquor was concentrated to dryness and the solid was again treated with ethanol at refluxing temperature, and the solid material was collected (crop 2). Both crops of the solid material were dissolved in water, and the resultant aqueous solutions passed in sequence through a Dowex 50 W X 8 ion-exchange column (100 g resin). The fractions containing the title compound were collected and concentrated to dryness. The solid material obtained was recrystallized from a mixture of ethanol (20 mL) and water (2 mL). The crystals were collected by filtration, dried in a vacuum oven at 60°C for 18 hours. Compound DU was obtained as fine white needles (860 mg, 24 % yield). 1H NMR (500 MHz, D2O) 5 1.16 (s, 9H), 3.02 (t, J= 6.8 Hz, 2H), 3.19 (t, J- 6.8 Hz, 2H). 13C NMR (125 MHz, D2O) 5 24.8,37.3,47.0, 57.8. ES-MS 182 (M+1) Preparation of 3-(cyclohexanemethyl)amino-l-propanesulfonic acid (Compound DV) A mixture of cyclohexanemethylamine (11.12 niL, 0.085 mol) and 1,3-propane sultone (11.00 g, 0.090 mol) in acetonitrile (120 mL) was heated at reflux for 2 hours. The mixture was cooled to room temperature. The solid was collected by filtration, air-dried for 20 minutes (19 g). The solid was suspended in methanol (100 mL) and the suspension was heat to reflux. Water (4 mL) was added dropwise until a clear solution was obtained at refluxing temperature. The mixture was then cooled to 5 °C with stirring. The solid was collected by suction filtration, air-dried for 45 minutes, and further dried in a vacuum oven at 60 °C for over 3 days. Compound DV was obtained as white flakes, (16.23 g, 81 % yield.). 1H NMR (500 MHz, D2O) 5 0.82 (br q, J=11 Hz, 2H), 0.91-1.09 (m, 3H), 1.43-1.53(m, 6H), L93 (qt, J=7.3 Hz, 2H), 2 Jl (d, J= 6.3 Hz, 2H), 2.80 (t, J= 7.3 Hz, 2H), 2.71 (t, J= 7.8 Hz, 2H), 13C NMR (125 MHz, D2O) 5 21.2, 25.0,25.5,29.9,34.7,46.8,48.1,53.7. ES-MS 236 (M+1) Preparation of 3-(14-diethyIpropargyI)ammo-l-propane$ulfonic acid (Compound DW) A mixture of 1,1-diethylpropargylaniine (5 g, 45 mmol) and 1,3-propane sultone (6.05 g, 49.5 mmol) in THF (25 mL) was heated at reflux for 5 hours. The mixture was cooled to room temperature. The solid was collected by filtration, rinsed with diisopropylether (2 x 10 mL) then dried overnight in the vacuum OVEN (7.16 g). The solid was suspended in ethanol (30 mL) and the suspension was heated at reflux for 1 hour. The mixture was then cooled to room temperature and the solid was collected by suction filtration, air-dried for 5 m, and further dried in a vacuum oven at 60 °C overnight (5.86 g). There was still a significant amount of ethanol present. The solid was further dried in the vacuum oven for 40 hours. Compound DW was obtained as a fine white solid, (5.66 g, 81 % yield). 'H NMR (500 MHz, D2O) 5 0.92 (t,J= 7.6 Hz, 2H), 1.71 (q,JJ=7,3 Hz, 3H), 1.93 (qt, J= 7.3 Hz, 2H), 2.81 (t,J=7.3 Hz, 2H), 2.94 (s, 1H), 3.13 (t, J=7.6 Hz, 2H), 13C NMR (125 MHz, D2O) 6 7.2, 21.6,27.8,41.4,48.1, 62.2, 78.6, 78.9. ES-MS 234 (M+1) Prejparation of 3-(l-ethynyIcycIohexyI)amiDO-l-propanesulfonic acid (Compound DX) A mixture of l-ethynylcyclohexylamine (6 g, 48.7 mmol) and 1,3-propane sultone (6.55 g, 53.6 mmol) in THF (35 mL) was heated at reflux for 2 hours (thick paste). The mixture was cooled to room temperature. The solid was collected by filtration, rinsed with THF (3x5 mL), air-dried 15 minutes (7.3 g). The solid was suspended in ethanol (30 mL) and the suspension was heated at reflux for 1 horn*. The mixture was then cooled to room temperature and the solid was collected by suction filtration, rinsed with ethanol (2x5 mL), air-dried for 10 min, and further dried in a vacuum oven at 60 °C overnight (cropl, 7.10g). The combined mother liquors were stirred overnight at room temperature. There was a lot of solid. The sohd was collected by filtration, rinsed with acetone (3x5 mL), air-dried for 30 minutes, and then suspended in ethanol (12 mL). The suspension was heated at reflux for 1 hour. The mixture was then cooled to room temperature and the solid was collected by suction filtration, rinsed with ethanol (2x5 mL), air-dried for 2 minutes, and further dried in a vacuum oven at 60 °C overnight (crop 2:1.85 g). Compound DX was obtained as a fine white solid (two crops in total 8.95 g, 75 % yield). 1H NMR (500 MHz, D2O) 5 0.95-1.05 (m, IH). 1.38-1.54 (m, 5H), 1.60-1.64 (m, 2H), 1.94 (qt, J= 7.8 Hz, 2H), 2.85 (t, J= 7.3 Hz, 2H), 3.01 (s, IH), 3.22 (t, J= 7.8 Hz, 2H). 13C NMR (125 MHz, D2O) ? 21.8, 22.3,24.2,34.4,40.9,48.0,59.2,78.6,79.3. ES-MS 243.0 (M-1). A mixture of (±)-2-Amino-l-phenyIethanol (9.9 g, 72 mmol) and 1,3-propane sultone (9.3 g, 76 mmol) in acetonitrile (70 mL) and ethanol (2 mL) was heated at reflux for 1.5 hours. The mixture was cooled to room temperature. The solid was collected by filtration, rinsed with acetonitrile (2 x 25 mL) air-dried for 20 minutes (21.3 g). The solid was suspended in methanol (110 mL) and the suspension was heated to reflux. Water (4 mL) was added dropwise until a clear solution was obtained. The mixture was then cooled to room temperature. The solid was collected by suction filtration, air-dried for 30 minutes, and further dried in a vacuum oven at 60 °C for 40 hours (crop 1,4.47 g). The combined mother Uquor was stored at-20 °C for 40 hours. A second crop of the solid was collected by filtration, rinsed with acetone (2x15 mL), air-dried (1 hour), and further dried in a vacuum oven at 60 °C for 24 hours. Compound DY was obtained in two crops (total 7.82 g, 42% yield), 1H NMR (500 MHz, D2O) 5,2.03-2.06 (m, 2H), 2.90 (t, J= 7.3 Hz, 2H), 3.16 (t, J= 73 Hz, 2H), 3.20-3.24 (m, 2H), 4.92-4.95(m, IH), 7.30-7.37 (m, 5H). 13C NMR (125 MHz, D2O) 5 21.3, 46.6,78.1,53.2,69.0, 126.1,129.0,129.2,139.6. ES-MS 260 (M+1). Preparation of 3-[(S)-l-(4-methoxyphenyI)ethyl]amino-l-propanesulfonic acid (Compound DZ) A mixture of (S)-(-)-(4-methoxyphenyl)ethylamine (1.83 g, 12,1 mmol) and 1,3-propane sultone (1.6 g, 13 mmol) in acetonitrile (25 mL) was heated at reflux for 2.5 hours. The mixture was cooled to room temperature. The solid was collected by filtration, rinsed with acetonitrile (2x5 mL) air-dried for 15 minutes (3.07 g). The solid was suspended in ethanol (15 mL) and the suspension was heated at reflux for 1 hour. The mixture was then cooled to room temperature. The solid was collected by suction filtration, rinsed with ethanol (2x10 mL), air-dried for 15 minutes, and fiirther dried in a vacuum oven at 60 °C for 18 hours. Compound DZ was obtained as a white solid (2.95 g, 10.8 mmol, 89 % yield). 1H NMR (500 MHz, D2O) 5 L52 (d, J= 6.8 Hz, 3H), 1.88-L98 (m, 2H), 2.76-2.79 (m, 3H), 2.80-2,98 (m, IH), 3.71 (s, 3H), 4.25 (qt, J= 6,7 Hz, 2H), 6.93 (d,J 8.3 Hz, 2H), 7.29 (d, J= 8.3 Hz, 2H). 13C NMR (125 MHz, D2O) 5 18,3, 21.5,44.2,48.1,55.6, 58.0,114.9,128.2,129.4,159.9. ES-MS 274. (M+1). [a]D= -28.8° (c=0.0038 in water) Preparation of 3-(4-bromophenethyl)amino-l-propanesulfonic acid (Compound EA) A mixture of 4-Bromophenethylamine (4 g, 20 mmol) and 1,3-propane sultone (2.56 g, 21 mmol) in acetonitrile (30 mL) was heated at reflux for 2,5 hours. The mixture was cooled to room temperature. The solid was collected by filtration, rinsed with acetonitrile (2x5 mL) air-dried for 15 minutes (9.57 g), and futher dried for 15 nainutes in vacuo (8,02 g). The solid was suspended in ethanol (40 mL) and the suspension was heated at reflux for 1 hour. The mixture was then cooled to room temperature. The solid was collected by suction filtration, rinsed with ethanol (2x5 mL), air-dried for 15 minutes, and furher dried in a vacuum oven at 60 °C for 18 hours. Compound EA was obtained as a white solid (6.04 g, 18.8 mmol, 94 % yield). 1HNMR (500 MHz, DMSO) 5 1.95 (t, J- 6.3 Hz, 3H), 2.63 (t, J= 6.1 Hz, 2H), 2.88 (t, J= 7.6 Hz, 2H), 3.09 (t, J- 6.3 Hz, 2H), 3.15 (t, J= 7.8 Hz, 2H), 7.25 (2, J= 7.8 Hz, 2H), 7.53 (2, J=7.8 Hz, 2H), 8.63 (br s, 2H). 13 NMR (125 MHz, DMSO) 5 21.8, 31.0,46.7,47.2,48.8,119.9,13L0,131.4,136.5. ES-MS 324 (M+1). Preparation of 3-[(S)-indanamino]-l-propanesuIfonic acid (Compound £B) A mixture of (S)-(-)-l-aminoindan (0.92 g, 6.9 mmol) and 1,3-propane sultone (0.93 g, 7.6 mmol) in acetonitrile (15 mL) was heated at reflux for 2.5 hours. The mixture was cooled to room temperature. The solid was collected by filtration, rinsed with acetonitrile (2x4 mL), air-dried for 15 minutes. The solid was suspended in ethanol (12 mL) and the suspension was heated at reflux for 1 hour. The mixture was then cooled to room temperature. The solid was collected by suction filtration, rinsed with ethanol (2x4 mL), air-dried for 15 minutes, and further dried in a vacuum oven at 60 °C over the weekend. Compound EB was obtained as alight pink solid (1.54 g, 87 % yield). 1H NMR (500 MHz, DjO) 5 2.00 (qt,JJ=7.3 Hz, 2H), 2.09-2.13 (m, IH), 2.40-2.45 (m, IH), 2.84-2.87 (m, 3H), 2.98-3.04 (m, IH), 3,12 (t,J= 7.8 Hz, 2H), 4.67-4.70 (m, IH), 7.22 (m, 2H), 7.29-7.32 (m, 2H), 7.40 (d, J= 7.8 Hz, IH). 13C NMR (125 MHz, D2O) 5 21.6,28.6,29.8,43.9,48.1,63.0,125.5,125.7,127.2,130.3,136.3, 145.4. ES-MS 256 (M+1). [αD=-1.0° (c=0.003095 in water). Preparation of 3-cycIobutyIamiDo-l-propanesulfonic acid (Compound EQ A mixture of cyclobutylamine (1.11g, 15.6 mmol) and 1,3-propane sultone (2 g, 17 mmol) in acetonitrile (18 mL) was heated at reflux. The mixture turned to a lump within 15 minutes. THF (10 mL) was added. The reflux was maintained for 1 hour. The mixture was cooled to room temperature. The solid was collected by filtration, rinsed with acetonitrile (2x4 mL), air-dried for 60 minutes (2.41 g). The solid was suspended in methanol (20 mL) and the suspension was heated at reflux until all the solid material was dissolved. The mixture was then cooled to room temperature- The solid thus formed was collected by suction filtration, rinsed with methanol (2x4 mL), air-dried for 20 minutes, and further dried in a vacuum oven at 40 °C for 18 hours. Compound EC was obtained as a white solid (1.81 g, 60 % yield).1H NMR (500 MEIz, D2O) 5 L70-1.77 (m, 2H), L94-2.03 (m, 4H), 2.18 (br s, 2H), 2.85 (t,J= 6,8 Hz, IH), 2.95 (t, J= 7.3 Hz, IH), 3.63-3.66 (m, IH). 13C NMR (125 MHz, D2O) 5 14.5,21.5, 26.1,43.6,48.0,51.8, ES-MS 194 (M+1). Preparation of 3-(4- mexiIetino)-l-propanesuIfonic acid (Compound £V) Mexiletine hydrochloride (2.45 g, 11.3 mmol) was freed with INNaOH (50 mL), extracted with ethyl acetate (2 x 50 mL). The combined extract was dried over sodium sulfate. The solvent was evaporated. A solution of 1,3-propane sultone (1.46 g, 11.9 mmol) in THF (35 mL) was added to the free amine. The mixture was heated at reflux for 4 hours. The mixture was cooled to room temperature; and the resultant solid material was collected by filtration, rinsed with THF (5 mL). The solid was dried overnight at 40 °C. The filtrated dried in air overnight to afford a brownish solid (1.45 g) it was less pure than the first crop thus discarded. Compound EV was obtained as a whitesoild(1.19 g, 56 % (99 % crade) yield). 1HNMR (500 MHz, DMSO) 5 1.39 (d, J= 6.3 Hz, 3H), 2,02 (t, J= 5.9 Hz, 2H), 2.26 (s, 6H), 2.67 (t, J= 5.9 Hz, 2H), 3.21 (br d, J= 19.5 Hz, 2H), 3.61 (br s, IH), 3.83-3.91 (m, 2H), 6.95 (t, J= 7.3 Hz, 1H), 7.04 (m, 2H), 8.91 (br s, 2H). 13V NMR (125 MHz, DMSO) 8 13.3,16.0,21.8,44.6,49.2,52.9, 70.8,124.3,128.9,130.4,154.2. ES-MS 302 (M+1). Preparation of 3-(l-benzyl-2-methoxyethyI))amino-l-propanesuIfonic acid (Compound EW) S-(+)-2-Amino-l-methoxy-3-phenylpropane hydrochloride (2.06 g, 10.0 mmol) was freed with saturated potassium carbonate (20 mL). The aqueous mixture was extracted with ethyl acetate (3x15 mL); and the combined extract was dried over sodium sulfate. The solvent was evaporated. A solution of 1,3-propane sultone (L29 g, 10.5 mmol) in THF (15 mL) was added to the free amine. The mixture was heated at reflux for 4 hours. The mixture was cooled to room temperature and stirred for 1 hour. The solid was collected by filtration, rinsed with acetone (5 mL). The solid was dried overnight 40 °C. Compound EW was obtained as a white solid (2.48 g, S3 % yield). 1H NMR (500 MHz, DMSO) 5 1.99 (m, 2H), 2,65 (t, J= 6.1 Hz, 2H), 2.80 (t, J= 12.0 Hz, IH), 3.05 (m, 2H), 3.17 (m, 3H), 3.22 (dd, J= 3.4 Hz, 10.7 Hz, 2H), 3.33 (m, IH), 3.43 (d, J= 10.7 Hz, 2H), 3.50 (m, IH), 7.27 (m, 3H), 7.35 (t, J= 7.1 Hz, 2H), 8.86 (br d, IH).13C NMR (125 MHz, DMSO) 5 2L8,33.4,45.0,49.2, 57.8,58.5, 68.1,126.9, 128.7,129.2,136.3. ES-MS 310 (M+1). [a]D=- 0.8 ° (c= 0.0025 in water). Preparation of 3-[l-(7V-hydroxycarbamoyI)-2-phenylethyI)amino-l-propanesulfonic acid (Compound FO) A solution of hydroxylamine 50% in water (wtywt, 7 mL) was added to a solution of L-N-(3-sulfopropyl)phenylalanine ethyl ester (1.00 g, 3.17 mmol in water (5 mL). The mixture was stirred at room temperature for 24 hours. The mixture was concentrated to dryness. The resulting solid was dissolved in a mixture of hot methanol (10 mL) and water; and the mixture was stored at 5 °C for 3 days. Only a very small amount of solid had formed. Upon addition of acetone (3 mL), a large amount of solid formed. The solid was collected by suction-filtration, rinsed with acetone (2x5 mL) then dried overnight at 40 °C in a vacuum. oven. Compound FO was obtained as a white solid (700 mg, 73 %). 1HNMR (500 MHz, D2O) 5 2.03-2.07 (m, 2H), 2,88-2.90 (M, '2H), 2.99-3.03 (M, IH), 3.07-3.12 (M, IH), 3.18-3.23 (m, IH), 3,82-3.85 (m, IH), 7.15 (d, J= 6.8 Hz, 2H), 7.26-7.31 (m, 3H). 13C (125 MHz, D2O) 5 19.3,33.8,43.2,45.8, 57.9,126.0,127.1,127.3,131.4,162.2, ES-MS303 (M+Na). [α]D= 40° (c= 0.001983 in water). REVISED CLAIMS 1. A compound of Formula I: wherein: R1 is a substituted or unsubstituted cycloalkyl, heterocyclic, aryl, arylcycloalky'l, bicyclic or tricyclic ring, a bicyclic or tricyclic fused ring group, or a substituted or unsubstituted C2-C10 alkyl group; R2 is hydrogen or alkyl; Y is SO3 X+; X* is hydrogen or a cationic group; and each of L1 and L2 is independently a substituted or unsubstituted C1-C5 alkyl group or absent, or a pharmaceutically acceptable salt,ester or prodrug thereof, provided that when R is alkyl, L is absent; provided that when R is benzyl, L is methylene, R is phenyl, L is -(CH2)3-, Y is not SO3'X , provided that when R2 is hydrogen, L2 is -(CH2)3-, L' is methylene, R1 is l,3-benzodioxol-5-yl or 3, 4-methoxybenzyl, Y is not S03 X , and provided that when R is hydrogen, L is -(CH2)3-, L1 is absent, R1 is t-butyl, isobutyl, pentyl, n-heptyl, n-octyl, n-nonyl, cyclohexyl, isopropyl, isoamyl, l-hydroxy-2-propyl, 3,5-dimethyl-l-adamantyl, l-hydroxy-2-pentyl, 3-methyl butyric acid, -4-methyl-pentanoic acid methyl ester, or 2,2-diphenyl-ethyl, Y is not S03X+. 2. A compound of Formula 11: wherein: R1 is a substituted or unsubstituted cyclic, bicyclic, tricyclic, or benzoheterocyclic group or a substituted or unsubstituted C2-C10 alkyl group; R is hydrogen, alkyl, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, benzoimidazolyl, or linked to R1 to form a heterocycle; Y is S03"X^, 0S03"X^, or SSO3X+; X+ is hydrogen, a cationic group, or an ester forming moiety; m is 0; n is 1,2, 3, or 4; L is substituted or unsubstituted C1-C3 alkyl group or absent, or a pharmaceutically acceptable salt, ester or prodrug thereof, provided that when R1 is alkyl, L is absent. 3 The compound of claim 1 or 2, wherem R is hydrogen. 4. The compound of any one of claims 1-3, wherein R1 is straight chain alkyl. 5. The compound of claim 4, wherein R1 is ethyl, n-pentyl, n-heptyl, n-octyl, or n- nonyl. 6. The compound of any one of claims 1-3, wherein R1 is t-butyl. 7. The compound of any one of claims 1-3, wherein R1 is carbocyclic. 8. The compound of any one of claims 1-3, wherein R1 is C7-C10 bicycloalkyl. 9. The compound of any one of claims 1-3, wherein R1 is tricycloalkyl. 10. The compound of claim 9, wherein R1 is tricyclo[3.3.1.03,7]decyl or adamantyl. 11. The compound of claim 9, wherein R1 is bicyclo[2.1.2]heptyl. 12. The compound of any one of claims 1-3, wherein said bicyclic fused ring group is indolyl. 13. The compound of anyone of claims 1-12, wherein L1 is CH2CH2. 14. The compound of any one of claims 1-3, wherein R1 is tetrahydronaphthyl. 15. The compound of any one of claims 1-12 or 14, wherein L1 is absent. 16. The compound of claim 1 or 2, wherein said compound is: wherein: A is nitrogen or oxygen; R11 is hydrogen, salt-forming cation, ester forming group, or (CH2)x Q; Q is hydrogen, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl; x is 0, 1, 2, 3, or 4; n is 0, 1 ,2.3.4, 5, 6, 7, 8, 9, or 10; R3 R3A R4 R4a R5 R5a, R6 R6A, R7 and R7a are each independently hydrogen, alkyL mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, cyano, halogen, amino, tetrazolyl, or two R groups on adjacent ring atoms taken together with the ring atoms form a double bond, pro\ided that one of R3 R3A, R5 R5a R6 and R6a is a moiety of Formula IIIa: wherein: m is 0, 1, 2, 3, or 4; RA, R", RC RD, and RE are independently selected from a group of hydrogen, halogen, hydroxyl, alkyl, alkoxyl, halogenated alkyl, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, cyano, thiazolyl, triazolyl, imidazolyl, tetrazolyl, benzothiazolyl, and benzoimidazolyl; and pharmaceutically acceptable salts, esters, and prodrugs thereof, provided that said compound is not 3-(4-phenyl-l, 2, 3, 6-tetrahydro-l-pyridyl)-l-propanesulfonic acid, and provided that when R3a, R4 R4A, R5 R5a, R6 R6a, R7 and R7a' are hydrogen, and R is not a moiety of Formula IIIa. 18. The compound of claim 17, wherein n is 2, 3 or 4. 19. The compound of claim 17 or 18, wherein R11 is a salt-forming cation. 20. The compound of claim 19, wherein said salt-forming cation is lithium, sodium, potassium, magnesium, calcium, barium, zinc, iron, or ammonium. 21. The compound of claim 17 or 18, wherein R11 is an ester-forming group. 22. The compound of claim 21, wherein said ester-forming group is substituted or unsubstituted alkyl, aryl, alkenyl, alkynyl, or cycloalkyl. 23. The compound of anyone of claims 17-22, wherein R3 and R4 are taken together form a double bond. 24. The compound of anyone of claim 17-22, wherein R , R , R , and R are each hydrogen. 25. The compound of anyone of claims 17-24, wherein R3a is hydroxyl, cyano, acyl, or hvdrox\^l. 26. The compound of any one of claims 17-25, wherein RA , RB , Rc , RD , and RE are each hydrogen. 27. The compound of any one of claims 17-25, wherein RA, RB, RD, and RE are each hydrogen, and R is halogen. 28. The compound of claim 27, wherein said halogen is fluorine, bromine, chlorine, or iodine. 29. The compound of any one of claims 17-28, wherein m is 0 or 1. 30. The compound of any one of claims 17-28, wherein m is 3. 31. The compound of any one of claims 17-30, wherein A is oxygen. 32. The compound of any one of claims 17-31, wherein R3' is a moiety of Formula ma. 33. The compound of claim 17, wherein said compound is: 1 or or a pharmaceutically acceptable salt, ester, or prodrug thereof. 34. A compound of Formula IV: wherein: A is nitrogen or oxygen; R11 is hydrogen, salt-forming cation, ester forming group, or (CH2) Q; Q is hydrogen, ihiazolyl, triazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl; x is 0, 1, 2, 3, or 4; n is 0, 1 ,2 ,3, 4, 5, 6, 7, 8, 9, or 10; R4 R4a, R5 R5a R6 R6A, R7 and R7a are each independently hydrogen, alkyl, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, cyano, halogen, amino, tetrazolyl, R4 and R5 taken together, with the ring atoms they are attached to, form a double bond, or R and R taken together, with the ring atoms they are attached to, form a double bond; m is 0, 1, 2, 3, or 4; R8, R9, R10, R11, and R12 are independently selected from a group of hydrogen, halogen, hydroxyl, alkyl, alkoxyl, halogenated alkyl, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, cyano, thiazolyl, triazolyl, imidazolyl, tetrazolyl, benzothiazolyl, and benzoimidazolyl; or pharmaceutically acceptable salts, esters, and prodrugs thereof. 35. The compound of claim 34, wherein m is 0. 36. The compound of claim 34 or 35, wherein n is 2, 3, or 4. 37. The compound of any one of claims 34-36, wherein R4 , R5 , R6 and R7 are each hydrogen. 38. The compound of any one of claims 34-36, wherein R8, R9, R10, R11 and R12 are each hydrogen. 39. The compound of any one of claims 34-36, wherein R8, R9, R11, and R12 are each hydrogen, and R10 is fluorine, chlorine, nitro, or alkyl. 40. The compound of any one of claims 34-36, wherein R9, R10, R11 and R12 are each hydrogen and R8 is fluorine. 41. The compound of claim 35, wherein said compound is: wherein: A is nitrogen or oxygen; R11 is hydrogen, salt-forming cation, ester forming group, (CH2)x Q, or when A is nitrogen, A and R11 taken together may be the residue of a natural or unnatural amino acid or a salt or ester thereof, wherein A and R11 taken together are not a leucine residue; Q is hydrogen, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl; X is 0, 1, 2, 3, or 4; n isO, 1 ,2 ,3, 4, 5, 6, 7, 8, 9, or 10; aa is a natural or unnatural amino acid residue; m is 0, 1, 2, or 3; R14 is hydrogen or protecting group; R15 is hydrogen, alkyl or aryl; and phaxmaceutically acceptable salts, esters, or prodrugs thereof. 43. The compound of claim 42, wherein n is 2, 3 or 4. 44. The compound of claim 42, wherein n is 3. 45. The compound of any one of claims 43-44, wherein m is 0. 46. The compound of any one of claims 43-45, wherein A-R11 is a residue of a natural amino acii or a salt or ester thereof. 47. The compound of claims 46, wherein A-R^^ is a phenylalanine residue. 48. The compound of any one of claims 42-47, wherein (aa)m is a residue of phenylalanine, glycine, or phe-phe. 49. The compound of any one of claims 42-48, wherein R15 is hydrogen or substituted alkyl. 50. The compound of claim 49, wherein R15 is arylalkyl. 51. The compound of claim 42, wherein said compound is: wherein: n is 1,2. 3,4, 5, 6, 7, 8, 9, or 10; A is oxygen or nitrogen; R11 is hydrogen, salt-forming cation, ester forming group, (CH2)x Q, or when A is nitrogen, A and R11 taken together may be the residue of a natural or unnatural amino acid or a salt or ester thereof; Q is hydrogen, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl; X is 0, 1, 2, 3, or 4; R19 is hydrogen, alkyl or aryl; Y1 is oxygen, sulfur, or nitrogen; Y2 is carbon, nitrogen, or oxygen; R is hydrogen, alkyl, amino, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, thiazolyl, triazolyl, tetrazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl; R21 is hydrogen, alkyl, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, thiazolyl, triazolyl, tetrazolyl, imidazolyl, benzothiazolyl, benzoimidazolyl, or absent if Y is oxygen; R22 is hydrogen, alkyl, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, thiazolyl, triazolyl, tetrazolyl, imidazolyl, benzothiazolyl, benzoimidazolyl; or R is hydrogen, hydroxyl, alkoxy or aryloxy if Y is nitrogen; or R22 is absent if Y1 is oxygen or sulfur;or R22 and R21 may be linked to form a cyclic moiety if Y1 is nitrogen; R is hydrogen, alkyl, amino, mercaptoalkyl, alkenyl, alkynyl, cycloalkyl, aryl, anlalkyl thiazolyl, triazolyl, tetrazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl or absent if Y is nitrogen or oxygen; or pharmaceutically acceptable salts, esters, or prodrugs thereof, provided that when n is 3, Y1 is oxygen, Y2 is oxygen, R21 is benzyl, A is oxgen, R19 is not hydrogen; and provided that when n is 3, Y1 is oxygen, Y2 is carbon, each of R20, R21 and R23 is methyl, R19 is not hydrogen, and provided that R21 and R22 are not linked to form an aryl ring. 53. The compound of claim 52, wherein R11 is a salt forming cation. 54. The compound of claim 52 or 53, wherein A is oxygen. 55. The compound of any one of claims 52-54, wherein Y1 is oxygen or sulfur, and R22 is absent 56. The compound of any one of claims 52-55, wherein Y2 is oxygen and R21 is absent. 57. The compound of any one of claims 52-56, wherein R^^ is benzyl, aryl, alkyl, or cycloalkyl. 58. The compound of any one of claims 52-55 and 57, Y is nitrogen. 59. The compound of any one of claims 52-55, wherein R21 is hydrogen. 61. The compound of any one of claims 52-55, wherein R is benzyl. 62. The compound of any one of claims 53-55 and 57-60, wherein Y1 is sulfur. 63. The compound of claim 53, wherein said compound is selected from the group consisting of: wherein: n is 2, 3, or 4; A is oxygen or nitrogen; R11 is hydrogen, salt-forming cation, ester forming group, (CH2)x Q, or when A is nitrogen, A and R11 taken together may be the residue of a natural or unnatural amino acid or a salt or ester thereof; Q is hydrogen, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, or benzoimidazolyl; X is 0, 1, 2, 3, or 4; G is a direct bond or oxygen, nitrogen, or sultur; z is0, L2. 3.4. or 5; m is 0 or 1; R24 is selected from a group consisting of hydrogen, alkyl, mercaptoalkyl, alkenyl, alkynyl, aroyl, alkylcarbonyl, aminoalkylcarbonyl, cycloalkyl, aryl, aryllalkyl, thiazolyl, triazolyl, imidazolyl, benzothiazolyl, and benzoimidazolyl; each R25 is independently selected from hydrogen, halogen, cyano, hydroxyl, alkoyl. thiol, amino, nitro, alkyl, aryl, carbocyclic, or heterocyclic; and pharmaceutically acceptable salts, esters, and prodrugs thereof. 65. The compound of claim 64, wherein R11 is hydrogen. 66. The compound of claim 64 or 65, wherein A is oxygen. 67. The compound of any one of claims 64-67, wherein n is 3. 68. The compound of any one of claims 64-68, wherein R is hydrogen. ^ A 69. The compound of any one of claims 64-68, wherein R is benzyl. 70. The compound of any one of claims 64-69, wherein m is 1. 71. The compound of any one of claims 64-70, wherein z is 0, 2, or 3. 72. The compound of any one of claims 64-71, wherein R25 is hydroxyl or alkoxy. 73. The compound of claim 72 , wherein said alkoxy R is methoxy. 74. The compound of claim 64, wherein said compound is selected from the group consisting of: 77. A compound of any one of claims 1-76, wherein said compound is not a compound of Table 2A. 78. A method of treating or preventing an amyloid-related disease in a subject comprising administering to a subject in need thereof a compound of any one of claims 1-77 or depicted in the Tables and Figures in an amount effective to treat or prevent an amyloid related disease. 79. The method according to claim 78, wherein said amyloid-related disease is Alzheimer's disease, cerebral amyloid angiopathy, inclusion body myositis, macular degeneration, MCI, or Down's syndrome. 80. A pharmaceutical composition comprising a compound according to any one of claims 1-77 or described in the Tables, Formulas or Schemes. 81. The pharmacuetical composition of claim 80, wherein said pharmaceutical composition comprises an effective amount of said compound and a pharmaceutically acceptable carrier. 82. The pharmaceutical composition of claim 81, wherein said effective amount is effective to treat or prevent an amyloid related disease.

Documents:

242-CHENP-2006 ABSTRACT.pdf

242-CHENP-2006 CLAIMS.pdf

242-CHENP-2006 CORRESPONDENCE OTHERS.pdf

242-CHENP-2006 CORRESPONDENCE PO.pdf

242-CHENP-2006 DESCRIPTION (COMPLETE).pdf

242-CHENP-2006 FORM 1.pdf

242-CHENP-2006 FORM 13.pdf

242-CHENP-2006 POWER OF ATTORNEY.pdf

242-chenp-2006-abstract.pdf

242-chenp-2006-assignement.pdf

242-chenp-2006-claims.pdf

242-chenp-2006-correspondnece-others.pdf

242-chenp-2006-correspondnece-po.pdf

242-chenp-2006-description(complete).pdf

242-chenp-2006-form 1.pdf

242-chenp-2006-form 18.pdf

242-chenp-2006-form 3.pdf

242-chenp-2006-form 5.pdf

242-chenp-2006-pct.pdf