Title of Invention	AZOLE-BASED KINASE INHIBITORS
Abstract	The invention discloses a compound of the general Formula (I): wherein A, W, R1, D & Y are as defined in the specification. The invention is also for the composition, comprising the said compound.

Full Text

AZOLE-BASED KINASE INHIBITORS FIELD OF THE INVENTION The present invention relates to the field of inhibitors of protein tyrosine kinases. BACKGROUND OF THE INVENTION Protein kinases are a family of enzymes that catalyse the phosphorylation of specific residues in proteins. In general protein kinases fall into several groups; those which preferentially phosphorylate serine and/or threonine residues, those which preferentially phosphorylate tyrosine residues and those which phosphorylate both tyrosine and Ser/Thr residues. Protein kinases are therefore key elements in signal transduction pathways responsible for transducing extracellular signals, including the action of cytokines on their receptors, to the nuclei, triggering various biological events. The many roles of protein kinases in normal cell physiology include cell cycle control and cell growth, differentiation, apoptosis, cell mobility and mitogenesis. Protein kinases include, for example, but are not limited to, members of the Protein Tyrosine Kinase family (FTKs), which in turn can be divided into the cytoplasmic PTKs and the receptor PTKs (RTKs). The cytoplasmic PTKS include the SRC family, (including: BLK; FGR; FYN; KCK; LCK; LYN; SRC;YES and YRK); the BRK Family (including: BRK; FKK, SAD; and SRM); the CSK family (including: CSK and CTK); the BTK family, (including BTK; ITK; TEC; MKK2 and TXK), the Janus kinase family, (including: JAK1, JAK2, JAK3 and Tyk2), the FAK family (including. FAK and FYK2); the Fee family (including FES and FER), the 2AP70 family (including ZAP70 and SYK); me ACK family (including ACK1 and ACK2); and the Ab1 family (including ABL and ARC). The RTK family includes the EGF-Reccptor family (including, EGFR, HER2, HER3 and HER4); the Insulin Receptor family (including INS-R and IGF1-R); the FDGF-Reccptor family (including VDGFRo, PDGFRp, CSF1R, KTT, FLK2 ); me VEGF-Receptor family (including; FLT1, FLK1 and FLT4V, the FGP-Receptor family (including FGFR1, FGFR2, FGFR3 and FGPR4 ); the CCK4 family (including CCK4); the MET family (including MET and RON); the TRK family (including TRKA, TRKB, and TRKC); the AXL family (including AXL, MER, and SKY); the TIE/TEK family (including TIE and TTE2/TEK); the EPH family (including EFHA1, EPH A2, EPHA3, EPH A4, EPHA5. EPHA6, EPHA7, EFHA8, EPHB1, EFHB2, EPHB3, EPHB4, EPHB5, EPHB6); the RYK family (including RYK); the MCK family (including MCK and TYRO10); the ROS family (including KOS);the RET family (including RET); the LTK family (including LTK" and ALK); the ROR family (including ROR1 and ROR2); The Musk family (including Musk); the LMR family inducting LMR1, LMR2 and LMR3); and the SuRTKK106 family (including SuRTK106). Similarly, the serine /threonine specific kinases comprise a number of distinct sub-families, including; the extracellular signal regulated kinases, (p42/ERK2 and p44/ERKI); c-Jun NH2-terminal kinase (JNK); cAMP-responsive element-binding protein kinases (CREBK); cAMP-dependent kinase (CAPK); mitogen-activated protein kinase-activated protein kinase (MAPK and its relatives); stress-activated protein kinase p38/SAPK2; mitogen-and stress-activated kinase (MSK); protein kinases, FKA, PKB and PKC inter alia. Additionally, the genomes of a number of pathogenic organisms possess genes encoding protein kinases. For example, the malarial parasite Plasmodium falciparum and viruses such as HPV and Hepatitis viruses appear to bear kinase related genes. Inappropriately high protein kinase activity has been implicated in many diseases resulting from abnormal cellular function. This might arise either directly or indirectly, for example by failure of the proper control mechanisms for the kinase, related for example to mutation, over-expression or inappropriate activation of the enzyme; or by over- or under-production of cytokines or growth factors also participating in the transduction of signals upstream or downstream of the kinase. In all of these instances, selective inhibition of the action of the kinase might be expected to have a beneficial effect. Diseases where aberrant kinase activity has been implicated include: diabetes; restenosis; atherosclerosis; fibrosis of the liver and kidney; ocular diseases; myelo- and lymphoproliforative disorders; cancer such as prostate cancer, colon cancer, breast cancer, head and neck cancer, leukemia and lymphoma; and, auto-immune diseases such as Atopic Dermatitis, Asthma, rheumatoid arthritis, Crohn's disease, psoriasis, Crouzon syndrome, achondroplasia, and thanatophoric dysplasia. The JAK family of protein tyrosine kinases (PTKs) play a central role in the cytokine dependent regulation of the proliferation and end function of several important cell types of the immune system. A direct comparison of the four currently known mammalian JAK family members reveals the presence of seven highly conserved domains (Harpur et al.,1992). In seeking a nomenclature for the highly conserved domains characteristic of this family of PTKs, the classification used was guided by the approach of Pawson and co-workers (Sadowski et al, 1986) in their treatment of the SRC homology (5H) domains. The domains have been enumerated accordingly with most C-terminal homology domain designated JAK Homology domain 1 (JH1). The next domain N-terminal to JH1 is the kinase-related domain, designated here as the JH2 domain. Each domain is then enumerated up to the JH7 located at the N-tumunus. The high degree of conservation of these JAK homology (JH) domains suggests that they are each likely to play an important role in the cellular processes in which these proteins operate. However, the boundaries of the JAK homology domains are arbitrary, and may or may not define functional domains. Nonetheless, their delineation is a useful device to aid the consideration of the overall structural similarity of this class of proteins. The feature most characteristic of the JAK family of PTKs is the possession of two kmase-related domains (JH1 and )H2) (Wilks et al., 1991). The putative FIX domain of JAK1 (JH1) contains highly conserved motifs typical of PTK domains, including the presence of a tyrosine residue at position 1022 located 11 residues C-terminal to sub-domain VII that is considered diagnostic of membership of the tyroelne-specific class of protein kinases. Alignment of the human JAK1 PTK domain (255 amino acids), with other members of the PTK class of proteins revealed homology with other functional PTKs (for example, 28% identity with c-fes (Wilks and Kurban, 1968) and 37% homology to TRK (Kozrna et al. 1988). The JH1 domains of each of the JAK family members poseem an interesting idiosyncrasy within the highly conserved sub-domain VU1 motif (residues 1015 to 1027 in JAK2) that Is believed to be closo to the active site, and define substrate specificity. The phenylalanine and tyrosine residues flanking the conserved tryptophan in this motif are unique to the JAK family of PTKs. Aside from this element, the JH1 domains of each of the members of the JAK family ore typical FTK domains. The central role played by the JAK family of protein tyrosine kinases in the cytokine dependent regulation of the proliferation and end function of several important cell types means that agents which inhibit JAK are useful in the prevention and chemotherapy of disease states dependant on these enzymes. Potent and specific inhibitors of each of the currently known four JAK family members will provide a means of inhibiting the action of those cytokines that drive immune pathologies, such as asthma (e.g. IL-13; JAK1, JAK2), and leukemia/lymphoma (eg. lL-2: JAK1 and JAK3). Furthermore, certain types of cancer such as prostate concur develop autocrine production of certain cytokines as a selectable) mechanism of developing growth and/ or metastatic potential An example of this is cancer of the prostate, where IL-6 is produced by and stimulates the growth of prostate cancer cell lines such as TSU and TC3 (Spiotto MT, and Chung TD, 2000). Interestingly, levels of CL-6 are elevated in sera of patients with metastatic prostate cancer. A great deal of literature covers the area of cytokine signalling. The present inventors have focusscd on the JAK/STAT pathway that is involved in the direct connection of cytokine receptor to target genes (such as cell cycle regulators (e.g. p21) and anti-apoptosis genes (such as BC1-XL)). The JAK/STAT Pathway The delineation of a particularly elegant signal transduction pathway downstream of the non-protein tyrosine kinase cytokine receptors has recently been achieved. In this pathway the key components are: (j) A cytokine receptor chain (or chains) such as the Interleukin-4 receptor or the Interferon γreceptor; (ii) a member (or members) of the JAK family of PTKs; (iii) a mcmber(s) of the STAT family of transcription factors, and (iv) a sequence specific DNA element to which the activated STAT will bind. A review of the JAK/STAT literature offers strong support to the notion that this pathway is important for the recruitment and marshalling of the host immune response to environmental insults, such as viral and bacterial infection. This is well exemplified in Table 1 and Table 2. Information accumulated from gene knock-out experiments have underlined the importance of members of the JAK family to the intracellular signalling triggered by a number of important immune regulatory cytokines. The therapeutic possibilities stemming from inhibiting (or enhancing) the JAK/STAT pathway are thus largely in the sphere of immune modulation, and as such are likely to be promising drugs for the treatment of a range of pathologies in this area. In addition to the diseases listed in Tables 1 and 2, inhibitors of JAKs could be used as immunosuppresive agents for organ transplants and autoimmune diseases such as lupus, multiple sclerosis, rheumatoid arthritis, Type I diabetes, autoimmune thyroid disorders, Alzheimer's disease and other autoimmune diseases. Additionally/ treatment of cancers such as prostate cancer by JAK inhibitors is indicated. SUMMARY OF THE INVENTION The present inventors have found that a group of compounds based upon the disubstituted pyrazine scaffold I, are inhibitors of tyrosine kinases. Accordingly, in a first aspect the present invention provides a compound of the general formula or pharmaceutically acceptable prodrugs, salts, hydrates, solvates, crystal forms or diastereomers thereof, wherein: D is a heterocyclic ring selected from: where X1, X2, X3, X4 are optionally substituted carbon, or one of X1, X2, X3, X4 is nitrogen and the rest arc optionally substituted carbon; R2 is 0-3 substituents independently chosen from H, halogen, C1-4 alkyl, CF3 OCF3, OCHF2, CN, aryl, hetaryl, C1-4alkylOH, C1-4alkylNR3R4, C1-4alkylhetaryl, OC1-4 alkyl, OC1-4alkylNR3R4, OC1-4alkylhetaryl, OC1-4 alkylOH, CO2R3, CONR3R4, NR3R4, nitro, NR3COR4, NR5CONR3R4, NR3SO2R4, C1-4alkylNR3COR4, C1-4alkylNR5CONR3R4, C1-4alkylNR3SO2R4; R3, R4 are each independently H, C1-4 alkyl, C1-4alkylOH, C1-4alkylNR19R20, C1-4 alkyl cycloalkyl, C1-4 cyclohetalkyl, aryl, C1-4 alkylaryl, hetaryl, C1-4 alkylhetaryl, or may be joined to form an optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; and R5 is selected from H, C1-4 alkyl, aryl or hetaryl; R6 is selected from H, C1-4 alkyl, C1-4alkylNR19R20, aryl, hetaryl, C1-4 alkyl aryl, C1-4 alkyl hetaryl; R19, R20 are each independently selected from H, C1-4alkyl; R1 is H, C1-4 alkyl, C1-6cycloalkyl, or may form a 5-8 membered ring onto the ortho position of ring A; Q is a bond, CH2, C1-4 alkyl; A is aryl hetaryl optionally substituted with 0-3 substituents independently chosen from halogen, C1-4 alkyl, CF3, OCF3, CN, NR8R9, aryl, hetaryl, C1-4aryl, C1-4hetaryl, C1-4 alkylNR8R9, OC1-4alkylNR8R9, nitre, NR10C1-4NK8R9, NR8COR9, NR10CONR8R9, NR8SO2R9, CONK8R9, CO2R8; R8 and R9 are each independently H, C1-4 alkyl, aryl or together form an optionally substituted 4-8 membered ring which may contain a heteroatom selected from O, S, NR11; R10 is selected from H, C1-4 alkyl; R11 is selected from H, C1-4 alkyl; W is selected from H, C1-4alkyl, C1-4alkenyl or may form a 5-8 membered ring onto the ortho position of ring A; where C1-4alkyl or C1-4alkenyl may be optionally substituted with C1-4akyl, OH, OC1-4alkyl, NR12R13; R12, and R13 are each independently H, C1-4alkyl, or may be joined to form an optionally substituted 3-8 membered ring optionally containing an atom selected from O, S, NR14; R14 is selected from H, C1-4 alkyl; V is 0-2 substituents selected from H, C1-4 alkyl NR15R16; R15 and R16 are independently selected from H, C1-4alkyl. In a second aspect the present invention provides a composition comprising a carrier and at least one compound of the first aspect of the invention. In a third aspect the present invention provides a method of treating a tyrosine kinase-assoriated disease state in a subject, the method comprising administering a therapeutically effective amount of at least one compound of the first aspect of the invention or a therapeutically effective amount of a composition of the second aspect of the invention. DETAILED DESCRIPTION OF THE INVENTION -The present inventory have found that a group of compounds based upon the disubstituted pyrazine scaffold I, are inhibitors of tyrosine kinases. Accordingly, in a first aspect the present invention provides a compound of the general formula or pharmaceutically acceptable prodrugs, salts, hydrates, solvates, crystal forms or diastereomers thereof, wherein: D is a heterocyclic ring selected from: where X1, X2, X3, X4 are optionally substituted carbon, or one of X1, X2, X3, X4 is nitrogen and the rest optionally substituted carbon; R2 is 0-3 substituents independently chosen from H, halogen, C1-4 alkyl, CF3, OCF3, OCHF2, CN, aryl, hetaryl, C1-4alkylOH, C1-4alkylNR3R4, C1-4alkylhetaryl, OC1-4alkyl, OC1-4alkylNR31R4, OC1-4alkylhctaryl OC1-4 alkylOH, CO2R3, CONR3R4, NR3R4, nitro, NR3COR4, NR5CONR3R4, NR3SO2R4, C1-4alkylNR3COR4, C1-4alkylNR5CONR3R4, C1-4alkylNR3SO2R4; R3, R4 are each independently H, C1-4 alkyl C1-4alkylOH, C1-4alkylNR19R20, C1-4 alkyl cycloalkyl, C1-4 cyclohetalkyl aryl, C1-4 alkylaryl, hetaryl, C1-4 alkylhetaryl, or may be joined to form on optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; and R5 is selected from H, C1-4 alkyl, aryl or hetaryl; R6 is selected from H, C1-4alkyl, C1-4alkylNR19R20, aryl, hetaryl, C1-4 alkyl aryl, C1-4 alkyl hetaryl; R19, R20 are each independendy selected from H, C1-4alkyl; R1 is H, C1-4 alkyl, C1-6 cycloalkyl, or may form a 5-8 membered ring onto the ortho position of ring A; Q is a bond, CH2, C1-4 alkyl; A is aryl, hetaryl optionally substituted with 0-3 substituents independently chosen from halogen, C1-4 alkyl, CF3, OCF3 CN, NR8R9, aryl, hetaryl, C1-4aryl, C1-4hetaryl, C1-4 alkylNR8R9, OC1-4alkylNR8R9, nitro, NR10C1-4NR8R9, NR8COR9, NR10CONR8R9, NR8SO2R9, CONR8R9, CO2R8; R8 and R9 are each independently H, C1-4 alkyl, aryl or together form an optionally substituted 4-8 membered ring which may contain a heteroatom selected from O, S, NR11; R10 is selected from II, C1-4 alkyl; R11 is selected from H, C1-4 alkyl; W is selected from H, C1-4alkyl, C2-6alkenyl or may form a 5-8 membered ring onto the ortho position of ring A; where C1-4alkyl or C1-4alkenyl may be optionally substituted with C1-4alkyl, OH, OC1-4alkyl, NR12R13; R12, and R13 ere each independently H, C1-4alkyl, or may be joined to form an optionally substituted 3-6 membercd zing optionally containing an atom selected from O, S, NR14; R14 is selected from H, C1-4 alkyl; Y is 0-2 substltuents selected from H, C1-4 alkyl, NR15R16; R15 and R16 arc independently selected from H, C1-4alkyl. In the above description it will be appreciated that- C1-4 alkyl means an unsubstituted or optionally substituted straight or branched alkyl chain Aryi moans unsubstituted or optionally substituted phenyl or naphthyl. Hetaryl means a unsubstituted or optionally substituted 5- or 6-membered hetoroaromadc ring containing one or more heteroatoms selected from O, N, S. Cycloalkyl means a 3-8 membcred saturated ring Cyclohetalkyl means a 3-8 membered saturated ring containing 1-3 heteroatoms selected from O, S, NR17, where R17 is H, C1-4 alkyl, aryl, hetaryl. In a further preferred embodiment the compound is selected from compounds of the general formula n. or pharmaceutically acceptable prodrugs, salts, hydrates, solvates, crystal forms or diastercomers thereof, wherein: D is a heterocyclic ring selected from; where X1, X2, X3, X4 are optionally substituted carbon, or one of X1, X2, X3, X4 is N and the rest optionally substituted carbon; R2 is 0-3 substiruents independently chosen from H, halogen, C1-4 alkyl, CF3, OCF3, OCHF3, CN, aryl, hetaryl, C1-4 alkylOH, C1-4alkylNR3R4, C1-4alkylhetaryl, OC1-4 alkyl, OC1-4alkylNR3R4, OC1-4alkylhetaryl, OC1-4alkylOH, CO2R3, CONR3R4, NR3R4, nitro, NR3COR4, NR5CONR3R4, NR3SOjR4, C1-4alkylNR3COR4, C1-4alkylNR5CONR3R4, C1-4alkylNR3SO2R4; R3, R4 are each independently II, C1-4 alkyl, C1-4alkylOH, C1-4alkkylNR19R20, C1-4 alkyl cycloolkyl, C1-4 cyclohetalkyl aryl, C1-4 alkylaryl, hetaryl, C1-4 alkylhetoryl, or may be joined to form an optionally- substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; and R5 is selected from H, C1-4 alkyl, aryl or hetaryl; R6 is selected from H, C1-4 alkyl, C1-4alkylNR19R20, aryl, hetaryl, C1-4 alkyl aryl. C1-4 alkyl hetaryl; R19, R20 are each independently selected from H, C1-4a1kyl; R1 is H, C1-4 alkyl, C1-4cycloalkyl, or may form a 5-8 membered ring onto the ortho position of ring A; A is aryl, hetaryl optionally substituted with 0-3 substiruents independently chosen from halogen, C1-4 alkyl CF3, OCF3, CN, NR8R9, aryl, hetaryl, C1-4aryl, C1-4hetaryl C1-4 alkylNR8R9, OC1-4 alkylNR8R9, nitro, NR10C1-4NR8R9, NR8COR9, NR10CONR8R9, NR8SO2R9, CONR8R9, CO2RS; R8 and R9 arc each independently H, C1-4 alkyl, aryl or together form an optionally substituted 4-8 membered ring which may contain a heteroatom selected from O, S, NR11; R10 is selected from H, C1-4 alkyl; R11 is selected from H, C1-4 alkyl; W is selected from H, C1-4alkyL C1-4alkenyl or may form a 5-8 membered ring onto the ortho position of ring A; where C1-4atkyt or C2-6alkenyl may be optionally substituted with C1-4alkyl, OH, OC1-4alkyl, NR12R13; R12, and R13 are each independently H, C1-4alkyl, or may be joined to form an optionally substituted 3-8 membered ring optionally containing an atom selected from O, S, NR14; R14 is selected from H, C1-4 alkyl; Y is 0-2 substitucnts selected from H, C1-4 atkyl, NR1SR16; R15 and K16 are independently selected from H, C1-4alkyl. In the above description it will be appreciated that: C1-4 alkyl means an unsubstituted or optionally substituted straight or branched alkyl chain Aryl means unsubstituted or optionally substituted phenyl or naphthyl. Hetaryl means a unsubstituted or optionally substituted 5- of 6-memborcd heteroaromatic ring containing one or more heteroatoms selected from O, N, S. Cycloalkyl means a 3-8 membered saturated ring Cyclohetalkyl means a 3-8 membered saturated ring containing 1-3 heteroatoms selected from O, S, NR17, where R17 is II, C1-4 alkyl, aryl, hetaryl. The compounds of this invention include all conformational isomers (eg. cis and trans isomers). The compounds of the present invention have asymmetric centers and therefore exist in different enantiomeric and diastercomcric forms. This invention relates to the use of all optical isomers and stereoisomers of the compounds of the present invention, and mixtures thereof, and to all pharmaceutical compositions and methods of treatment that may employ or contain them. In this regard, the invention includes both the E and Z configurations. Thecompounds of formula I may also exist as tautnmers. This invention relates to the use of all such tnutomers and mixtures thereof. This invention also encompasses pharmaceutical compositions containing prodrugs of compounds of the formula I. This invention also encompasses methods of treating or preventing disorders in a subject that can be treated or prevented by the inhibition of protein kinases, such AS JAK comprising administering prodrugs of compounds of the formula I. Compounds of formula I having free amino, amido, hydroxy or caxboxylic groups can be converted into prodrugs. Prodrugs include compounds wherein an amino acid residue, ot a polypeptide chain of two or more (eg, two, three or four) amino acid residues which are covalently joined through peptide bonds to free amino, hydroxy and carboxyiic acid groups of compounds of formula T. The amino acid residues include the 20 naturally occurring amino acids common ly designated by three letter symbols and also include, 4- hydroxyproline, hydroxylyainc, demoAine, isodemosine, 3-memylhistidine, norvlin, beta- olanme, gamma-etninobutyrk add, citnxlimc, homocysteine, homoeerine, ornithine and xnethioine autfone. Prodrugs also include compounds wherein carbonates, carbamates, amides and alkyl outers which are covakntly bonded to the above substituents of formula 1 through the carbonyl carbon prodrug sidocham. Prodrugs also include phosphate derivatives of compounds of formula 1 (such as adds, salts of acids, or eaters) joined through a phosphorus-oxygenbond to a free hydroxyl of compounds of formula I. In a still further preferred embodiment the compound possesses Schirality at the chiral carbon bearing W, where W is C1-4 alkyl. The compound can be used as a purified isomer or as a mixture of any ratio of isomers. 7t is however preferred that the mixture comprises at least 70%, 80%, 90%, 95%, or 99% of the preferred isomer. In a second aspect the present invention provides a composition comprising a comer and at least one compound of the first aspect of the Invention. In a third aspect the present invention provides a method of treating a tyrosine kmase-ossoclated disease state in a subject, the method comprising administering a therapeutically effective amount of at least one compound of the first aspect of the invention or a therapeutically effective amount of a composition of the second aspect of the Invention. In a further preferred embodiment the disease state involves JAK1, JAK2, JAK3 or TYK2. In a preferred embodiment of the present invention the disease state is selected from the group consisting of Atopy, such as Allergic Asthma, Atopic Dermatitis (Eczema), and Allergic Rhinitis; Cell Mediated Hypersensitivity, such as Allergic Contact Dermatitis and Hypersensitivity Pneomonitifl; Rheumatic Diseases, such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis. Juvenile Arthritis, Sjogren's Syndrome, Scleroderma, Polymyositis, Ankylosing Spondylitis, Psoriatic Arthritis; Other autoimmune diseases such as Type I diabetes, autoimmune thyroid disorders, and Alzheimer's disease; Viral Diseases, such as Epstein Barr Virus (EBV), Hepatitis B, Hepatitis C, HTV, HTLV1, Varicella Zoster Virus (VZV), Human Papilloma Virus (HP V); Cancer, such as Leukemia, Lymphoma and Prostate Cancer; Neurodegenerative Diseases such aa Motor Neuron Disease; Cardiovascular Diseases such as Cardiac Hypertrophy, ischemia, Pulmonary Hypertension, Atherosclerosis and Arteriosclerosis. As used herein the term "tyrosine kinase-assodated disease state" refers to those disorders which result from aberrant tyrosine kinase activity, in particular JAK activity and/ or which are alleviated by inhibition of one or more of these enzymes. In further, aspects the present invention provides the use of the compounds described in the preparation of medicaments for the treatment of JAK-associatsd disease states. As used herein the term "JAK", "JAK kinase" or "JAK family' refers to protein tyrosine kinases which possess the characterizing features of JAK1, JAK2, JAK3 and TYK as described herein. The present invention provides pharmaceutical compositions comprising at least one of the compounds of the present invention capable of treating a JAK-associated disorder in an amount effective therefor, and a pharmaceutically acceptable vehicle or diluent. The compositions of the present invention may contain other therapeutic agents as described below, and may be formulated, for example, by employing conventional solid or liquid vehicles or diluents, as well as pharmaceutical additives of a type appropriate to the mode of desired administration (for example, excipients, binders, preservatives, stabilizers, flavors, etc.) according to techniques such as those well known in the art of pharmaceutical formulation. The compounds of the present invention may be administered by any suitable means, for example, orally, such as in the form of tablets, capsules, granules or powders; sublingually buccally; parenterally, such as by subcutaneous, intravenous, intramuscular, or intracisternal injection or infusion techniques (e.g„ as sterile injectable aqueous or non-aqueous solutions or suspensions); nasally such as by inhalation spray; topically, such as in the form of a cream or ointment; or racially such as in the form of suppositories; in dosage unit formulations containing non-toxic, pharmaceutically acceptable vehicles or diluents. The compounds may, for example, be administered in a form suitable for immediate release or extended release. Immediate release or extended release may be achieved by the use of suitable pharmaceutical compositions comprising the present compounds, or, particularly in the case of extended release, by the use of devices such as subcutaneous implants or osmotic pumps. The compounds may also be administered liposomaliy. In addition to primates, such as humans, a variety of other mammals can be treated according to the method of the present invention. For instance, mammals including, but not limited to, cows, sheep, goats, horses, dogs, cats, guinea pigs, rats or other bovine, ovine, equine, canine, feline, rodent or murine species can be treated. However, the method can also be practiced in other species, such as avian species (e.g., chickens). Diseases and conditions associated with inflammation and infection can be treated using the method of the present invention. In a preferred embodiment, the disease or condition is one in which the actions of eosinophils and/or lymphocytes are to be inhibited or promoted, in order to modulate the inflammatory response. The subjects treated in the above methods, in whom which JAK inhibition is desired, are mammals, including, but not limited to, cows, aheap, goats, horses, dogs, cats, guinea pigs, rats or Other bovine, ovine, equine, canine, feline, rodent or murine species, and preferably a human being, male or female. The term "therapeutically effective amount" means the amount of the subject composition that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by the researcher, veterinarian, medical doctor or other clinician. The term "composition" as used herein is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the sped/ied amounts. By "pharmaceutically acceptable" it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. The terms "administration of and or "administering a" compound should be understood to mean providing a compound of the invention to the individual in need of treatment. The pharmaceutical compositions for the administration of the compounds of this invention may conveniently be presented in dosage unit form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active ingredient into association with the carrier which constitutes one or more accessory ingredients. In general, the pharmaceutical compositions are prepared by uniformly and intimately bringing the active ingredient into association with a liquid carrier or a finely divided solid earner or both, and then, if necessary shaping the product into the desired formulation. In the pharmacutical composition the active object compound is included in an amount sufficient to produce the desired effect upon the process or condition of diseases. As used herein, the tram "composition" to intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. The pharmaceutical compositions containing the active ingredient may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, disperable powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in admixture with non-toxic pharmaceurically acceptable excipients which are suitable for the manufacture of tablets. These excipients may be for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or tale. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl moreostearate or glyceryl distearate may be employed. They may also be coated to form osmotic therapeutic tablets for control release. Formulations fox oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient la mixed with water or an oil medium, for example peanut oil, liquid paraffin, ox olive oil. Aqueous suspensions contain the active materials in admixture with excipionts suitable for the manufacture of aqueous suspensions. Such, excipients are suspending agents, for example sodium carboxymethykellulose, methylcellulose.hydroxy-propylmethylcellulosc, sodium alginate, poly vinyl-pyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents may be a naturally-occurring phosphatide, fox example lescithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxycmylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty adds and hexitol anhydrides, for example polyethylene sorbltan monooleate. The aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyi, p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin. Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example araclus oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyi alcohol Sweetening agents such as those set forth above, and flavoring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid. Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example sweetening, flavoring and coloring agents, may also be present. The pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example liquid paraffin or mixtures of these. Suitable emulsifying agents may be naturally- occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening and flavoring agents. Syrups and elixirs may be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative and flavoring and coloring agents. The pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleaganous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agente which have been mentioned above. The sterile Injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parcnteraliy-acceptable diluent or solvent, for example as a solution in 1,3-butane diol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils arc conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglyccrides. In addition, fatty- acids ouch as oleic acid find use in the preparation of injectables. The compounds of the present invention may also be administered in the form of suppositories for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials are cocoa butter and polyethylene glycols. For topical use, creams, ointments, jellies, solutions or suspensions, etc, containing the compounds of the present invention ore employed. (For purposes of this application, topical application shall include mouthwashes and gargles.) The compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. liposomes are formed by mono- or multilamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolisable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilisers, preservatives, exclpients and the like. The preferred lipids are the phospholipids and phosphatidyl cholines, both natural and synthetic. Methods to form liposomes are known in the art. The pharmaceutical composition and method of the present invention may further comprise other therapeutically active compounds as noted herein which are usually applied in the treatment of the above mentioned pathological conditions. Selection of the appropriate agents for use in combination therapy may be made by one of ordinary- skill in the art, according to conventional pharmaceutical principles. The combination of therapeutic agents may act synergistically to effect the treatment or prevention of the various disorders described above. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects. Examples of other therapeutic agents include the following: cyclosporins (s.g., cyclosporin A), CTLA4-Ig, antibodies such as ICAM-3, anti-IL-2 receptor (Anti-Tac), anti CD45RB, anti-CD2, anti-CD3 (OKT-3), anrl-CD4, anti-CD80, anti-CD86, agents blocking the interaction between CD40 and gp39, such as antibodies specific for CD40 and/or gp39 (Le., CD154), fusion proteins constructed from CD40 and gp39 (CD401g and CD8gp39), inhibitorss, such aft nuclear translocation inhibitors, of NP-kappo B function, such as deoxyspergualin (DSG), cholesterol biosynthesis inhibitors such as HMG CoA reductase inhibitors (lovastatin and simvastatin), non-steroidal antiinflammatory drugs (NSAIDs) such as ibuprofen, aspirirt, acetaminophen and cyclooxygenase inhibitors such as rofecoxib, steroids such as prednisolone or dexamethasone, gold compounds, antiproliferative agents such as methotrexate, HK506 (tacrolimus, Prograf), mycophenolate mofotil, cytotoxic drugs such as azarhioprine. VP-16, etoposide, fludarabtae, daplatln and cyclophosphamide, TNF-II inhibitors such as terudap, anti-TNF antibodies ox soluble TNF receptor, and rapamycin (sirollmus or Rapamune) or derivatives thereof. When other therapeutic agents are employed in combination with the compounds of the present invention they may be used for example in amounts as noted in the Physician Desk Reference (PDR) or as otherwise determined by one of ordinary skill in the art. In the treatment or prevention of conditions which require protein tyrosine kinase inhibition an appropriate dosage level will generally be about 0.01 to 500 mg per kg patient body weight per day which can be administered in single or multiple doses. Preferably, the dosage level will be about 0.1 to about 250 mg/kg per day; more preferably about 0.5 to about 100 mg/kg per day. A suitable dosage level may be About 0.01 to 250 mg/kg per day, about 0.05 to 100 mg/kg per day, or about 0.1 to 50 mg/kg per day. Within this range the dosage may be 0.05 to 0.5,0..5 to 5 or 5 to 50 mg/kg per day. For oral administration, the compositions ore preferably provided in the form of tablets containing 1.0 to 1000 milligrams of the active ingredient, particularly 1.0,5.0,10.0,15.0. 20.0,25.0,50.0,75.0,100.0,150.0, 200.0,250.0,300.0,400.0,500.0,600.0,750.0,800.0,900.0, and 1000.0 milligrams of the active ingredient for the symptomatic adjustment of the dosage to the patient to be treated. The compounds may be administered on a regimen of 1 to 4 times per day, preferably once or twice per day. It will be understood, however, that the specific dose level and frequency of dosage for any particular patient may be varied and will depend upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, me age, body weight, general health, sex, diet, mode and time of administratian, rate of excretion, drug combination, the severity of the particular condition, and the host undergoing therapy. Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group o/ elements, integers or steps. All publications mentioned in this specification are herein incorporated by reference. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission mat any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed in Australia before the priority date of each claim oi this application. In order that the nature of the present invention may be more dearly understood preferred forms thereof will now be described by reference to the following non-limiting Examples. EXAMPLES Materials and Methods Compound Synthesis Compounds are generally prepared in a 2-step process starting from 2,6-dichloropyrazine. The first step is a nucleophilic aromatic substitution to generate a monoamino-rnonohalo intermediate. (Scheme 1). The nucleophilic aromatic substitution is typically carried out by addition of a primary amine to the dishalogenated heterocycle in a solvent such as eyhanol, isopropanol tert-butanol, dioxsne, THF, DMF, toluene or xylene. The reaction is typically performed at elevated temperature in the presence of excess amine or a non-nucleophilic base such as triethylaminc' or disopropylemylomine, or an inorganic base such as potassium carbonate or sodium carbonate. Alternatively, the amino substituent may be introduced through a transition metal catalysed amination reaction. Typical catalyst- systems for such transformations include Pd(OAc)2/P(t-Bu)a, Pd2(dba)3/BINAP and Pd(OAc)2/BINAP. The amines employed in the first step of the synthesis of these compounds are obtained commercially or are prepared using methods well known to those skilled in the art. Of particular interest are α-methylbenzylamines which are obtained commercially or may be prepared through reduction of oximes (Scheme 2). Typical reductants include lithium aluminium hydride, hydrogen gas in the presence of catalytic palladium on charcoal, Zn in the presence of hydrochloric acid, sodium borohydride in the presence of a Lewis acid such as TlCl3 ZrCl4, NiCl2 and MoO3 or sodium borohydride in conjunction with Amberlyst HI 5 ion exchange resin and LIC1. The oximes are obtained in one-step from the corresponding ketones through condensation with hydroxylamine. This reaction is generally performed in a protic solvent such as water or ethanol, at temperatures from 0°C to reflux. The hydroxylamine is generally used in the form of its hydrochloride salt, and therefore the reaction is performed in the presence of a base such as sodium hydroxide. The ketones employed as starting materials are generally obtained commercially ox via procedures well known to those skilled in the art. α-Methyl benzylamines of high optical purity may be prepared from chiral α-methyl benzyl alcohols using methods well known to those skilled in the art. Such methods include dorivatisation of the hydroxy1 as a mesylate or tosylate and displacement with a nitrogen nucleophile, such as phthalimide or ozidc which can then converted to the primary amine using conventional synthetic methods; or, displacement of the hydroxyl with a suitable nitrogen nucleophile under Miteunobu conditions. The chiral cc-methyl benzyl alcohols may be obtained through chiral reduction of the corresponding ketones. Chiral reducing methods are now well known in organic chemistry and include enzymatic processes, asymmetric hydrogenatlon procedures and chiral oxazaborolidines. The second step of the synthesis involves a nucleophilic aromatic substitution reaction of the monochloro- mono-amino pyrazine with benzimidazole or indazole. The reaction is typically performed using a salt of the benzimidazole or indazole in solvents such as tetrahydroruran, dimethylformamide, toluene, or xylene from room temperature to reflux. The benzunidazole or indazole salt is prepared by reaction with a metal hydride such as sodium or potassium hydride or by reaction with caesium carbonate. Alternatively, a metal-catalysed coupling reaction can be used to introduce the benzimidazole or indazole ring. The reaction is typically performed using a base such as caesium carbonate, rubidium carbonate, potassium carbonate, sodium tert-butoxide or potassium phosphate in a solvent such as xylene, toluene, and DMF from room temperature to reflux. Auxiliary reagents such as phase transfer agents (e.g. cctrimonlum bromide) or copper complexing agents (e.g. phenanthroline) may also be employed in the reaction. The benzlmldazole or indazole components used in mis reaction are obtained commercially or are prepared from commercially available benzimidazoles or indazoles via techniques well known to those skilled in the art. Alternatively, a benzunidazole or indazole derivative may be reacted with the mono-amino mono-chloro pyrazine and the subsequent product further derivatised using methods well known to those skilled in the art Representative syntheses arc reported below. EXAMPLE 1 A solution of S-(-)-1(4-fluorophenyl)-ethylamine (5.0 g, 35.9 mmol), 2,6-dichloropyrazine (5.90 g, 39.6 mmol), diisopropylethylamme (12.5 mL, 71.8 mmol) in ethoxyethanol (25 mL) was heated at 135°C under N2 overnight The solvent was removed in vacuo and the residue washed with H2O (2 x 30 mL) and dried (Na2SO4). The solvent was removed under reduced pressure and the residue triturated with hexanes (2 x 10 mL) to give a light brown solid. The washings were combined, concentrated and the residue obtained chromatographed using ethyl acetate-hexane (1:4 -1:2) to separate solid product which, combined with the original solids, gave the total product (7.07 g, 78%). EXAMPLE 2 To a stirred solution of benzimidazole (130 mg, 1.1 mmol) in anhydrous DMF (5 mL) at 0°C under N2 was added sodium hydride (56 mg, 60% dispersion in oil, 1.45 mmol) in portions over 2 min. The mixture was stirred at 0°C for 15 min and at RT for 60 min. To this was added a solution of (6-chloro-pyrazin-2-yl)-(1-benzyl)-amine (220 mg) in DMF (5 mL) and the resulting mixture was then heated at reflux for 18h. The DMF was removed under reduced pressure and the residue diluted with chloroform. The organic layer was washed with water, dried (Na2SO4) and the solvent removed under reduced pressure to furnish the crude product. Column chromatography using dichloromethane-methanol (20:1 → 10:1) as eluant separated the product (100mg). EXAMPLE 3 1-(6-chloropyrazin-2-yl)-1H-benzimidazole-6-carboxamide A mixture of 2,6-dichloropyrs7.me (2.0 g, 13.4 mmol), 1H-benzimidazole-5-carboxamide (2,0 g, 12.3 mmol) and cesium carbonate (5.6 g, 17.2 mmol) in DMF (10 mL) was heated at 90°C for 3h. The solution was cooled to RT and diluted with ethyl acetate (20 mL) and filtered. The solid material was washed with chloroform-mothanol (20mL, 4:1) and the combined filtrates concentrated in vacuo. The residue thus obtained (3.02 g) was used without further purification. m/z (EI) 273/275 (M+1) EXAMPLE 4 1-(6-Chloropyrazin-2-yl-1H-benzimidazole-5-carbonitrile and 1-(6-Chloropyrazin-2-yl-1H-benzimidazole-5-carbonitrile An approximately 1:1 mixture of 1-(6-chloropyrazin-2-yl)-1H-benzimidazole-5-carboxamide and -1-(6-chloropyrazin-2-yl)-1H-benzimidazole-5-carboxamide (0.3 g, 1.09 mmol) and thionyl chloride (03 mL, 33 mmol) in benzene (3 mL) was heated under reflux overnight. Upon cooling to RT the solution was poured onto ice and the resultant mixture basified to pH -11 with solid Na2CQ3; The mixture was then extracted with ethyl acetate (2 x 20 mL) and the combined organic layers washed with brine and dried (Na2SO4). The solvent was removed in vacua and the residue purified by column chromatography using dichloromethane-methanol (100:0 - 96:4) as eluant to give the desired product as a mixture of isomers (135 mg). m/z (EI) 255/257 (M+l) EXAMPLE 5 6-(1H-benzimidazole-yl)-N-[(1R)-1-phenylethyl]pyrazin-2-amine In a procedure analogous to example 2, reaction of 6-chloro-N-l(lR)-1-phenylethyl]pyrazin-2-amine (240mg, 1.03mmol) and benzimidazole (130mg, 1.10mmol) furnished the product (187mg, 59%). EXAMPLE 6 6-(1H-benzimidazole-yl)-N-l(1S)-1-phenylethyl]pyrazin-2-amine In a procedure analogous to example 2, reaction of 6-chloro-N-1(1.5)-1- pheny1ethyllpyrazin-2-amine (140 mg, 0.60 mmol) and benzimidazole (78 mg, 0.66 mmol) furnished the product (71 mg, 38%). EXAMPLE 7 In an analogous fashion to example 1, N-methyl-N-[(1S)-1-phenylethyl]amine (0.27 g, 2.0 mmol) was condensed with 2,6-dichloropyrazine (0.36 g, 2.4 mmol), to furnish the desired product as a light brown solid (192 mg, 39%). EXAMPLE $ 1-(6-[[1-3-Fluorophenyl)ethyl]ant ino]pyrazin-2-yl)-1H-benzimidazole-5-carboxamide and 1-(6-[[1-3-Fluorophenyl)ethyl]ant ino]pyrazin-2-yl)-1H-benzimidazole-5-carboxamide In an analogous fashion to Example 3,6-chloro-N-[1-(3-fluorophenyl)ethyl]pyrazin-2.amine (0.25 g, 1 mmol) was reacted with 1H-benzimidazole-5-carboxamide (0.2 g, 1.2mmol) to afford the product as a mixture of isomers. These were separated by chromatography using dichloromethane-methanol (98:2 - 92:8) as eluant to afford from the less polar fractions l-(6- [[1-(3-fluorophenyl)ethyllamino]pyrazin-2-yl)-1H-benzimidazole-6-carboxamide (80 mg). EXAMPLE 9 1-(6-[[1-3-Fluorophenyl)ethyl]ant ino]pyrazin-2-yl)-1H-benzimidazole-5-carboxamide From the more polar fractions was isolated l-(6-{[l-(3-fluorophenyl)ethyl]amino]pyrazin-2- y1)-1H-benzimidazole-5-carboxamide (63 mg). In an analogous procedure to that reported in Example 4, 1-(6-([1-(3- fluorophenyl)ethy1]amino]pyrazin-2-yl)-lH-enzimidazole-6-carboxamide (80 mg, 0.21 mmol) was reacted with phosphorus oxychloride to afford the product as a pale yellow solid (60 mg, 80%). EXAMPLE 10 1-(6-[[1-3-Dihydroisoquinolin-2(1H)-yl)pyrazin-2-yl)-1H-benzimidazole-5-carbonitrile In en antilogous fashion to Example 1/ an Approximately 1:1 mixture of l-(6-chloropyrazin-2- yl)-lH-banzimidazole-5-carbonitrile and 1-{6-chloropyrazin-2-yl)-1H-benzimidazole-6- carbonitrile (102 mg, 0.4 mmol) was condensed with 1,2,3,4-tetrahydroisoquinoline (64 mg, 0.48 mmol). The crudes product was triturated with cold ethyl acetate to acparate l-[6-(3,4- dihydroisoquinolin-2(1H)-yl)pyrazin-2-yl]-1H-benzimidazole-5-carbonitrile as an off-white solid (65 mg) The ethyl acetate washings were combined and concentrated in vacuo to furnish l-[6-(3,4- dihydroisoquinolin-2(1H)-yl)pyrazin-2-yl]-1H-benzimidazole-6-carbonitrile (41 mg) In an analogous fashion to Example 1, an approximately 1:1 mixture of 1-(6-chloropyrazin-2- yl)-1H-benzimidazole-5-carbonitrile and l-(6-chloropyrazin-2-yl)-1H-benzimidazole-6- carbonitrile (100 mg, 039 mmol) was condensed with (1S)-1,23,4-tetrahydronaphthalen-1- amino (69 mg, 0.47 mmol), The product was obtained as a mixture of regioisomers which were separated by column chromatography using dichloromethane-methanol (95:5) as cluant. From the less polar fractions 1-{6-[(1S)-1,2,3,4-tetrahydronaphthalen-1- ylamino]pyrazin-2-yl}-1H-benzimidazole-6-carbonitrile was obtained as a yellow semi-solid (26 mg). From the more polar fractions was isolated 1-6-[(1S)-1,2,3,4-tetrahydronaphthalen-1- ylamino]pyrazin-2-yl}-1H-benzamidazole-5-carbonitrile (19 mg) To a stirred suspension of benzimidazole-5-carboxylic Acid (5.0 g, 30.8 mmol) in benzene (25 mL) was added thionyl chloride (25 mL) dropwise at room temperature. To this mixture was added DMF (0.1 mL) and it was then heated under reflux for 6h. Benzene And thionyl chloride was evaporated off under reduced pressure and toluene (20 mL) added to the residue. This was removed under reduced pressure and the add chloride thus obtained suspended in tetrohydrofuran (20 mL). To this was the added 28% aqueous ammonia (20 mL) dropwise at 0°C, and the resultant mixture was then stirred at room temperature overnight. The precipitate was filtered and washed with cold H2O to give the primary amide as a brown solid (3.55 g). To a stirred solution of 5-amino-benzimidazole (290 mg, 2.2 mmol) in anhydrous DMF (10 mL) under N2 was added caesium carbonate (980 mg) The resulting mixture was stirred at 70°C for 60 min. To this was added a solution of 6-chloro-N-[(1S)-1-phenylethyl]pyrazin-2-amino (470mg) in DMF (5mL) and the resulting mixture was then heated at reflux for 48h. The DMF was removed under reduced pressure and the residue diluted with chloroform. The organic layer was washed with aqueous Na2CO3, dried (Na2SO4) and the solvent removed under reduced pressure to furnish the crude product. Column chromatography using dichloromethane-methanol (95:5 - 92:8) as eluant separated two fractions from unreacted starting material The higher Rf fraction was assigned as the 6-isomer (276mg, 42%). To a stirred solution of 2-(benzylamino)-6-(5-amino-benzimidazol-1-yl)-pyrazine (33 mg, 0.1mmol) in anhydrous THF (2 mL) under N2 was added triethylamine (38.l, 0.3 mmol). The solution was cooled at 0°C and to this was added pivalic add (12 mg, 0.11 mmol) and EDC (23 mg, 0.12 mmol) and the resulting mixture then stirred at RT. After 64h tine solution was diluted with H2O and the mixture extracted with CHCl3 (2 x 15 mL). The combined organic layers were washed with10% aqueous Na2CO3, dried (Na2SO4) and the solvent removed in vacuo. The residue was purified by column chromatography using dichloromethane-methonol (100:6) as eluant to separate the pure product (15mg). EXAMPLE 15 To a stirred solution of 2-(S-α-methylbenzylamino)-6-(5-amino-benzimidazo-1-yl)-pyrazine (66 mg, 0.2 mmol) in anhydrous THF (2 mL) under N2 was added triethylamlne (41 mg, 0.4 mmol) The solution was cooled at 0°C and to this was added acetyl chloride (17 mg, 0.22 mmol) and the resulting mixture then stirred at RT. After 18h the solution was poured into water (30 mL) and the product extracted into chloroform (2 x 20 mL). The combined organic layers were dried (Na2SO4) and the solvent removed under reduced pressure to furnish the crude product as a pale yellow solid. Column chromatography using dichloromethane-methanol (200:15) as eluant separated the product as a pale yellow solid (38 To a stirred solution of 2-(S-α-methylbenzylamino)-6-(5-amino-benzimidazo-1-yl)-pyrazine (33 mg, 0.1 mmol) in anhydrous THF (2 mL) under N2 was added triethylamine (40 mg, 0.4 mmol). The solution was cooled at 0°C and to this was added methanesulphohyl chloride (25 mg, 0.2 mmol) and the resulting mixture then stirred at RT. After 16h the solution was poured into water (30 mL) and the product extracted into chloroform (2 x 15 mL). The combined organic layers were was washed with 10% Na2CO3, dried (Na2SO4) and the solvent removed under reduced, pressure to furnish the crude product as a pale yellow solid. Column chromatography, using dichloromethane-methanol (100:6) as eluant, separated the product from the most polar fractions as a pale yellow solid (16mg). A solution of 3-[6-(S-α-methylbenzylamino)-pyrazin-2-yl]-3H-benzolmidazole-5-carboxylic acid N-mcthylpiperazinylamide (22mg, 0.05mmol) in dry THF (1mL) was added to a suspension of LiA1H4 (4mg, 0.1mmol) in THF (1mL) and the mixture heated at reflux for 4h. Upon cooling to RT, the solution was treated consecutively with H2O (1mL), aqueous NaOH (1mL, 2M) and H2O (5mL). The resulting mixture was extracted with CHCl3 (2 x 10mL) and the combined organic layers dried (Na2SO4,). The solvent was removed under reduced pressure and the product purified by flash chromatography using CH2Cl3-MeOH (10:1→ 1:1) as eluant to afford the product as a yellow solid (11mg, 52%). In a procedure analogous to Example 3, reaction of 6-chloro-N-[1-(4- fluorophenyl)ethyl]pyrazin-2-amino (1.80 g, 7.15 mmol) and 5-hydroxymethyl benzimidazole (126 g, 8.5 mmol) furnished the two products which were separated by column chromatography using dichloromethane-methanol (98:2 - 92:8) as eluant. From the less polar fractions was obtained [1-(6-[(1-(4-fluorophenyl)ethyllamino]pyrazin-2-yl)-1H- benzimidazol-6-yl]methanol as a pale yellow solid (210 mg). A solution of the alcohol (0.18 g, 03 mmol) in dichloromethane (5 mL) was cooled to 0°C and to this was added dilsopropylethylamine (0.13 mL, 0.75 mmol) and methanesulfonyl chloride (46 mL, 0.59 mmol). After stirring at RT for 2h. a further aliquot of diisopropylethylamine (30 µL) and methanesulfonyl chloride (20 UL) was added. After 1h. H2O (10 mL) was added and the organic layer collected. The aquoous phase was extracted with dichloromethanc (3x5 mL) and the organic layers combined dried (Na2SO4) and concentrated in vacuo. An aliquot of the crude mesylate thus obtained (100 mg) was dissolved in DMF (2 ml.) and to this was added diisoprypylethylamine (52 UL, 0.3 mmol) and 1-methy1piperazino (25 UL, 0.45 mmol). The solution was heated at 60ºC overnight. The solution was then concentrated in vacuo and the residue dissolved in dichloromethans (20 mL) and washed with H2O. The organic layer was dried (Na2SO4) and concentrated and the product punned by chromatography using dichloromethano-methanol-aqueous ammonia (95:5:0 - 95:5:1) to furnish the product as a pale yellow semi-solid (34 mg). To a solution of 1-thien-2-ylothanone (505 mg, 4 mmol) and ammonium formate (1.26 g, 20 mmol) in methanol (4 mL) under nitrogen was added dich1oro(pentamethylcyclopentadienyl)rhodium (III) dimer (14 mg, 0.023 mmol). The solution was heated at reflux for 7 h. after which tunc the solution was cooled to room temperature and acidified to pH ~2 with 2M HCl. The mixture was washed with dichloromethane (3 x 15 mL) and the aqueous phase then basified to pH ~12 by addition of 5M NaOH. The aqueous phase was extracted with dichloromethane (3 x 15 mL) and the combined organic layers dried (Na2SO4) and concentrated to give a pure product (280 mg, 55%). (S,R)-cis-1-amino-2-indanol (284.3 mg, 1.91 mmol, 0.1 eq) was dissolved in tetrahydrofuran (25 mL) in a dry two-necked round-bottomed flask fitted with a dropping funnel and nitrogen inlet. The solution was chilled to approximately 0ºC and N,N-diethylamline-borane complex (3.50 mL, 19.2 mmol, 1 eq) added dropwise. The mixture was allowed to stir at 0°C for 30 minutes at which time a solution of 3,4-difluoroacetophenone (2.40 mL) in tetrahydrofuran (40 mL) was added via the dropping funnel over approximately 90 minutes. The solution was allowed to slowly warm to room temperature and stirring continued overnight. Acetone (16 mL) was added to the reaction mixture and the solution allowed to stir for a further hour before being concentrated in vacuo. The residue was treated with toluene (100 mL) and washed with 1M sulphuric add (4 x 50 mL), water (2 x 50 mL) and brine (50 mL). The organic phase was then dried (Na2SO4) and concentrated in vacuo to afford the crude alcohol. Gradient flashmaster chromatography (20 g silica cartridge; 100% petroleum spirits to 100% ethyl acetate) afforded the desired alcohol as a clear oil (2.242 g, 74%). EXAMPLE 23 (1S)-1-(3,4-Difluorophenyl)ethanamine (977 mg, 6.2 mmol) and 2,6-dichloropyrazine (1.236 g, 83 mmol, 13 eq) was dissolved in dioxane (5 mL) and potassium carbonate (1.73 g, 2.0 eq) added to the solution. The mixture was then heated at reflux (110ºC under a nitrogen atmosphere for 65 hours. The crude reaction mixture was then poured onto cold water (30 mL) and extracted with diethyl ether (3 x 30 mL). The combined organic extracts were concentrated and subjected to flashmaster chromatography (20 g silica cartridge (8:2 petroluem spirits:ethyl acetate, followed by ethyl acetate flush) to afford the desired pyrazino-adduct as an off-white solid (587 mg, 35%). To a stirred mixture of 6-chloro-N-[(1S)-1-(3-fluorophenyl)ethyl]pyrazin-2-amine (242 mg, 0.% mmol) and 5-benzimidazole carboxamide (318 mg, 1.97 mmol, 2.1 eq) in N,N- dimethylformamidc (5 mL) was added cesium carbonate (460 mg, 1.41 mmol, 1.5 eq). Thus solution was then heated at 120°C under a nitrogen atmosphere for 48 hours at which time a second amount of cesium carbonate (180 mg, 0.6 eq) was added. The mixture was heated at 120ºC for a further 62 hours before being cooled to room temperature, diluted with chloroform (15 mL) and filtered. The filtrate was then concentrated in vacuo and subjected to silica column chromatography (stepwise gradient from dichloromethane to 9:1 SCREENING JAK Tyrosine Kinase Domain Production JAK kinase domains were produced in the following manner: JAK1 The kinase domain of human JAK1 was amplified from U937mRNA using the polymerase chain reaction with the following primers: JAK1 PCR products were cloned into the pFastBac HTb expression vector (Gibco) via the Xho I and Kpn I sites. The JAK1 plasmid was then transformed into competent DH10Bac cells (Gibco), and the recombinant baculovirus produced prepared for transection into Sf9 insect cells. JAK2 The kinase domain of humanJAK2 was amplified from U937mRNA using the polymerase chain reaction with the following primers: JAK2 PCR products were cloned into the pFastBac HTc expression vector (Gibco) via the Sal I and Not 1 sites. The JAK2 plasmid was then transformed into competent DHlOBac cells (Gibco), and the recombinant baculovirus produced prepared for transfection into Sf9 insect cells. dichloromethane:methanol) to yield the 5-carboxamide product (100.7 mg, 28%) along with the desired 6-carboxamide product (63.7 mg, 18%). The kinase domain of humanJAK3 was amplified from U937rnRNA using the polymerase chain reaction with the following primers: JAK3 PCR products were cloned into the pFastBac HTb expression vector (Gibco) via the Xho I and Kpn I sites. The JAK3 plasmid was then transformed into competent DH10Bac cells (Gibco)/ and the recombinant baculovirus produced prepared for transfection into Sf9 insect cells. TYK2 The kinase domain of humanTYK2 was amplified from A549 mRNA using the polymerase chain reaction with the following primers: TYK2 PCR products were cloned into pBVueBacHis2A (Invitrogen) via the EcoRI site. The recombinant TYK2 baculovirus produced was prepared for transfected into Sf9 insect cells. Large Scale Production Of Kinase Domains Baculovirus preparations from each of the JAK family members were infected into five litres of High Five cells (Invitrogen) grown in High Five serum free medium (Invitrogen) to a. cell density of approximately 1-2 X 106 cells/ml. Cells ore infected with virus at a MOI of 0.8-3.0. Cells were harvested and lysed. JAK kinase domains were purified by affinity chromatography on a Probond (Invitrogen) nickel chelate affinity column. Assay Protocols Kinase assays were performed either in a 96 well capture-based ELBA assay or In 384 well Optiplates (Packard) using an Alphascreen Protein Tyrosine Kinase kit. In either casse using approximately 15 µg of affinity purified PTK. domain in the presence of 50mM HEPES, pH 75, 10mM MgCl2, 150mM NaCl and 10µM-1mM ATP. The biotinylated substrate biotin-EGPWLEEEEEAYGWMDP-NH2 (final concentration 5µM) was used as substrate - in the ELISA assay tyrosine phosphorylation was quantitated following transfer to an avidin coated ELISA plate using peroxidasc-linked anti-phospho-tyrosine antibody PY20. In the Alphascreen assay, Alphascreen phosphotyrosine acceptor beads followed by streptavidin donor beads were added under subdued light. The ELISA plates were read on a BMG Fluorostar, the Alphascreen plates were read on a Packard Fusion Alpha. Inhibitors were added to the assays fifteen minutes prior to the addition of ATP. Inhibitors were added in aqueous DMSO, with DMSO concentrations never exceeding 1%. Results The activity of a range of compounds is shown in Table 3, Compounds that exhibited a capacity to inhibit 50% or greater of enzyme activity at a concentration of 20 µM (measured under standard conditions, see Methods), ore designated as "+", Compounds not tested are designated "NT"; while compounds that did not inhibit enzyme activity by 50% at 20 µM are designated "-". It will be appreciated by persona skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. REFERENCES 1. Kozroa SC, Redmond SM, Fu XC, Saurer SM, Groncr B, and Hynes NE. (J 98B) Activation of the receptor kinase domain of the trie oncogene by recombination with two different cellular sequences. EMBO J. 7,147-94 2. Splotto MT, and Chung TD. (2000) STAT3 mediates IL-6-induced growth inhibition in the human prostate cancer cull line LNCaP. Prostate 42,88-98 3. Wilks AF, Harpur AG, Kurbon RR, Ralph SJ, Zurcher G, Ziemiecki A. (1991) Two novel protoin-tyrosine kinases, each with a second phosphotransferose-related catalytic domain, define a new class of protein kinase. MolCell Biol. 11,2057-65 4. Wilks AF, and Kurban RR (1988) Isolation and structural analysis of murine c-fes cDNA clones. Oncogene 3,289-94 5. Sadowski I, Stone JC, Pawson T. (1986) A noncatalytic domain conserved among cytoplasmic protoin-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus Fl30gag-fps. Mol Cell Biol.6, 4396-408 wherein; D is heterocyclic ring selected from: where X1, X2, X3, X4 are optionally substituted carbon, or one of X1, X2, X3, X4 is nitrogen and the rest optionally substituted carbon; R2 is selected from the group consisting of CN; NR22R23 wherein R22 and R23 are joined to form an optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; an optionally substituted 3-8 membered (saturated or unsaturated) ring containing 2-5 nitrogen atoms; an unsubstituted or optionally substituted 5- membered heteroaromatic ring containing one or more heteroatoms selected from O, N, S; an unsubstituted or optionally substituted 6-membered heteroaromatic ring containing two or more heteroatoms selected from O, N, S; R21 is 0-2 substituents independently chosen from H, halogen. C1-4alkyl, CF3, OCF3, OCHF2, CN, aryl, hetaryl, C1-4alkylOH, C1-4alkylNR3R4, C1-4alkylhetaryl, OC1-4alkyl, OC1-4alkylNR3R4, OC1-4alkylhetaryl, OC1-4alkylOH, CO2R3, CONR3R4, NR3R4, nitro, KR3COR4, NR5CONR3R4, NR3SO2R4, C1-4alkylNR3COR4, C1-4alkylNR5CONR3R4, C1-4alkylNR3SO2R4; R3, R4 are each independently H, C1-4alkyl, C1-4alkylOH, C1-4alkylNR19R20, C1-4alkyl cycloalkyl, C3-8 cyclohetalkyl such as herein described, aryl, C1-4alkylaryl, hetaryl, C1- 4alky!hetaryl, or may be joined to form an optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; and R5 is selected from H, C1-4 alkyl, aryl or hetaryl; R6 is selected from H, C1-4alkyl, C1-4alkylNR19R20, aryl, hetaryl, C1-4alkyl aryl, C1-4alkyl hetaryl; R19, R20 are each independently selected from H, C1-4alkyl; R1 is H C1-4alkyl, C3-8cycloalkyl, or may form a 5-8 membered ring onto the ortho position of ring A; Q is a bend, CH2, C1-4alkyl; A is aryl. hetaryl optionally substituted with 0-3 substituents independently chosen from halogen, C1-4alkyl, CF3, OCF3, CN, NR8R9, aryl, hetaryl, C1-4aryl, C1-4hetaryl, C1-4alkyINR8R9, OC1-4alkylNR8R9, nitro, NR10C1-4NR8R9, NR8COR9, NR10CONR8R9, NR8SO2R9, CONR8R9, CO2R8; R8 and R9 are each independently H, C1-4alkyl, aryl or together form an optionally substituted 4-8 membered ring which may contain a heteroatom selected from O, S, NR11; Rl0 is selected from H, C1-4alkyl; R11 is selected from H, C1-4alkyl; W is selected from H, C1-4alkyl, C2-6alkenyl or may form a 5-8 membered ring onto the ortho position of ring A; where C1-4alkyl or C2-6alkenyl may be optionally substituted with C1-4alkyl, OH,OC1-4alkyl,NR12R13; M 2, and R 3 are each independently H, C1-4alkyl, or may be joined to form an optionally s lbstituted 3-8 membered ring optionally containing an atom selected from O, S, NR14: R14 is selected from H, C1-4alkyl; Y is 0-2 substituents selected from H, C1-4alkyl, NR15R16; R15 and R16 are independently selected from H, C1-4alkyl; or a cons pound selected from the group consisting of: 2. A compound of formula (I) as claimed in claim 1, wherein the compound is selected from compounds of the general formula (II): wherein: D is a heterocyclic ring selected from: where X1, X2, X3, X4 are optionally substituted carbon, or one of X1, X2, X3, X4 is N and the rest optionally substituted carbon; R2 is selected from the group consisting of CN; NR22R23 wherein R22 and R23 are joined to form an optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; an optionally substituted 3-8 membered (saturated or unsaturated) ring containing 2-5 nitrogen atoms; an unsubstituted or optionally substituted 5- membered heteroaromatic ring containing one or more heteroatoms selected from O, N, S; an unsubstitited or optionally substituted 6-membered heteroaromatic ring containing two or more heteroatoms selected from O, N, S; R21 is 0-2 substituents independently chosen from H, halogen, C1-4alkyl, CF3, OCF, OCHF2, CN, aryl, hetaryl, C1-4alkylOH, C1-4alkylNR3R4, C1-4alkylhetaryl, OC1-4alkyl, OC1-4alkyiNR3R4, OC1-4alkylhetaryl, OC1-4alkylOH, CO2R3, CONR3R4, NR3R4, nitro, NR3COR4, NR5CONR3R4, NR3SO2R4, C1-4alkylNR3COR4, C1-4alkylNR5CONR3R4, C1-4alkyNR3SO2R4; R3, R4 are each independently H, C1-4alkyl, C1-4alkylOH, C1-4alkylNR19R20, C1-4alkyl cycloalkyl, C3-8 cyclohetalkyl, aryl, C1-4alkylaryl, hetaryl, C1-4alkylhetaryl, or may be joined to form an optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; and R5 is selected from H, C1-4alkyl, aryl or hetaryl; R6 is selected from H, C1-4alkyl, C1-4alkylNR19R20, aryl, hetaryl C1-4alkyl aryl, C1-4 alkyl hetaryl; R19, R20 are each independently selected from H, C1-4alkyl; Rl is H. C1-4alkyl, C3-8cycloalkyl, or may form a 5-8 membered ring onto the ortho position of ring A; A is aryl, hetaryl optionally substituted with 0-3 substituents independently chosen from halogen. C1-4alkyl, CF3, OCF3, CN, NR8R9, aryl, hetaryl, C1-4aryl, C1-4hetaryl, C1-4alkylNR8R9, OC1-4alkylNR8R9, nitro, NR10C1-4NR8R9, NR8COR9, NR10CONR8R9, NR8SO2R9, CONR8R9, CO2R8; R8 and R9 are each independently H, C1-4alkyl, aryl or together form an optionally substituted 4-8 membered ring which may contain a heteroatom selected from O, S, NR11; R10 is selected from H, C1-4alkyl; R11 is selected from H, C1-4 alkyl; W is selected from H, C1-4alkyl, C2-6alkenyl or may form a 5-8 membered ring onto the ortho position of ring A; where C1-4alkyl or C2-6alkenyl may be optionally substituted with C1-4alkyl, OH,OC1-4alkyl,NR12R13; R12, and R13 are each independently H, C1-4alkyl, or may be joined to form an optionally substituted 3-8 membered ring optionally containing an atom selected from O, S, NR14; R14 is selected from H, C1-4alkyl: Y is 0-2 substituents selected from H, C1-4alkyl, NR15R16; R15 and R16 are independently selected from H, C1-4alkyl. 3. A compound as claimed in claim 1 or claim 2 wherein R2 is selected from the group consisting of CN, NR22R23 wherein R22 and R23 are joined to form an optionally substituted 3-8 membered (saturated or unsaturated) ring optionally containing an atom selected from O, S, NR6; an unsubstituted or optionally substituted 5-membered heteroaromatic ring containing one or more heteroatoms selected from O, N, S; an unsubstituted or optionally substituted 6- membered heteroaromatic ring containing two or more heteroatoms selected from O, N, S. 4. A compound as claimed in claim 3 wherein R2 is selected from CN and tetrazole. 5. A compound as claimed in formula (1) of claim 1 selected from the group consisting of: 6. A compound as claimed in formula (1) of claim 1 selected from the group consisting of 6 -(1H-Benzimidazol-1-yl)-N-benzylpyrazin-2-amine, 6 (1H-Benzimidazol-1-yl)-N-[(1R)-1-phenylethyl]pyrazin-2-amine, 6 (1H-Benzimidazol-l-yl)-N-[(1S)-1-phenylethyl]pyrazin-2-amine, 1-(6-{[1-(3- Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazole-5-carboxamide, 1-(6-{[1-(3- Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazole-6-carboxamide, 1-(6-{[1-(3- Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazole-6-carbonitrile, 1-[6-(3,4- Dihydroisoquinolin-2(1H)-yl)pyrazin-2-yl]-1H-benzimidazole-5-carbonitrile, 1-[6-(3,4- Dihydroisoquinolin-2(1H)-yl)pyrazm-2-yl]-1H-benzimidazole-6-carbonitrile, 1-{6-[(1S)- 1,2,3,4-Tetrahydronaphthalen-1-ylamino]pyrazin-2-yl)}-1H-benzimidazole-5-carbonitrile, 1 -[6-[(1S)-1,2,3,4-Tetrahydronaphthalen-1-ylamino]pyrazin-2-y]} -1H-benzimidazole-6- carbonirrile, 1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-amine, 1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzmidazol-6-amine, N-[1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-6-yl]-2,2- dimethyl propanamide, N-[1-(6-{[(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]acetamide, N-[1-(6-([(1S)-1-Phenylethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl] ethanesulfonamide, 2-(S-α-Methylbenzylamino)-6-(5-(N-methylpiperazin-4-yl-methyl)-benziraidazo-1-yl)-yrazine, [1-(6-{[1-(4-Fluorophenyl)ethyl]amino}pyrazin-2-yl)-1H-benzimidazol-5-yl]methanol, [1-(6- [1 -(4-Fluorophenyl)ethyl]amino} pyrazin-2-yl)-1H-benzinidazol-6-yl]methano1 and N-[1-(4- Fluorophenyl)ethyl]-6-{6-[(4-methylpiperazin-1-yl)methyl]-1H-benzinuidazol-1-yl} pyrazin-2- amine. 7. The compound: 8. The compound: 9. A composition comprising a carrier and at least one compound according to any one of claims 1 to 8. 10. The composition as claimed in claim 9, wherein said composition is useful for treating tyrosine kinase-associated disease state. 11. The composition as claimed in claim 10, wherein the disease state involves JAK1, JAK2, JAK3 or TYK2. 12. The composition as claimed in claim 10 or 11 wherein the disease state is selected from the group consisting of Atopy, Cell Mediated Hypersensitivity, Rheumatic Diseases, Other autoimmune diseases, Viral Diseases, Cancer, Neurodegenerative Diseases, and Cardiovascular Diseases. 13. The composition as claimed in claim 9, wherein the said composition is useful for treating diseases and conditions associated with inflammation and infection. The invention discloses a compound of the general Formula (I): wherein A, W, R1, D & Y are as defined in the specification. The invention is also for the composition, comprising the said compound.

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