Title of Invention	"A PIPERIDINYL INDOLE COMPOUND"
Abstract	The present invention discloses a piperidinyl indole compound of formula (MA).

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NOCICEPTIN ANALOGS This application claims priority from U. S. Provisional Application Serial Nos. 60/284,666; 60/284,667; 60/284. 668; 60/284, 669 all filed April 18, 2001, the disclosures of which are hereby incorporated by reference. BACKGROUND OF THE INVENTION Chronic pain is a major contributor to disability and is the cause of an untold amount of suffering. The successful treatment of severe and chronic pain is a primary goal of the physician with opioid analgesics being preferred drugs. Until recently, there was evidence of three major classes of opioid receptors in the central nervous system (CNS), with each class having subtype receptors. These receptor classes were designated as p, 6 and K. As opiates had a high affinity to these receptors while not being endogenous to the body, research followed in order to identify and isolate the endogenous ligands to these receptors. These ligands were identified as enkephalins, endorphins and dynorphins. Recent experimentation has led to the identification of a cDNA encoding an opioid receptor-like (ORL1) receptor with a high degree of homology to the known receptor classes. This newly discovered receptor was classified as an opioid receptor based only on structural grounds, as the receptor did not exhibit pharmacological homology. It was initially demonstrated that non-selective ligands having a high affinity for u.. 6 and K receptors had low affinity for the ORL1. This characteristic, along with the fact that an endogenous ligand had not yet been discovered, led to the term"orphan receptor". Subsequent research led to the isolation and structure of the endogenous ligand of the ORL1 receptor. This ligand is a seventeen amino acid peptide structurally similar to members of the opioid peptide family. The discovery of the OR1.1 receptor presents an opportunity in drug discovery for novel compounds which can be administered for pain management or other syndromes modulated by this receptor. All documents cited herein, including the foregoing, are incorporated by reference in their entireties for all purposes. OBJECTS AND SUMMARY OF THE INVENTION It is accordingly an object of certain embodiments of the present invention to provide new compounds which exhibit affinity for the OR1.I receptor. It is an object of certain embodiments of the present invention to provide new compounds which exhibit affinity lor the ORLI receptor and one or more of the u., 8 and K receptors. It is an object of certain embodiments of the present invention to provide new compounds for treating a patient suffering from chronic or acute pain by administering a compound having affinity for the ORLI receptor. It is an object of certain embodiments of the present invention to provide new compounds which have agonist activity at the µ and K receptors which is greater than compounds currently available e. g. morphine. It is an object of certain embodiments of the present invention to provide methods of treating chronic and acute pain by administering compounds which have agonist activity at the µ ,  and K receptors which is greater than compounds currently available. It is an object of certain embodiments of the present invention to provide methods of treating chronic and acute pain by administering non-opioid compounds which have agonist activity at the fa, 8 and K receptors and which produce less side effects than compounds currently available. It is an object of certain embodiments of the present invention to provide compounds useful as analgesics, anti-inflammatories, diuretics, anesthetics and neuroprotective agents, anti-hypertensives, anti-anxioltics ; agents for appetite control; hearing regulators ; anti-tussives, anti-asthmatics, modulators of locomotor activity, modulators of learning and memory, regulators of neurotransmitter and hormone release, kidney function modulators, anti-depressants, agents to treat memory loss due to Alzheimer's disease or other dementias, anti-epileptics, anti-convulsants, agents to treat withdrawal from alcohol and drugs of addiction, agents to control water balance, agents to control sodium excretion and agents to control arterial blood pressure disorders and methods for administering said compounds. The compounds of the present invention are useful for modulating a pharmacodynamic response from one or more opioid receptors (ORL-l, u., 6 and K) centrally and/or peripherally. The response can be attributed to the compound stimulating (agonist) or inhibiting (antagonist) the one or more receptors. Certain compounds can stimulate one receptor|(e. g., a u, agonist) and inhibit a different receptor (e. g., an ORL-1 antagonist). Other objects and advantages of the present invention will become apparent from the following detailed description thereof. The present invention in certain embodiments comprises compounds having the general formula (1) : (Formula Removed) wherein I) is a 5-8 membered cycloalkyl, 5-8 membered heterocyclic or a 6 membered aromatic or hcteroaromatic group; n is an integer from 0 to 3; A. B and Q are independently hydrogen, C1-10 alkyl, C3-12 cycloalkyl, C1-10alkoxy, C3-12 cycloalkoxy,-CH2OH, -MHSO2, hydroxyC1-10alkyl-, aminocarbonyl-, C1-4alkylaminocarbonyl-, diCualkylaminocarbonyl-, acylamino-, acylamindalkyl-, amide, sulfonylaminoC1-10aIkyl-, or A-B can together form a C2-6 bridge, or B-Q can together form a C3-7 bridge, or A-Q can together form a C1-5 bridge; / is selected from the group consisting of a bond, straight or branched C1-6 alkylene, -NH-, -CH2O-, -CH2NH-, -CH:N(CH3)-, -NHCH2, -CH2CONH-, -NHCH2CO-, -CH2CO-, -COCH2-, -CH2COCH2-, -CH(CH3)-, -CH=, -()- and -HC=CH-, wherein the carbon and/or nitrogen atoms are unsubstituted or substituted with one or more lower alkyl, hydroxy, halo or alkoxy group; R1 is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12cycloalkyl, C2-10alkenyl, amino, C1-10 alkylamino-, C3-12cyeloalkylamino-, -COOV1, -C1-4COOV1, cyano, cyanoC1-10alkyl-, cyanoC3-10cycloalkyl-, NH2SO2-, NH2SO2C1-4alkyl-, NH2SOC1-4alkyl-, aminocarbonyl-, C1-4alkylaminocarbonyl-, diC1. alkylaminocarbonyl-, benzyl, C3-12cycloalkenyl-, a monocyclic, bicyclic or tricyclic aryl or heteroaryl ring, a hetero- monocyclic ring, a hetero-bicyclic ring system, and a spiro ring system of the formula (V): (Formula Removed) wherein X1 and X2 are independently selected from the group consisting of NH, O, S and CH2; and wherein said alkyl, cycloalkyi, alkenyl, C1-10alkylamino-, C3-12cycloalkylamino-, or benzyl of R1 is optionally substituted with 1-3 substituents selected from the group consisting of halogen, hydroxy, CMO alkyl, C1-10 alkoxy. nitro, trifluoromethyl-, cyano, -COOV1, -C1-4COOV1, cyanoC1-10alkyl-,-C1-5(=O)Wi, -C1-5NHS ( -O)2W1, -C1-5NHS(=0)W1, a 5-membered heteroaromaticCo-4alkyl-, phenyl, benzyl, benzyloxy, said phenyl, benzyl, and benzyloxy optionally being substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl-, C1-10 alkoxy-, and cyano ; and wherein said C3-12 cycloalkyi, C3-12 cycloalkenyl, monocyclic, bicyclic dr tricyclic aryl, heteroaryl ring, hetero-monocyclic ring, hetero-bicyclic ring system, or spiro ring system of the formula (V) is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trifluoromethyl-, phenyl, benzyl, phenyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy or benzyloxy is optionally substituted with 1-3 substituents selected from the group consisting of halogen, CMO alkyl, CMO alkoxy, and cyano; W1 is hydrogen, C1-10 alkyl, C3-12 cycloalkyi, C1-10 alkoxy, C3-12 cycloalkoxy, - CH2OH, amino, C1 -1alkylamino-, diC1-4alltylamino-, or a 5-membered heteroaromatic ring optionally substituted with 1-3 lower alkyl ; V1 is H, C1-6 alkyl, C3-6cycloalkyi, benzyl or phenyl; R2 is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12 cycloalkyl- and halogen, said alkyl or cycloalkyi optionally substituted with an oxo, amino, alkylamino or dialkylamino group; and pharmaceutically acceptable salts thereof and solvates thereof. The present invention in certain embodiments comprises compounds having the general formula (IA) as follows: (Formula Removed) wherein n is an integer from 0 to 3; Z is selected from the group consisting of a bond,-CH2-,-NH-,-CH2O-,-CH2CH2- ,-CH2NH-, -CH2N(CH3)-, -NHCH2,-. -CH2CONH-, -NHCH2CO-, -CH2CO-, -COCH2-, - CH2COCH2-,-CH(CH3)-,-CH=, and-HO=CH-, wherein the carbon and/or nitrogen atoms are unsubstituted or substituted with a lower alkyl, halogen, hydroxy or alkoxy group: R1 is selected from the group consisting of hydrogen, C1-10alkyl, C3-12cycloalkyl, C2-10 alkenyl, amino, C1-10 alkylamino, C3-12cycloalkylamino, benzyl, C3-12 cycloalkenyl, a monocyclic, bicyclic or tricyclic aryl or hetcroaryl ring, a hetero-monocyclic ring, a hetero- bicyclic ring system, and a spiro ring system of the formula (V): (Formula Removed) wherein X1, and X2 are independently selected from the group consisting of NH, O, S and CH2; wherein said monocyclic aryl is preferably phenyl; wherein said bicyclic aryl is preferably naphthyl; wherein said alkyl, cycloalkyl, alkenyl, C1-10alkylamino, C3-12cycloalkylamino, or benzyl is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trilluoromethyl, cyano, phenyl, benzyl, benzyloxy, said phenyl, benzyl, and benzyloxy optionally being substituted with 1-3 stibstituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, and cyano : wherein said C3-12 cyclbalkyl, C3-12 cycloalkenyl, monocyclic, bicyclic or tricyclic aryl, heteroaryl ring, hetero-monocyclic ring, hetero-bicyclic ring system, and spiro ring system of the formula (V) are optionally substituted with 1-3 siibstituents selected from the group consisting of halogen, C1-10alkyl, C1-10alkoxy, nitro, trifluoromethyl, phenyl, benzyl, phenyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy and bcnzyloxy are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl. C1-10 alkoxy, and cyano; R2 is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12 cycloalkyl and halogen, said alkyl optionally substituted with an oxo group; and pharmaceutically acceptable salts thereof and solvates thereof. In certain preferred embodiments of formula (I), D is phenyl or a 6 membered heteroaromatic group containing 1-3 nitrogen atoms. In certain preferred embodiments of formula (I) or (IA), the RI alkyl is methyl, ethyl, propyl, butyl, pentyl, or hexyl. In certain preferred embodiments of formula (1) or (IA), the RI cycloalkyl is cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, or norbornyl. In other preferred embodiments of formula (I) or (IA), the R1 bicyclic ring system is naphthyl. In other preferred embodiments of formula (1) or (IA), the R1 bicyclic ring system is tetrahydronaphthyl, or decahydronaphthyl and the R1 tricyclic ring system is dibenzocycloheptyl. In other preferred embodiments R1 is phenyl or benzyl. In other preferred embodiments of formula (I) or (IA), the R] bicyclic aromatic ring is a 10-membered ring, preferably quinoline or naphthyl. In other preferred embodiments of formula (I) or (IA), the RI bicyclic aromatic ring is a 9-membered ring, preferably indenyl. In certain embodiments of formula (I) or (IA), Z is a bond, methyl, or ethyl. In certain embodiments of formula (I) or (IA), the Z group is maximally substituted as not to have any hydrogen substitution on the base Z group. For example, if the base Z group is-CH2-, substitution with two methyl groups would remove hydrogens from the- CH2-base Z group. In other preferred embpdiments of formula (I) or (IA), n is 0. In certain embodiments of formula (I) or (IA), X|, and X2 are both O. In certain embodiments of formula (I), ZR1 is cyclohexylethyl-, cyclohexylmethyl-, cyclopentylmethyl-, dimcthylcyclohexylmethyl-, phenylethyl-, pyrrolyltrifluoroethyl-, thienyltrifluoroethyl-, pyridylethyl-, cyclopcntyl-, eyclohexyl-, methoxycyclohexyl-, tetrahydropyranyl-, propylpiperidinyl-, indolylmethyl-, pyrazoylpcntyl-, thiazolylethyl-, phenyltrifluoroethyl-, hydroxyhexyl-, methoxyhexyl-, isopropoxybutyl-, hexyl-, or oxocanylprojpyl-. In certain embodimenis of formula (I), ZR1 is-CH2COOV1, tetrazolylmethyl-, cyanomethyl-, NH2SO2methyl-, NH2SOmethyl-, aminoicarbonylmethyl-, C1-4alkylaminocarbonylmethyl-, or did.C1-4alkylaminocarbonylmethyl-. In certain embodiments of formula (I), ZR1 is 3,3 diphenylpropyl optionally substituted at the 3 carbon of the propyl with-COOV1, tetrazolylCo-4alkyl-, cyano-, aminocarbonyl-, C1-4alkylaminocarbonyl-, or diC1 -lalkylarninocarbonyk The present invention jn certain embodiments comprises compounds having the general formula (II): (Formula Removed) wherein the dolled line represents an optional double bond; R is hydrogen, CMO alkyl, C3-12 cycloalkyl, C3-12 cycloalkylC1-4alkyl-, C1-10 alkoxy, C3-12 cycloalkoxy-, C1-10 alkenyl, C1-10 alkylidene, oxo, C1-10 alkyl substituted with 1-3 halogen, C3-12 cycloalkyl substituted with 1-3 halogen, C3-12 cycloalkylC1-4alkyl- substituted with 1-3 halogen, C1-10alkoxy substituted with 1-3 halogen, C3-12lycloalkoxy-substituied with 1-3 halogen, -COOV1,-C1-4COOV1, -CH2OH, -SO2N(V1)2, hydroxyC1-10alkyl-, hydroxylC1-10cycioalkyi-, cyanoC1-10alkyl-, cyanoC3.10cycloalkyl-, -CON(Vi)2, NH2SO2C1-4alkyl-, NH2SOC1, -1alkyl-, sulfonylamino C1-10alkyl-, diaminoalkyl-, -sulfonylC1-4alkyl, a 6- membered heterocyclic ring, a 6-mcmbcred heteroaromatic ring, a 6-membered heterocyclicC1-4alkyl-, a 6-membered heteroaromaticCmalkyl-, a 6-membered aromatic ring, a 6-membered aromaticC1-4 alkyl-, a 5-membered heterocyclic ring optionally substituted with an oxo or thio, a 5-membered heteroaromatic ring, a 5-membered heterocyclicC1-4alkyl-optionally substituted with an oxo or thio, a 5-membered heteroaromaticC1-4alkyl-, -C1-5(-O)W1, -C1-5(=NH) W1, -C1-5NHC(=O)W1, -C1-5NHS (=O)2W1,-C1-5NHS (=O)W1, wherein W1, is hydrogen, C1-10alkyl, C3-12 cycloalkyl. C1-10alkox|y, C3-12 cycloalkoxy, -CH2OH, amino, C1-4alkylamino-, diC1-4alkylamino-, or a 5-membered heteroaromfatic ring optionally substituted with 1-3 lower alkyl; wherein each V1, is independently selected from H, C1-6 alkyl, C3-6 cycloalkyl, benzyl and phenyl; n is an integer from 0 to 3 ; I) is a 5-8 membered cycloalkyl, 5-8 membered heterocyclic or a 6 membered aromatic or heteroaromatic group: n is an integer from 0 to 3; A, B and Q are independently hydrogen, C1-10 alkyl, C3-12 cycloalkyl, C1-10 alkoxy, C3-12 cycloalkoxy, C1-10 alkenyl, C1-10 alkylidepe, oxo,-CH2OH,-NHSO2, hydroxy C1-10alkyl-, aminocarbonyl-, C1-4alkylaminocarbonyl-. di C1-4 alkylaminocarbonyl-, acylamino-, acylaminoalkyl-, amide, sulfonylaminoC1-10alkyl-, or A-B can together form a C2-6 btiidge, or B-Q can together form a C3-7 bridge, or A-Q can together form a C1-5 bridge ; Z is selected from the group consisting of a bond, straight or branched C1-6 alkylene,-NH-,-CH2O-,-CH2NH-,-CII2N (CH3)-,-NHCH2-,-CH2CONH-,-NHCH2CO-, -CH2CO-,-COCH2-,-CH2COCH2-,-CH (CH3)-,-CH=,-O-and-11C -CH-, wherein the carbon and/or nitrogen atoms are unsubstituted or substituted with one or more lower alkyl, hydroxy, halo or alkoxy group; R1 is selected from the group consisting of hydrogen, C1-10alkyl, C3-12cycloalkyl, C2-10alkenyl, amino, C1-10 alkylamino-, C3-12cyploalkylamino-, -COOV1, -C1-4COOV1, cyano, cyanoC1-10alkyl-, cyanoC3-10 cycloalkyl-, NH2SO2,. NH2SO2C1-4alkyl, NH2SOC1-4alkyl-, aminocarbonyl-, C1-4alkylaminocarbonyl-, diC1-1alkylaminocarbonyl-, benzyl, C3-12 cycloalkenyl-, a monocyclic, bicyclic or tricyclic aryl or heteroaryl ring, a hetero- monocyclic ring, a hetero-bicyclic ring system, and a spiro ring system of the formula (V): (Formula Removed) wherein X1 and X2 are independently selected from the group consisting of NH, O, S and CH2; and wherein said alkyl, cycloalkyl, alkenyl, C1-10alkylamino-, C3-12cycloalkylamino-, or benzyl of R1 is optionally substituted with 1-3 substituents selected from the group consisting of halogen, hydroxy, C1-10 alkyl, C1-10 alkoxy. nitro. trifluoromethyl-, cyano, -COOV1, -C1-4COOV1, cyanoC1-10alkyl-, -C1-5(=O)W1, -C1-5 ,NHS( O)2W1,-C1-5NHS(=O)W1, a 5-membered heteroaromaticCo-4alkyl-, phenyl, benzyl, benzyloxy, said phenyl. benzyl, and benzyioxy optionally being substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl-, C1-10 alkoxy-, and cyano; and wherein said C3-12 cycloalkyl, C3-12 cycloalkcnyl, monocyclic, bicyclic or tricyclic aryl, heteroaryl ring, hetero-monocyclic ring, hetero-bicyclic ring system, or spiro ring system of the formula (V) is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trifluoromethyl-, phenyl, benzyl, phcnyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy or benzyioxy is optionally substituted with 1-3ubstituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, and cyano ; R2 is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12 cycloalkyl- and halogen, said alkyl or cycloalkyl optionally substituted with an oxo, amino, alkylamino or dialkylamino group; and pharmaceutically acceptable salts thereof and solvates thereof. The present invention in certain embodiments comprises compounds having the formula (IIA): (Formula Removed) wherein the doited line represents an optional double bond; Zis selected from the group consisting of a bond, -CH2-, -NH-, -CH2O-, -CH2CH2-,-CH2NH-,-CH2N (CH3)-,-Nl 1C1 l,-.-CH2CONH-,-NHCH2CO-,-CH2CO-,-COCH2-,- CH2COCH2-,-CH(CH3)-,-CH- and-HC=CH-, wherein the carbon and/or nitrogen atoms are unsubstituted or substituted with a lower alkyl, halogen, hydroxy or alkoxy group; R and Q are the same pr different and are each selected from the group consisting of hydrogen, halogen, C1-10 alkyl, C1-10 alkenyl, C1-10 alkylidene, C3-12 cycloalkyl, C1-10 alkoxy, and oxo; RI is selected from the group consisting of hydrogen, C1-10alkyl, C3-12cycloalkyl, C2-10alkenyl, amino, C3-12 alkylamino, C3-12cyclloalkylamino, benzyl, C3-12 cycloalkenyl, a monocyclic, bicyclic or tricyclic aryl or heteroaryl ring, a heteromonocyclic ring, a bicyclic ring system, and a spiro ring system of the formula (V): (Formula Removed) (V) wherein X1 and X2 are independently selected from the group consisting of NH, O, S and wherein said monocyclic aryl is preferably phenyl; wherein said bicyclic aryl is preferably naphthyl; wherein said alkyl, eycloalkyl, alkenyl, C1-10alkylamino, C3-12cycloalkylamino, or benzyl is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10alkoxy, nitro, trifluoromethyl, cyano, phenyl, benzyl, benzyloxy, said phenyl, benzyl, and benzyloxy optionally being substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, and cyano ; wherein said C3-12 cycloalkyl, C3-12 cycloalkenyl, monocyclic, bicyclic or tricyclic aryl, heteroaryl ring, heteromonocyclic ring, heterobicyclic ring system, and spiro ring system of the formula (V) are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trifluoromethyl, phenyl, benzyl, phenyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy and benzyloxy are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10alkoxy. and cyano ; R: is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12 cycloalkyl and halogen, said alkyl optionally substituted with an oxo group ; and pharmaceutically acceptable salts thereof. In certain preferred enribodiments Q of formula (II) or (IIA), is hydrogen or methyl. In certain preferred embodiments, R of formula (II) or (IIA), is hydrogen, methyl, ethyl, or ethylidene. In certain preferred embodiments of formula (II), D is phenyl or a 6 membered heteroaromatic group containing 1-3 nitrogen atoms. In certain preferred embodiments of formula (II) or (IIA), the R1 alkyl is methyl, ethyl, propyl, butyl, pentyl, or hexylI. In certain preferred embodiments of formula (II) or (IIA), the R1 cycloalkyl is cyclohexyl, cycloheptyl, eyclooclyl, cyclononyl, cyclodecyl, or norbornyl. In other preferred embodiments of formula (II) or (IIA), the R1 bicyclic ring system is naphthyl. In other preferred embodimenls of formula (II) or (IIA), the RI bicyclic ring system is tetrahydronaphthyl, or decahydronaphthyl and the R| tricyclic ring system is dibenzocycloheptyl. In other preferred embodiments RI is phenyl or benzyl. In other preferred embodiments of formula (II) or (IIA), the R1 bicyclic aromatic ring is a 10-membered ring, preferably quinoline of naphthyl. In other preferred embodiments of formula (II) or (IIA), the R1 bicyclic aromatic ring is a 9-membered ring, preferably indenyl. In certain embodiments of formula (II) or (IIA), Z is a bond, methyl, or ethyl. In certain embodiments of formula (II) or (IIA), the Z group is maximally substituted as not to have any hydrogen substitution on the base Z group. For example, if the base Z group is-CH2-, substitution with two methyl groups would rtmove hydrogens from the-CH2-base Z group. Inlflher preferred embpdiments of formula (II) or (IIA), n is 0. In certain embodiments of formula (II) or (IIA), X| and X2 are both O. In other preferred embodiments, the dotted line is a double bond. In certain embodiments of formula (II), R is-CH2C(=O)NH2,-C(NH)NH2, pyridylmethyl, cyclopentyl, cyclohexyl, furanylmethyl,-C(=O)CH3,- CH2CH2NHC(=O)CH3,-SO2CH3,CH2CH2NHSO2CH3, furanylearbonyk methylpyrrolylcarbonyl-, diazolecarbonyl-, azolemethyl-, trifluoroethyl-, hydroxyethyl-, cyanomethyl-. oxo-oxazolemethyl-, or diazolemethyl-. In certain embodiments of formula (II), ZR1 is cyclohexylethyl-, cyclohexylmethyl-, cyclopentylmethyl-, dimethylcyclohexylmathyl-, phenylethyl-, pyrrolyltrifluoroethyl-, thienyltrifluoroethyl-, pyridylethyl-, cyclopentyl-, cyclohqxyl-, methoxycyclohexyl-, tetrahydropyranyl-, propylpiperidinyl-, indolylmethyl-, pyra/oylpentyl-, thiastolylethyl-, phenyltrifluoroethyl-, hydroxyhexyl-, methoxyhexyl-, isopropoxybutyl-, hexyl-, or oxocanylpropyl-. In certain embodiments of formula (II), at least one of ZR1 or R is-CH2COOV1, tetrazolylmethyl-, cyanomethyl-, NH2SO2 methyl-, NH2SOmethyl-, aminocarbonylmethyl-, C1-4alkylaminocarbonylmethyl-, or diC1-4alky laminocarbonylmethyl-. In certain embodiments of formula (II), ZR1 is 3,3 diphenylpropyl optionally substituted at the 3 carbon of the propyl with-COOV1, tetrazolylCo.4alkyl-, cyano-, aminocarbonyl-, C1-4alkylaminocarbonyl-, or diC1-1 alkylaminocarbonyl-. The present invention in certain embodiments comprises compounds having the general formula (III): (Formula Removed) wherein R is hydrogen, CMO alkyl, €3.12 cycloalkyl, €3.12 cycloalkylCi^alkyl-, C].\o alkoxy, €3.12 cycloalkoxy-. C| Hi alkyl substitutad with 1-3 halogen, 03.12 cycloalkyl substituted with 1-3 halogen, €3.12 cycloalkyld. alkyl- substituted with 1-3 halogen, CMO alkoxy substituted with 1-3 halogen, C3-12 cycloalkoxy-substituted with 1-3 halogen, -COOV,, -C1-4COOV,, -CH2OH, -SO2N(V,)2, hydroxyC1-10alkyl-, hydroxyC3-10cycloalkyl-, cyanoC1-10 alkyl-, cyartoC3 locycloalkyl-, -CON(V])2, NH2SO2C1-4alkyl, NH2SOC1-4alkyl-, sulfonylaminoC1-10 alkyl-. diaminoalkyl-,-suironylC1-4alkyl, a 6-membered heterocyclic ring, a 6-membered heteroaromatic ring, a 6-membcred heterocytllicC1-4alkyl-, a 6-membered heteroaromaticC1-4alkyl-, a 6-membered aromatic ring, a 6-membered aromaticC1-4 alkyl-, a 5-membered heterocyclic ring optionally substituted with an oxo or thio, a 5-maribered heteroaromjuic ring, a 5-membered heterocyclicC1-4alkyl-optionally substituted with an oxo or thio, a Pmembered heteroah>maticC1-4alkyK -C1-5(=O)W,, -C1-5(=NH)W1, -C1-5NHC(=O)W1, -C1-5NHS(=O)2W|, -C1-5NHS(--O)W1, wherein W1 is hydrogen, C1-10 alkyl, C3-12 cycloalkyl, C1-10 alkoxy, C3-12 cycloalkoxy, -CH2OH, amino, C1-4alkylamino-, diC1-4alkylamino-, or a 5-membered heteroaromatic ring optionally substituted with 1-3 lower alkyl ; wherein each V|, is independently selected from H, C1-6alkyl, C3-6cycloalkyl, benzyl and phenyl; n is an integer from 0 to 3; D is a 5-8 membered: cycloalkyl, 5-8 membered heterocyclic or a 6 membered aromatic or heteroaromatic group; Z is selected from theigroup consisting of a bond, straight or branched C1-6 alkylene,-NH-,-CH2O-,-CH2NH-,-ClbN(ah)-,-NHCH2-,-CH2CONH-,-NHCH2CO-, -CH2CO-,-COCH2-,-CH2COCH2-,-CH(CH3)-,-CH=,-O-and-HC CH-. whereift the carbon and/or nitrogen atoms are unsubstituted or substituted with one or more lower alkyl, hydroxy, halo or alkoxy group; or Z is a cycloalkylamino system of the formula (VI): (Formula Removed) wherein A, B and Q ate independently hydrogen, CMO alkyl, Cs-ncycloalkyl, CMO alkoxy, C^u cycloalkoxy, -CIliOll. -NHSO2, hytlroxyCi-ioalkyl-, aminocarbonyl-, Ci-4alkylaminocarbonyl-, diCi.4alkylaminocarbonyl-, acylamino-, acylaminqialkyl-, amide, sulfonylaminoC].ioalkyl-, or A-B can together form a C2-6 bridge, or B-Q can together form a Cj.? bridge, or A-Q can together form a Cj.s bridge ; RI is selected from the group consisting of hydrogen, CMO alkyl, Cs-ncycloalkyl, C2.i0alkenyl, amino, C|. loalkylamino-, C3.|2cyploalkylamino, -COOV|, -C|.4COOVi, cyano, cyanoCi_|0alkyl-, cyanoCs.iocycloalkyl-, NH2SOr, NH2SO2Ci-4alkyl-, NH2SOC,.4alkyl-, aminocarbonyl-, d,4alkylaminocarbonyl-, did. ialkyiaminocarbonyl-,!ben/,yl, C$.\2 cycloalkenyl-, a monocyclic, bicyclic or tricyclic aryl or heteroaryl ring, a hctero- monocyclic rirtg, a hetero-bicyclic ring system, and a spiro ring system of the formula (V): (Formula Removed) wherein X1 and X2 are independently selected from the group consisting of NH, O, S and CH2 ; and wherein said alkyl, cycloalkyl, alkenyl, C1-10alkylamino-, C3-12cycloalkylamino-, or benzyl of RI is optionally substituted with 1-3 substituents selected from the group consisting of halogen, hydroxy, C1-10 alkyi, C1-10 alkoxy. nitro. trifluoromethyl-, cyano, -COOV1, -C1-4COOV1, cyanoC1-10alkyl-, -C1-5(=O)W1, -C1-•,NHS( O)2W1, -C1-5N!HS(=O)W1, a 5-membered heteroaromaticCo-4alkyl-, phenyl, benzyl, benzyloxy, said ptoyl, benzyl, and benzyloxy optionally being substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyi-, C1-10 alkoxy-, and cyano; and wherein said C3-12 cycloalkyl, C3-12 cycloalkcnyl, monocyelic, bicyclic or tricyclic aryl, heteroaryl ring, hetero-monocyclic ring, hetero-bicyclic ring system, or spiro ring system of the formula (V) is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyi, C1-10alkoxy, nitro, trifluoromethyl-, phenyl, benzyl, phcnyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy or benzyloxy is optionally substituted with 1 -3 substituents selected from the group consisting of halogen, C1-10 alkyi, C1-10 alkoxy, and cyano; R3 is selected from the group consisting of hydrogen, C1-10 alkyi, C3-12 cycloalkyl- and halogen, said alkyi or cycloalkyl optionally substituted with an oxo, amino, alkylamino or dialkylamino group; and pharmaceutically acceptable salts thereof and solvates thereof. The present invention in certain embodiments comprises compounds having the formula (I1IA): (Formula Removed) wherein n is an integer from 0 (o 3; wherein the carbon and/or nitrogen atoms are unsubstituted or substituted with a lower alkyi, halogen, hydroxy, phenyl, benzyl, or alkoxy group; Zis selected from the group consisting of a bond,-CH2-,-NH-,-CH2O-,-CH2CH2-,-CH2NH-,-CH2N (CH3)-,-NHCH ,-,-CH2CONH-,-NHCI l2CO-,-CH2CO-,-COCH2-,- CH2COCH2-,-CH(CH3)-,-CH=,-HC=CH-, and a cycloalkylamino system of the formula (VI): (Formula Removed) R, is selected from the-group consisting of hydrogen, C1-10 alkyl, C1-10 alkoxy, and C3.|2cycloalkyl; R, is selected from the group consisting of hydrogen, C1-10alkyl, C3-i2cycloalkyl, C2.,0alkenyl, amino, C|. H,alkylamino, C3-|2cyaloalkylamino, benzyl, C3.|2 cycloalkenyl, a monocyclic, bicyclic or tricyclic aryl or heteroaryl ring, a heteromonocyclic ring, a heterobicyclic ring system, and a spiro ring system of the formula (Formula Removed) (V) wherein X1 and X2 are; independently selected from the group consisting of NH, O, S and CH2 ; wherein said monocyclic aryl is preferably phenyl; wherein said bicyclic aryl is preferably naphthyl ; wherein said alkyl, eycloalkyl, alkenyl, C1-10alkylamino, C3-12cycloalkylamino, or benzyl is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trill uoromethyl, cyano, phenyl, benzyl, benzyloxy, said phenyl, benzyl, and benzyloxy optionally being substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, and cyano: wherein said C3-12 cycloalkyl, C3-12 cycloalkenyl, monocyclic, bicyclic or tricyclic aryl, heteroaryl ring, heleromonocyclic ring, heterobicyclic ring system, and spiro ring system of the formula (V) are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10alkoxy, nitro, irifluoromethyl, phenyl, benzyl, phenyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy and benzyloxy are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl. C1-10 alkoxy, and cyano; R2 is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12 cycloalkyl and halogen, said alkyl optionally substituted with an oxo group; and pharmaceutical ly acceptable salts thereof. In certain preferred embodiments of formula (III), D is phenyl or a 6 membered heteroaromatic group containing 1-3 nitrogen atoms. In certain preferred embodiments of formula (III) or (IIIA), the R1 alkyl is methyl, ethyl, propyl, butyl, pentyl, or hexyl. In certain preferred embodiments of formula (111) or (IIIA), the RI cycloalkyl is cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, or norbornyl. In other preferred embodiments of formula (III) or (IIIA), the RI bicyclic ring system is naphthyl. In other preferred embodiments of formula (III) or (IIIA), the RI bicyclic ring system is tetrahydronaphthyl, or decahydronaphthyl anil the RI tricyclic ring system is dibenzocycloheptyl. In other preferred embodiments RI is phenyl or benzyl. 13 In other preferred embodiments of formula (III) or (IIIA), the R1 bicyclic aromatic ring is a 10-membered ring, preferably quinoline or naphthyl. In other preferred embodiments of formula (III) or (IIIA), the R1 bicyclic aromatic ring is a 9-membered ring, preferably indenyl. In certain embodiments of formula (III) or (IIIA), Z is a bond, methyl, or ethyl. In certain embodiments of formula (III) or (IIIA), the Z group is maximally substituted as not to have any hydrogen substitution on the base Z group. For example, if the base Z group is-CH2-, substitution with two methyl groups would remove hydrogens from the-CH2: base Z group. In certain embodiments of formula (III) or (IIIA), Z is a cycloalkylamino system of the formula (VI): (Formula Removed) (VI) wherein the nitrogen atom is optionally substituted with a C1-3alkyl, phenyl, or benzyl. In other preferred embodiments of formula (III) or (IIIA), n is 0. In certain embodiments of formula (III) or (IIIA), X| and X2 are both O. In certain embodiments of formula (III), R is-CH2C(=O)NH2-C(NH)NH2, pyridylmethyl, cyclopentyl, cyclohexyl, futlanylmethyl,-C(=O)CH3,-CH2CH2NHC(=O)CH3,-SO2CH3, CH2CH2NHSO2CH3, furanylcarbonyl-, methylpyrrolylcarbonyl-, diazolecarbonyl-, azolemethyl-, trifluoroethyl-, hydroxyethyl-, cyanomelhyl-, oxo-oxayolemethyl-, or diazolemethyl-. In certain embodiments of formula (III), ZR|, is cyclohexylethyl-, cyclohexylmethyl- , cyclopentylmethyl-, dimethylcyclohexylmetthyl-, phenylethyl-, pyrrolyltrifluoroethyl-, thienyltrifluoroethyl-, pyridylethyl-, cyclopentyl-, cyclohexyl-, methoxycyclohexyl-, tetrahydropyranyl-, propylpiperidinyl-, indolylmethyl-, pyrazoylpentyl-, thiazolylethyl-, phenyltrifluoroethyl-, hydroxyhexyl-, methoxyhexyl-, isopropoxybutyl-, hexyl-. or oxocanylpropyl-. In certain embodiments of formula (III), at least one of ZR1 or R is-CH2COOV1, tetrazolylmethyl-, cyanomethyl-, NH2SO2methyl-, NH2SOmethyl-, aminocarbonylmethyl-, C1-4alkylaminocarbonylmethyl-, or dilVialkylaminocarbomylmethyl-. In certain embodiments of formula (III), ZR, is 3,3 diphenylpropyl optionally substituted at the 3 carbon of the prop> I with-COOV1, tetrazolylCo-4alkyl-, cyano-, aminocarbonyl-, C1-4alkylaminocarbonyl-, or diC1-4 alkylaminocarbonyl-. I he present invention in certain embodiments comprises, compounds having the general formula (IV): (Formula Removed) wherein R is hydrogen, C1-10 alkyl, C3-12 cycloalkyl, C3-12 cycloalkylC].4alkyl-, C1-10alkoxy, C3-12 cycloalkoxy-. C1-10 alkyl substituted with 1-3 halogen, C3-12 cycloalkyl substituted with 1-3 halogen, C3-12 cycloalkylC 1-1alkyl- substituted with 1-3 halogen, C1-10alkoxy substituted with 1-3 halogen, C3.12 cycloalkoxy- substituted with 1-3 halogen, -COOV,, -C1-4COOV1, -CH2OH, -SO2N(V|)2, hydroxyC1-10alkyl-, hydroxyC3-12cycloalkyl-, cyanoC1-10alkyl-, cyanoC3-12cycloalkyl-, -CON(V,)2, NH2SO2C1-4alkyl-, NH2SOC1-4alkyl-, sulfonylaminoC1-10 alkyl-. diaminoalkyls -sulfonylC1-4alkyI, a 6-membered heterocyclic ring, a 6-membered heteroaromatic ring, a 6-membered heterocyclicC1-4alkyl-, a 6-membered heteroaromaticC1-4alkyl-, a 6-membered aromatic ring, a 6-membered arbmaticC1-4 alkyl-, a 5-membered heterocyclic ring optionally substituted with an oxo or thio, a 5-membered heteroaromatic ring, a 5-membered heterocyclicC]_4alkyl-optionally substituted with an oxo or thio, a 5-membered heteroaromaticC1-4alkyl-, -C1-5(=O)W,, -C1-5(=NH)W1, -C1-5NHC (=O) W,,-C sNHS ( •O)2W1,-C1-5NHS(=O)W1 whereinW, is hydrogen, C1-10 aikyl, C3-12 cycloalkyl, C1-10 alkoxy, C3-12 cycloalkoxy, -CH2OH, amino, C1-4alkylamino-, diC1-4alkylamino-, or a 5-membered heteroaromatic ring optionally substituted with 1-3 lower alkyl ; wherein each V1 is independently selected from H, C3-6 alkyl, C3.6 cycloalkyl, benzyl and phenyl ; 1) is a 5-8 membered cycloalkyl, 5-8 membered heterocyclic or a 6 membered aromatic or heteroaromatic group: n is an integer from 0 to 3; A, B and Q are independently hydrogen, C1-10 alkyl, C3-12 cycloalkyl, C1-10 alkoxy, C3-12 cycloalkoxy,-CH2OH.-NHSO2, hydroxyC1-10alkyl-, aminocarbonyl-, C1-.4alkylaminocarbonyl-, diC1-4alkylaminocarbonyl-, acylamino-, acylamindalkyl-, amide, sulfonylaminoC1-10alkyl-, or A-B can together form a C2-6 bridge, or B-Q can together form a C3;7 bridge, or A-Q can together form a C1-5 bridge; Z is selected from the group consisting of a bond, straight or branched C1.6 alkylene, -NH-, -CH2O-, -CH2NH-, -CII,N((11,)-, -NHCH2-. -CH2CONH-, -NHCH2CO-, -CH2CO-,-COCH2-,-CH2COCH2-,-CH (CH3)-,-CH=,-O-and-IK CH-. wherein the carbon and/or nitrogen atoms are unsubstituted or substituted with one or more lower alkyl, hydroxy, halo or alkoxy group; KI is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12cycloalkyl, C2-10alkenyl, amino, C1-10. alkylamino-, C3-12cycloalkylamino-, -COOV1, -C1-4COOV1, cyano, cyanoCMoalkyl-, cyanoC3-12cycloalkyl-, NH2SO2-, NH2SO2C1-4alkyl-, NH2SOC1-4alkyl-, aminocarbonyl-, C1-4alkylaminocarbonyl-, diC1. alkylaminocarbonyl-, benzyl, C3-12cycloalkenyl-, a monocyclic, bicyclic or tricyclic aryl or heteroaryl ring, a hetero- monocyclic ring, a hetero-bicyclic ring system, and a spiro ring system of the formula (V): (Formula Removed) wherein X1 and X2 arc independently selected from the group consisting of NH, O, S and CHb; and wherein said alkyl. cycloalkyl, alkenyl, C1-10alkylamino-, C3-12cycloalkylamino-, or benzyl of RI is optionally substituted with 1-3 sfubstituents selected from the group consisting of halogen, hydroxy, C1-10 alkyl, C1-10 alkoxy. nitro, trifluorcjmethyl-, cyano, -COOVh -C1-4COOV,, cyanoC1-10alkyl-, -C1-5(=O)W|, -C,.5NHS(=O) ;>W|,-(YiNHS(=O)Wi, a 5-membered heteroaromaticCo-4alkyl-, phenyl, benzyl, benzyloxy, said phenyl, ben/.yl, and benzyloxy optionally being substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl-, C1-10 alkoxy-, and cyano ; and wherein said C3-12 cycloalkyl, C3-12 cycloalkenyl, monocyclic, bicyclic or tricyclic aryl, heteroaryl ring, hetero-monocyclic ring, hetero-bicyclic ring system, or spiro ring system of the formula (V) is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trifluoromethyl-, phenyl, benzyl, phenyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy or benzyloxy is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, and cyano ; R2 is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12 cycloalkyl- and halogen, said alkyl or cycloalkyl optionally substituted with an oxo,. amino, alkylamino or dialkylamino group ; and pharmaceutically acceptable salts thereof and solvates thereof. The present invention in certain embodiments comprises compounds having the formula (1VA): n is an integer from 0 to 3; Z is selected from the group consisting of a bond,-CH2-,-NH-,-CH2O-,-CH2CH2-,-CH2NH-,-CH2N (CH3)-,- NlICllr.-CH2CONH-,-NHCH2CO-,-CH2CO-,-COCH2-,-CH2COCH2-,-CH(CH3)-,-CH=, and-HC=CH-, wherein the carbon and/or nitrogen atoms are unsubstituted or substituted with a lower alkyl, halogen, hydroxy or alkoxy group; R IS selected from the group consisting of hydrogen, C1-10 alkyl, C1-10 alkoxy, and C3-12cycloalkyl; RI is selected from the group consisting of hydrogen, C1-10alkyl, C3-12cycloalkyl, C2-10aIkenyl, amino, C1-10. inalkylamino, C3-12cycloalkylamino, benzyl, C3-12 cycloalkenyl, a monocyclic, bicyclic or tricyclic aryl or heteroaryl ring, a heteromonocyclic ring, a heterobicyclic ring system, and a spiro ring system of the formula (V): (Formula Removed) wherein X1 and X2 are independently selected from the group consisting of NH, O, S and wherein said monocycilic aryl is preferably phenyl; wherein said bicyclic aryl is preferably naphthyl; wherein said alkyl, cycloalkyl, alkenyl, C1-10alkylamino, C3-12cycloalkylamino, or benzyl is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trifluoromethyl, cyan®, phenyl, benzyl, benzyloxy, said phenyl, benzyl, and benzyloxy optionally being substituted with 1-3 siibstituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, and cyano; wherein said C3-12 cycloalkyl, C3-12 cycloalkenyl, monocyclic, bicyclic or tricyclic aryl, heteroaryl ring, heteromonocyclic ring, heterobicyclic ring system, and spiro ring system of the formula (V) are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trifluoromethyl, phenyl, benzyl, phenyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy and benzyloxy are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, (Yin alkoxy, anil cyano ; R2 is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12 cycloalkyl and halogen, said alkyl optionally substituted with an oxo group; and pharmaceutically acceptable salts thereof. In certain preferred embodiments of formula (IV), D is phenyl or a 6 membered heteroaromatic group containing 1-3 nitrogen atoms. In certain preferred embodiments of formula (IV) or (IVA), the RI alkyl is methyl, ethyl, propyl, butyl, pentyl, or hexyl. In certain preferred embodiments of formula (IV) or (IVA), the RI, cycloalkyl is cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, or norbornyl. In other preferred embodiments of formula (IV) or (IVA), the RI bicyclic ring system is naphthyl. In other preferred embodiments of formula (IV) or (IVA), the RI bicyclic ring system is tetrahydronaphthyl, or decahydronaphthyl and the RI tricyclic ring system is dibenzocycloheptyl. In other preferred embodiments RI, is phenyl or benzyl. Injrther preferred embodiments of formula (IV) or (IVA), the R, bicyclic aromatic ring is a 10-membered ring, prererably quinoline or naphthyl. In other preferred embodiments of formula (IV) or (IVA), the RI bicyclic aromatic ring is a 9-membered ring, preferably indenyl. In certain embodiments of formula (IV) or (IVA), Z is a bond, methyl, or ethyl. In certain embodiments of formula (IV) or (IVA), the Z group is maximally substituted as not to have any hydrogen substitution on the base Z group. For example, if the base Z group is-CH2-, substitution with two methyl groups would ifemove hydrogens from the-CH2-base Z group. In other preferred embodiments of formula (IV) or (IVA), n is 0. In certain embodiments of formula (IV) or (IVA), Xi and X2 are both O. In certain embodiments of formula (IV), R is-CH2C(-O)NH2,-C(NH)NH2, pyridylmethyl, cyclopentyl, cyclohcxyl, furanylmethyl,-C(=O)CH3rCH2CH2NHC(=O)CH3,-SO2CH3 CH2CH2NHSO2CH3, iuranylcarbonyl-, melhylpyrrolylcarbonyl-, diazolecarbonyl-, azolemethyl-, trifluoroethyl-, hydroxyethyl-, cyanomethyl-, oxo-oxazolemethyl-, or diazolemethyl-. In certain embodiments of formula (IV), ZR] is cyclohexylethyl-, cyclohexylmethyl- , cyclopentylmethyl-, dimethylcyclohexylmothyl-, phenylethyl-, pyrrolyltrifluoroethyl-, thienyltrifluoroethyl-, pyridylethyl-, cyclopentyl-, cyclohexyl-, methoxycyclohexyl-, tetrahydropyranyl-, propylpiperidinyl-, indolylmethyl-, pyra/oylpentyl-, thiaxolylethyl-, phenyltrifluoroethyl-, hydroxyhexyl-, methoxyhexyl-, isopropoxybutyl-, hexyl-. or oxocanylpropyl-. In certain embodiments of formula (IV), at least one of ZR| or R is -ChbCOOV,, tetrazolylmethyl-, cyanomethyl-, NH2SO2bmethyl-, NH2SOmethyl-, aminocarbonylmethyl-, C1-4alkylaminocarbonylmethyl-, or diCYialkylaminocarbojnylmethyl-. In certain embodimentis of formula (IV), ZR| is 3,3 diphenylpropyl optionally substituted at the 3 carbon of the propyl with-COOV1, tetrazolyiCo-4alkyl-, cyano-, aminocarbonyl-, C1-4alkylaminocarbonyl-, or diC|. lalkylaminocarbonyl- In alternate embodiments of formulae (I), (IA), (II), (IIA), (III), (IIIA), (IV), and (IVA), ZRi can be the following (Formula Removed) wherein Yi is Rr(C,-Ci:) alkyl, R.»-aryl. R5-heteroaryl, Re- (C3-12 cyclo-alkyl, R7- (C3- C7) heterocycloalkyl, -CO2 ((',-('„) alkyl, CN or-(!' (O) NR8R; Y2 is hydrogen or YI; Y3 is hydrogen or (C,-C6) alkyl ; or Y,, Y2 and Y3, together with the carbdm to which they are attached, form one of the following structures: (Formula Removed) wherein r is 0 to 3; w and u are each 0-3, provided that the sum of w and u is 1-3; c and d are independently 1 or 2; s is 1 to 5 ; and ring E is a fused R4-phenyl or R5- heteroaryl ring; RIO is 1 to 3 substituents independently selected from the group consisting of H, alkyl-OR8.-NR8R,, and*- (C1- C6) alkyl-NR8R9; alkyl,-OR8,-(C1- C6) RH is 1 to 3 substituetits independently selected from the group consisting of RIO,- CF3,-OCF3, NO2 and halo, or R| i, substituents on adjacent ring carbon atoms may together form a methylenedioxy or ethylenedioxy ring; Rx and Ry are independently selected from the group consisting of hydrogen, (C1- C6) alkyl, (C3-C12) cycloalkyl, aryl and aryl (C1- C6) alkyl; Ri is 1 to 3 substiluents independently selected from the group consisting of H, R4- aryl, R6-(C3-Cl?)c>eioalkyl, R5-hel»roaryl, R7-(C3-C7)heterocycloalkyl, -NR8R9,-OR,2 and -S(O)0.2Ri2; R(, is 1 to 3 substituents independently selected from the group consisting of H, -OR,.and-SR|2; alkyl, R4-aryl, -NRgR«, R.I is I to 3 substitueiats independently selected from the group consisting of hydrogen, halo, (C1- C6) alkyl, R,3-aryl, (C3-C,2) cycloalkyl,-CN,-CF3,-ORg,-(C,- C6)alkyl-OR8, -OCF3, -NR8R9, -(C1- C6)alkyl -NR8R9, -N11S()?R«, -SO2N(R|4^2, -SO2R8, - SOR8, -SR8, -NO2, -CONR8R9, -NR9COR8, -COR8, -COCF3, -OCOR8, -()CO?R8, - COORg, -(CrC6)alkyl-NHCOOC(CH3)3, -(C1- C6)alkyl-NHCOCF3, -(C1- C6)alkyl-NHSO2- (C1- C6) l.-(C1- C6) alkyl-N|lCONH-(C1- C6)-alkyl and -(CH2)rNf~>N-R8 wherein f is 0 to 6; or R4 substituents on adjacent ring carbon atoms may together form a methylenedioxy or ethylenedioxy ring; Rs is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, (C1- C6) alkyl, Rn-aryl, (C3-C12)cyclpalkyl, -CN, -CF3, -OR8, -(C1- C6) alkyl- OR8, -OCF3,-NR8R9, -(C1- C6)alkyl-NR8R9, -NHSO.-.R8, -S02N(R14)2, -NO2, -CONR8R9, -NR9COR8,-COR8,.-OCOR8,-OC02R8and-COOR8; R7^s H. (C1- C6) alkyl, -OR8-, -(C1- C6)aIkyl-OR8, -NR8R9 or -(C1- C6)alkyl-NR8R9; R12 is 11, (C1- C6) alkyil, R4-aryl,-(C1- C6) alkyl-OR8,-(C1- C6) alkyl-NR8R9,-(C1- C6) alkyl-SR8, or aryl (C1- C6) alkyl : RM is 1-3 substituents independently selected from the group consisting of H, (C1- C6) alkyl, (C1- C6) alkoxy and halo; RI.I is independently selected from the group consisting of H, (C1- C6)alkyI and R13- C6H4-CH2- As used herein, the t4rm"alkyl"means a linear or branched saturated aliphatic hydrocarbon group having a single radical and l-l() carbon atoms. Examples of alkyl groups include methyl, propyl, isopropyl, butyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and pentyl. A branched alkyl means that one or more alkyl groups such as methyl, ethyl or propyl, replace one or both hydrogens in a-CH2-group of a linear alkyl chain. The term "lower alky!"means an alkyl qf 1-3 carbon atoms. The term"alkoxy"meai!is an"alkyl"as defined above connected to an oxygen radical. The term "cycloalkyl" means a non-aromatic mono-or multicyclic hydrocarbon ring system having a single radical and 3-12 carbqn atoms. Exemplary monocyclic cycloalkyl rings include cyclopropyl, cyclopentyl, and cyclohexyl. Exemplary multicyclic cycloalkyl rings include adamantyl and norbornyl. The term"alkenyl"meains a linear or branched aliphatic hydrocarbon group containing a carbon-carbon double bond having a single radical and 2-10 carbon atoms. A"branched"alkenyl means that one or more alkyl groups such as methyl, ethyl or propyl replace one or both hydrogens in a-CH2-©r-CH= linear alkenyl chain. Exemplary alkenyl groups include ethenyl, 1-and 2-propenyl, 1-, 2-and 3-tjutenyl, 3-methylbut-2- enyl, 2-propenyl, heptenyl, octenyl and decenyl. The term"cycloalkeny|"means a non-aromatic monocyclic or multicyclic hydrocarbon ring system containing a carbon-carbon double bond having a single radical and 3 to 12 carbon atoms. Exemplary monocyclic cycloalkenyl rings include cyclopropenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl. An exemplary multicyclic cycloalkeniyl ring is norbornenyl, The term"aryl"means a carbocyclic aromatic ring system containing one, two or three rings which may be attached together in a fendent manner or fused, and containing a single radical. Exemplary aryl groups include phenyl. naphthyl and ajcenaphthyl. The term"heterocyclic!'means cyclic compounds having one or more heteroatoms (atoms other than carbon) in the ring, and having a single radical. The ring may be saturated, partially saturated or unsaturated, and the heieroatoms may be selected from the group consisting of nitrogen, sulfur and oxygen. Examples of saturated hclerocyclic radicals iipclude saturated 3 to 6-membered hetero-monocyclic groups containing 1 to 4 nitrogen atoms, such as pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl ; saturated 3-to 6-membered hetero-monocyclic groups comtaining 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as morpholinyl ; saturated 3-to 6-membered hetero-monocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as thiazolidinyl. Examples of partially saturated heterocyclic radicals include dihydrothiophene, dihydropyran, and dihydrofuran. Othfer heterocyclic groups can be 7 to 10 carbon rings substituted with heteroatoms such as oxocanyl and thiocaryl. When the heteroatom is sulfur, the sulfur can be a sulfur dioxide such as thiocanyldioxide. The term"heteroaryl"means unsaturated heterocyclic radicals, wherein "heterocyclic"is as previously described. Kxemplary heteroaryl groups include unsaturated 3 to 6 membered hetero-monocyclic groups containing 1 to 4 nitrogen atoms, such as pyrrolyl, pyridyl, pyrimidyl, and pyrazinyl ; unsaturated condensed heterocyclic groups containing 1 to 5 nitrogen atoms, such as indolyl, quinolyl and isoquinolyl ; unsaturated 3 to 6-membered hetero-monocyclic groups containing an oxygen atom, such as furyl; unsaturated 3 to 6 membered hetero-monocyclic groups containing a sulfur atom, such as thienyl; unsaturated 3 to 6 membered herero-monocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as oxazolyl; unsaturated condensed heterocyclic groups containing 1 to 2 oxygen atoms, and 1 to 3 nitrogen atoms, such as benzoxazolyl; unsaturated 3 to 6 membered hetero-monocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as thiazolyl; and unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as benzothiazolyl. The term"neteroaryl"also includes unsaturated heterocyclic radicals, wherein "heterocyclic"is as previously described, in which the heterocyclic group is I used with an aryl group, in which aryl is as previously described. Exemplary fused radicals include henzofuran, benzdioxole and benzothiophene. As used herein, the term "heterocyclicC1-4alkyl", "heteroaromaticC1-4alkyP'and the like refer to the ring structure bonded to a C1-4alky! radical. All of the cyclic ring structures disclosed herein can be attached at any point where such connection is possible, as recognized by one skilled in the art. As used herein, the term"patient"includes a human or an animal such as a companion animal or livestock. As used herein, the term"halogen"includes fluoride, bromide, chloride, iodide or alabamide. The invention disclosed herein is meant to encompass all pharmaceutically acceptable salts thereof of the disclosed compounds. The pharmaceutically acceptable salts include, but are not limited to, metal salts such as sodium salt, potassium salt, cesium salt and the like; alkaline earth metals such as calcium salt, magnesium salt and the like; organic amine salts such as triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, d|cyclohexylamine salt, N, N'-dibenzylethylenediamine salt and the like ; inorganic acid salts such as hydrochloride, hydrobromide, sulfate, phosphate and the like; organic acid salts such as formate, acetate, irifluoroacetate, maleate, fumarate, tartrate and the like; sulfonates such as methanesulfonate, benzenesulfonate, p- toluenesulfonate, and the like; amino acid salts such as arginate, asparginate, glutamate and the like. The invention disclosed herein is also meant to encompass all prodrugs of the disclosed compounds. Prodrugs are considered to be any covalently bonded carriers which release the active parent drug in vivo. The invention disclosed herein is also meant to encompass the in vivo metabolic products of the disclosed compounds. Such products may result for example from the oxidation, reduction, hydrolysis, amidation, cstcrification and the like of the administered compound, primarily due to enzymatic processes. Accordingly, the invention includes compounds produced by a process comprising contacting a compound of this invention with a mammal for a period of time sufficient to yield a metabolic product thereof. Such products typically are identified by preparing; a radiolabelled compound of the invention, administering it parenterally in a detectable dose to an animal such as rat, mouse, guinea pig, monkey, or to man, allowing sufficient time for metabolism to occur and isolating ils conversion products from the urine, blood or other biological samples. The invention disclosed herein is also meant to encompass the disclosed compounds being isotopically-labelled by having one or more atoms replaced by an atom having a different atomic mass or mass number. Hxamples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine and chlorine, such as 2H, 3H,I3C,14C,15N,18O,17O, P, P, 5S, 18p-, and 36C1, respectively. Some of the compounds disclosed herein may contain one or more asymmetric centers and may thus -give rise to enantiomers, diastereomers, and other stereoisomeric forms. The present invention is also meant, to encompass all such possible forms as well as their racemic and resolved forms and mixtures thereof. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended to include both E and Z geometric isomers. All tautomers are intended to be encompassed by the present invention, as well As used herein, the term "stereoisomers" is a general term for all isomers of individual molecules that differ only in the orientation of their atoms in space. It includes enantiomers and isomers of compounds with more than one chiral center that are not mirror images of one another (diastereomers). The term "chiral center" refers to a carbon atom to which four different groups are attached. The term "enantiomer" or "enantiomeric" refers to a molecule that is nonsuperimposeable on its mirror image and hence optically active wherein the enantiomer rotates the plane of polarized light in one direction and its mirror image rotates the plane of polarized light in the opposite direction. The term "racemic" refers to a mixture of equal parts of enantiomers and which is optically inactive. The term "resolution" refers to the separation or concentration or depletion of one of the two enantiomeric forms of a molecule. The term "modulate" as used herein with respect to the ORL-1 receptor means the mediation of a pharmacodynamic response (e.g;, analgesia) in a subject from (i) inhibiting or activating the receptor, or (ii) directly or indirectly affecting the normal regulation of the receptor activity. Compounds which modulate the receptor activity include agonists, antagonists, mixed agonists/antagonists and compounds which directly or indirectly affect regulation of the receptor activity. Certain preferred compounds of formula (I) and (IA) include: 3- 3-3-3-3-3-3- 1 -(naphth-2-yl-methyl)-4-piperidinyl]-2H-benzoxazol-2-one ; I- (naphth-l-yl-methyl)-4-piperidinyl]-2H-benzoxazol-2-one ; 1- (p-phenylbenzyl|-4-piperidinyI]-2H-benzoxazol-2-one ; 1- (p-ben/.yloxyber|zyl)-4-piperidinyl]-2H-benzoxazol-2-one ; 1- (p-cyanoben/.yl)>4-piperidinyl]-2H-benzoxazol-2-one ; 1- (3, 3-diphenylpr0pyl)-4-piperidinyl]-2H-benzoxazol-2-one ; 1- |4,4-Bis- (4-fluorophenyl) butyl]-4-piperidinyl]-2H-benzoxazoI-2-one; 1 -(2-phenylethyl)-4-piperidinylj-2H-benzoxazol-2-one ; l-(cyclooctylmethyl)-4-piperidinyI|-2H-benzoxazol-2-one ; t -(1, 2,3,4-tetrahydro-2-naphthyl)-4-piperidinyl]-2H-benzoxazol-2-one; 1- (5-methylhex-2-yl)-4-piperidinyl]-2H-benzoxazol-2-one ; 1- (10, 1 l-Dihydn>5 H-dibenzo fa, d]-cyclohepten-5-yI)-4-piperidinyl]-2H- benzoxazol-2-one; 3- 1- (4-propyl-cyclohexyl)-4-piperidinyl]-2H-benzoxazol-2-one ; 1 -(norbornan-2-yl)f4-piperidinyl]-2H-benzoxazol-2-one ; 1- (decahydro-2-naphthyl)-4-piperidinyl]-2H-benzoxazol-2-one ; 3- 3- 3-| l-(3,3-dimethyl-l, S-dioxaspiro [5.5] undeca-9-yl)-4-piperidinyl]-2H-benzoxazol- 2-one; 3-11- |4-(l-methylethyl)-cyclohexyl]-4-piperidinyl]-2H-benzoxazol-2-one ; 3-11- ( 1, 3-dihydroinden-2-yl)-4-piperidinyl]-2H-benzoxazol-2-one ; 3-11- (cyclooctyl)-4-piperidinyl|-2H-benzoxazol-2-one ; and pharmaceutical ly acceptable salts thereof and solvates thereof. Certain preferred compounds of formula (II) and (HA) include: -[l-(5-mpthylhex-2-yl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; 1- (4-propylcyclohexyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2- one; 1- (1, 2,3,4-tetrahydro-2-naphthyl)-4-piperidinyl]-l,3-dihydro-2H- indole-2-one; 1- (l,3-dihydroinden-2-yl)-4-piperidinyl]-l,3-dihydro-2H-indole-2- one; 1 -(napihth-2-yl-methyl)-4-piperidinyl]-l ,3-dihydro-2H-indole-2- one; 3-ethylidene- 3-ethylidene- 3-ethylidene- 3-ethylidene- 3-ethylidene- 3-ethylidene-l-11- (p-ben/yloxybenzyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2- one; 3-cthylidene-l- [1- (befizyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one ; 3-ethylidene-l- [1- (cysclooctylmethyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one ; 3-ethylidene-l-11- (ndrbornan-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one; 3-ethylidcne-l-11- (3j-diphenylpropyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2- one; 3-ethylidene-l- [ 1- (p-cyanobenzyI)-4-piperidinyl]-l, 3,-dihydro-2H-indole-2-one; 3-elhyl-l-11- (5-methylhex-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one ; 3-ethyl-l- | ]-|4- (l-methylethyl)-cyc!ohexyl]-4-piperidinyl]-l, 3-dihydro-2H-indole- 2-one; 3-ethyl-l- 11- (4-propylcyclohexyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one; 3-cthyl-l- j 1- (1, 2,3, 4-tetrahydro-2-naphthyl)-4-piperidinyl]-l,3-dihydro-2H-indole- 2-one; 3-ethyl-l-11- (decahydro-2-naphthyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one; 3-eihyl-l-11- (1, 3-dihydroinden-2-yl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; 3-ffliyl-l-|l-(cycloocylmethyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; 3-ethyI-1 -| I -(norbornajn-2-yl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; I-11- (naphth-l-yl-melhyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; I- j 1- (naphth-2-yl-methyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; 1-1 l-(p-phenylbenzylJ)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one; I-11- (3. 3-Bis (phenyi) propyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; I-11- (p-cyanobenzyl)?-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; 1-11- (p-ben/yloxyben£yl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; I -11 - (1, 2,3,4-tetrahydronaphth-2-yl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; 1-11- (5~methylhex-2-jyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one; 1- |1- (norbornan-2-yl)t-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; 1 - I- (1, 3-dihydroind(jn-2-yl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; 1- 11- (cycooctylmeth>fl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one ; 1- [ I- (ben/yl)-3- (metjhyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one; 1-11- (4-propyl-cyclohj£xyl)-3~ (methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one; 1-11- (5-methylhex-2-yl)-3- (methyl)-4-piperidinyl|-l, 3-dihydro-2H-indole-2-one; 1-11- (decahydro-2-na|3hthyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2- one; 1-11- (4- (l-methylethy!l)-cyclohexyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H- indole-2-one; I-11- (cyclooctylmethyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one ; I-11- (3, 3-Bis (phenylj) propyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2- one; 3-ethyl-l-11- (3, 3-Bis (phenyi) propyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H- indole-2-one; 3-cthyl-l-11- (4-propyilcyclohexyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H- indole-2-one; 3-cthyl-l-11- (5-methylhex-2-yl)-3- (methyl)-4-piperidinyl]-l, 3-dihydrp-2H-indole- 2-one; 3-cthyl-l-11- [4- (l-mcthylethyl) cyclohexyl]-3-methyl-4-piperidinyl]-l, 3-dihydro- 2H-indole-2-one; 3-cthyl-l-1 l-(decahyd('o-2-naphthyl)-3-(methyl)-4-piperidinyl]-l, 3-dihydro-2H- indole-2-one; and pharmaccutically acceptable salts thereof and solvates thereof. Certain preferred compounds of formula (III) and (IIIA) include: 3-elhyl-l- (p-phenylbe|i/yl)-l,3-dihydro-2H-benzimidazol-2-one; 3-elhyl-1 - (5-methylheix-2-yI)-l ,3-dihydro-2H-benzimidazol-2-one; 3-ethyl-l- (4-propylcy(f;lohexyl)-l, 3-dihydro-2H-benzimidazol-2-one; 3-clhyI-1 - (decahydro-2-naphthyl)-1, 3-dihydro-2H-benzimidazol-2-one; 3-ethyl-l-(naphth-2-yl*methyl)-l, 3-dihydro-2H-benzimidazol-2-one I -(p-bcn/yloxyben/yli-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one; i -bcn/yl-3-ethyl-l ,3-d|hydro-2H-benzimidazol-2-one; 1-14- (bcn/ylamino)-cyclohexyl|-3-ethyl-l, 3-dihydro-2H-benzimidazol-2-one; 3-ethyl-l- (naphthylm«thyl)-l, 3-dihydro-2H-benzimidazol-2-one ; 3-cthyl-l-15- (3-fluordphenyl)-5- (4-fluorophenyl)-hexyl]-l, 3-dihydro-2H- benzimidazol-2-one; 1-14-1 (naphth-2-yl-rrtethyl)ethylamino]-cyclohexyl]-l,3-dihydro-2H-benzimidazol-2-one; 1-14- (norbornan-2-ylamino)-cyclohexyl]-l, 3-dihydro-2H-benzimidazol-2-one ; l-|4-||4-(l-methylethyll)-cyclohexyl] amino]-cyclohexyl]-l,3-dihydro-2H-benzimidazol-2-one; 1- 14- | (decahydro-2-naphthyl) amino]-cyclohexyl]-l, 3-dihydro-2H-benzimidazol-2- one; 1- 14- (ethylamino)-cyclohexyl|-l, 3-dihydro-2H-benzimidazol-2-one; 1- |4- (ben/ylamino)-cyclohexyl|-l, 3-dihydro-2H-benzimidazol-2-one; 1- |4- |(indan-2-yl) betl/.ylamino|-cyclohexyl]-3-ethyl-l, 3-dihydro-2H-benzimidazol- 2-one; 1- |4- | (cyclooctylmethyl)amino]-cyclohexyl]-3-ethyl-l,3-dihydro-2H-benzimidazol-2-one; 1-14-1 (naphth-2-yl) aminoJ-cyclohexyl]-3-ethyl-l, 3-dihydro-2H-benzimidazol-2- one ; 1-14- |(p-ben7,yloxybejn/yl)amino]-cyclohexyl]-3-ethyl-l, 3-dihydro-2H- benzimidazol-2-one; I-14- |(cyclooctylme%l) amino]-cyclohexyl]-3-ethyl-l, 3-dihydro-2H-benzimidazol- 2-one; I-14-1 (decahydro-2-naphthyl) amino]-cyclohexyl]-3-ethyl-l, 3-dihydro-2H- benzimidazol-2-one;. -[4- (benzylamino)-«ycIohexyl]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2-one; -14- (dibenzylamino)-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2- one; -14-1 (p-phenylbenzyl) amino]-cycIohexyl]-5-carbamoyl-l,3-dihydro-2H- benzimidazol-2-one; -|4-|(l, 2,3,4-tetrahydronaphthyl) amino]-cyclohexyl]-5-carbamoyl-l, 3-dihydro- 2H-benzimidazol-2-one ; -14-1 (4-propyl-cyclophexyl) amino]-cycIohexyl]-5-carbamoyl-l, 3-dihydro-2H- benzimidazol-2-one; - [4-1 (5-methylhex-J-yl) amino]-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H- benzimidazol-2-one; -1 (decahydro-2-naphthyl) amino]-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H- benzimidazol-2-one; - (cyclooctylaminb)-cyclohexyI]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2- one ; -14- |(indan-2-yl)amino-cyclohexyl]-5-carbamoyl-l,3-dihydro-2H-benzimidazol- 2-one; -14-1 (4-phenyl-cyclohexyI) amino]-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H- benzimidazol-2-one ; -14-1 (5-methylhex-2-yl) aminoJ-cyclohexyl]-7-carbamoyl-l, 3-dihydro-2H- benzimidazol-2-one; and pharmaceutical ly acceptable salts thereof and solvates thereof. Other preferred compdunds formula (IV) and (IVA) include: 2-cyanoimino-3-ethyl-l- [I- (p-phenylbenzyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; 2-cyanoimino-3 ethyl-l- [l-(p-benzyloxybenzyl)-4-piperidinyl] l,3-dihydro-2H-benzimidazole; 2-cyanoimino-3-ethyHl- [1- (naphth-2-yI-rnethyl)-4-piperidinyl] l,3-dihydro-2H- benzimidazole; 2-cyanoimino-3-ethyl-:l- [1- (4-propylcyclohexyI)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; 2-cyanoimino-3-ethyl-jl-11- [4- (2-propyl)-cyclohexyl]-4-piperidinyl]-l, 3-dihydro- 2H-benzimidazole; 2-cyanoimino-3-ethyl-i|- [1- (decahydro-2-naphthyl)-4-piperidinyl]-l, 3-dihydro- 2H-benzimidazole; 2-cyanoimino-3-ethyl-|-11- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; 2-cyanoimino-3-ethyHl- |l- (10,1 l-dihydro-5H-dibenzo[a, d]-cydohepten-5-yl)-4- piperidinyl]-!, 3-dihydro-211-ben/imida/ole; 2-cyanoimino-3-ethyNl- [1- (3, 3-Bis (phenyl) propyl)-4-piperidinyl]-l, 3-dihydro- 2H-benzimidazole; 2-cyanoimino-3-ethyI-;l -| 1 -(1, 2,3,4-tetrahydronaphthyl)-4-piperidinyl]-l ,3- dihydro-2H-benzimidazole; 2-cyanoimino-3-ethyI-il-| l-(5-methylhex-2-yl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; 2-cyanoimino-3-ethyl-j-11- (norbornan-2-yl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole ; 2-cyanoimino-3-ethyl-'l- [1- (l,3-dihydroinden-2-yl)-4-piperidinyl]-l,3-dihydro- 2H-benzimidazoIe; 2-cyanoimino-3-ethyl-|- [l-(cyclooctylmethyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; and pharmaceutically acceptable salts thereof and solvates thereof. Other preferred compoiunds of formula (IV) include 2-cyanoimino-3-(2-hy(Jroxy) ethyl-l-[l-(cyclooctyl)-4-piperidinyl]-l,3-dihydro-2H- benzimidazole ; 2-cyanoimino-3-methaxycarbonylmethyl-l- [1- (cyclooctyl)-4-piperidinyl]-l, 3- dihydro-2H-benzimidazole; 2-cyanoimino-3-cyanomethyi-l- [1- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; 2-cyanc)imino-3-butyl-l- [I- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; 2-cyanoimino-3-(2-me|thanesulfonamido)ethyl-l-[l-(cyclooctyl)-4-piperidinyl]-l,3-dihydro-2H-ben/imida/ole; 2-cyanoimino-3-acetoipido-l- (1- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole ; 2-cyanoimino-3-carboiymethyl-l- [I- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole ; 2-cyanoimino-3-(2-dinjiethylamino) ethyl-l -[l-(cyclooctyl)-4-piperidinyl]-l,3- dihydro-2H-benzimidazole; 2-cyanoimino-l- 11- (cfyclooctyl)-3-hydroxymethyl-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; 2-cyanoimino-l- [1- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H-7- azabenzimidazole; 2-cyanoimino-l-11- (cyclooctyl)-2, 6-ethano-4-one-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole; and pharmaceutically acceptable salts thereof and solvates thereof. The present invention ftlso provides use of any of the disclosed compounds in the preparation of a medicament for treating pain and otjher disease states modulated by an opioid receptor, e. g., the ORL-1 receptor. DETAILED DESCRIPTION OF THE INVENTION The compounds of the present invention can be administered to anyone requiring modulation of the opioid and OKU receptors. Administration may be orally, topically, by suppository, inhalation, or parenterally. I he present invention also encompasses all pharmaceutically acceptable salts of the foregoing compounds. One skilled in the art; will recognize that acid addition salts of the presently claimed compounds may be prepared by reaction of the compounds with the appropriate acid via a variety of known methods. Various oral dosage forms can be used, including such solid forms as tablets, gelcaps, capsules, caplets, granules, lozenges and bulk powders and liquid forms such as emulsions, solution and suspensions. The compounds of the present invention can be administered alone or can be combined with various pharmaceutically acceptable carriers and excipients known to those skilled in the art, including but not limited to diluents, suspending agents, solubilizers, binders, disintegrants, preservatives, coloring agents, lubricants and the like. When the compounds of the present invention are incorporated into oral tablets, such tablets can be compressed, tablet triturates, enteric-coated, sugar-coated, film-coated, multiply compressed or multiply layered. Liquid oral dosage forms include aqueous and nonaqueous solutions, emulsions, suspensions, and solutions and/or suspensions reconstituted from non-effervescent granules, containing suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, coloring agents, and flavoring agents. When the compounds of the present invention are to be injected parenterally, they may be, e. g., in the form of an isotonic sterile solution. Alternatively, when the compounds of the present invention are to be inhaled, they may be formulated into a dry aerosol or may be formulated into an aqueous or partially aqueous solution. In addition, when the compounds of the present invention are incorporated into oral dosage forms, it is contemplated that such dosage forms may provide an immediate release of the compound in the gastrointestinal tract, or alternatively may provide a controlled and/or sustained release through the gastrointestinal tract. A wide variety of controlled and/or sustained release formulations are well known to those skilled in the art, and are contemplated for use in connection with the formulations of the present invention. The controlled and/or sustained release may be provided by, e. g., a coating on the oral dosage form or by incorporating the compound (s) of the invention into a controlled and/or sustained release matrix. Specific examples of pharmaceutically acceptable carriers and excipients that may be used to formulate oral dosage forms, are described in the Handbook of Pharmaceutical Excipients, American Pharmaceutical Association (1986). Techniques and compositions for making solid oral dosage forms are described in Pharmaceutical Dosagp Forms : Tablets (Lieberman, Lachman and Schwartz, editors) 2nd edition, published by Marcel Dekker, Ino. Techniques and compositions for making tablets (compressed and molded), capsules (hard and soft gelatin and pills are also described in Remington's Pharmaceutical Sciences (Arthur Osol, editor). 1553BI593 (1980). Techniques and composition for making liquid oral dosage forms are described in Pharmaceutical Dosage Forms: Disperse Systems, (Lieberman, Rieger and Banker, editors) published by Marcel Dekker, Inc. When the compounds pf the present invention are incorporated for parenteral administration by injection (e. g., continuous infusion of bolus injection), the formulation for parenteral administration may be in the form of suspensions, solutions, emulsions in oily or aqueous vehicles, and such formulations may further comprise pharmaceutically necefsary additives such as stabilizing agents, suspending agents, dispersing agents, and the like. The compounds of the invention may also be in the form of a powder for reconstitution as an injectable formulation. In certain embodiments, the compounds of the present invention can be used in combination with at least one other therapeutic agent. Therapeutic agents include, but are not limited to, (a-opioid agonists; non-opioid analgesics; non-steroid antiinflammatory agents; Cox-II inhibitors; antiemetics; p-adrenergic blockers; anticonvulsants; antidepressants; Ca2+-channel blockers; anticancer agent and mixtures thereof. In certain embodiments, the compounds of the present invention can be formulated in a pharmaceutical dosage Form in combination with a (j,-opioid agonist, µ-opioid agonists, which may be included in the formulations of the present invention include but are not limited to include alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezytitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimcpheptanol, dimeithylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmcthylthiambutenie, ethylmorphine, etonitazene fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isornethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocirte, methadone, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazsocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, pirhramide, proheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tilidine, tramadol, pharmaceutically acceptable salts thereof, and mixtures thereof. In certain preferred embodiments, the u.-opioid agonist is selected from codeine, hydromorphone, hydrocodone, oxycodone, dihydrocodeine, dihydromorphine, morphine, tramadol, oxymorphone, pharmaceutically acceptable salts thereof, and mixtures thereof. In another embodiment of the invention, the medicament comprises a mixture of a Cox-II inhibitor and an inhibitor of 5-lipoxygenase for the treatment of pain and/or inflammation. Suitable Cox-II inhibitors and 5-lipoxygenase inhibitors, as well as combinations thereof are described in U. S. Patent No. 6,136,839, which is hereby incorporated by reference in its entirety. Cox-II inhibitors include, but are not limited to rofecoxib (Vioxx), celecoxib (Celebrex), DLJP-697, flosulide, meloxicam, 6-MNA, L- 745337, nabumetone, nimesulide, NS-398, SC-5766, T414, L-768277, GR-253035, JTE- 522, RS-57067-000, SC-58125, SC-078, PD-138387, NS-398, flosulide, D-1367, SC- 5766, PD-164387, etoricoxib, valdecoxib and parecoxib or pharmaceutically acceptable salts, enantomers or tautomers thereof. The compounds of the present invention can also be combined in dosage forms with non-opioid analgesics, e. g., non-steroidal anti-inflammatory agents, including aspirin, ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofbn, flubufen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprolen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindae, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam or isoxicam, pharmaceutically acceptable salts thereof, and mixtures thereof. Other suitable non-opioid analgesics whieh may be included in the dosage forms of the present invention include the following, non- limiting, chemical classes of analgesic, antipyretic, nonsteroidal antifmflammatory drugs: salicylic acid derivatives, including aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, salicylsalicylic acid, siulfasalazine, and olsalazin; para- aminophennol derivatives including acetaminophen; indole and indene acetic acids, including indomethacin, sulindae, and etodolac; heteroaryl acetic acids, including tolmetin, diclofenac, and ketorolac ; anthranilic acids (fenamates), including mefenamic acid, and meclofenamic acid; enolic acids, including oxicams (piroxicam, tenoxicam), and pyrazolidinediones (phenylbutazone, oxyphenthartazone); and alkanones, including nabumetone. For a more detailed description of the NSAlDs that may be included within the medicaments employed in the present invention, see Paul A. Insel Analgesic- Antipyretic and Antiinflammatory Agents and Drugs Employed in the treatment of Gout in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 617-57 (Perry B. Molinhoff and Raymond W. Ruddon, Eds., Ninth Edition, 1996), and Glen R. Hanson Analgesic, Antipyretic and Anit-Inflammatory Drugs in Remington: The Science and Practice of Pharmacy Vol II, 1196-1221 (A. R. Gennaro, Ed. 19th Ed. 1995) which are hereby incorporated by reference in their entireties. In certain embodiments, the compounds of the present invention can be formulated in a pharmaceutical dosage form in combination with antimigraine agents. Antimigraine agents include, but are not limited to, alpiropride, dihydroergotamine, dolasetron, ergocornine, ergocorninine, ergocryptine, ergot, ergotamine, flumedroxone acetate, fonazine, lisurtde, lomerizine, methysergide oxetorone, pizotyline, and mixtures thereof. The other therapeutic agent can also be an adjuvant to reduce any potential side effects such as, for example, an antiemetic agent. Suitable antiemetic agents include, but are not limited to, metoclopromide, domperidone, prochlorperazine, prortiethazine, chlorpromazine, trimethobenzamide, ondansetron, granisetron, hydroxyzine, acethylleucine monoetihanolamine, alizapride, azasetron, benzquinamide, bietanautine, bromopride, buclizine, clebopride. cyclizine, dimenhydrinate, diphenidol, dolasetron, meclizine, methallatal, metopimazine, nabilone, oxyperndyl, pipamazine, scopolamine, sulpiride, tetrahydrocannabinols, thiethylperazine, thioproperazine, tropisetron, and mixtures thereof. In certain embodiments, the compounds of the present invention can be formulated in a pharmaceutical dosage form in combination with p-adrenergic blockers. Suitable (3-adrenergic blockers include, but are not limited to, acebutolol, alprenolol, amosulabol, arotinolol, atenolol, befunolol, betaxolol, bevantolol, bisoprolol, bopindolol, bucumolol, bufetolol, bufuralol, bunitrolol, bupranolol, butidrine hydrochloride, butofilolol, carazoloi, carteolol, carvedilol, celiprolol, cetamolol, cloranolol, dilevalol, epanolol, esmolol, indenolol, labctalol, levobunolol, mepindolol, metipranolol, metoprolol, moprolol, nadolol, nadoxolol, nebivalol, nifenalol, nipradilol, oxprenolol, penbutolol, pindolol, practolol, pronethalol, propranolol, sotalol, sulfinalol, talinolol, tertatolol, tilisolol, timolol, toliprolol, and xibenolol. In certain embodiments, the compounds of the present invention can be formulated in a pharmaceutical dosage form in combination with anticonvulsants. Suitable anticonvulsants include, but are not limited to, acctylphcneturide, albutoin, aloxidone, aminoglutethimide, 4-amino-3-hydroxybutyric acid, atrolactamide, beclamide, buramate, calcium bromide, carbamazepine, cinromide, clomethiazole, clonazepam, decimemide, dicthadione, dimethadlone, doxenitroin, eterobarb, ethadione, ethosuximide, ethotoin, felbamate, fluoresone, gabapentin, 5-hydroxytryptophan, lamotrigine, magnesium bromide, magnesium sulfate, mephenytoin, mephobarbital, methafbital, methetoin, methsuximide, 5- methyI-5- (3-phenanthryl)-hydantoin, 3-methyl-5-phcnylhydantoin, nareobarbital, nimetazepam, nitrazepam, oxcarbazepine, paramethadione, phenacemide, pheneiharbital, pheneturide, phenobarbital, phensuximide, phenylmethylbarbituric acid, phenytoin, phethenylate sodium, potassium bromide, pregabaline, primidone, progabide, sodium bromide, solanum, strontium bromide, sulclofenide, sulthiame, tetrantoin, tiagabine, topiramate, trimethadione, valproic acid, valpromide, vigabatrin, and zonisamide. In certain embodiments, the compounds of the present invention can be formulated in a pharmaceutical dosage form in combination with antidepressants. Suitable antidepressants include, but are not limited to, binedaline, caroxazone, citalopram, dimethazan, fencamine, indalpine, indeloxazine hydrocholoride, nefopam, nomilensine, oxitriptain, oxypertine, paroxetine, sertraline, thiazesim, trazodone, benmoxine, iproclozide, iproniazid, isocarboxazid, nialamide, octamoxin, phenelzine, cotinine, rolicyprine, rolipram, maprotiline, melralindole, mianserin, mirtazepine, adinazolam, amitriptyline, amitriptylinoxide, amoxapine, butriptyline, clomipramine, demeikiptiline, desipramine, dibenzepin, dimetacrine, dothiepin, doxepin, fluacizine, imipramine, imipramine N-oxide, iprindole, lofepramine, melitracen, metapramine, nortriptyline, noxiptilin, opipramol, pizotyline, propizepine, protriptyline, quinupramine, tianeptine, trimipramine, adrafmil, bcnactyzine, bupropioh, butacetin, dioxadrol, duloxetine, etoperidone, febarbamate, femoxetine, fenpentadiol, fluoxetine, fluvoxamjne, hematoporphyrin, hypericin, levophacetoperane, medifoxamine, milnacipran, minaprine, moclobenfiide, nefazodone, oxaflozane, piberaline, prolintane, pyrisuccideanol, ritanserin, roxindole, rubidium cliloride, sulpiride, tandospirone, thozalinone, tofenacin, toloxatone, tranylcypromine, L-tryptophan, venlafaxinb, viloxazine, and zimeldine. In certain embodimentis, the compounds of the present invention can be formulated in a pharmaceutical dosage form in combination with Ca2+-channel blockers. Suitable Ca2+-channel blockers include, but are not limited to. bcpridil, clentiazem, diltiazem, fendiline, gallopamil, mibefradil, prenylamine, semotiadil, terodiline, vcrapamil, amlodipine, aranidipine, barnidipine, benidipine, cilnidipine, efonidipine, elgodipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nisoldipine, nitrcndipine, cinnarizine, flunarizine, lidoflazine, lomerizine, bencyclane, etafenone, fantofarone, and perhexiline. In certain embodiments, the compounds of the present invention can be formulated in a pharmaceutical dosage form in combination with anticancer agents. Suitable anticancer agents include, but are not limited to, acivicin; aclarubicin; acodazoleihydrochloride; acronine; adozelesin; aldesleukin; altretamine; ambomycin; ametantrone acetate: aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacitidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnafide dimesylate; bizelesin; blcomycin sulfate; brequinar sodium; bropirimine; busulfan; cactinomycin; calusterone; caracemide; carbctimer; carboplatin; carmustine; carubicin hydrochloride; carzelesin; cedefingol; chlorambucil; cirolemycin; cisplatin; cladribine; crisnatol mesylate; cyclophosphamide; cytarabine; dacarbazine; dactinomycin; daunorubicin hydrochloride; decitabine; dexormaplatin; dezaguanine; dezaguanine mesylate; diaziquone; docetaxixel; doxorubicin; doxorubicin hydrochloride; droloxifene; droloxifene citrate; dromostanolone proplonate; duazomycin; edatrexate; eflornithine hydrochloride; elsamitrucin; enloplatin; enpromate; epipropidjine; epirubicin hydrochloride; erbulozole; esorubicin hydrochloride; estramustine; cstramustine phosphate sodium; etanidazole; etoposide; etoposide phosphate; etoprine; fadrozole hydrochioride; fazarabine; fenretinide; floxuridine; fludarabine phosphate; fluorouracil; flurocitabine; fosquidone; fostriecin sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride; ifosfamlde; ilmofosine; interleukin II (including recombinant interleukin II, or rIL2), interferon alfa-2a; interferon alfa-2b; interferon alfa-nl; interferon alfa-n3; interferon beta-I a; interferon gamma-I b; iproplatin; irinotecan hydrochloride; lanreotide acetate; letrozole; leuprolide acetate; liarozole hydrochloride ; lometrexol sodium; lomustine; losoxantrone hydrochloride; masoprocol; maytansine; mechlorethamine hydrochloride; megestrol acetate; melengestrol acetate; melphalan; menogaril; mercaptopurine; methotrexate; methotrexate sodium; metoprine; meturedepa; mitindomide; mitocarcin; mitocromin ; mitogillin; mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone hydrochloride; mycophenolic acid; nocodazole; nogalamycin; ormaplatin; oxisuran; paclitaxel; pegaspargase; peliomycin; pentamustine; peplomycin sulfate; perfosfamide ; pipobroman; piposulfan; piroxantrone hydrochloride; plicamycin; plomestane; porfimer sodium; porfiromycin; prednimustine; procarbazine hydrochloride; puromycin; puromycin hydrochloride; pyrazofurin; riboprine; rogletimide; safingol; safingol hydrochloride; semustine; simtrazene; sparfosate sodium; sparsomycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin; sulofenur; talisomycin; iccogalari sodium; tegafur; teloxantrone hydrochloride; temoporfin; teniposide; teroxirone; testolactone; thiamiprine; thioguanirae; thiotepa; tiazofurin; tirapazamine ; toremifene citrate; trestolone acetate; triciribine phosphate: trimetrcxaiie; trimetrexate glucuronate; triptorelin; tubulozole hydrochloride; uracil mustard; uredepa; vapreotide; verteporfin; vinblastine sulfate; vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate; vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate; vinrosidine sulfate; vin/olidine sulfate; vofozole; zeniplatin; zinostatin; zorubicin hydrochloride. Other anti-cancer drugs include, but are not limited to: 20-epi-l, 25 dihydroxyvitamin D3; 5- ethynyluracil; abiraterone; aclarubicin; acylfulvene; adecypendl; adozelesin; aldesleukin; ALL-TK antagonists; altretamine; ambamustine; amidox; amifostine; aminolevuliinic acid; amrubicin; amsacrine; anagrelide; anastrozole; andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-dorsalizing morphogenetic protein-1; antiandrogen, prostatic carcinoma; antiestrogen; antineoplaston ; antisense oligonucleotides ; aphidicolin glycinate; apoptosis gene modulators; apoptosis regulators; apurinic acid; ara-CDP-DL-PTBA ; arginine deaminase; asulacrine; atamestane; atrimustine; axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxin; azatyrosine; baccatin III derivatives; balanot; batimastat; BCR/ABL antagonists; benzochlorins; benzoylstaurosporine; beta lactam derivatives; beta-alethine; betaclamycin B; betulinic acid; bFGF inhibitor; bicalutamide; bisantrene; bisa/.iridinylspermine; bisnafide; bistratene A; bizelesin; breflate; bropirimine; budotitane; buthionine sulibximine; calcipotriol; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carboxamide-amino- triazole; carboxyamidotriazole; CaRest M3; CARN 700; cartilage derived inhibitor; carzelesin; casein kinasc inhibitors (ICOS); castanospermine; cecropin B; cetrorelix; chlorlns; chloroquinoxaline sulfonamide; cicaprost; cis-porphyrSn; cladribine; clomifene analogues; clotrimazole; collismycin A; collismycin B; combretastatin A4; combretastatin analogue; conagenin; crambescidin 816; crisnatol; cryptophycin 8; cryptophycin A derivatives; curacin A; cyclopentanthraquinones; cycloplatam; cypemycin; cytarabine ocfosfatc; cytolytic factor; cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslorelin; dexamethasone; dexifosfamide; dexrazoxane ; dexverapamil; diaziquone; didemnin B; didox; diethylnorspermine; dihydro-5-azacytidine; dihydrotaxol, 9-; dioxamycin; diphenyl spiromustine; docetaxel; docosanol; dolasetron; doxifluridine; droloxifene; dronabinol; duocarmycin SA; ebselen; ecomustine; edelfosine; edrecolomab; eflornithine; elemene; emitefur; epirubicin; epristeride; estramustine analogue; estrogen agonists; estrogen antagonists; etanidaole; etoposide phosphate; exemestane; fadrozole; fazarabine; fenretinide; filgrastim; finaste-ride; flavopiridol; tlezelastine ; fluasterone; fludarabine ; fluorodaunorunicin hydrochloride; forfenimex; formestane; fostriecin; fotemustine; gadolinium texaphyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitors; gemcitabine; glutathione inhibitors; hepsulfam; heregulin ; hexamethylene bisacetamide; hypericin; ibandronic acid; idarubicin; idoxifene; idramantone; ilmofosine; ilomastat; imidazoacridones; imiquimod; immunostimulant peptides; insulin-like growth factor-1 receptor inhibitor; inlerferon agonists; interferons; interleukins; iobenguane; iododoxorubicin; ipomeanol, 4-; iroplact; irsogladine; isobengazole; isohomohalicondrin B; itasetron; jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide; leinamycin; lenograstim; lentinan sulfate; leptolstatin; letrozole; leukemia inhibiting factor: leukocyte alpha interferon; leuprolide+estrogen+progesterone; leuprorelin; levamisole; liarozole; linear polyamine analogue; lipophilic disaccharide peptide; lipophilic platinum compounds; lissoclinamide 7; lobaplatin; lombricine; lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine; lurtotecan; lutetium lexaphyrin; lysofyllinc; lytic peptides; maitansine; mannostatin A; marimastat; masoprocol; maspin; matrilysin inhibitors; matrix inetalloproteinase inhibitors; menogaril; merbarone; meterelin; methioninase; metoclopramide: M1F inhibitor; mifepristone; miltefosine; mirimostim; mismatched double stranded RNA; miloguazone; mitolactol; mitomycin analogues; mitonafide; mitotoxin fibroblast growth factor-saporin; mitoxantrone; mofarotene; molgramostim; monoclonal antibody, human chorionic gonadotrophin; monophosphoryl lipid A+myobacterium cell wall sk; mopidamol; multiple drug resistance gene inhibitor; multiple tumor suppressor 1- based therapy; mustard anticancer agent; mycaperoxide B; mycobacterial cell wall extract; myrmporone; N-acetyldinaline; N-substituted benzamides; nafarelin; nagrestip; naloxoneipentazocine; napavin; naphterpin; nartograstim; nedaplatin; nemorubicin; neridronic acid; neutral endopeptidase; nilutatnide; nisamycin; nitric oxide modulators; nitroxide antioxidant; nitrullyn; 06-benylguanine; octreotjde; okicenone; oligonucleotides; onapristone ; ondansetron; ondansetron; oracin ; oral cytikine inducer; ormaiplatin; osaterone; oxaliplatin; oxaunomycin; paclitaxel; paclitaxel analogues; paclitaxel derivatives; palauamme; palmitoylrhizoxin; pamidronic acid; panaxytriol; panomifene; parabactin; pazelliptine; pegaspargase; peldesine; pentosan polysulfate sodium; pentostatin; pentrozole; perflubron; perfosfamide; perillyl alcohol; phenazinomycin; phenylacetate; phosphatase inhibitors; picibanil; pilocarpine hydrochloride; pirarubicin; piritrexim; placetin A; placetin B; plasminogen activator inhibitor; platinum complex; platinum compounds; platinum-triamine complex; porfimer sodium; porfiromycin; prednisone; propyl bis- acridone; prostaglandin J2; proteasome inhibitors; protein A-based immune modulator; protein kinase (' inhibitor; protein kinase C inhibitors, microalgal; protein tyrosine phosphatase inhibitors; purine nucleoside phosphorylase inhibitors; purpurins; pyrazoloacridine; pyridoxylated hemoglobin polyoxyethylene conjugate; raf antagonists; raltitrexed; ramosetron ; ras farnesyl protein transferase inhibitors; ras inhibitors; ras-GAP inhibitor; retelliptine demethylated; rhenium Re 186 etidronate; rhizoxin; ribozymes; RI1 retinamide; rogletimidc; rohitukinc; romurtide; roquinimex; rubiginone Bl ; ruboxyl; safingol ; saintopin; SarCNU ; sarcophytol A; sargramostim; Sdi 1 mimetics; semustine; senescence derived inhibitor 1; sense oligonucleotides; signal transduction inhibitors; signal transduction modulators; single chain antigen binding protein: sizofiran; sobuzoxane; sodium borocaptate; sodium phenylacetate; solverol; somatomedin binding protein; sonermin; sparfosic acid; spicamycin D; spiromustine; splenopentin; spongistatin 1 ; squalamine; stem cell inhibitor; stem-cell division inhibitors; stipiamide; stromelysin inhibitors; sulfinosine; superactive vasoactive intestinal peptide antagonist; suradista; suramin; swainsonine; synthetic glycosaminoglycans; tallimustine; tamoxifen methiodide; tauromustine; tazarotene; tecogalan sodium; tegafur; tellurapyrylium; telomerase inhibitors; temoporfin ; temozolomide; teniposide; tetrachlorodecaoxide; tetrazomine; thaliblastine; thiocoraline; thrombopoietin; thrombopoietin mimetic; thymalfasin; thymopoietin receptor agonist; thymotrinan; thyroid stimulating hormone; tin ethyl etiopurpurin; tirapazamine; titanocene bichloride ; topsentin; toremifcne; totipotent stem cell factor; translation inhibitors; tretinoin; triacetyluridine; triciribine; trimetrexate; triptorelin: tropisetron ; turosteride; tyrosine kinase inhibitors; tyrphostins; UBC inhibitors; ubcnimex; urogenital sinus-derived growth inhibitory factor; urokinase receptor antagonists; vapreotide; variolin B; vector system, erythrocyte gene therapy; velaresol; veramine; verdins; verteporfin; vinorelbine; vinxaitine; vitaxin; vorozole;zanoterone; zeniplatin ; zilascorb; and zinostatin stimalamer. The compounds of the present invention and the other therapeutic agent can act additively or, more preferably, synergistically. In a preferred embodiment, a composition comprising a compounds of the present invention is administered concurrently with the administration of another therapeutic agent, which can be part of the same composition or in a different composition from that comprising the compounds of the present invention. In another embodiment, a composition comprising the compounds of the present invention is administered prior to or subsequent to administration of another therapeutic agent. The compounds of the present invention when administered, e. g., via the oral, parenteral or topical routes to mammals, can be in a dosage in the range of about 0.01 mg/kg to about 3000 mg/kg body weight of the patient per dav. preferably about 0,01 mg/kg to about 1000 mg/kg body weight per day administered singly or as a divided dose. However, variations will necessarily occur depending upon the weight and physical condition (e. g., hepatic and renal function) of the subject being treated, the affliction to be treated, the severity of the symptoms, the route of administration, the frequency of the dosage interval, the presence of any deleterious side-effects, and the particular compound utilized, among other things. The compounds of the present invention preferably have a binding affinity K, for the human ORL-1 receptor of about 500 nM or less; 100 nM or less; 50 nM or less; 20 nM or less or 5 nM or less. The binding affinity Ki can be measured by one skilled in the art by an assay utilizing membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) as described below. The following examples illustrate various aspects of the present invention, and are not to be construed to limit the claims in any manner whatsoever. EXAMPLE 1 SYNTHESIS OF BENZOXAZOLONE HEAD GROUPS. Thahead groups of the present invention were synthesized according to the followings procedure: (Procedure Removed) Procedure; To a mixture of 1 (1.09 g, 10 mmol), 2 (1.99 g, 10 mmol) and acetic acid (0.60 g, 10 mmol) in 50 mL of dichloroethane, was added sodium triacetoxyborohydride (2.97 g, 14 mmol). The mixture was stirred at room temperature overnight/The mixture was filtered through Celite and 1 N NaOH (50 mL) was added to quench the reaction. The organic layer was separated and the aqueous layer was extracted with EtOAc (2 x 30 mL). The combined organic layers were dried over K2CO3, filtered and evaporated in vacuum to give crude 3 as a brown solid (2.75 g, yield: 94%). 'I1NMR (CDC1.,): d 1.20-1.60.(m, 11H), 2,00 (dd, 2H), 2.9 (m, 2H), 3.40 (m, 1H), 4.00 (m, 2H), 6.60-6.85 (01,411). I'o an ice cooled solution of crude 3 (12.0 g, 40 mmol) and DIEA (20.8 mL, 120 mmol) in 200 mL of THF, was added a solution of triphosgene (4.32 g, 14.4 mmol) in 200 mL of THF. After the addition was complete the ice bath was removed and the mixture stirred at room temperature overnight. The solids were filtered off and the filtrate evaporated in vacuum. The residual brown oil was dissolved in EtOAc and washed with saturated aqueous K2CO3. The organic phase was dried over K2CO3, filtered and evaporated in vacuum to give a red oil which was filtered through a column of silica gel eluting with a mixture of 5% Et3N, 25% EtOAc and 70% hexanc. The selected fractions were combined and the solvent evaporated in vacuum to give a brown solid which was crystallized from EtOAc to give pure 4 (10.0 g, 78% yield). 111 NMR (CDC 13): d 1.50 (s, 9H), 1.85 (d, 2H), 2.25 (m, 2H), 2.85 (m, 2H), 4.20-4.45 (m, 3H), 7.00-7.25 (m, 411). A solution of 4(4.0 g, 17.2 mmol) in 30% TFA/dichloromethane (25 mL) was stirred at room temperature for 3 h. The solvent was evaporated in vacuum and saturated aqueous K2CO3 was added to the oily residue. The resulting mixture was extracted with dichloromethane (3 x 50 mL). The combined organic extracts were dried 30 over KoCOs, filtered and evaporated in vacuum to give the crude product. Chromatography on silica gel eluting with a mixture of 10% Et3N, 60% EtOAc and 30% hexane gave 5 as a yellow solid (1.82 g, 66% yield). MS: m//. 450 !H NMR (CDC13): d 1.75-2.10 (m, 3H), 2.30 (d, 2H), 2.80 (m, 2H), 3.20 (m, 2H), 4.25 (m, 1H), 7.00-7.25 (m, 4H). EXAMPLE 2 ATTACHMENT OF TAIL GROUPS Tail groups were attached to the head groups according to the following procedures: (Procedure Removed) General procedure for alkylation: lo a solution of the amine (1 eq) and triethylamine (1 eq) in dimethylformamide, was added 1 eq of alkyl bromide or chloride in one portion. The mixture was stirred and heated at 80°C over night. TLC indicated the reaction was complete, The reaction was quenched by the addition of water followed by 1 N NaOH to pH 10. The mixture was extracted 2x with Et2O. The combined organic extracts were dried over potassium carbonate and the solvent evaporated, followed by chromatography to give the pure product. General procedure far reductive animation: To a mixture of ketone or aldehyde (1 eq), amine (1 eq), and acetic acid (1 eq) in methanol, was added sodium cyanoborohydride (1.4 eq) in one portion. The mixture was stirred over night at room temperature. TLC indicated the reaction was complete. The reaction was quenched by the addition of water followed by 1 N NaOH to pH 10. The mixture was extracted 2x with Et2O. The combined organic extracts were dried over potassium carbonate and the solvent evaporated, followed by chromatography to give the pure product. I he following compounds were prepared by attaching the tail groups using the general procedures described: 3-| l-(naphth-2-yl-methyl)-4-piperidinyl]-2H-benzoxazol-2-one 3-| l-(naphth-l-yl-metfiyl)-4-piperidinyl]-2H-benzoxazol-2-one 3-11- (p-phenylben/.yl)-4-piperidinyl]-2H-benzoxazol-2-one 3-| 1 - (p-ben/yloxybenzyl)-4-piperidinyl]-2H-benzoxazol-2-one 3- 1- (p-cyanobenzyl)-4-piperidinyl]-2H-benzoxazol-2-one MS: in/z334.4 (M-H). 3-| 1 -(3.3-diphenylpropyl)-4-piperidinyl]-2H-benzoxazol-2-one 3- 1 1- |4.4-Bis- (4-fluopophenyI) butyl]-4-piperidinyl]-2H-benzoxazol-2-one MS: m// 463.6 (Mi 1). 3- 1 1- (2-phenylcthyl)-4-piperidinylj-2H-benzoxazol-2-one 3- 1 1- (cYclooclylmethyl)-4-piperidinyl]-2H-benzoxazol-2-one l.C: 100% 343.6 (M+l). 'll-NMK (CDC13): d 1.25 (m, 2H), 1.40-1.7 (m, 17H), 2.10 (m, 4H), 3.10 (m, 2H), 4.20 (m, 1H), 7.10-7.20 (411). I3C-NMR (CDCI3): d 26.02, 26.87, 27.55, 29.27, 31.23, 35.31, 53.39, 53.70, 66.28, 1 10.45, 1 10.51, 122.45, 123.96. 130.45, 143.08, 154.51. 3- 1 1-( I. 2,3,4-tctrahydro-2-naphthyl)-4-piperidinyl]-2H-benzoxazol-2-one l.C: 100% MS: 349.6 (MH) '11-NMR (CDCI3): d 1.70 (m, 1H), 2.00 (b, 2H), 2.10 (b, 1H), 2.40 (m, 4H), 2.90 (m, 5H), 3.10 (m, 2H), 4.20 (m. 111). 7. 10-7.30 (m,8H). 3- 1 1- (5-methylhex-2-yl)-4-piperidinyl|-2H-benzoxazol-2-one l.C: 100% VIS: 3 1 7.4 (MM) 1 11-NMR (CDC13): d 0.90 (d, 6H), 1.00 (d, 3H), 1.20 (m, 3H), 1.50-1.60 (m, 4H), 1.80 (m, 2H), 2.20-2.60 (m, 511), 2.90 (b, 21 1), 4.2 (m, 1 H), 6.90-7.30 (m, 4H). 3- 1 1- (10, 1 l-Dihydro-5H-diben/o [a, d]-cyclohepten-5-yl)-4-piperidinyl]-2H-benzoxazol-2-one l.C: 96.4% !1 1-NMR (CDClj): d 1,80 (dd, 2H), 2.00 (dt, 2H), 2.30 (dq, 2H), 2.80-2.95 (m, 4H), 4.01 (s, 1H), 4.05-4.22 (m, 311). 7.05-7.25 (m, 12H). 3- 1 1- (4-propyl-cyclohexyl)-4-piperidinyl]-2H-benzoxazol-2-one VIS: m/z343.0 3-| 1 -(iK>rbornan-2-yl)-4-piperidinyl]-2H-benzoxazol-2-one l.C: 97% MS: in/z 3 13. 41 (M+l) '1 1-NMR (CDC I.,) : d 0.90 (m, 1H), 1.30-2.50 (m, 17H), 3.20 (m, 2H), 4.3 (m, 1H), 6.90-7.30 (m, 4H). 3- 1 1 -(decahydro-2-naphthyl)-4-piperidinyl]-2H-benzoxazol-2-one MS: m/z 355.4 3-| 1- (3, 3-dimethyl- 1,5-dioxaspiro [5.5] undeca-9-yl)-4-piperidinyl]-2H-benzoxazol-2-one MS: in/ 40 1.3 3- 1 1- 14- (l-mcthylethyl)-cyclohexyr|-4-piperidinyl]-2H-benzoxazol-2-one MS: m/z 343.0 3-| I - ( 1 , 3-dihydroind l.C: 100% MS: m/z335.4(M+l) '11-NMR (CDC 1 3): d 1.90 (m, 1H), 2.40 (m, 2H), 2.50 (m, 2H), 2.90 (m, 2H), 3.10-3.40 (m, 6H), 4.20 (m, 111). 7. 10-7.30 (m,8H). 3- 1 l-(cyclooctyl)-4-piperidinyl]-2H-benzoxazol-2-one l.C: 100% MS: m/z 329.2 (Ml 1) 'll-NMR (CDC13): d 1.40-2.00 (m, 16H), 2.40-2.65 (m, 4H), 2.80 (m, 1H), 3.05 (m, 2H), 4.25 (m, 1H), 7.10- 7.40 (m, 411). Other compounds within the scope of formula (1) or (IA) of the present invention can be synthesized by analogous techniques. EXAMPLE 3 Nociceptin affinity at the ORL1 receptor for preferred compounds was obtained using the following assay: Membranes from recombinant HEK-293 cells expressing the human opioid receptor- like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES. pH 7.4) (10 ml/10 cm dish) followed by homogenization with a tissue grinder/teflon pestle. Membranes were collected by centrifugation at 30,000 x g for 15 min at 4°C and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/ml. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of the ORL-1 receptor membranes were stored at-80°C. I-unctional SGTPgS binding assays were conducted as follows. ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0.066 mg/ml ORL-1 membrane protein, 10 mg/ml saponin, 3 mM GDP and 0.20 nM [35S] GTPgStobindingbuffer(100 mM NaCI, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 ml/well) was transferred to 96-shallow well polypropylene plates containing 10 ml of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at room temperature with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GI-7B filler plates (Packard) using a 96-well tissue harvester (Brandel) and followed by three filtration washes with 200 ml ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50°C for 2-3 hours. Fifty ml/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. Data was analyzed using the curve fitting functions in GraphPad PR1SMO, v. 3.0 and the results are set forth in table 1 below: TABLE 1 Nuciqcptin Affinity (Table Removed) EXAMPLE 4 SYNTHESIS OF SUBSTITUTED INDOLE HEAD GROUPS (Procedure Removed) Procedure: To a mixture of 2 (23.3 g, 0.25 mol), 1 (47.3 g, 0.25 mol), acetic acid (15 g, 0.25 mol) and molecular sieves (15 g) in 500 mL of dichloroethane, sodium triacetoxyborohydride (74.2 g, 0. 35 mol) was added in one portion and the mixture stirred overnight. The molecular sieves were filtered off and 1 N NaOH (500 mL) was added to quench the reaction. The organic layer was separated and the aqueous layer extracted with EtOAc (2 x 300 mL). The combined organic extracts were dried over K2CO3, filtered and the solvent evaporated under vacuum to give crude 3 as a brown solid which was directly used in next step. Compound 3 'll-NVIR (CDC!.,): d 1.50 (m, 2H), 2.05 (m, 2H), 2.20 (bt, 2H), 2.85 (m, 2H), 3.30 (m, 1H), 3.52 (s, 2H), 6.60 (d. 211). 6.70 (t. 1H), 7.20 (m, 2H), 7.25-7.40 (m, 5H). I o an ice cooled solution of crude 3 (0.25 mol, 100% yield assumed) and D1EA (48.4 g, 0.38 mol) in 500 mL of dichloromethane, was added dropwise chloroacetyl chloride (42.4 g, 0.375 mol). After the addition was complete the ice bath was removed and the reaction mixture stirred overnight. The solvent was removed in vacuum and the residue dissolved in dichloromethane. The organic phase was washed with saturated aqueous K2CO. dried over K2CO3, filtered and the solvent removed in vaccum to give a brown gum which was filtered through a column of sjlica gel eluting with a mixture of 10% EtsN, 40% EtOAc and 50% hexane. The selected fractions were combined and the solvent evaporated in vacuum to give a brown solid which was further crystallized from EtOAc to give 42.2 g of 4 (49.2%, 2 steps). Compound 4 '11 NMR (DMSO): d 1,22 (m, 2H), 1.70 (b, 2H), 2.00 (t, 2H), 2.80 (b, 2H), 3.40 (s, 2H), 3.80 (s, 2H), 4.40 (m, 111). 7,15-7.30 (m, 7H), 7.45 (m, 3H). A mixture of 4 (42.2 g, 0.12 mol) and A1C13 (49.2 g, 0.369 mol) was mixed in a flask by rapid stirring. The mixture was then heated in an oil bath at 130 °C. Within a few minutes the solids melted and became a dark liquid with concomitant gas evolution. After heating for 1 h the reaction mixture was cooled somewhat and while still mobile poured into a beaker containing 500 mL of ice water. The solution was basified and extracted with dichloromethane. The organic layer was dried over Na2SO4, filtered and the solvent evaporated in vacuum to give a dark oil which was filtered through a column of silica gel eluting with a mixture of 10% 1 tfN, 40% EtOAc and 50% hexane. The selected fractions were combined and the solvent evaporated in vacuum to give 5 as a red oil which set to a pale solid (22. 0 g, 58. 5%), Compound 5 '11 NMR (CDC13): d 1.70 (m, 2H), 2.17 (m 2H), 2.50 (m, 2H), 3.05 (m, 2H), 3.55 (s, 2H), 3.60 (s, 2H), 4.33 (m. Ill), 7.00-7.40 (m, 911). To a solution of 5 (16.0 g, 0.052 mol) in 35 mL of methanol was added Pd (OH)2 (4.0 g). The resulting suspension was hydrogenated at 50 psi for 12 h at room temperature. The solution was filtered through a pad of ("elite and the pad washed with methanol (2 x 20 mL). Evaporation of the solvent in vacuum gave 6 as a pale solid (11.2 g, 100%). Compound 6 l.C: 100% MS: m/z217(M4l). '11 NMR (CDCl3): d 1.75 (m, 3H), 2.35 (m 2H), 2.75 (m, 2H), 3.25 (m, 2H), 3.50 (s, 2H), 4.33 (m, 1H), 7.00- 7.30 (m. 411) To a solution of 6 (8. 0 g, 37.0 mmol) in 50 mL of dichloromethane was added Et3N (4.07 g, 40.7 mmol) and HOC anhydride (8.87 g, 40.7 mmol). After stirring for 3 h saturated aqueous K2CO3 was added and the layers separated. The aqueous phase was extracted with dichloromethane (2 x 50 mL). The combined organic phase was dried over KiCOj, filtered and evaporated in vacuum to give a brown oil which was filtered through a column of silica gel eluting with a mixture of 10% Et3N, 40% EtOAc and 50% hexane. The selected fractions were combined and the solvent evaporated in vacuum to give 7 as an off white solid (8.50 g, 73%). Compound 7 '11 NMR(CDCI,): d 1.50 (m, 9H), 1.70 (m 2H), 2.20-2.50 (m, 2H), 2.80-3.00 (m, 2H), 3.50 (s, 2H), 4.20-4.50 (m, 311), 6.90-7.60 (m, 511). To a mixture of 7 (6.0 g, 19.0 mmol) and sodium acetate (2.58 g, 19.0 mmol) in 150 mL of methanol was added acetaldehyde (1.67 g, 38. 0 mmol). The mixture was refluxed for 2 h. The solvent was evaporated in vacuum to give a dark oil which was filtered through a column of silica gel eluting with a mixture of 10% Kt;N. 40% EtOAc and 50% hexane. The selected fractions were combined and the solvent evaporated in vacuum to give 8 as a red oil (5. 90 g, 91%). Compound 8 l.C: 2 isomers in a ratio of 2:1. 'll NMR (CDC13): (mixture of 2 isomers) d 1.50 (m, 9H), 1.70 (m 2H), 2.20-2.50 (m, 6H), 2.60-3.00 (m, 2H), 4.20-4.50 (m, 311), 6.90-7. 60(m, 5H). A solution of 8 (5.90 g, 17.2 mmol) in 30% TFA/dichloromethane (100 mL) was stirred at room temperature for 3 h. the solvent was evaporated in vacuum and saturated aqueous K.2CO3 was added to the oily residue. The resulting mixture was extracted with dichloromethane (3 x 150 mL). The combined organic extracts were dried over K2CO3, filtered and evaporated in vacuum to give the crude product. Chromatography on silica gel cluting with a mixture of 10% Et3N, 50% EtOAc and 40% hexane gave 9 (E/Z isomers) as a yellow foam (3.60 g, 82%). Compound 9 I.C: 2 isomers in a ratio of 2:1. MS:m/z 243.1 (MH). !11 NMR (CDCI3): (mixture of 2 isomers) d 0.85 (m, 1H), 1.50-2.00 (m, 4H), 2.20-2.50 (m, 5H), 2.60 (m, 1H), 3.10-3.50 (m, 2H), 4.30 (m. lH), 6.90-7.60 (m, 5H). EXAMPLE 5 (Example Removed) To a mixture of 5 (5.50 g, 18 mmol) and sodium acetate (2.45 g, 18 mmol) in 150 mL of methanol was added acetaldehyde (1.58 g, 36 mmol). The mixture was refluxed for 2 h. The solvent was evaporated in vacuum to give a dark oil which was filtered through a column of silica gel eluting with a mixture of 10% EtsN, 40% EtOAc and 50% hexane. The selected fractions were combined and the solvent evaporated in vacuum to give 10 as a red oil (5.90 g, 98%). Compound 10 IX' : 2 isomers in a ratio of 2: 1. VIS: mi/ 333.2 (1VH 1). 'II NMR (ClX'b): d 1.70 (m, 2H), 2.17 (m 2H), 2.30 (d, 3H), 2.50 (m, 2H), 3.05 (m, 2H), 3.55 (s, 2H), 4.33 (m. III). 7.00-7.40 (m, 911). 7.6 (d, 1 H). I'o a solution of 10 (5.90 g, 17.7 mmol) in 30 mL of methanol was added Pd(OH)2(3.0 g). The resulting suspension was hydrogenated at 50 psi for 12 h at room temperature. The solution was filtered through a pad ol'Celile and the pad -washed with methanol (2 x 20 mL). Evaporation of the solvent in vacuum gave a pale solid which was purified by chromatography on silica gel eluting with a mixture of 10% methanol and 90% 1-lOAc to give 11 as an off white solid (2.02 g, 50%). Compound 11 LC: 97% MS: m/y 245.2 (M-+1) 'II NMR (CDClj): d 0.85 (t, 3M), 1.26 (m, 2H), 2.00 (m, 2H), 2.43 (m, 2H), 2.90 (m, 2H), 3.3 (m, 2H), 3. 4 (m. 111). 4.4 (m, 111). 7.05 (m. III), 7.15-7.30 (m, 3H). EXAMPLE 6 (Example Removed) In a manner similar to the preparation of 6, compound 16 was prepared. Compound 13 I,C: 89.4% MS: in/z281.2 (Mi I) 'H-NMK (mixture of trans and cis) (CDCI3): d 0.95 (m, 3H), 1.50-2.75 (m, 5H), 2.80-3.20 (m, IH), 3.50 (m, 211), 3.60 (minor) O.70 (major) (two s, 2H), 6. 55-6. 80 (m, 2H), 7.05-7.45 (m, 8H). Compound 14 MS: m/z: 357.2 (M-H) 'll-NMR (mixture of trans and cis) (CDCI3):d 1.10(m, 3H), 1.40-4.20 (m, 11H), 4.40 (m, IH), 7.05-7.50 (m, 1011). Compound 15 1,C: 90.0% MS: m/z321.2 (M+1) 'H-NVlR(CIX:i.,):d 1.20(d,3H), 1.75 (m, lH),2.10(dt, lH),2.25(b, lH),2.30(dd, lH),2.75(dd, 1H),3.05 (m. 111). 3.20 (m, 111). 3.50 (m, 4H), 4.10 (m, 1 H), 6.99 (m, 2H), 7. 23 (m, 3H), 7.37 (m, 4H). Compound 16 IX': 92.5% MS: m/z231.2 (Mi 1) 'll-NMR (CDC13): d d 1.20 (d, 3H), 1.75 (m, IH), 2.10 (dt, IH), 2.25 (b, IH), 2.30 (dd, IH), 2.75 (dd, IH), 3,05 (m. 111), 3.20 (m. 111), 3.50 (m, 2H), 4.10 (m, IH), 6.99 (m, 2H), 7.23 (m, 3H), 7.37 (m, 4H). 37 EXAMPLE 7 (Example Removed) Procedure: In a manner similar to {he preparation of 11, compound 18 was prepared. Compound 17 MS: m/z347.3 (M+l) Compound 18 LC: 82.6% MS:Pm/z. 259.3 (M+l} 'H-NMR (CDCU): d 0,80 (t, 3H), 1.20 (d, 3H), 2.00 (m, 2H), 2.30 (m, 1H), 2.65 (m, 1H), 2.82 (m, 1H), 3.15- 3.25 (m. IH), 3.32 (m, 111), 3.45 (m, 1H), 3.65 (m, 1H), 3.75 (m, lH),4.25(m, 1H), 6.90 (d, lH),7.05(t, 1H), 7.25 (m. 211). EXAMPLE 8 ATTACHMENT OF TAIL GROUPS Tail groups were attached to the head groups according to the following procedures: (Procedure Removed) General procedure for alkylation: To a solution of the aimine (1 eq) and triethylamine (1 eq) in dimethylformamide, was added 1 eq of alkyl bromide or chloride in one portion. The mixture was stirred and heated at 80°C over night. TLC indicated the reaction was complete. The reaction was quenched by the addition of water followed by 1 N NaOH to pH 10. i he mixture was extracted 2x with Et2O. The combined organic extracts were dried over potassium carbonate and the solvent evaporated, followed by chromatography to give the pure product. General procedure for reductive amination: I o a mixture of ketone or aldehyde (1 eq), amine (1 eq); and acetic acid (1 eq) in methanol, was added sodium cyanohorohydridc (1.4 eq) in one portion. The mixture was stirred over night at room temperature. TLC indicated the reaction was complete. The reaction was quenched by the addition of water followed by 1 N NaOH to pi I 10. The mixture was extracted 2x with Et2O. The combined organic extracts were dried over potassium carbonate and the solvent evaporated, followed by chromatography to give the pure product. The following compounds were prepared by attaching the tail groups using the general procedures described: 1-11- (naphth-l-yl-methyl)-4-piperidinyI]-l, 3-dihydro-2H-indole-2-one MS: mlz 357.2 (MH). 1- 11- (naphth-2-yl-met;hyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one MS: m// 357.3 (MH). 1- |1- (p-phenylbc'n/yl)*4-piperidinyl]-l, 3-dihydro-2H-indole-2-one MS: m//383.2 (MH). 1-11- (3, 3-Bis (phenyl) propyl)-4-piperidinylj-l, 3-dihydro-2H-indole-2-one LC:98.7% MS:m//.411.2(M+l) 'll-NMR (CDC13) : d 1.65 (bd, 2H), 2.05 (bt, 2H), 2.30 (m, 4H), 2.45 (m, 2H), 3.02 (bd, 2H), 3.50 (s, 2H), 4.01 (t. 111), 4.30 (m, 1H), 7.00 (t, 1H), 7.15-7.35 (m, 13H). 1- 11- (p-cyanoben/.yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one MS: m//332.2 (M-H). 1-| l-(p-hen/yloxyben/yl)-4-piperidinylj-l,3-dihydro-2H-indole-2-one MS: m//413.3 (MM) l-|l-(l,2,3,4-tetrahydronaphth-2-yl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one LC: 100% MS: m//347.5 (Mil). '11 NMR (CDCh): d 1.70 (m, 3H), 2,10 (m, 1H), 2.40 (m, 4H), 2.90-3.00 (m, 5H), 3.10 (m, 2H), 3.60 (s, 2H), 4.3 (m. 111), 7.00-7.30 (m, 811). 1-11- (5-methylhex-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one I.C: 100% MS:m/z3l5.4(MH).- 111 NMR (CDCl3): d 0,90 (m. 6H), 1.00 (m, 3H), 1.20 (m, 3H), 1.5-1.8 (m, 2H), 2.2-2.6 (m, 5H), 2.90 (m, 2H), 3.60 (s. 211), 4.2 (m. 111), 6.90-7.30 (m, 4H). 1-11- (norbornan-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one I.C: c)7% MS: m/z. 311.41 (MH). 'II NMR (CDC13): d 0.90 (m. 1H), 1.30-2.00 (m, 7H), 2.10-2.30 (m, 5H), 3.20 (m, 2H), 3.60 (s, 2H), 4. 3 (m, 111). 6.90-7.30 (m, 411). 1-11- (I, 3-dihydroinden-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one I.C: 100% MS: m/z.332.4 (MH), '11NMR (CDCl,): d 1.80 (m, 2H), 2, 40 (m, 2H), 2.50 (m, 2H), 2.90 (m, 2H), 3.10-3,40 (m, 5H), 3.60 (s, 2H), 4.20 (m. 111), 7.10-7.30 (m, 811). I-11- (cycooctylmethy|)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one I.C: 97% MS: m/z341.50 (M-H). 'II NMR (CDCh): d 1.25 (m, 3H), 1-4-1.7 (m, 14H), 2.10 (m, 4H), 2.50 (m, 2H), 3.10 (m, 2H), 3.60 (s, 2H), 4,3 (m. Ill), 7.10-7.20 (m, 411); "C-NMR (CDCI3): d 23.07, 26.04, 26.89, 27.56, 28.63, 31.27, 32.00, 35.30, 36.33, 46.63, 50.65, 54.06, 66.47. I 10.90, 122.17, 124.90, 125.26, 127.94, 144.25, 175.31. 3-ethyl-1-| 1 -(1, 2,3,4-tetrahydro-2-naphthyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one MS. m/z375.3 (MM). 3-ethyl-1-| l-(4-propylcyclohexyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one MS: m/z. 369.2 (M-H). 3-ethyl-1-11- (5-methylhex-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one l.C: l"()0% MS : in/z 342.4 (M-H). 'II NMR (CDCh): d 0,80 (t, 3H), 0.90 (m, 6H), 1.00 (m, 3H), 1.20 (m, 3H), 1.5-1.8 (m, 2H), 2.2-2.6 (m, 5H), 2,90 (m. 211), 3.40 (m, I M), 4.3 (m, 1H), 6.90-7.30 (m, 4H). 3-ethyl-1-11- (norbornan-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one l.C: l'()0% MS: m/z339.41 (M+l). 'I IN MR (CDC13): d 0.80 (m, 3H), 0.90 (m, IH), 1.30-1.45 (m, 5H), 1.50-2.05 (m, 8H), 2.10 (m, IH), 2.20 (m, 211). 2.50 (m, 2H). 3.10 (m, 211), 3.40 (m, IH), 4.3 (m, IH), 6. 90-7.30 (m, 4H). 3-ethyl-1-| l-(decahydro-2-naphthyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one MS: m/z381.3(M+l). 3-ethyl-1-11-14- ( l-methylethyl)-cyclohexyl]-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one MS: m/z369.3 (M+l) 'll-NMR (CDCI3) : d 0.88 (t, 3H), 0.92 (d, 6H), 1.17 (m, IH), 1.40 (m, 2H), 1.50-1.70 (m, 9H), 2.05 (m, 2H), 2.25 (m. 211), 2.32-2.55 (m, 3H). 3.15 (b, 2H), 3.43 (t, IH), 4.35 (m, IH), 7.05 (t, IH), 7.22 (d, IH), 7.28 (m, 211). 3-ethyl-1- 11- (1. 3-dihydroinden-2-yl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2-one MS: m/z361.2 (M+l). 3-ethyl-1-11- (cyelooctylmethyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one l.C: 97% MS: m/z369.50 (M+l). :ll NMR (CDCh) :d().80(t. 3H), 1.25 (m, 3H), 1-4-1.7 (m, 14H), 2.10 (m, 6H), 2.50 (m, 2H), 3.10 (m, 2H), 3.40 (m, 111). 4.3 (m. 111), 7.10-7.20 (m, 4H). 3-ethylidonc-l-11- (ben/yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one MS: m/z333.2 (M+1) 'll-NMR (CDC1.0 : d 1.70 (m, 2H), 2.15 (dt, 2H), 2.28 (d, 3H), 2.47 (m, 2H), 3.05 (b, 2H), 3.57 (s, 2H), 4.34 (m. III). 7.02 (t, I H), 7.08-7.40 (m, 8H), 7.58 (d, 1 H). 3-ethylidene-l-11- (naphth-2-yl-methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one MS: m/z. 405.2 3-ethylidene-l-11- (3, 3-diphenylpropyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one l.C: -97% (2 isomers combined). MS: in/z437.5 (M* 1). '11 NMR (CDCI3): d 1. 70-1.80 (m, 3H), 2,10 (m, 2H), 2,. 20-2.40 (m, 8H), 3.10 (m, 2H), 4.10 (M, IH), 4.3 (m. 111). 7.00-7.30 (m, 1511). 3-elhylidene-l- 1 1- (p-cyanoben/yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one IX': >97% (2 isomers combined). MS: m/z. 358.5 (M+l). 'I.INMR (CDC13): d 1.80 (m, 4H), 2.10-2.60 (m, 5H), 3.10 (m, 2H), 3.70 (s, 2H), 4.3 (m, IH), 6.90-7.60 (m, 3-elhylidene-l- |l- (p-ben/yloxybenzyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one . MS: m/z 405.2. 3-cthylidcne-l- [ 1- (1, 2,3,4-tetrahydro-2-naphthyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one IX": >97% (2 isomers combined). MS: mlz 373. 5 (Mi 1). 1 1 1 NM K (CDC1 ,): d 1 .70-3. 1 0 (m, 1 8H), 4.3 (m, 1 H), 7.00-7.30 (m, 9H). 3-elhylidene-l- 11- (4-propylcyclohexyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one IX': >97% (2 isomers combined). MS: m/z. 367.5 (M+l). '11 NMR (CDCh): d 0.90 (m, IH), 1.30-2.00 (m, 7H), 2.10-2.30 (m, 5H), 3.20 (m, 2H), 3.60 (s, 2H), 4. 3 (m, 111). 6.90-7. 30 (m, 5H). 3-elhylidene-l- 1 1- (5-methylhex-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one IX': >97% (2 isomers combined). MS: m/z 34 1.4 (Mf 1). ]H NMR (CDCh): d 0.90-2.6 (m, 24H), 2.90 (m, 2H), 4.2 (m, IH), 6. 90-7.30 (m, 5H). 3-elhylidene-l- 1 1- (norboman-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one LC': >97% (2 isomers combined). MS: m/z 337.41 (M+l). '11 NMR (CDCl3) : d 0.90 (m. 111), 1.30-2.50 (m, 17H), 3.10 (m, 2H), 4.3 (m, IH), 6.90-7.30 (m, 5H). 3-elhylidene-l- 11- (1, 3-dihydroinden-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one I.C: >97% (2 isomers combined). MS: m// 359.4 (M-H). '11 NMR(CDCh): d 1.80-3.10(m, 17H). 4.20 (m, IH), 7.10-7.30 (m, 9H). 3-eihy I idene- 1 -| 1 -(cycloocly Imelhy l)-4-piperidinyl]- 1 ,3-dihydro-2H-indole-2-one IX': >97% (2 isomers combined). MS :m/x 367.50 (M -il). 'H NMR (CL)C13): d 1.25 (m, 3H), 1.4-1.7 (m, 21H), 2.10-2.50 (m, 2H), 3.10 (m, 2H), 4.3 (m, IH), 6.90-7.60 (m. 511). 1-| l-(3, 3-His (phenyl) propyl)-3- (melhyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one I.C: 100% VIS: IH//425.3 (MH) 'H-NMR (CDC1,): d 1,20 (d, 3H), 1.69 (bd, 1H), 1. 95 (dt, 1H), 2.13-2.30 (m, 5H), 2.72 (bd, 1H), 2.98 (bd, 111). 3.l5(dq, 1M), 3.50 (s,2H), 4.03 (dt, lH),4.12(t, lH),6.94(d, 1H),7. 00 (t, 1H), 7.10-7.30 (m, 12H). 1-| l-(ben/yl)-3-(methyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one IX'-. !00% 'll-NMR (CDCl3):d 1.20 (d, 3H), 1.70 (m, 1H), 2.10 (dt, lH),2.23(m, 1H), 2.35 (dd, lH),2.78(d, 1H), 3.05 (m. 111), 3.20 (dq, 1 H). 3.5 1 (m, 4H), 4.10 (dt, 1H), 7.00 (m, 2H), 7.25 (m, 3H), 7.38 (m, 4H). 1 -[ 1 -(4-propyl-cyclohexyI)-3-(methyl)-4-piperidinyl]-l,3-dihydro-2H-indoIe-2-one I.C: 96.2% MS: m// 355.2 (MM) !1I-NMR (CDC10: d 0.85 (m, 3H), 1.15 (m, 3H), 1.22-1.85 (m, 13H), 2.05-2.90 (m, 6H), 2.95- 3.20 (m, 2H), 3.50 (s, 21 1). 4.05 (m. 1 H), 7.00 (m. 2H), 7.22 (m, 2H). 1-| 1 -(5-mcthylhex-2-yl)-3-(methyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one I.C: 100% MS: m//. 329.2 (MH) 'll-NMR (CDCh): dO.85 (m, 9H), 1.15 (m, 3H), 1.20-1.75 (m, 6H), 2.25 (m, 1H), 2.45-2.75 (m, 4H), 2.88 (m, 1 1 1). 3. 1 0 (m, 1 1 1), 3.50 (s, 2H), 4.05 (m, 1 H), 6.98 (m, 2H), 7.25 (m, 2H). 1- 1 1- (decahydro-2-naphthyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one I.C: 95.3% MS: ml/ 367.2 (MH) 'll-NMR (CDCI,): d 1.1 1 (d, 311), 1. 16-1.85 (m, 16H), 2.20 (m, 1H), 2.35 (m, 2H), 2.52 (m, 2H), 2.75 (m, 1 11), 3.02 (m. 211), 3.50 (s, 211), 4.05 (m, 1H), 6.96 (m, 2H), 7.20 (m, 2H). I- 1 1- (4- ( l-methylethyl)-cyelohexyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one I.C: 96.1% MS: m//355.2(MH) 'll-NMR (CDCI3): d 0.80 (m, 6H), 1.15 (m, 3H), 1.22-1.48 (m, 3H), 1.50-1.90 (m, 6H), 2.15- 2.90 (m, 4H), 2.95-3.25 (m, 211), 3.50 (s, 2H), 4.10 (m, 1H), 6.95 (m, 2H), 7.22 (m, 2H). 1-| l-(cyclooctylmethyl)-3-(methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one 1 .C : 1 00% MS: m//355.2(M+l) !11-NMR (CDC13): d 1.12 (d, 3H), 1.15-1.75 (m, 16H), 1. 92-2.10 (m, 3H), 2.20 (m, 2H), 2.73 (m, 1H), 3.00 (m. II I), 3. 1 2 (dq, 1 H). 3.50 (s, 2H), 4.05 (dt, 1 H), 6.99 (m, 2H), 7.20 (m, 2H). 3-cthyl-l- [1- (3, 3-Bis(phenyl) propyl)-3-(methyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one IX': 96.3% MS: m// 453.3 (Mt 1) 'll-NMR (CDC I3) : d (two t, 3H), 1.18 (d, 3H), 1.70 (m, 1H), 1.90-2.05 (m, 3H), 2.12-2.30 (m, 5H), 7.73 (m, 111). 2.97 (bd. Ill), 3.10-3.30 (m, IH), 3.38 (t, 1H), 3.90-4.05 (m, 1H), 4.. 12 (q, 1H), 6.90-7.00 (two d, 1H), 7.02(1, 111), 7.l2-7.32(m, I2H). 3-cth\l-l- 1 1- (4-propy!cyclohexyl)-3- (methyl)-4-piperidinylj-l, 3-dihydro-2H-indole-2-one I.C: 93.2% MS: in// 383.3 (M+l) 'll-NMR (CDC 13) : d 0.75-0.95 (m, 6H), 1.05-1.20 (m, 5H), 1.20-1.35 (m, 4H), 1.35-1.75 (m, 6H), 1.75-1.90 (m. 211). 1.95-2.05 (m, 211), 2.15-2.45 (m, 3H), 2.55 (d, 0.5H), 2.75 (d, 0.5H), 2.95-3.15 (m, 2H), 3.38 (t, IH), 3.90-4. 1 0 (m, 1 H), 6.90-7.05 (2H), 7.20-7.25 (m, 2H). 3-ethyl-l- [ 1- (5-methylhex-2-yl)-3- (methyl)-4-piperidinyl]-l,3-dihydro-2H-indole-2-one; I.C: 92.3% MS: m// 357.4 (M+l) 'I I-NMR (CDC I3):d 0.75-0.95 (m, 10H), 1.10 (d, 3H), 1.15-1.40 (m, 3H), 1.40-1.75 (m, 4H), 1.97-2.10 (m, 2U). 2.20 (m, 1H), 2.43-2.75 (m, 4H), 2.80-2.95 (m, 1H), 3.00-3.25 (m, 1H), 3.40 (t, 1H), 3.90-4.10 (m, 1H), 6.90-7.05 (m, 211), 7.23 (m, 211). 3-eihyl-l- 1-14- (l-methylethyl) cyclohexyl]-3-methyl-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one L(T94.7% MS: m//383. 4 (Mil) 'll-NMR (CDC 13): d 0.75-1.05 (m, 8H), 1.10-1.50 (m, 7H), 1.50-1.90 (m, 7H), 1.90-2.10 (m, 2H), 2.15-2.43 (m, 311). 2.55 (d, 0. 5H), 2.75 (d, 0. 5H), 2.90-3.25 (m, 3H), 3.40 (t, 1H), 3.90-4.10 (m, 1H), 6.90-7.01 (m, 211), 7.25 (m, 211). 3-ethyl-l-11- (decahydro-2-naphthyl)-3- (methyl)-4-piperidinyl]-l, 3-dihydro-2H-indole-2-one l.C: 94.3% MS: m//395.3(M4l) 'll-NMK(CDC 13) :d 1.75-1.90 (two t, 3H), 1.10 (d, 3H), 1.15-1.90 (m, 15H), 2.00 (m, 2H), 2.20 (bs, 1H), 2.40 (m. 2M). 2.45-2.60 (m, 2H), 2.75 (m, 1H), 2. 90-3.20 (m, 2H), 3.40 (bs, 1H), 3.90- 4.15 (m, 1H), 6.90- 7.05 (m, 211), 7.25 (m, 211). Other compounds within the scope of formula (II) or (IIA) of the present invention can be synthesized by analogous techniques. EXAMPLE 9 Nociccptin affinity at the ORLI receptor for preferred compounds was obtained using the following assay: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM 1IEPHS. pll 7.4) (10 ml/10 cm dish) followed by homogenization with a tissue grinder/teflon pestle. Membranes were collected by centrifugation at 30,000 x g for 15 min at 4°C and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/ml. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of the ORL-1 receptor membranes were stored at-80°C. Functional SGTPgS binding assays were conducted as follows. ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0.066 mg/ml ORL-1 membrane protein, 10 mg/ml saponin, 3 mM GDP and 0.20 nM [3SSJ GTPgS to binding buffer (100 mM NaCI, 10 mM MgCI2, 20 mM HEPES, pH 7. 4) on ice. The prepared membrane solution (190 ml/well) was transferred to 96-shallow well polypropylene plates containing 10 ml of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at room temperature with shaking. Reactions were terminated by rapid filtration onto 96- well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Brandel) and followed by three filtration washes with 200 ml ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50°C for 2-3 hours. Fifty ml/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in aPackard Top-Count for 1 min/well. Data was analy/ed using the curve fitting functions in GraphPad PRISMO, v. 3.0 and the results are set forth in table 2 below: TABLE 2 Nociceptin Affinity (Table Removed) EXAMPLE 10 SYNTHESIS OF CERTAIN HEAD GROUPS. SCHEME 1: (Scheme Removed) Procedure: To a mixture of 4 (21.6 g, 0.2 mole), 5 (15.6 g, 0.1 mole), acetic acid (6 g, O.lmole) in 500 ml of dichloroethane, 29.7 g of sodium triacetoxyborohydride (0.14 mol, 1. 4 eq) was added in one portion. Gas evolves between 30 min and 1 hr. The mixture was stirred over night. TLC indicated the reaction is complete. 1 N NaOl I (500 ml) was added to quench the reaction. The organic layer was separated and the aqueous layer was extracted by EtOAC (300 ml x2). The combined organics were dried over potassium carbonate and the solvent evaporated to give a red oil which was column filtrated (5% Et3N, 25% EtOAc and 70% Hexane) to give 14 g o!'product 6 as a white solid (54%). Compound 6 MS: m//249.3 (MH). 'H NMK(CDCh): d 1.50-1.90 (m, 6H), 2.05 (m, 2H), 3.30 (m, 4H), 3.95 (s, 4H), 6.60-6.80 (m, 4H). To a solution of 13.5 g of 6 (54.4 mmol) in 50 ml of acetonitrile, 11.02 g of carbonyldiimidazole was added in one portion. The mixture was stirred over night. Solid precipitated out of solution which was filtered and washed by 1I2O and TBME to give 7.5 g of product. The filtrate was evaporated and the crude material was dissolved in htOAc, washed with water and saturated potassium carbonate solution. The organics were dried over potassium carbonate. The solvent was evaporated to give a second batch of solid with a pink color which was column filtrated (10% Et3N, 40% EtOAc and 50% Hexane) to give another 4.5 g of product 7 (81 %, combined). Compound 7 MS: m//274.7 (M+l). 'H NMR(CDC13): d 1.50-1.90 (m, 7H), 2.50 (m, 2H), 4.00 (m, 4H), 4.50 (m, 1H), 7.10 (m, 3H), 7.25 (m, 1H). A mixture of 7 (7.5 g, 27.4 mmole) and 8.26 g of PPTS in 50 ml of acetone and H2O (10: 1) was stirred in refluxed over night. The mixture was cooled to room temperature and acetone was evaporated. Addition of water to the mixture initiated crystalization to give 3 g of product 8 (47.4%). ~**" Compound 8 MS: m//231 (MH). '11 NMR(CDCI3) : d 2.20 (m, 2H), 2.60 (m, 2H), 4.50 (m, 1H), 7.10 (m, 4H), 9.5 (br, 1H). To a mixture of 8 (7.75 g, 33.65 mmole), benzylamine (3.61 g, 33.65 mmole), acetic acid (2.0 g, 33.65 mmole) in 150 ml of dichlorouthane, 10.3 g of sodium triacetoxyborohydride (47.1 mmol, 1.4 eq) was added in one portion. Gas evolves between 30 min and 1 hr. The mixture was stirred over night. TLC indicated the reaction was complete. 1 N NaQH (500 ml) was added to quench the reaction. The organic layer was separated and the aqueous layer was extracted with EtOAc (300 ml x2). The combined organics were dried over potassium carbonate and the solvent was evaporated to give a brown solid, which was column filtrated (5% Et3N, 25% I-tOAc and 70% Hexane to 10% Et3N, 40% EtOAc and 50% Hexane) to give 4.7 g of product 10 as a white solid (53.4%) and 3.01 g of product 9 as a white solid (34.2%). Compound 9 MS: m//.322(M-H). 'llNMR(CDCI3):d 1.40 (m, 2H), 1.80-2.35 (m, 6H), 2. 70 (m, 1H), 3.86 (s, 2H), 4.30 (m, 1H), 7.10-7.50 (m, 911). 9.6 (br, 111). Compound 10 MS:m//.322(M + l). 'II NMR(CDCI3):d 1.60(m,4H), 1.90 (m, 2H), 2.60 (m, 2H), 3,10 (m, 1H), 3.84 (s, 2H), 4.50 (m, 1H), 7.10-7.50 (m,9H), 9.6 (br, 1H). 2 g of Pd (OH) 2 was added into a solution of 30 ml of methanol containing 4.7 g of compound 10. The resulting suspension was hydrogenated at 50 psi for 12 hrs at room temperature. TLC indicated the reaction was complete over night. The solution was filtered through a pad of celite to remove the catalyst. The celite was washed with methanol twice (20 ml). The organics were combined and solvent was removed to give a pale solid which was purified by chromatography (10% MeOH, 90% EtOAc) to give an off white product 11 (1.79 g, 50.7%). Compound 11 MS: m//232 (Mi 1), IHNMR(CDCI3): d 1. 50-1. 85 (m, 8H), 2.60 (m, 2H), 4.30 (m, 1H), 7.10 (m, 3H), 7.30 (m, 1H). To a mixture of 11 (1.7 g, 7.4 mmole), acetaldehyde (0.33 g, 7.4 mmole) in 50 ml of dichloroethane, 2.2 g of sodium triacetoxyborohydride (10. 36 mmol, 1.4 eq) was added in one portion. Gas evolves between 30 min and 1 hr. The mixture was stirred over night. TLC indicated the reaction was complete. 1 N NaOH (500 ml) was added to quench the reaction. The organic layer was separated and the aqueous layer was extracted with HtOAc (300 ml x2). The combined organics were dried over potassium carbonate and the solvent was evaporated to give a brown oil which was chromatographed (10% Et3N, 40% EtOAc and 50% Hexane) to give i .5 g of product 2 as a sticky oil which recrystalized from TBME to give a white solid (78%). Corn pound 2 MS :m//259. 7(M+1). !11 NMR(CDCI3): d 1.15 (t, 3H), 1.50-1.95 (m, 6H), 2.40-2.75 (m, 4H), 2.95 (m, 1H), 4.35 (m ; 1H), 7.10 (m, 31 IK 7.35 (m, 111).. 1.5 g of Pd (OH): a was added into a solution of 30 ml of methanol containing 3.01 g of compound 9. The resulting suspension was hydrogenated at 50 psi for 12 hrs at room temperature. TLC indicated the reaction was complete over night. The solution was filtered through a pad of celite to remove the catalyst. The celite was washed with methanol twice (20 ml). The organics were combined and solvent was removed to give a pafe solid which was purified by chromatography (10% MeOH, 90% EtOAc) to give an off white product 1 (1.68 g, 77.4%). Compound 1 VIS: m//232 (Mil). 'I IN MR (CDCI,): d 1.50 (m, 2H), 1.90-2.35 (m, 6H), 3.00 (m, 1H), 4.30 (m, 1H), 7.10-7.30 (m, 4H). SCHEME 2: (Scheme Removed) Procedure : About 2.5 g of NaH was washed by THF twice, suspended in 100 ml of DMF, then 8.15 g of 7 (38 mmole) was added to the mixture. Gas evolves, and after 5 minutes, 7.13 g of ethyl iodide (45.7 mmole) was added. The mixture was stirred over night. LC/MS indicated that the starting material was completely consumed. The reaction was cooled down and H20 was added to the mixture. The product started to precipitated out of solution. The crystals was collected by filtration to give 9.7 g of 12 (84. 7%). Compound 12 MS: m//303.3 (M+l). 'II NMR(CDC13): d 1.30 (t, 311), 1.70-1.90 (m, 6H), 2.50 (m, 2H), 3.85-4.00 (m, 6H), 4.50 (m, 1H), 7.05 (m, 31I).7.25 (m, 111). A mixture of 12 (9.7 g, 32.2 mmole) and 9.72 g of PPTS in 50 ml of acetone and H2O (10: 1) was refluxed over night. The mixture was cooled to room temperature and acetone was evaporated. Addition of water to the mixture initiated crystali/.ation to give 6.85 g of product 13 (82.3%). Compound 13 MS: m//259(MH). '11 NMR(CDClj): d I. 35 (t. 3H), 2.20 (m, 2H), 2.60 (m, 6H), 3.95 (q, 2H), 4.85 (m, 1H), 7.10 (m, 4H). To a mixture of 1 3 (6.85 g, 26.5 mmole), benzylamine (2.84 g, 26.5 mmole), acetic acid (1.59 g, 26. 5 mmole) in 150 ml of dichloroethane, 7.86 g of sodium triacetoxyborohydride (37.1 mmol, 1.4 eq) was added in one portion. Gas evolves between 30 min and 1 hr. The mixture was stirred over night. TLC indicated the reaction was complete. 1 N NaOH (500 ml) was added to quench the reaction. The organic layer was separated and the aqueous layer was extracted with EtOAc (300 ml x2). The combined organics were dried over potassium carj^mate and the solvent was evaporated to give a brown solid, which was column filtrated. (5% Et3N ; 25% HtdAe and 70% llexane to 10% Et3N, 40% EtOAc and 50% Hexane) to give 1.52g of product 14 as a white solid and 1. 08 g of product 15 as a white solid. Compound 14 VIS: m//350(M-H). '11 NlvlR(CDCI3): d 1. 35 (t, 3H), .1.50 (m, 2H), 1.65 (m, 4H), 1.95, (m, 2H), 2.60 (m, 2H), 3,02 (m, 1H), 3.83 (s. 211). 3.95 (ddd, 2M), 4.45 (m, 1H), 7.00-7.50 (m, 9H). Compound 15 MS: m// 350 (Mi 1). '11 NMR(CDC1,): d 1.35 (m, 5H), 1.90 (m, 2H), 2.10-2.35 (m, 4H), 2.70 (m, 1H), 3.83 (s, 2H), 3.95 (ddd, 2H), 4.40 (m. Ill), 7.00-7.50 (m, 9H). 0.3 g of Pd (OH)2 was added into a solution of 20 ml of methanol containing 0.5 g of compound 14. The resulting suspension was hydrogenated at 50 psi for 12 hr at room temperature. TLC indicated the reaction was complete over night. The solution was filtered through a pad of celite to remove the catalyst. The celite was washed with methanol twice (20 ml). The organics were combined and solvent was removed to give a pale solid which was purified by chromatography (10% MeOH, 90% EtOAc) to give an off white product 3 (300 ing. 50%). Compound 3 MS: m//. 232 (M-H ). 'II NMR(CDC13): d 1.35 (t, 3H), 1.50-1.85 (m, 8H) ; 2.60 (m, 2H), 3.20 (m, 1H), 3.95 (ddd, 2H), 4.30 (m, 111), 7,10. (m,3H), 7.30 (m, 1H). EXAMPLE 11 ATTACHMENT OF TAIL GROUPS Tail groups were attached to the head groups according to the following procedures: (Procedure Removed) General procedure for alkylation: To a solution of the amine (I eq) and triethylamine (1 eq) in dimethylformamide, was added 1 eq of alky! bromide or chloride in one portion. The mixture was stirred and heated at 80°C over night. TLC indicated the reaction was complete. The reaction was quenched by the addition of water followed by 1 N NaOH to pH 10. The mixture was extracted 2x with Et2O. The combined organic extracts were dried over potassium carbonate e solvent evaporated, followed by chromatography to give the pure product. General procedure for reductive animation: To a mixture of ketone or aldehyde (1 eq), amine (1 eq), and acetic acid (1 eq) in methanol, was added sodium cyanoborohydride (1.4 eq) in one portion. The mixture was stirred over night at room temperature. TLC indicated the reaction was complete. The reaction was quenched by the addition of water followed by 1 N NaOII to pll 10. The mixture was extracted 2x with Et2O. The combined organic extracts were dried over potassium carbonate and the solvent evaporated, followed by chromatography to give the pure product. The following compounds were prepared by attaching the tail groups using the general procedures described: 1 - |4-(bcn/ylamino)-cyclohexyl|-3-ethyl-l, 3-dihydro-2H-benzimidazol-2-one 1- |4-(ben/.ylamino)-cyclohexyl]-3-ethyl-l, 3-dihydro-2H-benzimidazol-2-one 1- |4-|(naphth-2-yl-methyl)ethylamino]-cyclohexyl]-l, 3-dihydro-2H-benzimidazol-2-one MS: m// 400.2 (M+l) 1 - 1 4-( norbornan-2-y lamino)-cyclohexy 1]- 1 , 3-dihydro-2H-benzimidazol-2-one MS: m// 326.3 (MH) l-|4-||4-( l-methylethyl)-cyclohexyl|aminoj-cyclohexyl]-l, 3-dihydro-2H-benzimidazol-2-one MS : m// 356.4 (MM) I- |4-|(ilecahydro-2-naphthyl)amino]-cyclohexyl]-l, 3-diliydro-2H-benzimidazol-2-one MS : m// 368.2 (M-tl) 1- |4-(ethylamino)-cyclohexylj-l, 3-dihydro-2H-benzimidazol-2-one 1 - |4-(ben/.ylamino)-cyclohexyl]-l, 3-diliydro-2H-benzimidazol-2-one I- |4-(ben/.ylamino)-cyclohexyr]-l, 3-dihydro-2H-benzimidazol-2-one l-|4-|(indan-2-yl)ben/ylamino]-cyclohexyr]-3-ethyl-l,3-dihydro-2H-benzimidazol-2-one MS: m// 466.3 (Mt 1)' 'll-NMRd'DCh): dl.3() (I, 311), 1. 50-1.75 (m, 2H), 1.90 (b, 2H), 2.02 (b, 2H), 2.20 (m, 2H), 2. 80 (m, 1H), 2.99 (m. 411), 3.75 (s, 211), 3.90 (m, 3H), 4.25 (m, 1H), 6.95-7.45 (m, 13H). l-|4-|(cyclooctylmethyl)amino|-cyclohexyl]-3-ethyl-l,3-dihydro-2H-benzimidazol-2-one l.(':99% MS: ml/. 384.5 'HNMR(CDCI3): d 1.40- 1.90 (m, 24H), 2. 30 (m,2H), 2.50 (m, 2H), 2.90 (m, 1H), 3.90 (ddd, 2H), 4.20 (m, 111). 7. I0(m, 311), 7.30 (m, 1H). 1- 14- |(naphth-2-yl) annino|-cyclohexyl]-3-ethyl-l, 3-dihydro-2H-benzimidazol-2-one IX': 97% MS: m// 399 'II NMR(CDCli):. dl.50 (t, 311), 1.80 (m, 5H), 2.0 (m, 2H), 2.70 (m, 2H), 3.10 (m, 1H), 3.90 (m, 2H), 4.0 (m, 211), 4. 40 (m. 111). 7.10 (m. 3H), 7.50 (m, 4H), 7.90 (m, 4H). 1- |4- | (p-ben/yloxyben/.yl)aminol-cyclohexyl]-3-ethyl-l, 3-dihydro-2H-benzimidazol-2-one IX': 97% MS: ml/ 455 'H NMR(CDC13): d 1.40 (t, 3H), 1.70 (m, 2H), 1.90 (m, 3H), 2.60 (m, 4H), 3.10 (m, IH), 3.80 (s, 2H), 4.0 (m, 211). 4.50 (m, 1 H), 5.10 (s, 2H), 7.10 (m, 6H), 7.50 (m, 6H), 7.90 (m, 1 H). l-|4-|(cyclooctylmethyl) amino|-cyclohexyl]-3-ethyI-l, 3-dihydro-2H-benzimidazol-2-one I t j, 99% MS: m// 369 '1INMR (CDC 13): dl.40 (t, 3H), 1.70 (m, 5H), 1.90 (m, 12H), 2.10 (m, 3H), 2.40 (m, 2H), 2.50 (d, 2H), 3.30 (m. Ill), 3.90 (m,2H), 4.20 (m, lH),7.10(m, IH), 7.30 (m, 3H). 1- |4- | (dccallydro-2-rmphthyl) amino]-cyclohexyl]-3-ethyl-l, 3-dihydro-2H-benzimidazol-2-one I.C: 99% MS: m// 395 !!I-NMR(CDCIj): dl. 40 (t, 3H), 1.70 (m, 3H), 1.80 (m, 3H), 1.90 (m, 12H), 2.20 (m, 2H), 2.30 (m, 3H), 2.50 (q. 211), 3.10 (m, 1 H), 3.90 (m, 2H), 4.20 (m, IH), 4.30 (m, IH), 7.0 (m, IH), 7.30 (m, 3H). l-|4- [ (p-phenylbenzyt)amino|-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2-one 1,C: 100% MS: m//.440. 8(M+1) 'H-NMR(MeOH-d4): d 1,75 (m, 2H), 2.00 (m, 2H), 2.40-2.55 (m, 4H), 3.35-3.52 (m, 2H), 4.35 (s, 2H), 7.40 (m, 211), 7.59 (t, 2H), 7. 60-7.72 (m, 6H), 7.78 (d, 2H). 1 -|4-|( 1, 2,3,4-tetrahydronaphthyl)amino]-cyclohexyl]-5-carbamoyl-l,3-dihydro-2H- benzimidazol-2-one I.C: 93.9% MS: m//405.7 (foM 1) 'il-NMRtMeOH-d,,): dl.70 (m. 2H), 1.85 (m, IH), 2.02 (m, 2H), 2.39 (b, 3H), 2.50 (m, 2H), 2.90 (m, IH), 3.00 (b. 2H), 3.35 (m, IH), 3.60 (m, IH), 3.72 (b, IH), 4.35 (m, IH), 7.15 (b, 4H), 7.40 (d, IH), 7.60 (s, IH), 7.65 (ci. ill). l-|4-|(4-propyl-cyclohexyl)amino|-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2- one I.C: 100% MS: m//399.6 (M+l) 'H-NMK(MeOH-d4) : dO.95 (t, 3H), 1.10 (m, IH), 1.20-1.60 (m, 6H), 1.70 (b, 5H), 1.80-2.00 (m, 4H), 2.10 (m. 111), 2.30 (b, 2H), 2.45 (m, 2H), 3.25 (m, IH), 3. 50 (m, IH), 4.40 (m, IH), 7.40 (d, IH), 7. 60 (s, IH), 7.65 (d. ill). l-|4-|(5-methylhex-2-yl)amino]-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2-one I.C: 100% MS: m//373.5 (Mil) !H-NMR(MeOH-d4): dO.95 (d, 6H), 1.25-1.40 (m, 5H), 1.50-1.75 (m, 4H), 1.85 (m, IH), 1.95 (b, 2H), 2.30 (m, 211). 2. 40-2.55 (m, 2H), 3.35-3.55 (m, 2H), 4.38 (m, IH), 7.40 (d, IH), 7.60 (s, IH), 7.70 (d, IH). l-|4-|(decahydro-2-naphthyl)amino]-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2- one I.C: 100% MS: m//4II. 7 (M+l) 'I l-NMR(Me()H-d4): dO. 90-2.10 (m, 18H), 2.10-2.50 (m, SH), 2.82 (m, IH), 3.50 (m, 2H), 4.35 (m, IH), 7.42 (d. 111), 7.60 (s. IH), 7.70 (d, 1 H). I- 14- ((,'\clooctylamino)-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2-one ; I.C : 95,4% MS: m//.385.7 (M+l) li-NMR(Me()H-d.,): dl.50-2.10 (m, 13H), 2.30 (m, 2H), 2.40-2.52 (m, 3H), 2.80-2.95 (m, 3H), 3.45 (m, 2H), 3.70 (m. 111). 4.38 (m, IH),7.40(d, IH), 7.63 (s, lH),7.70(d, IH). l-|4-|(indan-2-yl)amino|-cycIohexyl]-5-carbamoyl-l,3-dihydro-2H-benzimidazol2-one I.C: 100% MS: m//391.6 (M+l) 1ll-NMR(MeOH-d4): dl.70 (m, 2H), 2.00 (m, 2H), 2.40-2.60 (m, 4H), 3.10-3.20 (m, 2H), 3.50 (m, 3H), 4.30- 4.45 (m. 211), 7.25 (m, 211). 7.35 (m, 2H), 7.42 (d, 1H), 7.60 (s, 1H), 7.72 (d, 1H). l-|4-(ben/.ylamino)-cyclohexylj-5-carbamoyl-l,3-dihydro-2H-benzirnidazol-2-one LC^.100% MS : m//399.5 (M+l) 'H-NMR(MeOH-d4): d 1.40-1.85 (m, 15H), 2.00 (m, 4H), 2.25-2.50 (m, 4H), 2.93 (d, 2H), 3.30 (m, 1H), 4.30 (m, 111). 7.36 (d. 1H), 7.60 (s, 1H), 7.65 (d, 1H). 1 -|4-|(4-phenyl-cyclohexyl) amino]-cyclohexyl]-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2- one I.C': 100% MS: m//. 433.7 (M+l) 'll-NMR(Me()H-d4): dl.65 (m, 2H), 1.85-2.20 (m, 8H), 2.25-2.50 (m, 5H), 3.90 (m, 1H), 3.50 (m, 2H), 3.58 (m. 111), 4.30 (m, 1H), 7.15-7.40 (m, 6H), 7.60 (s, 1H), 7.65 (d, 1H). l-|4-(dibcn7.ylamino)-cyclohexyl|-5-carbamoyl-l, 3-dihydro-2H-benzimidazol-2-one I.C: 100% MS: m//455.6 (Mil) 'H-NMR(MeOH-d4): d 2.00-2.25 (m, 4H), 2.40 (m, 4H), 3.52 (m, 2H), 4.25-4.65 (m, 4H), 7.30 (d, 1H), 7.45- 7.58 (m, 1 OH), 7.60 (s, 1 H), 7.65 (d, 1 H). l-[4-|(5-methylhex-2-yl) amino]-cyclohexyl]-7-carbamoyl-l, 3-dihydro-2H-benzimidazol-2-one 11': 99.1% MS: m//.373.3 (M+l) 'll-NMR(MeOH-d4) : dO.95 (d, 6H), 1.30 (d, 3H), 1.45-1.68 (m, 5H), 1.75 (m, 1H), 2.00 (m, 2H), 2.18-2.32 (m. 311), 2.60 (m. 2H), 3.20-3.40 (m, 2H), 4.30 (m, 1 H), 7.05-7.20 (m, 3H). Other compounds within the scope of formula (III) or (IIIA) of the present invention can be synthesized by analogous techniques. EXAMPLE 12 Nociccptin affinity at the ORL1 receptor forpreferred compounds was obtained using the following assay: Membranes from recombinant HEK-293 cells expressing the human opioid receptor-like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50mM lll:PI S, pH7.4) (10 ml/10 cm dish) followed by homogenization with a tissue grinder/teflon pestle. Membranes were collected by centrifugation at 30, 000 x g for 15 min at 4°C and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/ml. Protein concentrations were determined using the BtoRad protein assay reagent with bovine serum albumen as standard. Aliquots of the ORL-1 receptor membranes were stored at-80°C. i unciional SGTPgS binding assays were conducted as follows. ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0. 066 mg/ml ORL-1 membrane protein, 10 mg/ml saponin, 3 mM GDP and 0.20 nM |35S| GTPgS to binding buffer (100 mM NaCI, 10 mM MgCI2, 20 mM HEPES, pH 7. 4) on ice. 1 he prepared membrane solution (190 ml/well) was transferred to 96-shallow well polypropylene plates containing 10 ml of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at room temperature with shaking. Reactions were terminated by rapid filtration onto 96- well Unifilter Gl'/B filter plates (Packard) using a 96-well tissue harvester (Brandel) and followed by three filtration washes with 200 ml ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at SOT for 2-3 hours. Fifty ml/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. Data was analy/cd using the curve fitting functions in GraphPad PRISMO, v. 3.0 and the results are set forth in table i below: TABLE 3 Nociceptin Affinity (Table Removed) EXAMPLE 13 SYNTHESIS OF SUBSTITUTED BENZIMIDAZOLE HEAD GROUPS. (Formula Removed) Procedure: Sodium hydride 60% dispersion in mineral oil (0.67 g, 16.7 mmol) was washed with dry pentane and then suspended in 80 mL of dry TI IF under N2. Compound 1 (European patent 0029707) (3.80 g, 11.1 mmol) was added, the mixture stirred at room temperature for 15 min and then warmed to 50°C. Ethyl bromide (1.06 mL, I 3.3 mmol) was added and the resulting mixture stirred at 50°C for 18 hr. TLC (SiO2, CH2C12: MeOH 96: 4) showed that the reaction was ca 40% complete. Additional sodium hydride (0.67 g) and ethyl bromide (1.06 mL) were added. After heating at 50°C for an additional 24 hr the reaction mixture was cooled to room temperature and quenched with water. The layers were separated and the aqueous layer extracted with ethyl acetate (Ix). The combined organic extracts were washed with aqueous sodium bicarbonate solution (Ix), dried over MgS()4 and the solvent was evaporated to give the crude product as a yellow solid. Trituration with diethyl ether gave pure 2 as a white solid (3.38 g, 82%). '||-NMR(CDC13): d 1.45-1.55 (m, 12H), 1.82 (bs, 2H), 2.30 (m, 2H), 2.87 (m, 2H), 4.30 (bs, 2H), 4.41 (q, 211). 4.82 (m, 1H), 7.10-7.30 (m, 4H). To a solution of 2 (3. 60 g, 9.74 mmol) in 100 mL of ethyl acetate was added a 25 mL of a 1: 1 mixture of ethyl acetate and concentrated HC1. The mixture was stirred vigorously at room temperature for 2hr. and evaporated to dryness. The residue was neutralized with 50 mL of methanolic ammonia 10:1 and again evaporated to dryness. The residue was suspended in 100 mL a 1: 1 mixture of MeOH and CH2C12, filtered and the filtrate evaporated to dryness to leave an off-white solid. Flash chromatography on silica gel, eluting v\ith CI LCkMeOILNII, (300:10: 1) gave pure 3 as a white crystalline solid (1.98 g, 76%). !H-NMR(CDCI,): d 1.45 (t, 3H), 1.82 (bs, 2H), 2.33 (m, 2H), 2.80 (m, 2H), 4.40 (q, 2H), 4.80 (m, 1H), 7.10-7.30 (m, 311), 7.45 (d, 111). 55 EXAMPLE 14 ATTACHMENT OF TAIL GROUPS lail groups were attached to the head groups according to the following procedures: (Prcedure Removed) General procedure for alkylation: To a solution ofthe amine (1 eq) and triethylamine (1 eq) in dimethylformamide, was added 1 eq of alkyl bromide or chloride in one portion. The mixture was stirred and heated at 80°C over night. TLC indicated the reaction was complete. The reaction was quenched by the addition of water followed by 1 N NaOH to pH 10. The mixture was extracted 2x with Et2O. The combined organic extracts were dried over potassmm carbonate and the solvent evaporated, followed by chromatography to give the pure product. General procedure for reductive amination: To a mixture of ketone or aldehyde (1 eq), amine (1 eq), and acetic acid (1 eq) in methanol, was added sodium cyanoborohydridc (1.4 eq) in one portion. The mixture was stirred over night at room temperature. ILC indicated the reaction was complete. The reaction was quenched by the addition of water followed by 1 N NaOll to nil 10 The mixture was extracted 2x with Et2O. The combined organic extracts were dried over potassium carbonate and the solvent evaporated, followed by chromatography to give the pure product. The following compounds were prepared by attaching the tail groups using the general procedures described: 2-cyanoimino-3-ethyl-l- 1 1- (P-phenylbenzyl)-4-piPeridinyl]-l, 3.dihydro-2H-benZimidazole •ll-NMRCCDClj): dl. 50 (t, 3H), 1-88 (m, 2H), 2.28 (m, 2H), 2.62 (m, 2H), 3.12 (m, 2H), 3.65 (s, 2H), 4.48 (q, 211). 4.80 (m, 1H), 7.15-7.70 (m, 13H). 2-cyanoimino-3-ethyl-l- 1 1- (p-benzyloxybenzyl)-4-piperidinyl] 1, 3-dihydro-2H- benzimidazole LC: 96.5% bMKSS (t, 3H), 1.82 (m, 2H), 2.25 (m, 2H), 2.50 (m, 2H), 3.10 (m, 2H), 3. 55 (s, 2H), 4.48 (q. 21 1 ). 4.78 (m, 1 H), 5.20 (s, 2H), 7.00 (d, 2H), 7. 1 5-7.65 (m, 1 1 H). 2-cvanoimino-3-ethyl-l- 1 1- (naphth-2-yl-methylH-piperidinyl] 1, 3-dihydro-2H-benzimidazole l.C: 93.9% ^NMR(CDCh): dl.55 (t, 311). 1.80 (m, 2H), 2.30 (t, 2H), 2.52 (m, 2H), 3.18 (bd, 2H), 3.78 (s, 2H), 4.50 (q, 21 1), 4.80 (m. Ill), 7.20-7.90 (m, 11H). 2-cyanc)imino-3-ethyl-I- 1 1- (4-propylcyclohexyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole MS: ml/. 394.4 (M+l) 111-NMR(CDCI;!): dO.90-2.28 (m, 21H), 3.10 (m, 4H), 3.62 (m, 2H), 4.42 (q. 2H), 5. 15 (m, 1H), 7.20 (d, 1H), 7.30 (m. Ill), 7.50 (t, lH),7.80(b, 1H). 2-cyanoimino-3-ethyl-l-11-14- (2-propyl)-cyclohexyl]-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole LC: 100% VIS: m// 394.5 (MH) 'lLNiMR(CDCl;}): d 0.90 (d, 311), 0.98 (d, 3H), 1.15-2.35 (m, 14H), 3.10 (m, 5H), 3.70 (m, 2H), 3.92 (bs, 1H), 4.40 (q, 211), 5.20 (m, 1H). 7.20 (d, lH),7.38(d, 1H), 7.52 (t, 1H), 7.80 (m, 1H). 2-cyanoimino-3-ethyl-l-11- (decahydro-2-naphthyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole l.C: 93.9% MS: m//406.6 (Mil) 111-NMR(CDCI3): d 1.25-2.35 (m, 24H), 1.15 (m, 4H), 3.60 (m, 2H), 4.40 (m, 2H), 4.20 (m, 1 H), 7.20-7.80 (m, 411). 2-cyanoimino-3-ethy!-l- [1- (cyclooctyl)-4-piperidinyI]-l, 3-diliydro-2H-benzimidazole LC: 100% MS: m//380.3 (Mil) 'li-NMRfCDCI,): d 1.50-1.80 (m, 13H), 1.90 (m, 2H), 2.10 (m, 4H), 3.05 (m, 3H), 3.30 (m, 1H), 3.45 (m, 211). 3.90 (m, 111), 4.42 (q, 211), 5.15 (m, 1H), 7.20 (d, lH),7.35(d, 1H), 7.50 (m, 1H), 7.78 (m, 1H). 2-cyanoimino-3-ethyl-l- |1- (10, 1 l-dihydro-5H-dibenzb [a,d]-cyclohepten-5-yl)-4-piperidinyl]- 1,3-dihydro- 211-hcn/imida/ole l.C: 94.5% MS: m//462.2 (MM.) 'lI-NMR(CDCl.i): d 1.40 (t, 3H), 1.70 (bs, 2H), 2.01 (m, 2H), 2.28 (m, 2H), 2.80 (m, 4H), 3.95 (s, 1H), 4.02 (m, 211), 4.32 (q, 2H), 4.65 (m, 1 H), 7.00-7.32 (m, 12H). 2-cyanoimino-3-ethyl-l-11- (3, 3-Bis (phenyl) propyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole MS: m//. 464.2 (M+l) I11-NMR(CDC1!): dl.40 (t, 3H), 1.73 (bs, 2H), 2.09 (m, 2H), 2.18-2.45 (m, 6H), 2.98 (b, 2H), 3.93 (t, 1H), 4.35 (q. 211). 4.63 (m. Ill), 7.10-7.30 (m, 13H), 7.40 (d, 1H). 2-cyanoimino-3-ethyl-l-11- (l,2,3,4-tetrahydronaphthyl)-4-piperidinyl]-l,3-dihydro-2H- benzimidazole l.C: 94.0% MS: m//400.2 (Mfl) !1I-NMR(C1X'I,): dl.30-1.70 (m, 6H), 1.85 (m, 2H), 2.05 (m, 1H), 2. 45 (m, 3H), 2.85 (m, 4H), 3. 10 (m, 2H), 4.35 (q. 211). 4.71 (m, I H), 7.00-7.60 (m, 8H). 2-cyanoimino-3-ethyl-l- [1- (5-methylhex-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole LC: 94. 9% MS: m//368.3 (M+l) !H-NMR(ClX:ii): dO.85 (d, 6H), 0.95 (d, 3H), 1.12-1.65 (m, 8H), 1.80 (m, 2H), 2.27-2.60 (m, 5H), 2.85 (m, 211), 4.38 (m, 2H). 4.62 (m, 111), 7. 08-7. 30 (m, 3H), 7.45 (m, 1H). 2-cyanoimino-3-ethyl-1-11- (norbornan-2-yl)-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole l.C:99.2% MS: m// 364.7 (M» I) 'H-NMRtCDCli): dl.10-2.10 (m, 13H), 2.35 (m, 1H), 2.50-2.70 (m, 3H), 2.70-2.90 (m, 3H), 3.50 (m, 2H), 4.50 (q. 211). 4.80 (m, 1H), 7.35 (m, 2H), 7.48 (m, 1H), 7.75 (m, 1H). 2-cyanoimino-3-ethyl-l-11- (1, 3-dihydroinden-2-yl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole LC: 92.1 % MS: m//386.2 (M+l) 'II-NMR(CDC13): dl.42 (t, 3H), 1.82 (m, 2H), 2.21 (m, 2H), 2.43 (m, 2H), 2.88 (m, 2H), 3.02-3.19 (m, 4H), 3.23 (m, 1 H), 4.38 (q, 2H), 4.80 (m, 1H), 7.08-7.30 (m, 7H), 7.45 (d, 1H). 2-cyanoimino-3-ethyl-l-11- (cyclooctylmethyl)-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole. l.C: 100%. MS: m//394. 7 (Mil) 'H-NMR(MeOH): dl.35-2.00 (m, 20H), 2.60-2.85 (m, 6H), 3.40 (m, 2H), 2.52 (q, 2H), 4.90 (m, 1H), 7.35 (m, 211). 7.48 (m. 111), 7.70 (m, 1H). -.»*»• 2-cyanoimino-3- (2-hydroxy)ethyl-l- [l-(cyclooctyl)-4-piperidinyl]-l,3-dihydro-2H- benzimidazole l.C: 100% MS: m//396.3 (Mil) 'H-NMR(DMSO): 7.52 (dt, IN), 7.45 (dt, IH), 7.21 (m, 2H), 4.97 (t, lH),4.55(m, 1H), 4.38 (t, 2H), 3.76 (q, 211), 2.88 (m, 211), 2.61 (bt, IH), 2.33 (m, 4H), 1.76-1.37 (m, 16H). 2-cyanoimino-3-methoxycarbonylmethyl-l- [1- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H- benzimidazole l.C': 98.3% MS: m//424.2 (M+l) 'H-NNIR(l)MSO): 7.56 (dd, IH), 7.51 (dd, IH), 7. 25 (m, 2H), 5.26 (s, 2H), 4.56 (m, IH), 3.72 (s, 3H), 3.34 (m. 211). 2.78 (m. 2H), 2.62 (bt, IH), 2.32 (m, 4H), 1.80-1.35 (m, 16H). 2-cyanoimino-3-cyanomethyl-l- [1- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole I,C: 100% MS: m//391.2 (M + l) 'll-NMK(l)MSO): 7.60 (m, 211), 7.31 (m, 2H), 5. 48 (s, 2H), 4.77 9m, IH), 3.33 (d, 2H), 2.88 (m, 2H), 2.62 (hi. 111). 2.33 (m, 4H), 1.86-1.37 (m, 16H). 2-cyanoimino-3-butyl-|- [ l-(cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole l.C: 95,4% MS: m//352.2 (Mi 1) 'H-NMR(l)MSO): 7.58 (dd, 111), 7.49 (dd, IH), 7.24 (m, 2H), 6.55 (s, 2H), 4.59 (m, IH), 4.34 (t, 2H), 2. 97 (m, 211). 2.80 (m, 1H). 2.55 (m, 2H), 2.38 (m, 2H), 1.80-1.30 (m, 18H), 0.90 (t, 3H). 2-cyanuimino-3-(2-methanesulfonamido)ethyl-l-[l-(cyclooctyl)-4-piperidinyl]-l,3-dihydro-2H-benzimidazole l.C: 100% MS: m//473.2 (M+l) !1I-NMR(DMSO): 7.53 (dd, 1 H), 7.44 (dd, IH), 7.23 (m, 2H), 4.60 (m, IH), 4.35 (t, 2H), 3.37 (t, 2H), 2.87 (m, 211). 2.82 (s, 311), 2.60 (bt, 1H),2.31 (m, 4H), 1.76-1.37 (m, 15H). 2-cyanoimino-3-acetomido-l-11- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole l.C: 100% MS: m//.409.2 (M+l) 11 l-NMR(l)MSO): 7.75 (s, 1 H), 7.52 (dd, 1 H), 7.37 (s, 1 H), 7.30 (dd, 1 H), 7.20 (m, 2H), 4.96 (s, 2H), 4.55 (m, 111). 3.33 (d, 211), 2.88 (m, 2H), 2.62 (bt, IH), 2.30 (m, 4H), 1.80-1.37 (m, 15H) 2~cyanoimino-3-carboxymethyl-l- [1- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole LC: 97.5% MS: m//409.9 (M+l) 'll-NMR(DMSO): 7.45 (dd, IH), 7.14 (m, 3H), 4.57 (s, 2H), 4.50 (m, IH), 2.87 (m, 2H), 2.61 (bt, IH), 2.33 (m,41l). 1.75-1.37 (m, 1511). 2-cyanoimino-3-(2-dimethylamino) ethyl-l-[l-(cyclooctyl)-4-piperidinyl]-l,3-dihydro-2H- benzimidazole 1C: 100% MS: m//423. 3 (M+l) ' 1 l-NMR(DMSO): 7.60-6.96 (m, 4H), 6.54 (2H, s), 4.65 (m, IH), 4.40 (t, 2H), 3.90 (t, 2H), 3.05 (m, 4H), 2.90 (m. Ill), 2.63 (m, 311), 2.56-2.37 (m, 4H), 1.85-1.35 (m, 15H). 2-cyanoimino-l-11- (cyclooctyl)-3-hydroxymethyl-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole; 2-eyanoimino-l- 1 1- (cyclooctyl)-4-piperidinyl]-l, 3-dihydro-2H-7-azabenzimidazole; 2-cyanoimino-l- 11- (cyclooctyl)-2, 6-ethano-4-one-4-piperidinyl]-l, 3-dihydro-2H-benzimidazole Other compounds within the scope of formula (IV) or (IVA) of the present invention can be synthesized by s techniques. EXAMPLE 15 Noeiceplin affinity at the ORL I receptor for preferred compounds was obtained using the following assay: Membranes from recornbinant HEK-293 cells expressing the human opioid receptor- like receptor (ORL-1) (Receptor Biology) were prepared by lysing cells in ice-cold hypotonic buffer (2.5 mM MgCl2, 50 mM 1IEPKS, pH 7.4) (10 ml/10 cm dish) followed by homogenization with a tissue grinder/teflon pestle. Membranes were collected by centrifugation at 30,000 x g for 15 min at 4°C and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/ml. Protein concentrations were determined using the BioRad protein assay reagent with bovine serum albumen as standard. Aliquots of the ORL-1 receptor membranes were stored at -80°C. Functional SGTPgS binding assays were conducted as follows. ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0.066 mg/ml ORL-1 membrane protein, 10 mg/ml saponin, 3 mM GDP and 0.20 nM |3SS| GTPgS to binding buffer (100 mM NaCI, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared merrlbrane solution (190 ml/well) was transferred to 96-shallow well polypropylene plates containing 10 ml of 20.x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min al room temperature with shaking. Reactions were terminated by rapid filtration onto 96- well Unifilter GF/U Illter plates (Packard) using a 96-weIl tissue harvester (Brandel) and followed by three filtration washes with 200 ml ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 30°C for 2-3 hours. Fifty ml/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well. Data was analyzed using the curve fitting functions in GraphPad PRISMO, v. 3.0 and the results are set forth in table 4 below: TABLE 45 Nociceptin Affinity (Table Removed) Example 16 Affinity at the u receptor for compounds was obtained according to the following assay: Mu opioid receptor membrane solution was prepared by sequentially adding final concentrations of 0 075 ,^1 of the desired membrane protein, 10 ug/m. saponin, 3 uM GDP and 0.20 nM [35S] GTPyS tc, b.nd.ng bulfcr (100 mM NaCL 10 mM MgCl2, 20 mM HEPES, PH 7.4) on ice. The prepared membrane so u on^(190 Hi/well) was transferred to 96-shallow well polypropylene plates containing 10 ul of 20x concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at room temperature with shaking. Reactions were termed by rapid filtration onto 96-well Unifi.ter GF/B filter plates (Packa,J) usmg; a 96-wcll tissue harvester (Brandel) and followed by three filtration washes with ^^'^^^'^f.^f rf \" mM Nall,P04. 10 mM Na2HPO4, PH 7.4). Filter plates were subsequently dried at 50 C for 2- J hours. Htty ul/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-C'ount for 1 min/well. Data were analy/.ed using the curve fitting functions in GraphPad PRISM™, v. 3.0 and the results for several compounds are set forth in table 5 below: TABLE 5 (Table Removed) WE CLAIM: 1. A piperidinyl indole compound of the formula (IIA): (Formula Removed) wherein the dotted line represents an optional double bond; Z is selected from the group consisting of a bond,-CH2-, -NH-, -CH2O-, -CH2CH2-, - CH2NH-, -CH2N(CH3)-, -NHCH2-, -CH2CONH-, -NHCH2CO-, -CH2CO-, -COCH2.-, -CH2COCH2-, -CH(CH3)-, -CH= and -HC=CH-, wherein the carbon and/or nitrogen atoms are unsubstituted or substituted with a lower alkyl, halogen, hydroxy or alkoxy group; R and Q are the same or different and R is selected from the group consisting of halogen, C1-10 alkyl, CMO alkenyl, CMO alkylidene, C3-12 cycloalkyl and CMO alkoxy and Q is selected from the group consisting of hydrogen, halogen, CMO alkyl, CMO alkenyl, CMO alkylidene, C3-12 cycloalkyl and CMO alkoxy; R1 is selected from the group consisting of hydrogen, CMO alkyl, C3-12 cycloalkyl, C2-10 alkenyl, amino, CMO alkylamino, C3-12 cycloalkylamino, benzyl, C3-12 cycloalkenyl, a monocyclic, bicyclic or tricyclic aryl ring system, and a spiro ring system of the formula (V): (Formula Removed) wherein X1 and X2 are independently selected from the group consisting of NH, O, S and CH2; wherein said alkyl, cycloalkyl, alkenyl, C1-10 alkylamino, C3-12 cycloalkylamino, or benzyl is optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trifluoromethyl, cyano, phenyl, benzyl, benzyloxy, said phenyl, benzyl, and benzyloxy optionally being substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, and cyano; wherein said C3-12 cycloalkyl, C3-12 cycloalkenyl, monocyclic, bicyclic or tricyclic aryl, heteroaryl ring, heteromonocyclic ring, heterobicyclic ring system, and spiro ring system of the formula (V) are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, nitro, trifluoromethyl, phenyl, benzyl, phenyloxy and benzyloxy, wherein said phenyl, benzyl, phenyloxy and benzyloxy are optionally substituted with 1-3 substituents selected from the group consisting of halogen, C1-10 alkyl, C1-10 alkoxy, and cyano; R2 is selected from the group consisting of hydrogen, C1-10 alkyl, C3-12 cycloalkyl and halogen, said alkyl optionally substituted with an oxo group; or a pharmaceutically acceptable salt thereof. 2. A compound as claimed in claim 1, wherein Q is hydrogen or methyl. 3. A compound as claimed in claim 1, wherein R is methyl, ethyl, or ethylidene. 4. A compound as claimed in claim 1, wherein R1 is alkyl selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl and hexyl. 5. A compound as claimed in claim 1, wherein R1 is cycloalkyl selected from the group consisting of cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, and norbornyl. 6. A compound as claimed in claim 1, wherein R1 is tetrahydronaphthyl, decahydronaphthyl or dibenzocycloheptyl. 7. A compound as claimed in claim 1, wherein R1 is phenyl or benzyl. 8. A compound as claimed in claim 1, wherein R1 is a bicyclic aromatic ring. 9. A compound as claimed in claim 8, wherein said bicyclic aromatic ring is indenyl, quinoline or naphthyl. 10. A compound as claimed in claim 1, wherein Z is a bond, methyl, or ethyl. 11. A compound as claimed in claim 1, wherein n is 0. 12. A compound as claimed in claim 1, wherein X1 and X2 are both O. 13. A compound as claimed in claim 1, wherein the dotted line is a double bond. 14. A piperidinyl indole compound as claimed in claim 1 selected from the group consisting of: 3-ethylidene-1- [1- (5-methylhex-2-yl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2-one; 3-ethylidene-1- [1- (4-propylcyclohexyl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethylidene-1- [1- (1, 2,3, 4-tetrahydro-2-naphthyl)-4-piperidinyl]-1, 3-dihydro-2H- indole-2-one; 3-ethylidene-1- [1- (1, 3-dihydroinden-2-yl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethylidene-1- [1- (naphth-2-yl-methyl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethylidene-1- [1- (p-benzyloxybenzyl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethylidene-1- [1-(benzyl)-4-piperidinyl]-1,3-diliydro-2H-indole-2-one; 3-ethylidene-1- [1- (cyclooctylmethyl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2-one; 3-ethylidene-1- [1- (norbornan-2-yl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2-one; 3-ethylidene-1-1- (3, 3-diphenylpropyl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethylidene-1- [1- (p-cyanobenzyl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2-one; 3-ethyl-1-[1- (5-methylhex-2-yl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethyl-1- [1- [4- (1-methylethyl)-cyclohexyl]-4-piperidinyl]-1, 3-dihydro-2H-indole-2- one; 3-ethyl-1- [1- (4-propylcyclohexyl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2-one; 3-ethyl-1- [1- (1,2,3,4-tetrahydro-2-naphthyl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2- one; 3-ethyl-1-[1-(decahydro-2-naphthyl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethyl-1- [1- (1, 3-dihydroinden-2-yl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethyl-1- [1- (cyclooctylmethyl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethyl-1-[1-(norbornan-2-yl)-4-piperidinyl]-1,3-dihydro-2H-indole-2-one; 3-ethyl-1- [1- (3, 3-Bis (phenyl) propyl)-3-(methyl)-4-piperidinyl]-1,3-dihydro-2H-indole- 2-one; 3-ethyl-1- [1- (4-propylcyclohexyl)-3- (methyl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2- one; 3-ethyl-1- [1- (5-methylhex-2-yl)-3- (methyl)-4-piperidinyl]-1, 3-dihydro-2H-indole-2-one; 3-ethyl-1- [1- [4- (1-methylethyl)cyclohexyl]-3-methyl-4-piperidinyl]-1, 3-dihydro-2H- indole-2-one; 3-ethyl-1- [1- (decahydro-2-naphthyl)-3- (methyl)-4-piperidinyl]-1, 3-dihydro-2H-indole- 2-one; and pharmaceutically acceptable salts thereof. 15. A piperidinyl indole compound as claimed in claim 1, whenever used for the manufacture of a pharmaceutical composition useful as an analgesic.

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