Title of Invention

"A BICYCLIC OXOPYRIDINE COMPOUND"

Abstract

Compounds of formulae (1 a) and (Ib) are described: in which the dashed line represents an optional bond; A is a N aitom or a N(Rb) . -C(R'') or -C(Rh)(R( ) group; R". Rh and Rc is each independently a hydrogen atom or an optionally substituted C 'alky I group. X is an 0- 01 S atom or -NH- group or substituted N atom; each Y is independently a N atom or CM group or substituted C atom: n is /.ero or the integer 1, Alk1 is an optionally substituted aliphatic or heteroaliphatic chain L1 is a covalent bond or ,i linker atom or group: Cy1 is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocy-i loaliphatic, polyht-Merocycloiiliphalic. aromatic or hclenwroraalic group; Ar is an-optionally substituted aromatic or heteroarornatic I'toiip; and the sails, solvalcs. liydnites and N oxides ihereol'; The compounds arc potent inhibitors of p38 kinasc and are use in the prnphylaxis or treatment of p38 kinasc mediated diseases or disorders, such as rheumatoid arthritis.

Full Text

BICYCLIC OXOPYRIDINE AND OXOPYRIMIDINE DERIVATIVES This invention relates to a series of 5-6 fused ring bicyclic heteroaromatic derivatives, to compositions containing them, to processes for their preparation and to their use in medicine. Immune and inflammatory responses involve a variety of cell types with control and co-ordination of the various interactions occurring via both cell-cell contacts (e.g integrin interactions with their receptors) and by way of intercellular signalling molecules. A large number of different signalling molecules are involved including cytokines, lymphocytes, chemokines and growth factors. Cells respond to such intercellular signalling molecules by means of intracellular signalling mechanisms that include protein kinases, phosphatases and phospholipases. There are five classes of protein kinase of which the major ones are the tyrosine kinases and the serine/threonine kinases [Hunter, T., Methods in Enzymology (Protein Kinase Classification) p. 3, Hunter, T. and Sefton, B.M.; eds. Vol. 200, Academic Press; San Diego, 1991], One sub-class of serine/threonine kinases is the mitogen activating protein (MAP) kinases of which there are at least three families which differ in the sequence and size of the activation loop [Adams, J. L et al, Progress in Medicinal Chemistry p. 1-60, King, F. D. and Oxford, A. W.; eds. vol 38, Elsevier Science, 2001]: the extracellular regulated kinases (ERKs), the c-Jun NH2 terminal kinases or stress activated kinases (JNKs or SAP kinases) and the p38 kinases which have a threonine-glycine-tyrosine (TGY) activation motif. Both the JNKs and p38 MAP kinases are primarily activated by stress stimuli including, but not limited to, proinflammatory cytokines e.g. tumour necrosis factor (TNF) and interleukin-1 (IL-1), ultraviolet light, endotoxin and chemical or osmotic shock, Four isoforms of p38 have been described (p38o/P/Y/6). The human p38a enzyme was initially identified as a target of cytokine-suppressive anti-inflammatory drugs (CSAIDs) and the two isoenzymes found were initially termed CSAID binding protein-1 (CSBP-1) and CSBP-2 [Lee, J. C. et al, Nature (London) 1994, 372. 739-46], CSBP-2 is. now widely referred to as p38a and differs from CSBP-1 in an internal sequence of 25 amino acids as a result of differential splicing of two exons that are conserved in both mouse and human [McDonnell, P. C. et al, Genomics 1995, 29, 301-2]. CSBP-1 and p38cx are expressed ubiquitously and there is no difference between the two isoforms with respect to tissue distribution, activation profile, substrate preference or CSAID binding. A second isoform is p38p which has 70% identity with p38cc. A second form of p38p termed p38|J2 is also known and of the two this is believed to be the major form. p38a and p38(32 are expressed in many different tissues. However in monocytes and macrophages p38oc is the predominant kinase activity [Lee, J. C., ibid; Jing, Y. et al, J. Biol. Chem. 1996, 271, 10531-34; Hale, K. K. et al, J. Immun. 1999, 162. 4246-52]. p38y and p388 (also termed SAP kinase-3 and SAP kinase-4 respectively) have 63% and -61% homology to p38a respectively. p38y is predominantly expressed in skeletal muscle whilst p388 is found in testes, pancreas, prostate, small intestine and in certain endocrine tissues. All p38 homologues and splice variants contain a 12 amino acid activation loop that includes a Thr-Gly-Tyr motif. Dual phosphorylation of both Thr-180 and Tyr-182 in the TGY motif by a dual specificity upstream kinase is essential for the activation of p38 and results in a >1000-fold increase in specific activity of these enzymes [Doza, Y. N. et al FEBS Lett., 1995, 364, 7095-8012]. This dual phosphorylation is effected by MKK6 and under certain conditions the related enzyme MKK3 (see Figure 1) [Enslen, H. et al J. Biol. Chem., 1998, 273, 1741-48]. MKK3 and MKK6 belong to a family of enzymes termed MAPKK (mitogen activating protein kinase kinase) which are in turn activated by MAPKKK (mitogen activating kinase kinase kinase) otherwise known as MAP3K, Several MAPSKs have been identified that are activated by a wide variety of stimuli including environmental stress, inflammatory cytokines and other factors. MEKK4/MTK1 (MAP or ERK kinase kinase/MAP three kinase-1), ASK1 (apoptosis stimulated kinase) and TAK1 (TGF-p-activated kinase) are some of the enzymes identified as upstream activators of for MAPKKs. MEKK4/MTK1 is thought to be activated by several GADD-45-like genes that are induced in response to environmental stimuli and which eventually lead to p38 activation [Takekawa, M. and Saito, H. Cell, 1998, 95, 521-30]. TAK1 i ias been shown to activate MKK6 in response to transforming growth factor-(•$ (TGF-fi). TNF-stimulated activation of p38 is believed to be mediated by the recruitment of TRAF2 [TNF receptor associated factor] and the Fas adaptor protein, Daxx, which results in the activation of ASK1 and subsequently p38. Several substrates of p38 have been identified including other kinases [e.g. MAPK activated protein kinase 2/3/5 (MAPKAP 2/3/5), p38 regulated/activated protein kinase (PRAK), MAP kinase-interacting kinase 1/2 (MNK1/2), mitogen- and stress-activated protein kinase 1 (MSK1/RLPK) and ribosomal S6 kinase-B (RSK-B)], transcription factors [e.g. activating transcription factor 2/6 (ATF2/6), monocyte-enhancer factor-2A/C (MEF2A/C), C/EBP homologous protein (CHOP), Elk1 and Sap-1a1] and others substrates [e.g. cPLA2, p47phox]. MAPKAP K2 is activated by p38 in response to environmental stress. Mice engineered to lack MAPKAP K2 do not produce TNF in response to lipopolysaccharide (LPS). Production of several other cytokines such as IL-1, IL-6, IFN-g and IL-10 is also partially inhibited [Kotlyarov, A. et al Nature Cell Biol. 1999, 1, 94-7]. Further, MAPKAP K2 from embryonic stem cells from p38a null mice was not activated in response to stress and these cells did not produce IL-6 in response to IL-1 [Allen, M. et al, J. Exp. Med. 2000, 191. 859-69], These results indicate that MAPKAP K2 is not only essential for TNF and IL-1 production but also for signalling induced by cytokines. In addition MAPKAP K2/3 phosphorylate and thus regulate heat shock proteins HSP 25 and HSP 27 which are involved in cytoskeletal reorganization. Several small molecule inhibitors of p38 have been reported which inhibit IL-1 and TNF synthesis in human monocytes at concentrations in the low \M range [Lee, J. C. et al, Int. J. Immunopharm. 1988, 10, 835] and exhibit activity in animal models which are refractory to cyclooxygenase inhibitors [Lee, J. C. et ai, Annals N. Y. Acad. Sci. 1993, 696. 149]. In addition these small molecule inhibitors are known to also decrease the synthesis of a wide variety of pro-inflammatory proteins including IL-6, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF) and cyclooxygenase-2 (COX-2). TNF-induced phosphorylation and activation of cytosolic PLA2, TNF-induced expression of VCAM-1 on endothelial cells and IL-1 stimulated synthesis of collagenase and stromelysin are also inhibited by such small molecule inhibitors of p38 [Cohen, P. Trends Cell Biol. 1997, 7, 353-61]. A variety of cells including monocytes and macrophages produce TNF and IL-1. Excessive or unregulated TNF production is implicated in a number of disease states including Crohn's disease, ulcerative colitis, pyresis, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions, toxic shock syndrome, endotoxic shock, sepsis, septic shock, gram negative sepsis, bone resporption diseases, reperfusion injury, graft vs. host reaction, allograft rejection, adult respiratory distress syndrome, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcoisosis, cerebral malaria, scar tissue formation, keloid formation, fever and myalgias due to infection, such as influenza, cachexia secondary to acquired immune deficiency syndrome (AIDS), cachexia secondary to infection or malignancy, AIDS or AIDS related complex. Excessive or unregulated IL-1 production has been implicated in rheumatoid arthritis, osteoarthritis, traumatic arthritis, rubella arthritis, acute synovitis, psoriatic arthritis, cachexia, Reiter's syndrome, endotoxemia, toxic shock syndrome, tuberculosis, atherosclerosis, muscle degeneration, and other acute or chronic inflammatory diseases such as-the inflammatory reaction induced by endotoxin or inflammatory bowel disease. In addition IL-1 has been linked to diabetes and pancreatic |3 cells [Dinarello, C. A. J. Clinical Immunology, 1985, 5, 287-97]. IL~8 is a chemotactic factor produced by various cell types including endothelial cells, mononuclear cells, fibroblasts and keratinocytes. IL-1, TNF and LPS all induce the production of IL-8 by endothelial cells. In vitro IL-8 has been shown to have a number of functions including being a chemoattractant ior neutrophils, T-lymphocytes and basophils. IL-8 has also been shown to increase the surface expression of Mac-1 (CD11b/CD18) on neutrophils without de novo protein synthesis which may contribute to increased adhesion of neutrophils to vascular endothelial cells. Many diseases are characterised by massive neutrophil infiltration. Histamine release from basophils (in both atopic and normal individuals) is induced by IL-8 as is lysozomal enzyme release and respiratory burst from neutrophils. The central role of IL-1 and TNF together with other leukocyte derived cytokines as important and critical inflammatory mediators is well documented. The inhibition of these cytokines has been shown or would be expected to be of benefit in controlling, alleviating or reducing many of these disease states. The central position that p38 occupies within the cascade of signalling molecules mediating extracellular to intracellular signalling and its influence over not only IL-1, TNF and IL-8 production but also the synthesis and/or action of other pro-inflammatory proteins (e.g. IL-6, GM-CSF, COX-2, collagenase and stromelysin) make it an attractive target for inhibition by small molecule inhibitors with the expectation that such inhibition would be a highly effective mechanism for regulating the excessive and destructive activation of the immune system. Such an expectation is supported by the potent and diverse anti-inflammatory activities described for p38 kinase inhibitors [Adarns, ibid; Badger, et al, J. Pharm. Exp. Ther. 1996, 279. 1453-61; Griswold, etal, Pharmacol. Comm., 1996, 7, 323-29]. Japanese patent application No. JP09059276 describes a series of pyrazalopyridinones and analogs with utility as herbicides. We have now found a group of compounds which are potent and selective inhibitors of p38 kinase (p38a, p, 6 arid y)and the isoforms and splice variants thereof, especially p38a, p38p and p38|32. The compounds are thus of use in medicine, for example in the prophylaxis and treatment of immune or inflammatory disorders as described herein. Thus according to one aspect of the invention we provide a compound of formula (1 a) or (1b): (Figure Remove) wherein: the dashed line represents an optional bond; A is a -N= atom or a -N(Rb)-, -C(Rb)= or -C(Rb)(R°)- group; Ra, Rh and R': is each independently a hydrogen atom or an optionally substituted d.6alkyl group; X is an -O- or -S- atom or -NH- group or substituted N atom; each Y is independently a N atom or CH group or substituted C atom; n is zero or the integer 1 ; Alk1 is an optionally substituted aliphatic or heteroaliphatic chain L1 is a covalent bond or a linker atom or group; Cy1 is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycioaliphatic, aromatic or heteroaromatic group; Ar is an optionally substituted aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof; for the manufacture of a medicament for the prophylaxis or treatment of a p38 kinase mediated disease or disorder. This invention also relates to a compound of formula (1a) or (1b) for use in the prophylaxis or treatment of a p38 kinase mediated disease or disorder in a mammal in need thereof. This invention also relates to a compound of formula (1a) or (1b) for use in the prophylaxis or treatment of a cytokine mediated disease or disorder in a mammal in need thereof. This invention more specifically relates to a method of inhibiting the production of IL-1 in a mammal in need thereof. This invention more specifically relates to a method of inhibiting the production of IL-6 in a mammal in need thereof. This invention more specifically relates to a method of inhibiting the production of IL-8 in a mammal in need thereof. This invention more specifically relates to a method of inhibiting the production of TNF in a mammal in need thereof. This invention more specifically relates to the administration to a mammal of an effective amount of a p38 kinase or cytokine, specifically IL-1, IL-6, IL-8 or INF, inhibitor of formula (1 a) or (1 b). Compounds according to the invention are potent and selective inhibitors of p38 kinases, including all isoforms and splice variants thereof. More specifically the compounds of the invention are inhibitors of p38ce, p38p and p38(i2. The ability of the compounds to act in this way may be simply determined by employing tests such as those described in the Examples hereinafter. The compounds of formula (1) are of use in modulating the activity of p38 kinases and in particular are of use in the prophylaxis and treatment of any p38 kinase mediated diseases or disorders in a human, or other mammal. The invention extends to such a use and to the use of the compounds for the manufacture of a medicament for treating such diseases or disorders. Further the invention extends to the administration to a human an effective amount of •,; a p38 inhibitor for treating any such disease or disorder. The invention also extends to the prophylaxis or treatment of any disease or disorder in which p38 kinase plays a role including conditions caused by excessive or unregulated pro-inflammatory cytokine production including for example excessive or unregulated TNF, IL-1, IL-6 and IL-8 production in a human, or other mammal. The invention extends to such a use and to the use of the compounds for the manufacture of a medicament for treating such cytokine-mediated diseases or disorders. Further the invention extends to the administration to a human an effective amount of a p38 inhibitor for treating any such disease or disorder. Diseases or disorders in which p38 kinase plays a role either directly or via pro-inflammatory cytokines including the cytokines TNF, IL-1, IL-6 and IL-8 include without limitation autoimmune diseases, inflammatory diseases, destructive-bone disorders, proliferative disorders, neurodegenerative disorders, viral diseases, allergies, infectious diseases, heart attacks, angiogenic disorders, reperfusion/ischemia in stroke, vascular hyperplasia, organ hypoxia, cardiac hypertrophy, thrombin-induced platelet aggregation and conditions associated with prostaglandin endoperoxidase synthetase-2 (COX-2). Autoimmune diseases which may be prevented or treated include but are not limited to rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, multiple sclerosis, diabetes, glomerulonephritis, systemic lupus erythematosus, scleroderma, chronic thyroiditis, Grave's disease, s hemolytic anemia, autoimmune gastritis, autoimmune neutropenia, thrombocytopenia, chronic active hepatitis, myasthenia gravis, atopic dermatitis, graft vs, host disease or psoriasis. The invention further extends to the particular autoimmune disease rheumatoid arthritis. Inflammatory diseases which may be prevented or treated include but are not limited to asthma, allergies, respiratory distress syndrome or acute or chronic pancreatitis. Destructive bone disorders which may be prevented or treated include but are not limited to osteoporosis, osteoarthritis and multiple myeloma-related bone disorder. Proliferative diseases which may be prevented or treated include but are not limited to acute or chronic myelogenous leukemia, Kaposi's sarcoma, metastic melanoma and multiple myeloma, Neurodegenerative diseases which may be prevented or treated include but are not limited to Parkinson's disease, Alzheimer's disease, cerebral ischemias or neurodegenerative disease caused by traumatic injury. Viral diseases which may be prevented or treated include but are not limited to acute hepatitis infection (including hepatitis A, hepatitis B and hepatitis C), HIV infection and CMV retinitis. infectious diseases which may be prevented or treated include but are not limited to septic shock, sepsis and Shigellosis, In addition, p38 inhibitors of this invention also exhibit inhibition of expression ot inducible pro-inflammatory proteins such as prostaglandin endoperoxidase synthetase-2, otherwise known as cyclooxygenase-2 (COX-2) and are therefore of use in therapy. Pro-inflammatory mediators of the oyclooxygenase pathway derived from arachidonic acid are produced by inducible COX-2 enzyme. Regulation of COX-2 would regulate these pro-inflammatory mediators such as prostaglandins, which affect a wide variety of cells and are important and critical inflammatory mediators of a wide variety of disease states and conditions. In particular these inflammatory mediators have been implicated in pain, such as in the serisitization of pain receptors, or edema. Accordingly additional p38 mediated conditions which may be prevented or treated include edema, analgesia, fever and pain such as neuromuscular pain, headache, dental pain, arthritis pain and pain caused by cancer. As a result of their p38 inhibitory activity, compounds of the invention have utility in the prevention and treatment of diseases associated with cytokine production including but not limited to those diseases associated with TNF, IL-1, IL-6 and IL-8 production. Thus TNF mediated diseases or conditions include for example rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions, sepsis, septic shock syndrome, adult respiratory distress syndrome, cerebral malaria, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcoiosis, bone resportion disease, reperfusion injury, graft vs. host reaction, allograft rejections, fever and myalgias due to infection, cachexia secondary to infection, AIDS, ARC or malignancy, keloid formation, scar tissue formation, Crohn's disease, ulcerative colitis, pyresis, viral infections such as HIV, CMV, influenza and herpes; and vetinary viral infections, such as lentivirus infections, including but not limited to equine infectious anemia virus, caprine arthritis virus, visna virus or maedi virus; or retrovirus infections, including feline immunodeficiency virus, bovine immunodeficiency virus or canine immunodeficiency virus. Compounds of the invention may also be used in the treatment of viral infections, where such viruses elicit TNF production in vivo or are sensitive to upregulation by TNF. Such viruses include those that produce TNF as a result of infection and those that are sensitive to inhibition, for instance as a result of decreased replication, directly or indirectly by the TNF inhibiting compounds of the invention. Such viruses include, but are not limited to, HIV-1, HIV-2 and HIV-3, Cytomegalovirus (CMV), Influenza, adenovirus and the Herpes group of viruses such as Herpes Zoster and Herpes Simplex. IL-1 mediated diseases or conditions include for example rheumatoid arthritis, osteoarthritis, psoriatic arthritis, traumatic arthritis, rubella arthritis, inflammatory bowel disease, stroke, endotoxemia and/or toxic shock syndrome, inflammatory reaction induced by endotoxin, diabetes, pancreatic \\-ce\\ disease, Alzheimer's disease, tuberculosis, atherosclerosis, muscle ciegeneration and cachexia. IL-8 mediated diseases and conditions include for example those characterized by massive neutrophil infiltration such as psoriasis, inflammatory bowel disease, asthma, cardiac, brain and renal reperfusion injury, adult respiratory distress syndrome, thrombosis and glomerulonephritis. The increased IL-8 production associated with each of these diseases is responsible for the chemotaxis of neutrophils into inflammatory sites. This is due to the unique property of IL-8 (in comparison to TNF, IL-1 and IL-6) of promoting neutrophil chemotaxis and activation. Therefore, inhibition of IL-8 production would lead to a direct reduction in neutrophil infiltration. It is also known that both IL-6 and IL-8 are produced during rhinovirus (HRV) infections and contribute to the pathogenesis of the common cold and exacerbation of asthma associated with HRV infection [Turner et al, Clin. Infec. Dis., 1997, 26, 840; Grunberg et al, Am. J. Grit. Care Med. 1997, 155. 1362; Zhu etal, J. Clin. Invest. 1996, 97, 421]. It has also been demonstrated in vitro that infection of pulmonary epithelial cells (which represent the primary site of infection by HRV) with HRV results in production of IL-6 and IL-8 [Sabauste ef al, J. Clin. Invest. 1995, 96, 549]. Therefore, p38 inhibitors ot the invention may be used for the treatment or prophylaxis of the common cold or respiratory viral infection caused by human rhinovirus infection (HRV), other enteroviruses, coronavirus, influenza virus, parainfluenza virus, respiratory syncytial virus or adenovirus infection. For the prophylaxis or treatment of a p38 or pro-inflammatory cytokine mediated disease the compounds according to the invention may be administered to a human or mammal as pharmaceutical compositions, and according to a further aspect of the invention we provide a pharmaceutical composition which comprises a compound of formula (1a) or (1b) together with one or more pharmaceutically acceptable carriers, excipients or diluents. Pharmaceutical compositions according to the invention may take a form suitable for oral, buccal, parenteral, nasal, topical, ophthalmic or rectal administration, or a form suitable for administration by inhalation or insufflation. For oral administration, the pharmaceutical compositions may take the form of, for example, tablets, lozenges or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g. pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g. lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g. magnesium stearate, talc or silica); disintegrants (e.g. potato starch or sodium glycollate); or wetting agents (e.g. sodium lauryl sulphate). The tablets may be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents, emulsifying agents, non-aqueous vehicles and preservatives. The preparations may also contain buffer salts, flavouring, colouring and sweetening agents as appropriate. Preparations for oral administration may be suitably formulated to give controlled release of the active compound. For buccal administration the compositions may take the form of tablets or lozenges formulated in conventional manner. The compounds of formula (1a) or (1b) may be formulated for parenteral administration by injection e.g. by bolus injection or infusion. Formulations for injection may be presented in unit dosage form, e.g. in glass ampoule or multi dose containers, e.g. glass vials. The compositions for injection may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilising, preserving and/or dispersing agents. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g. sterile pyrogen-free water, before use. in addition to the formulations described above, the compounds of formula (1a) or (1b) may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation or by intramuscular injection. For nasal administration or administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation for pressurised packs or a nebuliser, with the use of suitable propellant, e.g. dichlorodifluoromethane, trichloro-fluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas or mixture of gases. The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack or dispensing device may be accompanied by instructions for administration. For topical administration the compounds for use according to the present invention may be conveniently formulated in a suitable ointment containing the active component suspended or dissolved in one or more pharmaceutically acceptable carriers. Particular carriers include, for example, mineral oil, liquid petroleum, propylene glycol, polyoxyethylene, polyoxypropylene, emulsifying wax and water. Alternatively the compounds for use according to the present invention may be formulated in a suitable lotion containing the active component suspended or dissolved in one or more pharmaceutically acceptable carriers. Particular carriers include, for example mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, oetearyl alcohol, benzyl alcohol, 2-octyldodecanol and water. For ophthalmic administration the compounds for use according to the present invention may be conveniently formulated as microionized suspensions in isotonic, pH adjusted sterile saline, either with or without a preservative such as bactericidal or fungicidal agent, for example phenylmercuric nitrate, benzylalkonium chloride or chlorhexidine acetate. Alternatively for ophthalmic administration compounds may be formulated in an ointment such as petrolatum. For rectal administration the compounds for use according to the present invention may be conveniently formulated as suppositories. These can be prepared by mixing the active component with a suitable non-irritating excipient which is solid at room temperature but liquid at rectal temperature and so will melt in the rectum to release the active component. Such materials include for example cocoa butter, beeswax and polyethylene glycols. The quantity of a compound of the invention required for the prophylaxis or treatment of a particular condition will vary depending on the compound chosen, and the condition of the patient to be treated. In general, however, daily dosages may range from around lOOng/kg to 100mg/kg e.g. around 0.01rng/kg to 40mg/kg body weight for oral or buccal administration, from around 10ng/kg to SOmg/kg body weight for parenteral administration and around O.OSmg to around "lOOOmg e.g. around O.Smg to around 1000mg for nasal administration or administration by inhalation or insufflation. Particular compounds of formula (1a) and formula (1b) form a further aspect of the invention. Thus we provide a compound of formula (1a): (Figure Remove) wherein: the dashed line represents an optional bond; A is a -N= atom or a -N(Rb)-, -C(Rb)= or -C(Rb)(Rc)- group; Ra, Rb and Rc is each independently a hydrogen atom or an optionally substituted Ci.6alkyl group; X is an -O- or-S- atom or-NH- group or substituted N atom; Y is a N atom or CH group or substituted C atom; n is zero or the integer 1; Alk' is an optionally substituted aliphatic or heteroaliphatic chain L.' is a covalent bond or a linker atom or group; Cy' is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroarornatic group; Ar is an optionally substituted aromatic or heteroarornatic group; and the salts, solvates, hydrates and N-oxides thereof; Particular compounds of formula (1a) in which Cy1 is an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroarornatic group form a further aspect of the invention. In another particular aspect of the invention and we provide a compound of formula (1b): (Figure Remove) wherein: the dashed line represents an optional bond; A is a -N= atom or a -N(Rb)-, -C(Rb)= or -C(Rb)(R°)- group; Ra, Rb and R° is each independently a hydrogen atom or an optionally substituted C-i-ealkyl group; each Y is independently a N atom or CH group or substituted C atom; n is zero or the integer 1; Alk1 is an optionally substituted aliphatic or heteroaliphatic chain L1 is a covalent bond or a linker atom or group; Cy1 is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group; Ar is an optionally substituted aromatic or heteroacomatic group; and the salts, solvates, hydrates and N-oxides thereof; with the proviso that when the compound of formula (1b) is a compound of formula (1c): (Figure Remove) in which each Y is a N atom or a CH group, Ar is a 2,6-dichloro-4- trifluoromethylphenyl or 2-chloro-6-fluoro-4-trifluoromethylphenyl group, L1 is a covalent bond, n is the integer 1 and Alk1 is a ~CH2-, -CH2CH2-, - CH2CH2CH2-, -CH(CH3)CH2-, -CH2CH=CH-, -CH2CH=CCI-, -CH2CC- or - CF2- chain then Cy1 is other than a hydrogen atom; or in which each Y is a N atom or a CH group, Ar is a 3-chloro-5-trifluoromethylpyridin-2- yl group, L1 is a covalent bond, n is the integer 1 and Alk1 is a -CH2-, - CH;>CH2- or -CH2CH2CH2- chain then Cy1 is other than a hydrogen atom; or in which each Y is a N atom or a CH group, Ar is a 2,6-dichloro-4- irifluoromethylphenyl or 2-chloro-6-fluoro-4-trifluoromethylphenyl group, L1 is n covalent bond and n is zero then Cy1 is other than a cyclopropyl group; or in which each Y is a N atom or a CH group, Ar is a 2,6-dichloro-4- trifluoromethylphenyl, 2-chloro-6-fluoro-4-trifluoromethylphenyl or 3-chloro-5- trifluoromethylpyridin-2-yl group, L1 is a covalent bond and n is zero then Cy1 is other than a hydrogen atom; and with the further proviso that when the compound of formula (1b) is a compound of formula (1d): (Figure Remove) in which: L1 is a covalent bond, n is the integer 1 and Alk1 is a -CH2- chain then Ar is other than a 3-methyl-5-trifluoromethylpyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 3-trifluoromethylpyridin-2-yl, 3,5-difluoropyridin-2-yl, 3,5-dichloropyridin-2-yl or 2-chloro-4-trifiuoromethylphenyl group. Particular compounds of formula (1b) form a further aspect of the invention and we therefore provide a compound of formula and (1 b'): (Figure Remove) wherein: the dashed line represents an optional bond; A is a -N= atom or a -N(Rb)-, -C(Rb)= or -C(Rb)(Rc)- group; Rd, Rb and R° is each independently a hydrogen atom or an optionally substituted Ci-6alkyl group; each Y is independently a N atom or CH group or substituted C atom; n is zero or the integer 1; Alk1 is an optionally substituted aliphatic or heteroaliphatic chain I.' is a covalent bond or a linker atom or group; Cy1 an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group; Ar is an optionally substituted aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof; with the proviso that when the compound of formula (1 b") is a compound of formula (1c): (Figure Remove) in which each Y is a N atom or a CH group, Ar is a 2,6-dichloro-4-trifluoromethylphenyl or 2-chloro-6-fluoro-4-trifluoromethylphenyl group, L1 is a covalent bond and n is zero then Cy1 is other than a cyclopropyl group. It will be appreciated that in the following detailed description of the invention all references to formula (1b) are also references to formulae (1b') unless specifically stated otherwise. II will be further appreciated that compounds of formulae (1a) and (1b) may have one or more chiral centres, and exist as enantiomers or diastereomers. The invention is to be understood to extend to all such enantiomers, (iiastereomers and mixtures thereof, including racemates. Formulae (1a) and (I b) and the formulae hereinafter are intended to represent all individual isomers and mixtures thereof, unless stated or shown otherwise. In addition, compounds of formulae (1a) and (1b) may exist as tautomers, for example keto (CH2C=O)-enol (CH=CHOH) tautomers. Formulae (1a) and (1b) and the formulae hereinafter are intended to represent all individual tautomers and mixtures thereof, unless stated otherwise. The following general terms as used herein have the stated meaning unless specifically described otherwise. As used herein the term "alky!" whether present as a group or part of a group includes straight or branched CvealkyI groups, for example Ci-4alkyl groups uuch as methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl or t-butyl groups. Similarly, the terms "alkenyl" or "alkynyl" are intended to mean straight or branched C2-6alkenyl or Cs-eaikynyl groups such as Ca^alkenyl or C2.4alkynyl groups. Optional substituents which may be present on these groups include those optional substituents mentioned hereinafter in relation to Alk' when Alk1 is an optionally substituted aliphatic chain. The term halogen is intended to include fluorine, chlorine, bromine or iodine atoms. The term "haloalkyl" is intended to include those alkyl groups just mentioned sustituted by one, two or three of the halogen atoms just described. Particular examples of such groups include -CF3, -CCI3, -CHF2, -CHCI2, -CH2F and -CH2CI groups. The term "alkoxy" as used herein is intended to include straight or branched C-|.6alkoxy e.g. C^alkoxy such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, i-butoxy and t-butoxy. "Haloalkoxy" as used herein includes any of these alkoxy groups substituted by one, two or three halogen atoms as described above. Particular examples include -OCF3( -OCCta, -OCHF2, -OCHCI2, -OCH?F and -OCH2CI groups. As used herein the term "alkylthio" is intended to include straight or branched Cvealkylthio, e.g. Ci.4alkylthio such as methylthio orethylthio. As used herein the term "alkylamino or dialkylamino" is intended to include the groups -NHR1 and -N(R1)2 [where R1 is an optionally substituted straight or branched alkyl group]. Where two R1 groups are present these may be the same or different. In addition where two R1 groups are present these may be joined together with the N atom to which they are attached to form an optionally substituted heterocycloalkyl group which may contain a further heteroatom or heteroatom containing group such as an -O- or -S- atom or -N(R')- group. Particular examples of such optionally substituted heterocycloalkyl groups include optionally substituted pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl and N'-Ci-6alkyl-piperazinyl groups. The optional ,'iubstituents which may be present on such heterocycloalkyl groups include those optional substituents as described hereinafter in relation to aliphatic chains. When Alk1 is present in compounds of formulae (1a) and (1b) as an optionally substituted aliphatic chain it may be an optionally substituted Ci-i0aliphatic chain. Particular examples include optionally substituted straight or branched chain d.6alkylene, C2.6alkenylene, or C2.6alkynylene chains. Particular examples of aliphatic chains represented by Alk1 include optionally substituted -CH2-, -CH2CH2-, -CH(CH3)CH2-, -(CH2)2CH2-, -(CH2)3CH2-, -CH(CH3)(CH2)2CH2-, -CH2CH(CH3)CH2-, -C(CH3)2CH2-, -CH2C(CH3)2CH2-, -(CHR)2CH(CH3)CH2-, -CH(CH3)CH2CH2-, -CH(CH3)CH2CH(CH3)CH2-, -CH^H(CH3)CH2CH2-, -(CH2)2C(CH3)2CH2-, -(eH2)4CH2-, -(CH2)5CH2-, -CHCH-, -CHCHCH2-, -CH2CHCH-, -CHCHCH2CH2-, -CH2CHCHCH2-, -(CH2)aCHCH-, -CC-, -CCCH2-, -CH2CC-, -CCCH2CH2-, -CH2CCCH2- or -(CH2)2CCH- chains. Heteroaliphatic chains represented by Alk1 in the compounds of formulae (1a) and (1b) include the aliphatic chains just described but with each additionally containing one, two, three or four heteroatoms or heteroatom-containing groups. Particular heteroatoms or groups include atoms or groups L2 where L2 is a linker atom or group. Each L2 atom or group may interrupt the aliphatic group, or may be positioned at its terminal carbon atom to connect the group to an adjoining atom or group. Particular examples include optionally substituted -L2CH2-, -CH2L2-, -L2CH(CH3)-, -CH(CH3)L2-, -CH2L2CH2-, -L2CH2CH2-, -L2CH2CH(CH3)-, -CH(CH3)CH2L2"> -CH2CH2L2-, -CH2L2CH2CH2-, -CH2L2CH2CH2L2-, -(CH2)2L2CH2-, -(CH2)3L2CH2-, -L2(CH2)2CH2-, -L2CH2CHCH-, -CHCHCH2L2- and -(CH2)2L2CH2CH2- chains. When L2 is present in heteroaliphatic chains as a linker atom or group it may he any divalent linking atom or group. Particular examples include -O- or -S-atoms or -C(O)-, -C(O)O-, -OC(O)-, -C(S)-, -S(O)-, -S(O)2-, -N(R2)- [where R2 is a hydrogen atom or a straight or branched alky] group], -N(R2)O-, -N(R2)N-, -CON(R2)-, -OC(O)N(R2)-, -CSN(R2)-, -N(R2)CO-, -N(R2)C(O)O-, -N(R2)CS-, -S(0)2N(R2K -N(R2)S(O)2-, -N(R2)CON(R2)-, -N(R2)CSN(R2)- or -N(R2)SO?N(R2)- groups. Where L2 contains two R2 groups these may be the same or different. The optional substituents which may be present on aliphatic or heteroaliphatic chains represented by Alk1 include one, two, three or more substituents where each substituent may be the same or different and is selected from halogen atoms, e.g. fluorine, chlorine, bromine or iodine atoms, or -OH, -CO2H, -CO2R4 [where R4 is an optionally substituted straight or branched Ci-ealkyI group], e.g. -CO2CH3 or ~C02C(CH3)3, -CONHR4, e.g. -CONHCH3, -CON(R4)2) e.g. -CON(CH3)2, -COR4, e.g. -COCH3, Ci-6alkoxy, e.g. methoxy or ethoxy, haloCi. (;alkoxy, e.g. trifluoromethoxy or difluoromethoxy, thiol (-SH), -S(O)R4, e.g. - S(O)CH3, -S(O)2R4, e.g. -S(0)2CH3) C^alkylthio e.g. methylthio or ethylthio, amino, -NHR4, e.g. -NHCH3 or -N(R4)2, e.g. -N(CH3)2 groups. Where two R4 groups are present in any of the above substituents these may be the same or different. In addition when two R4 alkyl groups are present in any of the optional substituents just described these groups may be joined, together with the N atom to which they are attached, to form a heterocyclic ring. Such heterocyclic rings may be optionally interrupted by a further heteroatom or heteroatom containing group selected from -O-, -S-, -N(R4)-, -C(O)- or -C(S)- groups. Particular examples of such heterocyclic rings include piperidinyl, pyrazolidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, imidazolidinyl and piperazinyl rings. When L1 is present in compounds of formulae (1a) and (1b) as a linker atom or group it may be any such atom or group as hereinbefore described in relation to L2 linker atoms and groups. Optionally substituted cycloaliphatic groups represented by the group Cy1 in compounds of the invention include optionally substituted C3.i0cycloaliphatic groups. Particular examples include optionally substituted C3-i0cycloalkyl, e.g. 03.7cycloalkyl or C3-i0cycloalkenyl, e.g C3.7cycloalkenyl groups. Optionally substituted heterocycloaliphatic group represented by the group Cy1 include optionally substituted C3.10heterocycloaliphatic group. Particular examples include optionally substituted C3.ioheterocycloalkyl, e.g. C3. 7heterocycloalkyl or C3-ioheterocycloalkenyl, e.g. Cs-yheterocycloalkenyl groups, each of said groups containing one, two, three or four heteroatoms or heteroatom containing groups L4 in place of or in addition to the ring carbon atoms where L4 is an atom or group as previously defined for L2. Optionally substituted polycycloaliphatic groups represented by the group Cy1 include optionally substituted C7-i0bi-or tricycloalkyl or C7.10bi- or tricycloalkenyl groups. Optionally substituted heteropolycycloaliphatic groups represented by the group Cy1 include optionally substituted C7.i0bi- or tricycloalkyl or C7-i0bi- or tri-cycloalkenyl groups containing one, two, three, four or more L4 atoms or groups in place of or in addition to the ring carbon atoms. Particular examples of cycloaliphatic, polycycloaliphatic, heterocycloaliphatic and heteropolycycloaliphatic groups represented by the group Cy1 include optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 2-cyclobuten-1-yl, 2-cyclopenten-1 -yl, 3-cyclopenten-1-yl, adamantyl, norbornyl, norbornenyl, dihydrofuranyl, tetrahydrofuranyl, tetrahydropyranyl, dihydrothiophenyl, tetrahydrothiophenyl, pyrroline, e.g. 2-or 3-pyrrolinyl, pyrrolidinyl, pyrrolidinone, oxazolidinyl, oxazolidinone, dioxolanyl, e.g. 1,3-dioxolanyl, imidazolinyl, e.g. 2-imidazolinyl, imidazolidinyl, pyrazolinyl, e.g. 2-pyrazolinyl, pyrazolidinyl, 5,6-dihydro-2(1 H)-pyrazinone, tetrahydropyrimidinyl, thiazolinyl, thiazolidinyl, pyranyl, e.g. 2- or 4-pyranyl, piperidinyl, homopiperidinyl, heptamethyleneiminyl, piperidinone, 1,4-dioxanyl, morpholinyl, morpholinone, 1,4-dithianyl, thiomorpholinyl, piperazinyl, homopiperazinyl, 1,3,5-trithianyl, oxazinyl, e.g. 21-1-1,3-, 6H-1,3-, BH-1,2-, 2H-1,2~ or 4H-1,4-oxazinyl, 1,2,5-oxathiazinyl, isoxazinyl, e.g. o- or p-isoxazinyl, oxathiazinyl, e.g. 1,2,5 or 1,2,6-oxathiazinyl, 1,3,5-oxadiazinyl, dihydroisothiazolyl, dihydroisothiazole 1,1-dioxide , e.g. 2,3-dihydroisothiazole 1,1-dioxide, dihydropyrazinyl and tetrahydropyrazinyl groups. The optional substituents which may be present on the cycloaliphatic, polycycloaliphatic, heterocycloaliphatic or heteropolycycloaliphatic groups represented by the group Cy1 include one, two, three or more substituents selected from halogen atoms, or Ci-6alkyl, e.g. methyl or ethyl, haloCi-6alkyl, o.g. halomethyi or haloethyl such as difluoromethyl or trifluoromethyl, optionally substituted by hydroxyl, e.g. -C(OH)(CF3)2, Ci-6alkoxy, e.g. inethoxy or ethoxy, haloCi-ealkoxy, eg. halomethoxy or haloethoxy such as difiuoromethoxy or trifluoromethoxy, thiol, Ci-ealkylthiol, e.g. methylthiol or othylthiol, carbonyl (=O), thiocarbonyl (=S), imino (=NR4a) [where R4a is an -OH group or a Ci-ealkyI group], or -(Alk3)vR5 groups in which Alk3 is a straight or branched C,.3alkylene chain, v is zero or the integer 1 and R5 is a C3. acycloalkyl, -OH, -SH, -N(R6)(R7) [in which R6 and R7 is each independently selected from a hydrogen atom or an optionally substituted alkyl or C3. ncycloalkyl group], -OR6, -SR6, -CN, -NO2> -CO2R6, -SOR6, -SO2R6, -SO3R6, -OC02R6, -C(0)R6, -OC(O)R6, -C(S)R6, -C(O)N(R6)(R7), -OC(O)N(R6)(R7), -N(R6)C(0)R7. -C(S)N(R6)(R7), -N(R6)C(S)R7, -SO2N(R6)(R7), -N(R6)SO2R7, -N(R(3)C(0)N(R7)(R8) [where R8 is as defined for R6], -N(R6)C(S)N(R7)(R8), -N(R6)SOSN(R7)(R8) or an optionally substituted aromatic or heteroaromatic group. Particular examples of Alk3 chains include -CH2-, -CH2CH2-, -CH2CH2CH2-and ~CH(CH3)CH2- chains. When R5, R6, R7 and/or R8 is present as a C3.8cycloalkyl groups it may be for example a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group. Optional substituents which may be present on such groups include for example one, two or three substituents which may be the same or different selected from halogen atoms, for example fluorine, chlorine, bromine or iodine atoms, or hydroxy or Ci-6alkoxy, e.g. methoxy, ethoxy or /-propoxy groups. When the groups R6 and R7 or R7 and R8 are both alkyl groups these groups may be joined, together with the N atom to which they are attached, to form a heterocyclic ring. Such heterocyclic rings may be optionally interrupted by a further heteroatom or heteroatom containing group selected from -O-, -S-, -N(R7)-, -C(O)- or -C(S)- groups. Particular examples of such heterocyclic rings include piperidinyl, pyrazolidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, imidazolidinyl and piperazinyl rings. When R6 is an optionally substituted aromatic or heteroaromatic group it may be any such group as described hereinafter in relation to Cy1. Additionally, when the group Cy1 is a heterocycloaliphatic or heteropolycycloaliphatic group containing one or more nitrogen atoms each nitrogen atom may be optionally substituted by a group -(L5)p(Alk4)qR9 in which L5 is a -C(O)-, -C(O)O, -C(S)-, -S(O)2-, -CQN(R6)- or -SO2N(R6)-; p is zero or the integer 1; Alk4 is an optionally substituted aliphatic or heteroaliphatic chain; q is zero or the integer 1; and R9 is a hydrogen atom or an optionally substituted cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycioaliphatic, aromatic or heteroaromatic group as herein described in relation to Cy1. When Alk4 is present as an aliphatic or heteroaliphatic chain it may be for example any aliphatic or heteroaliphatic chain as hereinbefore described for Alk1. Optionally substituted aromatic groups represented by the groups Cy1 include tor example monocyclic or bicyclic fused ring C6-i2aromatic groups, such as phenyl, 1- or 2-napthyl, 1- or 2-tetrahydronapthyl, indanyl or indenyl groups. Heteroaromatic groups represented by the groups Cy1 include for example Ci-gheteroaromatic groups containing for example one, two, three or four heteroatoms selected from oxygen, sulphur or nitrogen atoms. In general, the heteroaroinatic groups may be for example monocyclic or bicyclic fused ring heteroaromatic groups. Monocyclic heteroaromatic groups include for example five- or six-membered heteroaromatic groups containing one, two, three or four heteroatoms selected from oxygen, .sulphur or nitrogen atoms. Eiicyclic heteroaromatic groups include for example eight- to thirteen-membered fused ring heteroaromatic groups containing one, two or more heteroatoms selected from oxygen, sulphur or nitrogen atoms. Particular examples of heteroaromatic groups of these types include pyrrolyl, furyl, thienyl, imidazolyl, N-Ci-ealkylimidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,5- oxadiazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,3-triazinyl, benzofuryl, [2,3-dihydro]benzofuryl, benzothienyl, [2,3-dihydro]benzothienyl, benzotriazolyl, indolyl, indolinyl, indazolinyl, benzimidazolyl, imidazo[1,2- a]pyridyl, benzothiazolyl, benzoxazolyl, benzisoxazolyl, benzopyranyl, [3,4- dihydro]benzopyranyl, quinazolinyl, quinoxalinyl, naphthyridinyl, imidazo[1,5- ajpyridinyl, imidazo[1,5-a]pyrazinyl, imidazo[1,5-c]pyrimidinyl, pyrido[3,4- l)]pyridyl, pyrido[3,2-b]pyridyl, pyrido[4,3-b]pyridyl, quinolinyl, isoquinolinyl, phthalazinyl, tetrazolyl, 5,6,7,8-tetrahydroquinolinyl, 5,6,7,8- tetrahydroisoquinolinyl, imidyl, e.g. succinimidyl, phthalimidyl or naphthalimidyi such as 1,8-naphthalimidyl, pyrazolo[4,3-d]pyrimidinyl, furo[3,2-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, pyrrolo[3,2-d]pyrimidinyl, pyrazolo[3,2-b]pyridinyl, furo[3,2-b]pyridinyl, thieno[3,2-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, thiazolo[3,2-a]pyyridinyl, pyrido[1,2-a]pyrimidinyl, tetrahydroimidazo[1,2-a]pyrimidinyl and dihydroimidazo[1,2-a]pyrimidinyl groups. Optional substituents which may be present on aromatic or heteroaromatic groups represented by the group Cy1 include one, two, three or more substituents, each selected from an atom or group R10 in which R10 is R10a or - L6Alk5(R10a)r, where R10a is a halogen atom, or an amino (-NH2), substituted amino, nitro, cyano, hydroxyl (-OH), substituted hydroxyl, formyl, carboxyl (- CO2H), esterified carboxyl, thiol (-SH), substituted thiol, -COR11 [where R11 is an -L6Alk3(R10a)r, aryl or heteroaryl group], -GSR11, -S03H, -SOR11, -SO2R11, -S03R11, -S02NH2, -SO2NHR11, -S02N(R11)2, -CONH2l -CSNH2, -CONHR11, - CSNHR11, -CON(R11)2, -CSN(R11)2, -N(R12)SO2R11 [where R12 is a hydrogen atom or a straight or branched alkyl group], -N(SO2R11)2, -N(R12)SO2NH2, - N(R12)SO2NHR11, -N(R12)S02N(R11)2, -N(R12)COR11, -N(R12)CONH2, - N(R12)CONHR11, -N(R12)CON(R11)2, -N(R12)CSNH2l -N(R12)CSNHR11, - N(R12)CSN(R11)2) -N(R12)CSR11, -N(R12)C(O)OR11, -SO2NHet1 [where - NHet1 is an optionally substituted C5.7cyclicamino group optionally containing one or more other --O- or -S- atoms or -N(R12)-, -C(O)- or -C(S)- groups], - CONHet1, -CSNHet1, -N(R12)SO2NHet1, -N(R12)CONHet1, -N(R12)CSNHet1, - SO2N(R12)Het [where -Met is an optionally substituted monocyclic C5. /carbocyclic group optionally containing one or more other -O- or -S- atoms or -N(R12)-, -C(O)-, -S(O)- or -S(O)2- groups], -Met, -CON(R12)Het, - CSN(R'2)Het, -N(R12)CON(R12)Het, -N(R12)CSN(R12)Het, N(R1?)SO2N(R12)Het, aryl or heteroaryl groups; L6 is a covalent bond or a linker atom or group as hereinbefore defined for L2; Alk5 is an optionally substituted straight or branched d-ealkylene, C2.6alkenylene or C2-t>alkynylene chain, optionally interrupted by one, two or three -O- or -S-atoms or -S(O)n- [where n is an integer 1 or 2] or -N(R12)- e.g. -N(CH3)-groups; and r is zero or the integer 1, 2, or 3. It will be appreciated that when two Rr or R12 groups are present in one of the above substituents the R11 and R12 groups may be the same or different. When in the group -L6Alk5(R10a)r r is an integer 1, 2 or 3, it is to be understood that the substituent or substituents R10a may be present on any suitable carbon atom in -Alk5. Where more than one R10a substituent is present these may be the same or different and may be present on the same or different atom in -Alk5. Clearly, when r is zero and no substituent R10a is present the alkylene, alkenylene or alkynylene chain represented by Alk5 becomes an alkyl, alkenyl or alkynyl group. When R10a is a substituted amino group it may be for example a group -NHR11 Iwhere R11 is as defined above] or a group -N(R11)2 wherein each R11 group is the same or different. When R10n is a halogen atom it may be for example a fluorine, chlorine, bromine, or iodine atom. When R10a is a substituted hydroxyl or substituted thiol group it may be for example a group -OR11 or a -SR12 group respectively. Esterified carboxyl groups represented by the group R10a include groups of formula -CO2Alk6 wherein Alk6 is a straight or branched, optionally substituted C,.8alkyl group such as a methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl or t-butyl group; a Ce-iaarylCi-salkyI group such as an optionally substituted benzyl phenylethyl, phenylpropyl, 1-naphthylmethyl or 2-naphthylmethyl group; a C6.12aryi group such as an optionally substituted phenyl, 1-naphthyl or 2-naphthyl group; a C6-i2aryloxyCi.8alkyl group such as an optionally substituted phenyloxymethyl, phenyloxyethyl, 1 -naphthyloxymethyl, or 2-naphthyloxymethyl group; an optionally substituted Ci-salkanoyloxyCvaalkyl group, such as a pivaloyloxymethyl, propionyloxyethyl or propionyloxypropyl group; or a C6. loaroyloxyd-aalkyl group such as an optionally substituted benzoyloxyethyl or benzoyloxypropyl group. Optional substituents present on the Alk6 group include R10a atoms and groups as described above. When Allo1 is present in or as a substituent it may be for example a -CH2-, -CH(CH3)-, -C(CH3)sr, -CH2CH2-, -CH2CH2CH2-, -CH(CH3)CH2-, -CH2CH2CH2CH2-, -CH2CH(CH3)CH2-, -CH(CH3)CH2CH2-, -C(CH3)2CH2-, -CH=CH-, -CH=CCH2-, -CH2C=CH-, -CH=CHCH2CH2-, -CH2CH=CHCH2-, -CH2CH2CH=CH2-, -CC-, -CCCH2-, -CH2CC-, -CC£H2CH2-, -CH2CCCH2- or -CHpCHgCC- chain, optionally interrupted by one, two, or three -O- or -S-, atoms or -S(O)-, -S(O)r or -N(R12)-, e.g. -N(CH3)- groups. The aliphatic chains represented by Alk6 may be optionally substituted by one, two or three halogen atoms in addition to any R10a groups that may be present. Aryl or heteroaryl groups represented by the groups R10a or R11 include mono-or bicyclic optionally substituted C6-12 aromatic or C^g heteroaromatic groups as described above for the group Cy1. The aromatic and heteroarornatic groups may be attached to the group Cy1 in compounds of formula (1) by any carbon or hetero e.g. nitrogen atom as appropriate. It will be appreciated that when -NHet1 or -Met forms part of a substituent R10 the heteroatoms or heteroatom containing groups that may be present within the ring -NHet1 or -Met take the place of carbon atoms within the parent carbocyclic ring. Thus when -NHet1 or -Het forms part of a substituent R10 each may be for example an optionally substituted pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, piperidinyl or thiazolidinyl group. Additionally Het may represent for example, an optionally substituted cyclopentyl or cyclohexyl group. Optional substituents which may be present on -NHet1 include those substituents described above when Cy1 is a heterocycloaliphatic group. Particularly useful atoms or groups represented by R10 include fluorine, chlorine, bromine or iodine atoms, or d-ealkyl, e.g. methyl, ethyl, n-propyl, i-propyl, n- butyl or t-butyl, optionally substituted phenyl, pyridyl, pyrimidinyl, pyrrolyl, furyl, thiazolyl, or thienyl, Ci.ehydroxyalkyl, e.g. hydroxymethyl or hydroxyethyl, carboxyd-ealkyl, e.g. carboxyethyl, d.6alkylthio e.g. methylthio or ethylthio, oarboxyd-ealkylthio, e.g. carboxymethylthio, 2-carboxyethylthio or 3-carboxy- propylthio, d-ealkoxy, e.g. methoxy or ethoxy, hydroxyd.6alkoxy, e.g. 2- hydroxyethoxy, optionally substituted phenoxy, pyridyloxy, thiazolyoxy, phenylthio or pyridylthio, Cs-ycycloalkyl, e.g. -cyclobutyl, cyclopentyl, 65- /cycloalkoxy, e.g. cyclopentyloxy, halod-salkyl, e.g. trifluoromethyl, halod- .alkoxy, e.g. trifluoromethoxy, d-ealkylamino, e.g. methylamino, ethylamino, - CH(CH3)NH2 or -C(CH3)2NH2> halod-ealkylamino, e.g. fluorod-ealkylamino.e.g. -CH(CF3)NH2 or -C(CF3)2NH2, amino (-NH2), aminod-ealkyl, e.g. aminomethyl or aminoethyl, d-edialkylamino, e.g. dimethylamino or diethylamino, d- oalkylaminod-fsalkyl, e.g. ethylaminoethyl, d-edialkylaminod-ealkyl. e.g. diethylaminoethyl, aminoCi-6alkoxy, e.g. aminoethoxy, d-ealkylaminod-ealkoxy, e.g. rnethylaminoethoxy, d-edialkylaminod-ealkoxy, &-Q- dimethylaminoethoxy, diethylaminoethoxy, diisopropylaminoethoxy, or dimethylaminopropoxy, imido, such as phthaiimido or naphthalimido, e.g. 1,8-naphthalimido, nitro, cyano, hydroxyl (-OH), formyl [HC(O)-], carboxyl (-CO2H), -CO2Alk6 [where Alk6 is as riefined above], d-fi alkanoyl e.g. acetyl, optionally substituted benzoyi, thiol (- SH), thioCi.6alkyl, e.g. thiomethyl or thioethyl, sulphonyl (-SO3H), d- >(alkylsulphonyl, e.g. methylsulphonyl, amino'sulphonyl (-SO2NH2), Ci- ,,aikylarninosulphonyl, e.g. methylaminosulphonyl or ethylaminosulphonyl, d- odialkylaminosulphonyl, e.g. dimethylaminosulphonyl or diethylaminosulphonyl, l>henylaminosulphonyl, carboxamido (-CONH2), C^alkylaminocarbonyl, e.g. i nethylaminocarbonyl or ethylaminocarbonyl, d-edialkylarninocarbonyl, e.g. dimethylaminocarbonyl or diethylaminocarbonyl, aminod-ealkylaminocarbonyl, e.g. arninoethylamino-carbonyl, Ci-edialkylaminod-ealkylaminocarbonyl, e.g. cliethylaminoethyl-aminocarbonyl, aminocarbonylamino, C^ (jalkyiaminocarbonylamino, e.g. methylaminocarbonylamino or ethylaminocarbonylamino, d-edialkylamino-carbonylamino, e.g. dimethylaminocarbonylamino or diethylamino-carbonylamino, d- oalkylaminocabonyld-Balkylamino, e.g. methylamino-carbonylmethylamino, aminothiocarbonylamino, d.6alkylaminothiocarbonyl-amino, e.g. methylaminothiocarbonylamino or ethylaminothiocarbonylamino, d-fidialkylaminothiocarbonylamino, e.g. dimethylaminothiocarbonylamino or diethylaminothiocarbonylamino, CvealkylaminothiocarbonylCi^alkylamino, e.g. ethylaminothiocarbonylmethylamino, -CONHC(=NH)NH2, d.6alkylsulphonyl-amino, e.g. rnethylsulphonylamino or ethylsulphonylamino, d-edialkyl-sulphonylamino, e.g. dimethylsulphonylamino or diethylsulphonylamino, optionally substituted phenylsulphonylamino, aminosulphonylamino (-NHSO?NHg), d-ealkylaminosulphonylamino, e.g. methylaminosulphonylamino or ethylaminosulphonylamino, d.6dialkylaminosulphonylamino, e.g. dimethyl-aminosulphonylamino or diethylaminosulphonylamino, optionally substituted inorpholinesulphonylamino or morpholinesulphonyld-6alkylamino, optionally substituted phenylaminosulphonylamino, d.6alkanoylamino, e.g. acetylamino, aminod-ealkanoylamino e.g. aminoacetylamino, d-edialkylaminod-salkanoyl-amino, e.g. dimethylaminoacetylamino, Ci-6alkanoylaminoCi-6alkyl, e.g. acetylaminomethyl, d-6alkanoylaminod-6alkylamino, e.g. acetamidoethyl-arnino, C,.6alkoxycarbonylamino, e.g. methoxycarbonylamino, ethoxycarbonyl-iimino or t-butoxycarbonylamino or optionally substituted benzyloxy, pyridylmethoxy, thiazolylmethoxy, benzyloxycarbonylamino, benzyloxy-carbonylaminoCi.6alkyl e.g. benzyloxycarbonylaminoethyl, benzothio, pyridyl-methylthio or thiazolylmethylthio groups. A further particularly useful group of substituents represented by R10 when present on aromatic or heteroaromatic groups includes substituents of formula -L6AlkGR10a where L6 is preferably a covalent bond or an -O- or -S- atom or -N(R2)-, -C(0)-( -0(0)0-, -0-0(0)-, -N(R2)CO-, -CON(R2)- or -N(R2)S(O)2- group, Alk5 is an optionally substituted d.6alkyl group optionally interrupted by one or two -O- or -S- atoms or -N(R12)-, -C(O)-, -C(S)-, -CON(R12)- or -N(R12)CO- groups and R10a is an optionally substituted Met group as herein defined or an optionally substituted heteroaromatic group as hereinbefore described in relation to Cy1. Where desired, two R10 substituents may be linked together to form a cyclic group such as a cyclic ether, e.g. a C-i-ealkylenedioxy group such as methylenedioxy or ethylenedioxy. It will be appreciated that where two or more R10 substituents are present, iliese need not necessarily be the same atoms and/or groups. In general, the substituent(s) may be present at any available ring position on the aromatic or heteroaromatic group represented by the group Cy1. When in compounds of formula (1a) X is a substituted -N- atom or in compounds of formulae (1a) or (1b) Y is a substituted C atom the substituents which may be present on the N or C atom include those R10 atoms and groups as hereinbefore defined. When Ar is present in compounds of formulae (1a) or (1b) as an optionally substituted aromatic or heteroaromatic group it may be any such group as hereinbefore described for Cy1. Optional substituents which may be present include those R10 atoms and groups as described in relation to Cy1 aromatic and heteroaromatic groups. One useful group of compounds according to the invention is that where Y is a CH group or a substituted C atom where the substituent on the C atom may in general be any R10 atom or group as hereinbefore described or in particular a R20 group as hereinafter defined. A particularly useful group of compounds according to the invention is represented by the compounds of formula (1a). An especially useful group of compounds according to the invention has the formula (2a): (Figure Remove) (2a) in which R20 is a hydrogen atom or an atom or group R10 as hereinbefore defined; the dashed line, A, Ra, Alk1, n, L1, Cy1, X and Ar are as generally and specifically defined previously; and the salts, solvates, hydrates and N-oxides thereof. In general in compounds of formula (1a), (1b) and (2a) Ra is preferably a hydrogen atom or a Ci-4alkyl group, especially a methyl, ethyl, n-propyl or i-propyl group. Most preferably Ra is a methyl group or most especially a hydrogen atom. In one particularly preferred class of compounds of formula (1a), (1b) and (2a) the dashed line represents a bond and A is a -C(Rb)= group. In this class of compounds Rb is preferably a d-4alkyl group, especially a methyl, ethyl, n-propyl or i-propyl group. Most preferably Rb is a methyl group or most especially a hydrogen atom. In one preferred class of compounds of formulae (1a) and (2a) X is a -O- or •-S- atom, most preferably a-S- atom. In another preferred group of compounds of formulae (1a), (1b) and (2a) n is zero. In another preferred group of compounds of formulae (1a), (1b) and (2a) n is the integer 1 and Alk1 is preferably an optionally substituted Ci-6alkylene chain, especially an optionally substituted -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH(CH3)CH2- or -CH2CH(CH3)- chain, most especially a -CH2- or -CH2CH2- chain. In compounds of formula (2a) and in general in compounds of the invention L1 is preferably a covalent bond or an -O- or -S- atom or an -N(R2)-, especially -NH- or -N(CH3)-, -C(O)-, -C(S)-, -S(O)- or -S(O)2- group. Most preferably L1 is a covalent bond or an -O- or -S- atom or -NH- group. L1 is most especially preferably is a covalent bond. In compounds of formula (2a) and in general in compounds of the invention Cy1 is preferably an optionally substituted cycloaliphatic, aromatic or heteroaromatic group as hereinbefore generally and particularly defined. Particularly preferred Cy1 optionally substituted cycloaliphatic groups include optionally substituted Ca-ycycloalkyl groups, especially cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl groups. Particularly preferred optional substituents which may be present on Cy1 optionally substituted cycloaliphatic groups include halogen atoms, especially fluorine, chlorine or bromine atoms, or d-ealkyl groups, especially d.3alkyl i jroups, most especially a methyl group, or a haloCi.6alkyl group, especially a group, most especially a -CF3 group, or a Ci-6alkoxy, especially methoxy, ethoxy, propxy or i-propoxy group, or a haloCi-6alkoxy, especially a fluoroCi-6alkoxy, most especially a ~OCF3 group, or a cyano (-CN), esterified carboxyl, especially -CO2CH3 or -CO2C(CH3)3, nitro (-NO2), amino (-NH2), substituted amino, especially -NHCH3 or -N(CH3)2, -C(O)R6, especially -C(O)CH3) or-N(R6)C(0)R7, especially-NHCOCH3 group. Particularly preferred Cy1 aromatic groups include optionally substituted phenyi groups. Particularly preferred heteroaromatic groups include optionally substituted monocyclic heteroaromatic groups, especially optionally substituted five- or six-membered heteroaromatic groups containing one, two, three or four heteroatoms selected from oxygen, sulphur or nitrogen atoms. Particularly preferred optionally substituted monocyclic heteroaromatic groups include optionally substituted furyl, thienyl, pyrrolyl, oxazoly!, thiazolyl, pyridyl, pyrimidinyl ortriazinyl group. Particularly preferred optional substituents which may be present on Cy1 aromatic or heteroaromatic groups include atorjns or groups -R10a or -l..liAlk0(R10a)r as hereinbefore defined. Particularly useful optional substituents include halogen atoms, especially fluorine, chlorine or bromine atoms, or Ci-,,alkyl groups, especially Ci-3alkyl groups, most especially a methyl group, or a haloCi-6alkyl group, especially a fluoroCi-6alkyl group, most especially a -nF.i group, or a Ci-6alkoxy, especially methoxy, ethoxy, propxy or i-propoxy group, or a haloCi-ealkoxy, especially a fluorod-ealkoxy, most especially a -OCF3 group, or a cyano (-CN), carboxyl (-C02H), esterified carboxyl (-COf»Alk6), especially -CO2CH3, -CO2CH2CH3, or -CO2C(CH3)3> nitro (-NO2), amino (-NH2), substituted amino, especially -NHCH3 or -N(CH3)2, -COR11, especially -COCH3, or-N(R12)COR11, especially -NHCOCH3 group. Further preferred optional substituents which may be present on Cy1 aromatic or heteroaromatic groups include groups of formula -L6Alk5(R10a)r in which r is the integer 1, L6 is a covalent bond or an -O- or -S- atom or a -N(R2)-, especially -NH- or -N(CH3)-, -C(O)-, -C(S)-, -C(O)O-, -OC(O)-, -N(R2)CO--, especially -NHCO-, or -CON(R2)-, especially -CHNH-group, Alk5 is a d-ealkyl chain, especially a -CH2-, -CH2CH2-, -CH2CH2CH2- or -CH2CH2CH2CH2- chain and R10a is a substituted hydroxyl group, especially a -OCH3, -OCHSCH3 or -OCH(CH3)2 group or a substituted amino group, especially a ~N(CH3)2 or -N(CH2CH3)2 group or a -Met group, especially an optionally substituted monocyclic Cs-ycarbocyclic group containing one, two or three -O-, -S-, -N(R12)-, especially -NH- or -N(CH3)-or -C(O)- groups within the ring structure as previously described, most especially an optionally substituted pyrrolidinyl, imidazolidinyl, piperidinyl, e.g. N-methylpiperidinyl, morpholinyl, thiomorpholinyl orpiperazinyl group or R10a is an optionally substituted heteroaromatic group, especially a five- or six-membered monocyclic heteroaromatic group containing one, two, three or lour heteroatoms selected from oxygen, sulphur or nitrogen atoms, such as optionally substituted pyrrolyl, furyl, thienyl, imidazolyl, triazolyl, pyridyl, pyrimidinyl, triazinyl, pyridazinyl, or pyrazinyl group. Particularly preferred optional substituents on the -Met groups just described include hydroxyl (-OH) and carboxyl (-CO2H) groups or those preferred optional substituents just described in relation to the group Cy1. In one preferred class of compounds of formula (2a) R20 is an atom or group -R10a or ~L6Alk5(R10a)r as hereinbefore defined. Preferably R20 is a preferred atom or group as just defined for Cy1. In one particularly preferred class of compounds of formula (2a) R20 is a hydrogen atom or a carboxyl (-CO2H), esterified carboxyl (-CO2Alk6), especially -CO2CH3) -CO2CH2CH3, or -C02C(CH3)3, -CN, -NH2l -CONH2, -CONHR11, -N(R12)SO2R11, -N(RI2)C(O)OR11 or-SO2R11 group. In one particularly preferred group of compounds of formula (1), (1a) and (2a) Cy1 is an optionally substituted phenyl group, especially a phenyl group optionally substituted by one, two or three optional substituents where at least one, and preferably two optional substituents are located ortho to the bond joining Cy1 to the remainder of the compound of formula (1), (1a) or (2a). Particularly preferred ortho substituents include halogen atoms, especially fluorine or chlorine atoms, or Ci-3alkyl groups, especially methyl groups, Ci-3alkoxy groups, especially methoxy, halod-3alkyl groups, especially -CF3 Particularly preferred Ar aromatic groups include optionally substituted phenyl groups. Particularly preferred heteroaromatic groups include optionally substituted monocyclic heteroaromatic groups, especially optionally substituted five- or six-membered heteroaromatic groups containing one, two, three or four heteroatoms selected from oxygen, sulphur or nitrogen atoms. Particularly preferred optionally substituted monocyclic heteroaromatic groups include optionally substituted furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, pyridyl, pyrimidinyl ortriazinyl group. Particularly preferred optional substituents which may be present on Ar aromatic or heteroaromatic groups include atoms or groups -R10a or -L6Alk5(R10a)r as hereinbefore defined. Particularly useful optional substituents include halogen atoms, especially fluorine, chlorine or bromine atoms, or Ci_ 6alkyl groups, especially Ci-3alkyl groups, most especially a methyl group, or a haloCvealkyl group, especially a fluoroCi-6alkyl group, most especially a -CF3 group, or a Ci-6alkoxy, especially methoxy, ethoxy, propxy or i-propoxy group, or a haloCi-6alkoxy, especially a fluoroCi.ealkoxy, most especially a -OCF3 group, or a cyano (-CN), esterified carboxyl, especially -C02CH3 or -CO2C(CH3)3, nitro (-NO2), amino (-NH2), substituted amino, especially -NHCH3 or -N(CH3)2, -COR11, especially -COCH3, or -N(R12)COR11, especially -NHCOCH3 group. In one particularly preferred class of compounds of formula (2a) the dashed line is present, A is a -CH= group, Ra is a hydrogen atom and X is a -S- atom. A further particularly useful class of compounds according to the invention has the formula (1b) in which the dashed line is present, A is a -CH= group, Ra, Ar, Alk1, n and L1 are as defined for formula (1b), each Y is independently a CH group or substituted C atom and Cy1 is an optionally substituted aromatic or heteroaromatic group Particularly useful compounds of the invention include: Ethyl 6-oxo-3,7-diphenyl-6,7-dihydrothieno[2,3-jb]pyridine-2-carboxylate; Ethyl 7-cyclopropylmethyl-6-oxo-3-phenyl-6,7-dihydrothieno[2,3-d]pyridine-2- carboxylate; Ethyl 6-oxo-3-phenyl-7-(3-thienyl)-6,7-dihydrothieno[2,3-£>]pyridine-2- oarboxylate; Ethyl 3-(4-fluorophenyl)-6-oxo-7-phenyl-6,7-dihydrothieno[2,3-jb]pyridine-2- carboxylate; Ethyl 3-(2-methoxyphenyl)-6-oxo-7-phenyl-6,7-dihydrothieno[2,3-i>]pyridine- 2-carboxylate; Ethyl 6-oxo-7-phenyl-3-(4-tolyl)-6,7-dihydrothieno[2,3-fc]pyridine-2- carboxylate; Ethyl 3-(3-methoxyphenyl)-6-oxo-7-phenyl-6,7-dihydrothieno[2,3-d]pyridine- 2-carboxylate; 6-Oxo-3,7-diphenyl-A/-(2-piperidinoethyl)-6,7-dihydrothieno[2,3-£)]pyridine-2- carboxamide; 6-Oxo-3,7-diphenyl-6,7-dihydrothieno[2,3-i)]pyridine-2-carbonitrile; 3,7-Diphenylthieno[2,3-£>]pyridin-6(7H)-one; Ethyl 3-(2,4-difluorophenyl)-7-[4-(4-methylpiperazin-1-yl)phenyl]-6-oxo-6,7- dihydrothieno[2,3-(b]pyridine-2-carboxylate; 1,4-Diphenyl-1,4-dihydro-pyrrolo[3,2-£)]pyridin-5-one; Ethyl 7-(2-chlorophenyl)-6-oxo-3-phenyl-6,7-dihydrothieno[2,3-£)]pyridine-2- carboxylate; and the salts, solvates, hydrates and N-oxides thereof. The compounds of the invention may be prepared by a number of processes as generally described below and more specifically in the Examples hereinafter. In the following process description, the symbols Ar, Cy1, Alk1, n, I 1 Ra Rb R'; A, X and Y when used in the formulae depicted are to be understood to represent those groups described above in relation to formulae (1a) and (1b) unless otherwise indicated. In the reactions described below, it may be necessary to protect reactive functional groups, for example hydroxy, amino, thio or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups may be used in accordance with standard practice [see, for example, Green, T. W. in "Protective Groups in Organic Synthesis", John Wiley and Sons, 1999]. In some instances, deprotection may be the final step in the synthesis of a compound of formula (1) and the processes according to the invention described hereinafter are to be understood to extend to such removal of protecting groups. For convenience the processes described below all refer to a preparation of a compound of formula (1a) or (1b) but clearly the description applies equally to the preparation of compounds of formula (2a). Thus according to a further aspect of the invention a compound of formula 11 a) in which Y is a substituted e.g. -CO2CH2CH3 substituted C atom may be prepared according to the reactions set out in Scheme 1: (Figure Remove) Thus a compound of formula (1a) in which Y is a substituted C atom may be prepared by reaction of a compound of formula (7) with an alkylating agent of formula Cy1L1(Alk1)nZ, where Z is a leaving group such as a halogen atom, (j.g. a chlorine, bromine or iodine atom or a sulphonyloxy group such as an alkylsulphonyloxy e.g. trifluoromethylsulphonyloxy or arylsulphonyloxy e.g. phenylsulphonyloxy group. The reaction may be performed in the presence of a solvent, for example a substituted amide such as dimethylformamide, optionally in the presence of a base, for example an inorganic base such as sodium hydride, or an organic base such as an organic amine, e.g. a cyclic amine such as 1,5- diazabicyclo[4.3.0]non-5-ene or a resin bound organic amine such as resin bound 2-ter?-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2- diazaphosphorine (PS-BEMP), at an elevated temperature, for example 80 to 100SC. In a further aspect of the invention a compound of formula (1a) in which, for example, L1 is a covalent bond and n is zero may be prepared by the reaction of a compound of formula (7) with a boronic acid of formula Cy'B(OH)2. The reaction may be performed in an organic solvent, for example a halogenated hydrocarbon such as dichloromethane or dichloroethane in the presence of a copper reagent, for example a copper (II) reagent such as copper (II) acetate, optionally in the presence of an oxidant, for example 2,2,6,6-tetramethyM-piperidinyloxy or pyridine-N-oxide, optionally in the presence of a base, for example an organic amine such as an alkylamine, e.g. triethylamine or an aromatic amine, e.g. pyridine at a temperature from around ambient to the reflux temperature [see for example Chan, D.T, et al Tetrahedron Letters, 1998, 2933; Lam, P.Y.S. et al, Tetrahedron Letters, 2001, 3415] Clearly the reactions just described may be used to prepare other compounds of the invention starting from intermediates of formula (7a) or (7b): (Figure Remove) lor instance compounds of formula (7a) in which Y is a CH group. Intermediates pyridinones of formula (7) may be prepared from pyridine N-oxides of formula (6) by sequential reaction with an anhydride, for example acetic anhydride at an elevated temperature, for example the reflux temperature followed by reaction with an inorganic base, for example a carbonate such as aqueous potassium carbonate in a solvent such as an ether for example a cyclic ether e.g. tetrahydrofuran at around ambient temperature. Pyridine N-oxides of formula (6) may be formed from pyridines of formula (5) by standard methods of formation of N-oxides as described hereinafter. Pyridines of formula (5) may be formed from 2-halopyridyl-(hetero)aryimethanones of formula (4) by reaction with a reagent of formula HXCH3CO2R30 [where R30 is a Ci-6alkyl group such as a methyl or ethyl group]. The reaction may be performed in the presence of a solvent such as a substituted amide for example dimethylformamide or an ether e.g. a cyclic ether such as tetrahydrofuran in the presence of a base, for example an inorganic base such as a hydride e.g. sodium hydride or an organic base such as 1,5-diazabicyclo[4.3.0]non-5-ene or a trialkylamine such as triethylamine at a temperature between about 0SC and ambient temperature. 2-Halopyridyl-(hetero)arylmethanones of formula (4) may be prepared from 2-halopyridines of formula (3) by reaction with a base, for example a strong base such as lithium diisopropylamide or butyl lithium to form a 2-halopyridyl an ion and quenching with a (hetero)aryl amide such as a Weinreb amide. The reaction may be performed in the presence of a solvent such as a substituted amide for example dimethylformamide or an ether e.g. a cyclic ether such as, at a temperature of around-78QC. According to another aspect of the invention further compounds of formula (1 a) may be prepared according to the reactions set out in Scheme 2. (Figure Remove) Thus further compounds of formula (1a) may be prepared from intermediates of formula (13), and intermediates of formula (14) may be prepared from intermediates of formula (12), by functionalisation at the 6-membered ring nitrogen according to the methods as previously described for the conversion of compounds of formula (7) to compounds of formula (1a). Further compounds of formula (1a) may also be prepared from halogen substituted e.g. bromine substituted intermediates of formula (14), and intermediates of formula (13) may be prepared from halogen substituted e.g. bromine substituted intermediates of formula (12) by reaction with a boronic acid of formula ArB(OH)2. The reaction may be performed in a solvent such as an acyclic ether, for example ethylene glycol dimethyl ether or a cyclic ether, for example tetrahydrofuran or an aromatic hydrocarbon, for example toluene in the presence of an inorganic catalyst such as a palladium catalyst e.g. tetrakis(triphenylphosphine) palladium (0) in the presence of a base, for example an aqueous inorganic base such as aqueous sodium, potassium or caesium carbonate at an elevated temperature, for example around 80eC. Pyridinones of formula (12) and pyridine N-oxides of formula (11) may be prepared by the methods as hereinbefore described. Halides, for example bromides, of formula (10) may be prepared by such well known methods as for example the Sandmeyer reaction. Thus for example a bromide of formula (10) may be prepared by treatment of an aryl amine of formula (9) with an alkyl nitrite, for example t-butyl nitrite and a copper salt, for example copper (II) bromide in the presence of a solvent, for example a nitrile such as acetonitrile at a temperature from about 0B to around 652C. Aryl amines of formula (9) may be prepared from halo nitriles of formula (8) by analogous methods to those used to prepare compounds of formula (5) as herein described. Further 5-6 fused ring bicyclic heteroaromatic intermediates of formulae (15) and (17) may be prepared from intermediates of formula (4) by the methods shown in Scheme 3. Scheme 3 (Figure Remove) Thus pyrazolo[3,4-b]pyridines of formula (15) may be prepared by reaction of a 2-halopyridyl (or 2-halopyrimidinyl)-(hetero)arylmethanone of formula (4) with an optionally substituted hydrazine of formula R10NHNH2. The reaction may be performed in a solvent such as an amide for example a substituted amide e.g. dimethylformamide, at an elevated temperature, for example from about 60QC to the reflux temperature. Similarly intermediate isoxazolo[3,4-b]pyridines of formula (17) may be prepared by reaction of a 2-halopyridyl (or 2-halopyrimidinyl)-(hetero)arylmethanone of formula (4) with hydroxylamine in the presence of an proton source for example hydrogen chloride in a solvent such as an alcohol, e.g. methanol or ethanol at a temperature from ambient to the reflux temperature to give an intermediate of formula (16) which may be cyclised to an intermediate of formula (17) by reaction with a base, for example an organic base such as 1,5-diazabicyclo[4.3.0]non-5-ene (DBU) or an inorganic base such as a hydride e.g. sodium hydride in a solvent such as an amide for example a substituted amide e.g. dimethylformamide or an ether such as a cyclic ether e.g. tetrahydrofuran at a temperature from about OeC to ambient temperature. Further pyrrolo[3,2-b]pyrimidine intermediates of formula (20) may be prepared from intermediates of formula (18) by the methods shown in Scheme 4. (Figure Remove) Thus a 1 H-pyrrolo[3,2-b]pyridine (A=CH) or 1 H-pyrrolo[3,2-b]pyrimidine (A=N) of formula (19) may be converted to an intermediate of formula (20) by reaction with a compound of formula Ar-L (in which L is a leaving group such as a halogen atom e.g. a fluorine, chlorine, bromine or iodine atom or a aryl sulfonate such as a triflate). The reaction may be performed in the presence of a base, for example a hydride such as sodium hydride or a carbonate such as potassium or caesium carbonate, in a solvent such as a sulfoxide e.g. dimethyl sulfoxide or an amide e.g. dimethylacetamide or dimethylformamide, at an elevated temperature e.g. from about 608C to 1209C [according to the methods of Glamkowski, E. J. etal, J. Med. Chem., 1985, 28, 66 and Stabler, S. R. et al, Synth. Commun., 1994, 24, 123-29]. Alternatively the reaction may be performed with a compound of formula Ar-L (in which L is a leaving group such as a halogen atom e.g. a bromine atom or a aryl sulfonate such as a triflate) in the presence of a catalyst such as a copper catalyst e.g. copper (I) bromide in the presence of an inorganic base such as a carbonate e.g. potassium or caesium carbonate in a solvent such as an aromatic amine e.g. pyridine [according to the method of Ishii, H. et al, J. Chem. Soc. Perkin Trans. 1, 1989, 2407], Alternatively the reaction may be performed with a compound of formula Ar-L (in which L is a leaving group such as a halogen atom e.g. a bromine atom or a aryl sulfonate such as a triflate) in the presence of a catalyst such as a palladium catalyst e.g. palladium (ii) acetate in the presence of an iron catalyst e.g. 1,1'-bis(diphenylphosphino)ferrocene in a solvent such as an aromatic hydrocarbon e.g. toluene at an elevated temperature e.g. between 80-C and the reflux temperature [according to the method of Mann, G. etal, J. Am. Chem. Soc., 1998, 120, 827-8]. Intermediates of formula (19) may be formed from nitropyridines (A=CH) or nitropyrimidines (A=N) of formula (18) by sequential reaction with a (iialkoxymethyl-dimethyl-amine such as dimethoxymethyl-dimethyl-amine followed by catalytic reduction with a palladium catalyst such as palladium on carbon [according to the method of Mahadevan, I. et al, J. Heterocyclic Chem., 1992,29,359-67]. Further 5-6 fused ring bicyclic heteroaromatic intermediates for use in the preparation of compounds of formula (1a) and (1b) may be prepared according to the methods of Japanese Patent Application JP9059276. Such 5-6 fused ring bicyclic heteroaromatic intermediates of formula (15), (17), (19) and (20) as just described may be converted into further compounds of the invention by the particular methods as described above arid general methods described below. Further compounds of the invention in which A is a -N= atom may be prepared according to the methods shown in Scheme 5. Scheme 5 (Figure Remove) Thus an intermediate of formula (25) may be converted to a compound of the invention according to the methods as herein described for the conversion of compounds of formula (7) to compounds of formula (1a). Intermediates of formula (25) may be prepared from intermediates of formula (24) by cleavage of an ether group. Thus when R31 is a benzyl group it may be cleaved by such well known methods as catalytic reduction with hydrogen acetonitrile [according to the methods of Kundu, N. G. et al, J. Chem. Soc. Perkin Trans. I, 1990, 1822]. Intermediates of formula (25) may also be prepared from intermediates of formula (23) sequential by base hydrolysis, for example soudium or potassium hydroxide hydrolysis in a solvent such as an alcohol, e.g. tnethanol or ethanol at an elevated temperature, e.g. the reflux temperture, followed by re-esterification by reaction with .an acidified alcohol, e.g hydrogen chloride saturated ethanol at an elevated temperature, e.g. the reflux temperature. Intermediates of formula (24) may be prepared from intermediates of formula (23) by reaction with an alkoxide, e.g. sodium methoxide or sodium benzyloxide in a solvent such as an alcohol, e.g. methanol or ethanol at a temperture between about OeC and the reflux temperature. Alternatively the reaction may be performed with an alcohol, e.g. methanol or benzyl alcohol in the presence of a strong base, e.g. a hydride such as sodium hydride in an inert solvent such as an amide, e.g. dimethylformamide at a temperature between about OaC and 809C Intermediates of formula (23) may be formed from intermediates of formula (22) in a similar manner to that described for the preparation of intermediates of formula (5) form intermediates of formula (4). intermediates of formula (22) may be formed from intermediates of formula (21) by reaction with a strong base, e.g. lithium tetramethylpiperidine (LiTMP) in a solvent or mixture of solvents, for example an ether such as diethyl ether of tetrahydrofuran or a mixture thereof at a low temperature, e.g. around -100SC to form a lithium anion [according to the methods of Queguiner et al, J. Met. Chem. 1990, 27, 1377 and Mattson era/, J. Org. Chem. 1990, 55, 3410] which may be further reacted with a Weinreb amide at a temperature from about -78SC to ambient temperature. As an alternative a lithium anion as just described may be reacted with an aldehyde of formula ArCHO under the reaction conditions just described to give an intermediate alcohol which may be oxidised give an intermediate of formula (22) by such well known methods as manganese dioxide in a solvent, e.g. a halogenated hydrocarbon such as dichloromethane. Compounds of the invention and intermediates thereto where A represents a -N(Rb)- or -C(Rb)(Rc)- group may be generated from compounds of the invention or intermediates thereto where A represents a -N= or -C(Rb)= group by reduction, for instance by catalytic hydrogenation using a metal catalyst such as palladium on charcoal in the presence of hydrogen gas at an elevated pressure in a solvent such as an alcohol, e.g. ethanol optionally at an elevated temperaure e.g. between 40 and 60e. Where in the general processes described above intermediates such as alkylating agents of formula Cy1L1(Alk1)nZ, amides of formula ArC(O)N(OMe)Me, reagents of formula HXCH2CO2Et and nitroaromatics of formula (18) and any other intermediates required in the synthesis of compounds of the invention are not available commercially or known in the literature, they may be readily obtained from simpler known compounds by one or more standard synthetic methods employing substitution, oxidation, reduction or cleavage reactions. Particular substitution approaches include conventional alkylation, arylation, heteroarylation, acylation, thioacylation, halogenation, sulphonylation, nitration, formylation and coupling procedures. It will be appreciated that these methods may also be used to obtain or modify other intermediates and in particular compounds of formulae (1a) and (1b) where appropriate functional groups exist in these compounds. Particular examples of such methods are given in the Examples hereinafter. Thus for example aromatic halogen substituents in the compounds may be subjected to halogen-metal exchange with a base, for example a lithium base such as n-tautyl or t-butyl lithium, optionally at a low temperature, e.g. around 78°C, in a solvent such as tetrahydrofuran and then quenched with an electrophile to introduce a desired substituent. Thus, for example, a formyl group may be introduced by using dimethylformamide as the electrophile, a thiomethyl group may be introduced by using dimethyldisulphide as the olectrophile, an alcohol group may be introduced by using an aldehyde as electrophile and an acid may be introduced by using carbon dioxide as eiectrophile. Aromatic acids of formula ArCOaH may also be generated by quenching Grignard reagents of formula ArMgHal with carbon dioxide. Aromatic acids of formula ArCO2H generated by this method and acid containing compounds in general may be converted to activated derivatives, e.g. acid halides by reaction with a halogenating agent such as a thionyl halide e.g. thionyl chloride, a phosphorous trihalide such as phosphorous trichloride or a phosphorous pentahalide such as phosphorous pentachloride optionally in an inert solvent such as an aromatic hydrocarbon e.g. toluene or .1 chlorinated hydrocarbon e.g. dichloromethane at a temperature from about 0°C to the reflux temperature, or may be converted into Weinreb amides of formula ArC(O)N(OMe)Me by conversion to the acid halide as just described and subsequent reaction with an arnine of formula HN(OMe)Me or a salt thereof, optionally in the presence of a base such as an organic amine, e.g. triethylamine in an inert solvent such as an aromatic hydrocarbon e.g. toluene or a chlorinated hydrocarbon e.g. dichloromethane at a temperature from about 0°C to ambient temperature. Compounds of the invention and intermediates thereto such as compounds of formulae (5), (6), (7), (13) and (14) may be prepared by alkylation, arylation or heteroarylation. For example, compounds containing a -L1H group (where L1 is a linker atom or group) may be treated with an alkylating agent Cy1!2 in which Z2 is a leaving atom or group such as a halogen atom, e.g. a fluorine, chlorine, bromine or iodine atom or a sulphonyloxy group such as an alkylsulphonyloxy, e.g. trifluoromethylsulphonyloxy or arylsulphonyloxy, e.g. p-toluenesulphonyloxy group. The reaction may be carried out in the presence of a base such as a carbonate, e.g. caesium or potassium carbonate, an alkoxide, e.g. potassium i-butoxide, or a hydride, e.g. sodium hydride, in a dipolar aprotic solvent such as an amide, e.g. a substituted amide such as dimethylformamide or an ether, e.g. a cyclic ether such as tetrahydrofuran.' In another example, compounds containing a -L2H group as defined above may be functionalised by acylation or thioacylation, for example by reaction with the alkylating agents just described but in which Z2 is replaced by a -C(O)Z3, C(S)Z3, -N(R2)COZ3or -N(R2)C(S)Z3 group in which Z3 is a leaving atom or group as described for Z2. The reaction may be performed in the presence of a base, such as a hydride, e.g. sodium hydride or an amine, e.g. triethylamine or N-methylmorpholine, in a solvent such as a halogenated hydrocarbon, e.g. dichloromethane or carbon tetrachloride or an amide, e.g. dimethylformamide, at for example ambient temperature. Alternatively, the acylation may be carried out under the same conditions with an acid (for example one of the alkylating agents described above in which Z2 is replaced by a -COjH group) in the presence of a condensing agent, for example a diimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or N,N'-ciicyclohexylcarbodiimide, or a benzotriazole such as [O-(7-azabenzo-triazol-i-yl)-1/1,3,3-tetramethyluronium]hexafluorophosphate advantageously in the presence of a catalyst such as a N-hydroxy compound e.g. a N-hydroxytriazole such as 1-hydroxybenzotriazole. Alternatively the acid may he reacted with a chloroformate, for example ethylchloroformate, prior to the desired acylation reaction In a further example compounds may be obtained by sulphonylation of a compound containing an -OH group by reaction with one of the above alkylating agents but in which Z2 is replaced by a -S(O)Hal or -SO2Hal group I'in which Hal is a halogen atom such as chlorine atom] in the presence of a base, for example an inorganic base such as sodium hydride in a solvent such as an amide, e.g. a substituted amide such as dimethylformamide at for example ambient temperature. In another example, compounds containing a -L2H group as defined above may be coupled with one of the alkylation agents just described but in which Z? is replaced by an -OH group in a solvent such as tetrahydrofuran in the presence of a phosphine, e.g. triphenylphosphine and an activator such as diethyl, diisopropyl- or dimethylazodicarboxylate. . Ester groups such as -CO2Alk6 and -COaR4 in the compound of formula (1) and intermediates thereto may be converted to the corresponding acid [-CO?H] by acid- or base-catalysed hydrolysis depending on the nature of the qroup Alkb or R4. Acid- or base-catalysed hydrolysis may be achieved for example by treatment with an organic or inorganic acid, e.g. trifluoroacetic acid in an organic solvent e.g. dichloromethane or a mineral acid such as hydrochloric acid in a solvent such as dioxan or an alkali metal hydroxide, e.g. lithium hydroxide in an aqueous alcohol, e.g. aqueous methanol. In a further example, -OR6 [where R6 represents an alkyl group such as methyl group] in compounds of formula (1) and intermediates thereto may be cleaved to the corresponding alcohol -OH by reaction with boron tribromide in a solvent such as a halogenated hydrocarbon, e.g. dichloromethane at a low temperature, e.g. around -78°C. Alcohol [-OH] groups may also be obtained by hydrogenation of a corresponding -OCH2R31 group (where R31 is an aryl group) using a metal catalyst, for example palladium on a support such as carbon in a solvent such as ethanol in the presence of ammonium formate, cyclohexadiene or hydrogen, from around ambient to the reflux temperature. In another example, -OH groups may be generated from the corresponding ester [e.g. -cOf.Alk6] or aldehyde [-CHO] by reduction, using for example a complex metal hydride such as lithium aluminium hydride or sodium borohydride in a solvent such as methanol. In another example, alcohol -OH groups in the compounds may be converted to a corresponding -OR6 group by coupling with a reagent R6OH in a solvent such as tetrahydrofuran in the presence of a phosphine, e.g. triphenylphosphine and an activator such as diethyl-, diisopropyl-, or dimethylazodicarboxylate. Aminosulphonylamino [-NHSO2NH2] groups in the compounds may be obtained, in another example, by reaction of a corresponding amine [-NH2] with sulphamide in the presence of an organic base such as pyridine at an elevated temperature, e.g. the reflux temperature. In another example compounds containing a -NHCSR7 or -CSNHR7 group may he prepared by treating a corresponding compound containing a -NHCOR7 or -CONHR7 group with a thiation reagent, such as Lawesson's Reagent or P2S5, in an anhydrous solvent, for example a cyclic ether such as tetrahydrofuran, at an elevated temperature such as the reflux temperature. In a further example amine (-NH2) groups may be alkylated using a reductive alkylation process employing an aldehyde and a reducing agent. Suitable reducing agents include borohydrides for example sodium triacetoxyborohyride or sodium cyanoborohydride. The reduction may be carried out in a solvent such as a halogenated hydrocarbon, e.g. dichloromethane, a ketone such as acetone, or an alcohol, e.g. ethanol, where necessary in the presence of an acid such as acetic acid at around ambient temperature. Alternatively, the amine and aldehyde may be initially reacted in a solvent such as an aromatic hydrocarbon e.g. toluene and then subjected to hydrogenation in the presence of a metal catalyst, for example palladium on a support such as carbon, in a solvent such as an alcohol, e.g. ethanol. In a further example, amine [-NH2] groups in compounds of formula (1) and intermediates thereto may be obtained by hydrolysis from a corresponding imide by reaction with hydrazine in a solvent such as an alcohol, e.g. ethanol at ambient temperature. In another example, a nitro [-NO2] group may be reduced to an amine [-NH2], for example by catalytic hydrogenation using for example hydrogen in the presence of a metal catalyst, for example palladium on a support such as carbon in a solvent such as an ether, e.g. tetrahydrofuran or an alcohol e.g. methanol, or by chemical reduction using for example a metal, e.g. tin or iron, in the presence of an acid such as hydrochloric acid. In a further example amine (-CH2NH2) groups in compounds of formula (1) and intermediates thereto may be obtained by reduction of nitriles (-CN), for example by catalytic hydrogenation using for example hydrogen in the presence of a rnetal catalyst, for example palladium on a support such as carbon, or Raney® nickel, in a solvent such as an ether e.g. a cyclic ether such as tetrahydrofuran or an alcohol e.g. methanol or ethanol, optionally in ihe presence of ammonia solution at a temperature from ambient to the reflux temperature, or by chemical reduction using for example a metal hydride e.g. lithium aluminium hydride, in a solvent such as an ether e.g. a cyclic ether such as tetrahydrofuran, at a temperature from 0°C to the reflux temperature. In another example, sulphur atoms in the compounds, for example when present in a group L1 or L2 may be oxidised to the corresponding sulphoxide or sulphone using an oxidising agent such as a peroxy acid, e.g. 3-chloroperoxybenzoic acid, in an inert solvent such as a halogenated hydrocarbon, e.g. dichloromethane, at around ambient temperature. fri a further example N-oxides of compounds of formula (1) may in general be prepared for example by oxidation of the corresponding nitrogen base using an oxidising agent such as hydrogen peroxide in the presence of an acid such as acetic acid, at an elevated temperature, for example around 70QC to BOQC, or alternatively by reaction with a peracid such as peracetic acid or m-chloroperoxybenzoic acid in a solvent.such as a halogenated hydrocarbon e.g. dichloromethane or an alcohol e.g. tert-butanol at a temperature from the ambient temperature to the reflux temperature. In another example compounds of formula (12) may be converted to further compounds as formula (13) in which Ar is an optionally substituted aromatic or heteroaromatic group for use in the synthesis of for example compounds of formula (1), using such well know and commonly used palladium mediated reaction conditions as are to be found in the general reference texts Rodd's Chemistry of Carbon Compounds, Volumes 1-15 and Supplemental (Elsevier Science Publishers, 1989), Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-19 (John Wiley and Sons, 1999), Comprehensive Heterocyclic Chemistry, Ed. Katritzky et a/, Volumes 1-8, 1984 and Volumes 1-11, 1994 (Pergamon), Comprehensive Organic Functional Group Transformations, Ed. Katritzky et al, Volumes 1-7, 1995 (Pergamon), Comprehensive Organic Synthesis, Ed. Trost and Flemming, Volumes 1-9, (Pergamon, 1991), Encyclopedia'of Reagents for Organic Synthesis, Ed. Paquette, Volumes 1-8 (John Wiley and Sons, 1995), Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989) and March's Advanced Organic Chemistry (John Wiley and Sons, 5th Ed., 2001). Salts of compounds of formula (la) or (1b) may be prepared by reaction of compounds of formula (1a) or (1b) with an appropriate base in a suitable solvent or mixture of solvents e.g. an organic solvent such as an ether e.g. rliethyiether, or an alcohol, e.g. ethanol using conventional procedures. Where it is desired to obtain a particular enantiomer of a compound of formula (1a) or (1b) this may be produced from a corresponding mixture of enantiomers using any suitable conventional procedure for resolving enantiomers. hus for example diastereomeric derivatives, e.g. salts, may be produced by reaction of a mixture of enantiomers of formula (1a) or (1b) e.g. a racemate, and an appropriate chiral compound, e.g. a chiral base. The diastereomers may then be separated by any convenient means, for example by crystallisation and the desired enantiomer recovered, e.g. by treatment with an acid in the instance where the diastereomer is a salt. In another resolution process a racemate of formula (1a) or (1b) may be separated using chiral High Performance Liquid Chromatography. Alternatively, if desired a particular enantiomer may be obtained by using an appropriate chiral intermediate in one of the processes described above. Alternatively, a particular enantiomer may be obtained by performing an enantiomer specific enzymatic biotransformation e.g. an ester hydrolysis using an esterase and then purifying only the enantiomerically pure hydrolysed acid from the unreacted ester antipode. Chromatography, recrystallisation and other conventional separation procedures may also be used with intermediates or final products where it is desired to obtain a particular geometric isomer of the invention. The following Examples illustrate the invention. All temperatures are in °C. The following abbreviations are used: NMM - N-methylmorpholine; EtOAc - ethyl acetate; MeOH - methanol; BOG - butoxycarbonyl; DCM - dichloromethane; AcOH - acetic acid; DIPEA - diisopropylethylamine; EtOH - ethanol; Pyr - pyridine; Ar - aryl; DMSO - dimethylsulphoxide; iPr - isopropyl; L£t2O - diethylether; Me - methyl; THF tetrahydrofuran, DMF - N,N-dimethylformamide; MCPBA - 3-chloroperoxybenzoic acid NBS - N-bromosuccinimide FMOC - 9-fluorenylmethoxycarbonyl r.t. - room temperature DBU - 1,8-Diazabicyclo[5,4-0]undec-7-ene EDC - 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride HOBT - 1-hydroxybenzotriazole hydrate Ail NMRs were obtained either at 300MHz or 400MHz. Compounds were named with the aid of either Beilstein Autonom supplied by MDL Information Systems GmbH, Theodor-Heuss-Allee 108, D-60486 Frankfurt, Germany or ACD Labs Name (v.5.0) supplied by Avanced Chemical Development, Toronto, Canada. LCMS retention times (RT) quoted were generated on a Hewlett Packard 1100 LC/MS using the following following method: Phenomenex Luna 3u,Ci8(2) 50x4.6mm column; mobile phase A = 0.1% formic acid in water; mobile phase B = 0.1% formic acid in MeCN; flow rate of 0.9mLmin"1, column temperature 40°C. (Table Remove) Gradient:- Intermediate 1 3-Benzovl-2-fluoropvridine To a freshly prepared solution of lithium diisopropylamide (22mmol) in dry THF (20ml_) under nitrogen and cooled to -78° was added a solution of 2-fluoropyridine (1.94g, 20mmol) in dry THF (10mL). The reaction was stirred for 2.5h at -78° before adding a solution of N-methoxy-N-methyl benzamide (3.47g, 21mmol) in THF (8mL). The reaction mixture was allowed to warm to room temperature over 1.5h and stir at room temperature for 1h. The reaction was quenched with water (50mL), extracted with EtOAc (2x50mL), the extracts dried (MgSCU) and concentrated in vacua. The crude product was purified by chromatography on silica (5-20% EtOAc in isohexane) to give the title compound as a colourless oil (1.05g, 26%). 5H (CDCI3) 8.44 (1H, ddd, J 4.9, 2.0, 1.1 Hz), 8.06 (1H, ddd, J 9.3, 7.4, 2.0Hz), 7.84 (2H, dm, J 8.4Hz), 7.66 (1H, tt, J 7.4, 1.3 Hz), 7.52 (2H, tm, J 7.8Hz), 7.38 (1H, ddd, J 6.8, 4.9, 1.9Hz). LCMS (ES+) RT 3.27 minutes, 202 (M+H)+ Intermediate 2 Ethyl 3-Phenvlthienor2.3-d1pvridine-2-carboxvlate To a solution of ethyl 2-mercaptoacetate (0.6mL, 5.5 mmol) in dry DMF (lOmL) under nitrogen and cooled with an ice bath was added sodium hydride (220mg of 60% dispersion in oil, 5.75mmol). After hydrogen evolution had ceased the cooling bath was removed and the reaction stirred at room temperature for 30 mins. A solution of Intermediate 1 (920mg, 4.6mmol) in DMF (5mL) was added and the reaction stirred at room temperature for 3h. The reaction was quenched with water (50ml_) and extracted with EtOAc (3x50mL). The combined EtOAc layers were washed with brine (50mL), dried (MgSO4) and concentrated in vacuo to give a mixture of the title compound and uncyclised ethyl 2-(3-benzoylpyridin-2-ylsulfanyl)acetate. This crude mixture was dissolved in EtOH (10mL) and sodium ethoxide (10ml_ of 0.5M solution in EtOH, 5.0mmol) added. The reaction was stirred at room temperature for 45 mins after which time complete conversion of uncyclised material to title compound was observed. The reaction was diluted with (EtOAc (SOrnL), washed with water (20mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica (10%EtOAc in isohexane) to give the title compound as a white solid (780mg, 60%). ftH (CDCI3) 8.63 (1H, dd, J 4.5, 1.4Hz), 7.78 (1H, dd, J 8.2, 1.5Hz), 7.41 (3H, m), 7.33-7.32 (2H, m), 7.24 (1H, dd, J 8.2, 4.6Hz), 4.18 (2H, q, J 7.1 Hz), 1.15 (3H, t, J 7.1 Hz) LCMS (ES+) RT3.90 minutes, 284 (M+H)+. Intermediate 3 Ethyl 3-phenvlthienof2.3-frlpyridine-2-carboxvlate N-oxide To a solution of Intermediate 2 in DCM (10mL) was added MCPBA (738mg of 60%w/w, 2.57mmoi) and the reaction stirred at r.t. for 6h. The reaction mixture was diluted with DCM (20ml_), washed with 2M NaOH (aq), dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica (80% EtOAc in isohexane - EtOAc) to give the title compound as a white solid (670mg, 90%). 5H (CDCI3) 8.36 (1H, d, J 6.1 Hz), 7.55-7.49 (4H, m), 7.44-7.39 (2H, m), 7.26 (1H, dd, J 8.2, 6.2 Hz), 4.20 (2H, q, J 7.1 Hz), 1.16 (3H, t, J 7.1Hz). LCMS (ES+) RT3.18 minutes, 300 (M+H)+ Intermediate 4 Ethyl 6-oxo-3-phenvl-6.7-dihvdrothienor2.3-dlPvridine-2-carboxvlate A mixture of Intermediate 3 (400rng, 1.34mmol) and acetic anhydride (20ml_) was heated to reflux for 18h. The reaction mixture was concentrated in vacua and the residue co-evapourated with toluene (4x20mL). The crude material was dissolved in THF (20mL) and treated with 10% aqueous K2CO3 (20mL). The reaction was stirred at room temperature for 18h and then extracted with EtOAc (3x25mL). The EtOAc extracts were dried (MgSO4) and concentrated in vacua. The crude product was purified by chromatography on silica (40-50% EtOAc in isohexane) to give the title compound as a white solid (193mg, 48%). 6H (CDCI3) 7.48 (1H, d, J 9.5Hz), 7.43-7.36 (3H, m), 7.31-7.28 (2H, m), 6.53 (1H, d, J 9.5Hz), 4.13 (2H, q, J 7.1Hz), 1.12 (3H, t, J 7.1Hz). LCMS (ES+) RT 3.25 minutes, 322 ((M+Na)+, 24%), 300 ((M+H)+, 100%). Intermediate 5 Ethyl 3-aminothienor2.3-b1pvridine-2-carboxvlate A mixture of 2-chloro-3-cyanopyridine (330 g), ethyl 2-mercaptoacetate (361.2 g), sodium carbonate (265 g) and EtOH (1.2L) was heated to reflux for 4.5 hours. It was then cooled to ambient temperature, added to water (10L) and the addition was washed in with water (5L). The resulting slurry was stirred for 30 minutes and then it was filtered. The filter cake was washed with two portions of water (2 x 2.5L) and dried at the pump. The solids were ihen dried to constant weight under vacuum at 45° to yield the title compound as a brown solid (493.1 g, 93.2%). 8H (CDCI3) 8.68 (1H, dd, J 4.7, 1.2 Hz), 7.93 (1H, dd, J 8.5, 1.2 Hz), 7.29 (1H, dd, J 8.5, 4.7 Hz), 5.90 (2H, b), 4.38 (2H, q, J 7.0 Hz}, 1.40 (3H, t, J 7.0 Hz). LCMS RT 2.9 minutes, 223 (M+H)+ Intermediate 6 Ethyl 3-bromothienor2,3-frlPvridlne-2-carboxvlate Intermediate 5 (363. 6g) was added in portions over two hours to a mixture of copper(ll) bromide (403.3g), t-butyl nitrite (220.6 g) and acetonitrile (3.6L) stirred at a temperature of 20 to 25°. The mixture was stirred at 20° for 2 hours before it was slowly added to 2M HCI(aq) (4.2L). The reaction mixture slurry was filtered and the solids were washed with water (500 ml). The combined filtrate was extracted with EtOAc (8L), and the EtOAc solution was washed with 2M HCI(aq) (2.2L). The solids were dissolved in EtOAc (6L) and this solution was washed twice with 2M HCI(aq) (4.4L and 2.2L). The two EtOAc solutions were then combined and washed with 2M HCI(aq) (2.2L) and twice with water (2 x 2L). The EtOAc solution was then dried (MgSO4), filtered and concentrated in vacua at 40 mbar and 60° to give a solid residue. This was broken up and dried to constant weight under vacuum at 45° to yield the title compound as a brown solid (458.5g, 97.9%). 8H (DMSO-d6) 8.89 (1 H, d, J 4.7 Hz), 8.47 (1 H, d, J 8.6 Hz), 7.71 (1 H, dd, J 8.6, 4.7 Hz), 4.46 (2H, q, J 7.2 Hz), 1.40 (3H, t, J 7.2 Hz). LCMS RT 3.8 minutes, 288 intermediate 7 Ethyl 3-Bromothienof2.3-blpyridine-2-carboxvlate N-oxide To a slurry of Intermediate 6 (21 4g, 0.747Mol) in DCM (2140mL) under nitrogen was added MCPBA (240g @ 70% = 168g, 0.97Mol) portion wise over 0.5h. The reaction was then stirred at r.t. for 18h. The reaction mixture was quenched with water (800mL) and pH adjusted to 8.5 with 10%w/v sodium carbonate solution (1250mL). The basic aqueous layer was removed and the organic layer washed with water until pH 7. The organic layer was concentrated in vacua and the crude title product was recovered as a tan solid. The crude product was purified by slurrying in methyl te/f-butyl ether (600ml) for 1 hr at 0-5° to give the title compound (174g, 77%). 8H (CDCI3) 8.44 (1H, dd, J 6.2, 0.8 Hz), 7.87 (1H, dd, J 8.3, 0.8 Hz), 7.48 (1H, dd, J 8.3, 6.2 Hz), 4.49 (2H, q, J 7.1 Hz), 1.48 (3H, t, J 7,1 Hz). LCMS (ES+) RT 2.61 minutes, 302(M)' Intermediate 8 Ethyl 3-bromo-6-oxo-6.7-dihvdrothienof2.3-/7lpvridine-2-carboxylate A mixture of Intermediate 7 (SOOrng, 1.66mmol) and DMF (10ml_) was set to stir at 0° under nitrogen. To this reaction mixture was added trifluoroacetic anhydride (3.49g, 2.36ml_, 16.6mmol) in one portion via syringe. After stirring for 16 hours the volatiles were removed in vacuo and the residue co-evaporated with toluene (2x20ml_). The crude material was then extracted with EtOAc (2x100ml_). The EtOAc extracts were dried (MgSO4) and concentrated in vacuo. The crude product was purified by a re-slurry in toluene (10mL) to give the title compound as a beige solid (260mg, 52%). 8H (DMSO-d6) 12.20 (1H, brs), 7.75 (1H, d, J 9.0Hz), 6.50 (1H, d, J 9.0Hz), 4.15 (2H, q, J 7.1 Hz), 1.12 (3H, t, J 7.1 Hz). LCMS (ES+) RT 2.86 minutes, 302 ((M+H)1, 100%). MP =261.7-268.1 °C. Intermediate 9 Ethyl 3-bromo-6-oxo-7-phenvl-6.7-dihvdrothienor2.3-felPvridine-2- carboxvlate To a 2 necked round bottomed flask was added in sequence Intermediate 8 (302mg, l.OOmmol), copper(ll) acetate (278mg, 1.50mmol, 150mol%), phenylboronic acid (488mg, 4.00mmol), DCM (5mL) and pyridine (158mg, 2.00mmol). The reaction was stirred at room temperature for 18h with the exclusion of moisture. The reaction was then diluted with DCM (50mL), washed with 2M HCI(aq) (50mL), the aqueous was re-extracted with DCM (50mL). The combined organics were then washed with water (50ml_), dried (MgSO4) and concentrated in vacuo. The crude product was purified by a slurry in methanol (12mL), to give the title compound as a beige solid (270mg, 72%). ftH (CDCI3) 7.82 (1H, d, J 8.5Hz), 7.70-7.62 (3H, m), 7.54-7.42 (2H, m), 6.70 (1H, d, J 8.5Hz), 4.15 (2H, q, J 7.1 Hz), 1.14(3H, t, J7.1 Hz). LCMS (ES+) RT 3.75 minutes, 378 (M+H)+. MP = 201.6-206.0°C. Intermediate 10 Ethyl 3-{4-fluorophenvl)-6-oxo-6.7-dihvdrothienor2.3-blpyridine-2- carboxylate A mixture of Intermediate 8 (241 mg, O.Smmol), tetrakis(triphenylphosphine)palladium(0) (92mg, O.OSmmol, 10mol%), 2M K2C03 (aq) (0.8ml, 1.6mmol) and 4-fluorophenylboronic acid in ethylene glycol dimethyl ether (10mL) was heated to reflux under nitrogen for 20h. Solvent was removed in vacua and the crude product purified by chromatography on silica (10% THF in DCM) to give the title compound as a white solid (210mg). LCMS (ES+) RT3.24 minutes, 318 (M+H)+. Intermediate 11 6-Oxo-3-phenvl-6.7-dihvdrothienor2.3-blpyridine-2-carboxamide To a solution of Intermediate 4 (5.13g, 17 mmol) in 1:1 THF water (200mL) was added lithium hydroxide monohydrate (1.6g, 37.4mmol) and the reaction stirred at r.t. overnight. The reaction was incomplete at this time and was therefore concentrated on a rotary evaporator' by approx. half and the reaction heated at 60° for 20h. Reaction showed complete conversion to the uarboxylic acid at this time. The reaction was diluted with water (50mL) and 2M HCI(aq) added with stirring until a precipitate had formed (pH 1-2). The solid was filtered, washed with several portions of water and dried in a vacuum oven to afford 6-oxo-3-phenyl-6,7-dihydrothieno[2,3-b]pyridine-2-carboxylic acid as a solid (3.0g). LC RT 2.72 minutes. This compound was suspended in anhydrous DMF (30ml_), 1,1'-carbonyldiimidazole (2.14g, 13.2 mmol) added and the reaction stirred for 30 mins. Ammonia (75mL of 25% aqueous solution) was added and the reaction stirred at r.t. for 1h before being concentrated in vacua. The resultant solid was suspended in 2M HCI(aq), collected by filtration and dried in a vacuum oven to give the title compound as a white solid (2.63g). 5H (DMSO-d6) 7.63-7.49 (4H, m), 7.45-7.42 (2H, m), 6.51 (1H, d, J 9.2Hz), 6.28 (1H, bs). LCMS (ES+) 271 (M+H)+. Intermediate 12 6-oxo-3-phenvl-6J-dihvdrothienor2.3-blpyridine-2-carbonitrile To a solution of Intermediate 11 (270mg, LOmmol) and pyridine (141(j,L, LOmmol) in dry DCM (10mL) was added trifluoroacetic anhydride (160^L, 2.0mmol) and the reaction stirred at r.t. for 16h. Solvent was removed in vacua and the resultant solid suspended in water (30mL) and acidified with 2M HCI(aq) (10ml_). The solid was collected by filtration, washed with water (25mL) and dried in vacua to afford the title compound as a white solid (220mg, 87%). SH (DMSO-d6) 7.85 (1H, d, J 9.1 Hz), 7.63-7.58 (5H, m), 6.69 (1H, d, J 9.1 Hz). LCMS (ES+) 253 (M+H)+. Intermediate 13 6-Oxo-3,7-diPhenvl-6.7-dihvdrothienor2.3-6lDvridine-2-sulfonvl chloride To a solution of the compound of Example 84 (675mg, 2.5mmol) in dry DCM (20mL) cooled to -78° was added chlorosulfonic acid (1.72g, 14.7mmol) over 5 mins. After 15 minutes reaction was removed from the cooling bath and stirred at r.t. for 1h. Reaction was poured onto ice-water and extracted with DCM. The combined DCM extracts were dried (MgSC>4) and concentrated in vacua to give the title compound as a yellow solid (65mg). Intermediate 14 Ethyl 3-(2.4-difluorophenvl)-6-oxo-6.7-dihvdrothienor2.3-b1pyridine-2- carboxvlate The title compound was prepared from Intermediate 8 and 2,4-difluorophenylboronic acid following the analogous procedure described for Intermediate 10. This gave the title compound as a white solid LCMS (ES+) 336 (M+H)+. Intermediate 15 1 -Phenvl-1 A-/-pvrrolor3.2-fr|pvridine 1 H-Pyrrolo[3,2-d]pyridine (0.5g, 4.24mmol), phenylboronic acid (1.03g, 8.44mmoi), copper(ll) acetate (1.54g, 8.48mmol), and 4A molecular sieves (2g), were suspended in DCM (10mL). Triethylamine (1.19mL, 8.5mmol) and pyridine (0.7mL, 8.65mmol) were added and the reaction stirred at r.t. for three days. The reaction mixture was diluted with further DCM, filtered and concentrated in vacua. Chromatography (silica, EtOAc) gave the title compound (325mg). SH (CDCI3) 7.80 (1H, d, J 8.2Hz), 7.54-7.30 (7H, m), 7.15 (1H, brs), 6.88 (1H, brs). LCMS (ES+) RT 1.20 minutes, 195 (M+H)+. Intermediate 16 1 -Phenvl-1 H-pyrrolof3.2-blpyridme 4-oxide Intermediate 15 (307mg, 1.58mmol) was dissolved in DCM (5mL) and treated with MCPBA (356mg, 2.06mmol). After stirring for eighteen hours at r.t. the reaction was diluted with DCM, washed twice with 2M sodium hydroxide, dried (sodium sulphate) and concentrated in vacua to give the title compound (285mg). «H (CDCI3) 8.15 (1H, d, J 6.2Hz), 7.55-7.47 (2H, m), 7.42-7.37 (5H, in). 7.07, (1H, dd, J 0.7, 3.5Hz), 7.01 (1H, dd, J 6.2, 8.4Hz). LCMS (ES+) RT 2,527 minutes, 211 (M+H)+. Intermediate 17 1 -Phenyl-1.4-dihvdro-pvrrolor3.2-frlpvridin-5-one Intermediate 16 (273mg, 1.3mmol) was dissolved in DMF (3mL) and treated at 0° with trifluoroacetic anhydride (1.8mL, 13mmol), was allowed to warm to r.t. and stir for two hours. The reaction was diluted with toluene and concentrated in vacua, re-dissolved in EtOH and concentrated again to give the title compound as an olive coloured solid (420mg). 8H (CDCI3) 8.10 (1H, Example 1 Ethyl 6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3-/?lpyridine-2-carboxvlate To an oven dried flask was added in sequence 4A molecular sieves (33mg), phenylboronic acid (82mg, 0.67mmol), DCM (3mL), pyridine (53mg, 0.67mmol), Intermediate 4 (100mg, 0.33mmol), copper(ll) acetate (6mg, 0.033mmol, 10mol%) and pyridine N-oxide (34mg, 0.36mmol). The reaction was stirred at room temperature for 18h with the exclusion of moisture. The reaction was then diluted with DCM (20mL), washed with 2M HCl(aq) (2x1 OmL), 2M NaOH(aq) (3x1 OmL), dried (MgSO4) and concentrated in vacua. The crude product was purified by chromatography on silica (DCM -1% MeOH in DCM) to give the title compound as a buff solid (95mg, 77%). :SH (CDCI3) 7.68-7.56 (3H, m), 7.54-7.42 (6H, m), 7.40-7.38 (2H, m), 6.70 (1H, d, J 9.6Hz), 4.15 (2H, q, J 7.1 Hz), 1.14 (3H, t, J 7.1 Hz). LCMS (ES4) RT 3.87 minutes, 376 (M+H)+. Example 2 Ethyl 7-cvclopropvlmethvl-6-oxo-3-phenvl -6.7-dihvdrothienor2.3- frlPvridine-2-carboxvlate To a solution of Intermediate 4 (90mg, O.Smmol) in dry DMF (3mL) was added polystyrene supported 2-te/t-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine (PS-BEMP, 177mg) and cyclopropylmethyl bromide (101mg, 73|xL, 0.75mmol). The reaction was then heated to 80° under nitrogen for 18h. The crude reaction mixture was filtered to remove PS-BEMP and the resin washed with EtOAc. The filtrate was concentrated in vacua and the residue purified by chromatography (DCM - 1% MeOH in DCM) to give the title compound as a brown gum (57mg, 54%). Recrystallisation from diisopropyl ether gave the title compound as brown needles (30mg), 5H (CDCI3) 7.44-7.35 (3H, m), 7.31-7.24 (4H, m), 6.45 (1H, ti, J 9.5Hz), 4.14 (2H, q, J7.1Hz), 4.04 (2H, d, J7.1Hz), 1.42 (1H, m), 1.12 (3H, t, J 7.1 Hz), 0.53 (4H, m). LCMS (ES+) RT 4.04 minutes, 354 (M+H)"". Example 3 Ethyl 7-(4-dimethvlaminoDhenvh-6-oxo-3-phenvi-6.7-dlhvdrothienor2.3- 01 pyrid i ne-2-carboxvlate To an oven dried flask was added in sequence 4-dimethylaminophenylboronic acid (551 mg, 3.34mmol), DCM (10ml_), pyridine (0.27mL, 3.34mmol), Intermediate 4 (500mg, 1.67mmol), copper(ll) acetate (34mg, 0.17mmol, 10mol%) and pyridine N-oxide (318mg, 3.34mmol). The teaction was stirred at r.t. for 24h with the exclusion of moisture. The reaction was then diluted with DCM (20mL), washed with saturated NH4CI(aq), NaHCO3 (aq), dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica (5-10% EtOAc in DCM) to give the title compound as a white solid (150mg, 21%). 8H. (DMSO-dB) 7.51-7.49 (3H, m), 7.42-7.40 (3H, m), 7.30 (2H, d, J 9,OHz), 6.89 (2H, d, J 9.0Hz), 6.53 (1H, U, J 9.6Hz), 4.07 (2H, q, J 7.1 Hz), 3.31 (6H, s), 1.06 (3H, t, J 7.1 Hz). LCMS (ES") RT4.10 minutes, 419 (M+H)+. General procedure for the preparation of Ethyl 7-arvl-6-oxo-3-Dhenvl-6,7-tetrahvdrothienor2.3-blpyridine-2-carboxvlates The compounds of the following Examples 4-16 were prepared by parallel synthesis using a Radleys Carousel reaction station (Radleys Ltd., Saffron Walden, U.K.) following a procedure similar to that described for Example 3. Therefore to each oven dried reaction tube in the Carousel was added a magnetic stirrer, the appropriate arylboronic acid (I.Ommol), DCM (5mL), pyridine (O.OSmL, I.Ommol), Intermediate 4 (150mg, O.Smmol), copper(ll) acetate (10mg, O.OSmmol, 10mol%) and pyridine N-oxide (95mg, LOmmol). The reactions were stirred at r.t. for 18h with the exclusion of moisture. Each reaction was then diluted with DCM (20ml_)', washed with saturated NHUCI(aq), NaHCOalaq), dried (MgSO4) and concentrated in vacuo. The crude products were purified on silica eluting with 0-25% EtOAc in DCM to give the title compounds as solids. Exampte.4 Ethyl _ 7-(4-methoxvphenvl)-6-oxo-3-phenyl-6,7-dihvdrothienof2,3- blpyridine-2-carboxvlate SH (DMSO-d6) 7.51-7.39 (8H, m), 7.19 (2H, d, J 9.0Hz), 6.55 (1H, d, J 9.6Hz), 4.08 (2H, q, J 7.1 Hz), 3.88 (3H, s), 1.05 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.85 minutes, 406 (M+H)+. Example 5 Ethyl _ 7-(3-methoxvphenvh-6-oxo-3-phenvl-6.7-dihvdrothienof2.3- blpyridine-2-carboxvlate oH (DMSO-d6) 7.59 (1H, t, J 8.3Hz), 7.51 (3H, m), 7.49 (1H, m), 7.46 (2H, m), 7.18 (2H, m), 7.11 (1H, m), 6.57 (1H, d, J 9.7Hz), 4.06 (2H, q, J 7Hz), 3.82 (3H, s), 1 .07 (3H, t, J 7Hz). LCMS (ES+) RT 3,87 minutes, 406 (M+H)+. Example 6 Ethyl _ 6-oxo-3-phenvl-7-f4-tolvl)-6.7-dihvdrothienor2.3-d1pvridine-2- carboxylate iSH (DMSO-d6) 7.53-7.40 (10H, m), 6.55 (1H, d, J 9.7Hz), 4.07 (2H, q, J 7.1 Hz), 2.45 (3H, s), 1.06 (3H, t, J 7.1 Hz). LCMS (ES+) RT4.11 minutes, 390 Example 7 Ethyl 7-f5-indolvh-6-oxo-3-phenvl-6.7-dihvdrothienor2.3-felPvridine-2-oarboxvlate oH (DMSO-d6) 11.48 (1H, bs), 7.71 (1H, s), 7.64 (1H, d, J 8.6Hz), 7.55-7.16 (7H, m), 7.13 (1H, d, J 2.1 Hz), 6.58 (1H, m), 6.57 (1H, d, J 9.6Hz), 4.05 (2H, q, J 7.1 Hz), 1.03 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.73 minutes, 415 (M+H)+. Example 8 Ethyl 6-oxo-3-phenvl-7-(3-thienvn-6.7-dlhvdrothienor2.3-f?lpyridine-2- carboxvlate H (DMSO-d6) 8.04 (1H, dd, J 3.1, 1.4Hz), 7.85 (1H, dd, J 5.1, 3.1Hz), 7.41 (3H, rn), 7.39 (3H, m), 7.28 (1H, d, J 1.4Hz), 6.55 (1H, d, J 9.7Hz), 4.09 (2H, (|, J 7.1 Hz), 1.06 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.83 minutes, 382 (M+H)+. Example 9 Ethyl 6-oxo-3-phenvl-7-(4-trifluoromethoxvphenvl)-6.7- dihvdrothienor2.3-fr]pvridine-2-carboxvlate I CMS (ES1) RT 4.20 minutes 460 (M+H)+. Example 10 bthyl 7-(3-fluorophenvl)-6-oxo-3-phenv[-6.7-dihvdrothienor2.3- /?lpyridine-2-carboxylate [.CMS (ES+) RT 3.91 minutes 394 (M+H)+. Example 11 Ethyl 7-(4-fluorophenvl)-6-oxo-3-phenvl-6.7-dihvdrothienor2.3- dlpyridine-2-carboxvlate LCMS (ES+) RT 3.88 minutes 394 (M+H)+. Example 12 Ethyl 7-(4-chlorophenvn-6-oxo-3-phenvl-6.7-dihvdrothienor2.3- £j|pyridine-2-carboxvlate i CMS (ES1) RT 4.14 minutes 410 (M+H)+. Example 13 Ethyl 7-(3-cvanophenvl)-6-oxo-3-phenvl-6.7-dihvdrothienof2.3- fr|pvridme-2-carboxvlate LCMS (ES+) RT 3.72 minutes 401 (M+H)+. Example 14 Ethyl 6-oxo-3-phenvl-7-(3-tolvl)-6.7-dihvdrothienor2.3-blDvridine-2- carboxylate .CMS (ESH-) RT 4.09 minutes, 390 (M+H)+. Example 15 Ethyl 6-oxo-3-phenvl-7-(4-trifluoromethvlphenvn-6.7-dihvdrothienor2.3- tf|pvridine-2-carboxvlate LCMS (ES+) RT 4.22 minutes, 444 (M+H)+. Example 16 Ethyl 7-(3-bromophenvl)-6-oxo-3-phenvl-6.7-dihvdrothienor2.3- iblpvridine-2-carboxvlate LCMS (ES+) RT 4.24 minutes, 454 (M+H)+. Example 17 Ethyl 3-(4-fluorophenvl)-6-oxo-7-phenvl-6.7-dihvdrothienor2.3- fr|pvridme-2-carboxvlate To an oven dried flask was added in sequence phenylboronic acid (78mg, 0.64mmol), DCM (5mL), pyridine (0.64mmol), Intermediate 10 (100mg, 0.32mmol), copper(ll) acetate (0.032mmol, 10mol%) and pyridine N-oxide (0.35mmol). The reaction was stirred at r.t. for 48h with the exclusion of moisture. The reaction was then diluted with DCM (20ml_), washed with saturated NH4CI(aq), dried (MgS04) and concentrated in vacua. The crude product was purified by chromatography on silica (0-5% THF in DCM) to give the title compound as a white solid (75mg). 8H (CDCI3) 7.70-7.56 (3H, m), 7.50-7.42 (3H, m), 7.40-7.32 (2H, m), 7.25-7.15 (2H, m), 6.64 (1H, d, J 9.6Hz), 4.16 (2H, q, J 7Hz), 1.17 (3H, t, J 7Hz). LCMS (ES+) RT 3.77 minutes, 394 (M+H)*. C22Hi6NFO3S requires C 67.16%, H 4.10%, N 3.56%; found C 67.16%, H 4.10%, N 3.54%. Example 18 Ethvi 7-(3-chlorophenvl)-3-(4-fluorophenvn-6-oxo-6.7-dihvdrothienor2.3- frlPvridine-2-carboxvlate To an oven dried flask was added in sequence 3-chlorophenylboronic acid (108mg, 0.688mmol), dichloroethane (5mL), pyridine (0.056mL, 0.688mmol), Intermediate 10 (109mg, 0.344mmol), copper(ll) acetate (8mg, 0.034mmol, 10mol%) and pyridine N-oxide (36mg, 0.38mmol). The reaction was heated at 70° for 48h with the exclusion of moisture. The reaction was then diluted with DCM (20mL), washed with saturated NH4CI(aq), dried (MgSO4) and concentrated in vacua. The crude product was purified by chromatography on silica (0-5% THF in DCM) to give the title compound as a white solid (75mg). LCMS (ES+) RT 3.93 minutes, 428 (M+H)+. Example 19 Ethyl 6-oxo-7-phenvl-3-(2-tolvU-6.7-dihvdrothienor2.3-dlpyridine-2- carboxvlate 2M K2CO3(aq) (0.25mL, O.Smmol) was added to a solution of Intermediate 9 (100mg, 0.266mmol), Tetrakis(triphenylphosphine)palladium(0) (30mg, 0.027mmol, 10mol%) and 2-tolylboronic acid (44mg, 0.32mmol) in ethylene glycol dimethyl ether (4mL) and the reaction heated to reflux for 24h under nitrogen. The mixture was diluted with water (10mL), extracted with DCM (2x8ml_), the combined DCM extracts dried (MgSO4) and concentrated in vacua. The crude product was purified by chromatography on silica (0-20% EtOAc in DCM) to give the title compound as a white solid (57mg). 8H (CDCI3) 7.60-7.48 (3H, m), 7.40 (2H, m), 7.27-7.10 (4H, m), 7.07 (1H, m), 6.51 (1H, d, J 9Hz), 4.03 (2H, q, J 7Hz), 2.06 (3H, s), 0.99 (3H, t, J 7Hz). I .CMS (ES+) RT 3.87 minutes, 390 (M+H)+. C23H19NO3S requires C 70.93%, H 4.92%, N 3.60%; found C 70.66%, H 4.95%, N 3.52%. General procedure for the preparation of Ethvl 3-arvl-6-oxo-7-phenvl-6,7-tetrahvdrothienof2.3-blPvridine-2-carboxvlates I he compounds of the following Examples 20-43 were prepared by parallel synthesis using a Radleys Carousel reaction station (Radleys Ltd., Saffron Walden, U.K.) following a procedure similar to that described for the compound of Example 19. Each reaction tube in the Carousel was charged with the appropriate arylboronic acid (0.32mmol, 1.2equiv.), Intermediate 9 (!00mg, 0.266mmol), tetrakis(triphenylphosphine)palladium(0) (30mg, 10mol%) and a magnetic stirrer bar. Ethylene glycol dimethyl ether (4ml_) was added to each tube followed by 2M K2CO3(aq) (0.25mL, Smmol) and the reactions heated to reflux under nitrogen for 24h. Each reaction was then diluted with water (10ml_), extracted with DCM (2x8mL) and the combined PCM extracts dried (MgSO4) and concentrated in. vacua. The crude products were purified on silica eluting with 0-25% EtOAc in DCM to give the title compounds as solids. Example 20 Ethyl 6-oxo-7-phenvl-3-(3-tolvlV6.7-dihvdrothienor2.3-felpyridine-2- carboxylate (SH (DMSO-d6) 7.70-7.60 (3H, m), 7.56 (2H, m), 7.45 (1H, d, J 10Hz), 7.37 (1H, d, J 7Hz), 7.36 (1H, m), 7.27 (2H, m), 6.55 (1H, d, J 10Hz), 4.03 (2H, q, J 7Hz), 2.38 (3H, s), 1.05 (3H, t, J 7Hz). LCMS (ES+) RT 3.93 minutes, 390 (M+H)'. C23H19NO3S requires C 70.93%, H 4.92%, N 3.60%; found C 70.74%, H 4.95%, N 3.60%. Example 21 Ethyl 6-oxo-7-phenvl-3-f4-tolvn-6.7-dihvdrothienor2.3-/JlPvridine-2- carboxvlate SH (CDC!3) 7.70-7.50 (3H, m), 7.48-7.30 (3H, m), 7.25-7.15 (4H, m), 6.52 (1H, d, J 10Hz), 4.07 (2H, q, J 7Hz), 2.36 (3H, s), 1.08 (3H, t, J 7Hz). LCMS (ES+) RT 3.94 minutes, 390 (M+H)+. CaaH^NOsS requires C 70.93%, H 4.92%, N 3.60%; found C 70.42%, H 4.92%, N 3.58%. Example 22 Ethyl 3-f2-methoxvphenvl)-6-oxo-7-phenvl-6.7-dihvdrothienor2.3- fr|pvridine-2-carboxylate 6H (CDCI3) 7.60-7.50 (3H, rn), 7.48-7.30 (3H, m), 7.27 (1H, d, J 10Hz), 7.16 (1H, m), 7.01-6.94 (2H, m), 6.51 (1H, d, J 10Hz), 4.05 (2H, q, J 7Hz), 3.71 (3H, s), 1.03 (3H, t, J 7Hz). LCMS (ES+) RT 3.67 minutes, 406 (M+H)+. C23H19NO4S requires C 68.13%, H 4.72%, N 3.45%; found C 67.87%, H 4.71%, N 3.37%. Example 23 Ethyl 3-(2-fluorophenvlV6-oxo-7-phenvl-6.7-dihvdrothienor2.3- ij|pyridine-2-carboxvlate 5H (CDCI3) 7.80-7.50 (3H, m), 7.49-7.25 (3H, m), 7.48-7.10 (4H, m), 6.55 (1H, d, J 10Hz), 4.07 (2H, q, J 7Hz), 1.06 (3H, t, J 7Hz). LCMS (ES+) RT 3.71 minutes, 394 (M+H)+. C22Hi6NFO3S requires C 67.16%, H 4.10%, N 3.56%; found C 66.99%, H 4.05%, N 3.49%. Example 24 Ethyl 3-(3-chlorophenvl)-6-oxo-7-phenvl-6.7-dihvdrothienor2.3- dlpvridine-2-carboxvlate iSH (CDCI3) 7.68-7.58 (3H, m), 7.48-7.32 (5H, m), 7.28 (2H, m), 6.66 (1H, d, J lOHz), 4.17 (2H, q, J 7Hz), 1.16 (3H, t, J 7Hz). LCMS (ES+) RT 3.96 minutes, 410 (M+H)+. C82H16NCI03S requires C 64.47%, H 3.93%, N 3.42%; found C 64.47%, H 3.94%, N 3.35%. Example 25 Ethyl 3-(2-chlorophenvn-6-oxo-7-phenvl-6J-dihvdrothienor2.3- blPVridine-2-carboxvlate (SH (CDCI3) 7.60-7.05 (10H, m), 6.53 (1H, d, J 10Hz), 4.04 (2H, q, J 7Hz), 1.01 (3H, t, J 7Hz). LCMS (ES+) RT 3.87 minutes, 410 (M+H)+. C22H16NCIO3S requires C 64.47%, H 3.93%, N 3.42%; found C 64.19%, H 3.97%, N 3.41%. Example 26 Ethyj 3-f5-chloro-2-methoxvphenvO-6-oxo-7-phenvl-6.7- dihvdrothienor2.3-frlpyridine-2-carboxvlate ftH (CDCIg) 7.60-7.45 (3H, m), 7.43-7.34 (2H, m), 7.32 (1H, dd, J 9, 3Hz), 7.26 (1H, d, J 10Hz), 7.14 (1H, d, J 3Hz), 6.88 (1H, d, J 8Hz), 6.53 (1H, d, J 10Hz), 4.08 (2H, m), 3.69 (3H, s), 1.06 (3H, t J 7Hz). LCMS (ES+) RT 4.27 minutes, 440 (M+H)+. Example 27 Ethyl 3-(4-fluoro-2-methvlphenvl)-6-oxo-7-phenvl-6.7-dlhvdrothienor2.3- blpyridine-2-carboxylate oH (CDCI3) 7.60-7.48 (3H, m), 7.45-7.37 (2H, m), 7.18 (1H, m), 7.04 (1H, dd, ,] 8, 6Hz), 6.98-6.89 (2H, m), 6.52 (1H, d, J 9Hz), 4.04 (2H, q, J 7Hz), 2.06 (3H, s), 1.03 (3H, t, J 7Hz). LCMS (ES+) RT4.28 minutes, 408 (M+H)+. Example 28 Ethyl 3-(2.3-dichlorophenvn-6-oxo-7-phenvl-6.7-dihvdrothienor2.3- frlPvridine-2-carboxvlate iSH (CDCI3) 7.60-7.53 (2H, m), 7.51-7.46 (2H, m), 7.45-7.30 (2H, m), 7.25 (1H, t, J 7.5Hz), 7.19 (1H, d, J 10Hz), 7.13 (1H, dd, J 7.5, 1.5Hz), 6.54 (1H, d, J 10Hz), 4.04 (2H, m), 1.02 (3H, t, J 7Hz). LCMS (ES+) RT 4.49 minutes, 444 (M+H)f. Example 29 Ethyl 3-(2.4-difluorophenvl)-6-oxo-7-phenvl-6.7-dlhvdrothienor2.3- /yipyridine-2-carboxvlate «H (CDCI3) 7.60-7.47 (3H, m), 7,42-7.33 (2H, m), 7.31 (1H, dd, J 10, 1Hz), 7.23 (1H, q with F coupling, J 8Hz), 6.98-6.85 (2H, m), 6.56 (1H, d, J 10Hz), 4.12 (2H, m), 1,08 (3H, t J 7Hz). LCMS (ES+) RT4.09 minutes, 412 (M+H)+. Example 30 Ethyl 3-t3-methoxvphenvn-6-oxo-7-phenvl-6.7-dihvdrothienof2.3- frlpyridine-2-carboxylate I .CMS (ESf) RT 3.74 minutes, 406 (M+H)+. Example 31 Ethyl 3-(4-methoxyphenvl)-6-oxo-7-phenvl-6.7-dihvdrothienor2.3- ib|pvridine-2-carboxvlate I CMS (ES+) RT 3.72 minutes, 406 (M+H)+. C23H19NO4S requires C 68.13%, H 4.72%, N 3.45%; found C 67.96%, H 4.70%, N 3.40%. Example 32 Ethyl 3-(3-cvanophenvn-6-oxo-7-phenvl-6.7-dihvdrothienor2.3- /j|pyridine-2-carboxvlate LCMS (ES+) RT 3.57 minutes, 401 (M+H)+. Example 33 Ethyl 3-(4-cvanophenvl)-6-oxo-7-phenvl-6.7-dihydrothienof2.3- /)]pyridine-2-carboxvlate I .CMS (ES+) RT 3.58 minutes, 401 (M+H)+. Example 34 Ethyl 3-(3-f>uorophenvl)-6-oxo-7-phenvl-6.7-dlhvdrothienor2.3- blPvridine-2-carboxvlate LCMS (ES+) RT 3.78 minutes, 394 (M+H)+. CaaHisNFOaS requires C 67.16%, H 4.10%, N 3.56%; found C 67.06%, H 4.10%, N 3.54%. Example 35 Ethyl 3-f4-chloroDhenvl)-6-oxo-7-phenvl-6.7-dihvdrothlenor2.3- blpyridine-2-carboxvlate LCMS (ES+) RT 4.05 minutes, 410 (M+H)+. C22Hi6NCIO3S requires C 64.47%, H 3.93%, N 3.42%; found C 64.31%, H 3.93%, N 3.45%. Example 36 Ethyl 3- /y|pvridine-2-carboxvlate LCMS (ES") RT 4.70 minutes, 445 (M+H)+. Example 37 Ethyl 3-(2,5-dlchlorophenviV6-oxo-7-phenvl-6.7-dihvdrothienor2.3- /3lpyridine-2-carboxvlate LCMS (ES+) RT 4.57 minutes, 445 (M+H)+. Example 38 Ethyl 3-(5-fluoro-2-methoxvphenvl)-6-oxo-7-phenvl-6.7- dihvdrothienor2.3-falpyridine-2-carboxvlate 1..CMS (ES+) RT 3.98 minutes, 424 (M+H)+. Example 39 Ethvl 3-(2.6-dimethvlphenvn-6-oxo-7-phenvl-6.7-dihvdrothienor2.3- frlpvridine-2-carboxvlate [.CMS (ES+) RT 4.04 minutes, 404 (M+H)+. Exam pie 40 Ethvl 6-oxo-7-phenvl-3-(3-pvridvn-6J-dihvdrothienor2.3-blPvridine-2- carboxylate LCMS (ES+) RT 3.00 minutes, 377 (M+H)+. Example 41 Ethvl 6-oxo-7-phenvl-3-(2-trifluoromethvlphenvl)-6,7-dihvdrothienof2.3- /jlpyridine-2-carboxylate LCMS (ES+) RT 3.80 minutes, 444 (M+H)+. Example 42 Ethvl 6-oxo-7-phenvl-3-(3-trifluoromethvlphenvO-6.7-dihvdrothienor2.3- frlPvridine-2-carboxvlate LCMS (ES+) RT 3.97 minutes, 444 (M+H)+. Example 43 Ethvl 6-oxo-7"phenvl-3-f4-trifluoromethvlphenvl)-6.7-dihvdrothienor2.3- dlpvridine-2-carboxvlate I CMS (ES+) RT 3.99 minutes, 444 (M+H)+. Example 44 Ethvl 6-oxo-3"phenvl-7-(3-pvridinvn-6.7-dihvdrothienor2.3-blpvridine-2- carboxylate A mixture of Intermediate 4 (299mg, LOmmol), pyridine-3-boronic acid (246mg, 2.0rnmol), pyridine-A/-oxide (115mg, 1.2mmol), copper(ll) acetate (I82mg, LOmmol) and pyridine (0.160mL, 2.0mmol) in DCM (20mL) was stirred at r.t. for 3 days. The mixture was diluted with DCM (30ml_) and washed with saturated NH4CI(aq) plus ammonia (pH 10, 2 x 100mL), dried (Na2SO4) and concentrated in vacua. The crude product was purified by column chromatography on silica (3% MeOH in DCM) to give the title compound as a white solid (35mg, 9%). 5H (CDCI3) 9.00 (1H, d, J 4.5Hz), 8.95 (1H, s), 8.01 (1H, ddd, J 1.5, 2.4, 8.1 Hz), 7.76 (1H, dd, J 4.7, 8.1 Hz), 7.68-7,52 (4H, m), 7.55-7.52 (2H, m), 6.77 (1H, d, J 9.7Hz), 4.31 (2H, q, J 7.1 Hz), 1.30 (3H, t, J 7.1 Hz), m/z (ES+) 377.0 (M+H)+. Example 45 Ethyl 7-benzvl-6-oxo-3-phenvl-6.7-dihvdrothlenor2.3-blPvridine--2- carboxylate Sodium hydride (32mg of 60% w/w suspension in oil, O.Smmol, 1.2equiv.) was added to a solution of Intermediate 4 (200mg, 0.67mmol) in anhydrous DMF (5mL) under nitrogen and cooled with an ice bath. The reaction was stirred for 5 minutes before adding benzyl bromide (0.12mL, LOmmol, 1.5 equiv.). The reaction was heated at 60° for 18h. The reaction was partitioned between water and EtOAc, the EtOAc extracts were dried (MgSCU) and then concentrated in vacuo. The crude residue was purified by chromatography on silica (0-20% EtOAc in DCM) to give the title compound as an off-white solid (80mg). 8H (CDCI3) 7.60-7.20 (11H, m), 6.51 (1H, d, J 10Hz), 5.33 (2H, s), 4.08 (2H, q, J 7Hz), 1.07 (3H, t, J 7Hz). LCMS (ES+) RT 4.05 minutes, 390 General procedure for the preparation of Ethyl 7-alkvl-6-oxo-3-phenvl-i>.7-tetrahvdrothienor2.3-blpyridine-2-carboxvlates The compounds of the following Examples 46-56 were prepared by parallel synthesis using a Radleys Carousel reaction station (Radleys Ltd., Saffron Walden, U.K.) following a procedure similar to that described for Example 2. Each reaction tube in the Carousel was charged with the appropriate alkyl or arylalkyi halide (1.5mmol, 1.5equiv.), Intermediate 4 (200mg, 0.67mmol), polystyrene supported 2-te/t-butylimino-2-diethylamino-1 ,3-dimethyl-perhydro-1,3,2-diazaphosphorine (PS-BEMP, 364mg, O.Smmol, 1.2equiv.) and a magnetic stirrer bar. Anhydrous DMF (4mL) was added to each tube and the reactions stirred at 65° under nitrogen for 48h. Each reaction was partitioned between water and DCM and the combined DCM extracts dried (MgSO/O and concentrated in vacuo. The crude products were purified on silica eluting with 0-20% EtOAc in DCM to give the title compounds as solids. Example 46 Ethvi _ 7-(cvclohexvlmethvU-6-oxo-3-phenvl-6.7-dihvdrothienor2.3- folpyridine-2-carboxylate 6H (CDCIa) 7.40-7.35 (3H, m), 7.27-7.24 (3H, m), 6.42 (1H, d, J 10Hz), 4.12 (2H, q, J 7Hz), 3.95 (2H, d, J 7.5Hz), 2.08-2.05 (1H, m), 1.67-1.53 (5H, m), 1.16-1.09 (5H, m), 1.11 (3H, t, J 7Hz). LCMS (ES+) RT 5.17 minutes, 396 Example 47 Ethyl 6-oxo-7-(1-phenvlethvn-3-phenvl-6.7-dihvdrothlenof2.3-blpyridme- 2-carboxylate fiH (CDCI3) 7.30-7.18 (11H, m), 6.72 (1H, m), 6.49 (1H, d, J 10Hz), 4.05-3.99 (2H, m), 1.91 (3H, d, J 7Hz), 1.01 (3H, t, J 7Hz). LCMS (ES+) RT 4.29 minutes, 404 (M+H)+. Example 48 Ethyl _ 7-(3-methoxvbenzvl)-6-oxo-3-phenyl-6.7-dihvdrothienof2.3- blpyridine-2-carboxvlate iSH (CDCI3) 7.40-7.35 (3H, m), 7.29 (1H, d, J 10Hz), 7.25-7.17 (3H, m), 6.93 (1H, m), 6.90 (1H, bs), 6.77 (1H, m), 6.50 (1H, d, J 10Hz), 5.30 (2H, s), 4.08 (2H, q, J 7Hz), 3.72 (3H, s), 1.07 (3H, t, J 7Hz). LCMS (ES+) RT 4.09 minutes, 420 (M+H)+. Example 49 Ethyl 7-(2.6-difluoroben2vl)-6-oxo-3-phenvl-6.7-dlhvdrothienor2.3- l) \ pyrid i ne-2-carboxvlate oH (CDCIa) 7,41-7.35 (3H, m), 7.29-7.15 (4H, m), 6.85 (2H, t, J 8Hz), 6.45 OH, d, J lOHz), 5.45 (2H, s), 4.08 (2H, q, J 7Hz), 1.06 (3H, t, J 7Hz). LCMS (ES+) RT 4.06 minutes, 426 (M+H)+. Example 50 Ethyl 7-(3-methvlbutvn-6-oxo-3-phenvl-6.7-dihvdrothienor2.3-Jblpvridine- 2-carboxvlate LCMS (ES+) RT 4.64 minutes, 370 (M+H)+. Example 51 Ethyl 7-allvl-6-oxo-3-phenvl-6.7-dihvdrothienor2.3-blpvridine-2- carboxylate LCMS (ES+) RT 3,84 minutes, 340 (M+H)+. Example 52 Ethyl 6-oxo-7-(2-phenvlethvn-3-phenyl-6J-dihvdrothienor2.3-blpvridlne- 2-carboxvlate LCMS (ES") RT 3.45 minutes, 404 (M+H)+. Example 53 Ethyl 7-(2-chlorobenzvl)-6-oxo-3-phenvl-6.7-dlhvdrothienor2.3- dlpyridine-2-carboxvlate LCMS (ES+) RT 4.40 minutes, 424 (M+H)+. {Example 54 Ethyl 7-(3-chlorobenzvn-6-oxo-3-phenvl-6,7-dihvdrothlenor2.3- fr|pyridine-2-carboxvlate LCMS (ES+) RT 4.45minutes, 424 (M+H)+. Example 55 Ethyl 7-(4-chlorobenzvl)-6-oxo-3-phenvl-6.7-dihvdrothienor2.3- frlPVridine-2-carboxvlate LCMS (ES+) RT 4.49 minutes, 424 (M+H)+. Example 56 Ethv! 7-(2-morpholinoethvl)-6-oxo-3-phenvl-6.7-dihvdrothienor2.3- dlpyridine-2-carboxvlate This compound was purified by chromatography on silica eluting with 0-20% THF in DCM. LCMS (ES+) RT 2.52 minutes, 413 (M+H)+. Example 57 Ethyl 7-(4-bromophenvl)-6-oxo-3-phenvl-6.7-dihydrothienor2.3- jt?|pvridine-2-carboxvlate To an oven dried flask was added in sequence 4-bromophenylboronic acid (fi.Og. 25mmol), DCM (100mL), pyridine (2.7mL), Intermediate 4 (3.74g, I2.5mmol), copper(ll) acetate (2.26g, 12.5mmol) and pyridine N-oxide (l.46g). The reaction was stirred at room temperature for 72h with the exclusion of moisture. The reaction was then diluted with DCM (100mL), washed with 2M HCI(aq), NaHCO3 (aq), dried (MgSO-O and concentrated in vacua. The crude product was purified by chromatography on silica (0-20% EtOAc in DCM) to give the title compound as a white solid (2.03g). 5H (DMSO-d6) 7.89 (2H, J 8.7Hz), 7.58 (2H, J 8.7Hz), 7.53-7.49 (3H, m), 7.46 (IH, d, J 9,7Hz), 7.42-7.40 (2H, m), 6.57 (1H, d, J 9.7Hz), 4.07 (2H, q, J 7.1 Hz), 1.06 (3H, t, J 7.1Hz). LCMS (ES+) RT4.25 minutes, 456 (M+H)+. Example 58 Ethvl 7-(4-morpholinophenvt)-6-oxo-3-phenvl-6.7-dihvdrothienor2.3- fr|pyridine-2-carboxvlate To a mixture of the compound of Example 57 (100mg, 0.22mmol), caesium carbonate (101mg, 0.31 mmol), Pd(OAc)2 (5mg, 0.022mmol, 10mol%) and 2,2'-bis(diphenylphosphino)-1-1'-binaphthyl (BINAP) (21 mg, 0.033mmol, I5mol%) in toluene (2mL) and under nitrogen was added morpholine (0.024mL, 0.27mmol). The reaction mixture was heated to 100° for 18h. Solvent was removed in vacua and the crude product purified by chromatography on silica (0-20%THF in DCM) to give the title compound as a white solid (40mg). fiH (CDCI3) 7.50-7.18 (8H, m), 7.01 (2H, d, J 9Hz), 6.52 (1H, d, J 10Hz), 4.06 (2H, q, J 7Hz), 3.82 (4H, m), 3.22 (4H, m), 1.06 (3H, t, J 7Hz). LCMS (ES+) RT 3.82 minutes, 461 (M+H)+. Example 59 F)-oxo-317-diphenvl-6.7-dihvdrothienor2,3-blpyridine-2-carboxvlic acid To a solution of the compound of Example 1 (4.53g, 12.1 mmol) in 2:1 THF-water (150mL) was added LiOH.H2O (1.50g, 36.2mmol) and the reaction stirred for 36h at r.t. The reaction was diluted with water 50mL and 2M HCI(aq) added with stirring until a precipitate had formed (pH 1-2). The solid was filtered, washed with several portions of water and dried in a vacuum oven (50°C) to afford the title compound as a white solid (4.2g). 8H (DMSO-d6) 13.00 (1H, bs), 7.70-7.40 (11H, m), 6.55 (1H, d, J 10Hz). LCMS (ES+) RT 3.10 minutes, 348 (M+H)+. Example 60 2-r(4-Methvlpiperazino)carbonvn-3J-dlphenvlthlenof2.3-dlpyridin-6(7M- one To a suspension of the compound of Example 59 (100mg, 0.29mmol) in DCM (2mL) was added EDC (67mg, 0.348mmol) and HOBT (43mg, 0,32mmol) and the mixture stirred at r.t. for 15 minutes. A solution N-methyl piperazine (28mg, 0.32mmol) in DCM (0.5ml_) was added and the reaction stirred at r.t. for 18h. The reaction mixture was diluted with DCM (10mL), washed with water (2x5mL), dried (MgSO/O and concentrated in vacuo. The crude product was purified by chromatography on silica (0-20%THF in DCM) to give the title compound as an off-white solid (82mg). 8H (DMSO-d6) 7.67 (!H, dd, J 10, 1Hz), 7.62-7.52 (3H, m), 7.51-7.40 (5H, m), 7.35-7.31 (2H, m), 6.51 (1H, dd, J 10, 1Hz), 2.44 (8H, m), 1.88 (3H, s). LCMS (ES+) RT 2.18 minutes, 430 (M+H)+. Example 6.1 N"Ethvl-6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3-blpyridine-2- carboxamide EDC (66mg, 0.35mmol) and HOBT (43mg, 0.32mmol) were added to the compound of Example 59 (100mg, 0.29mmol) in DCM (2mL). After 15min ethylamine hydrochloride (26mg, 0.32mmol) and NMM (0.070mL, 0.63mmol) were added and the reaction mixture was stirred at r.t. overnight. Water (2mL) and DCM (2mL) were added, the suspension filtered through a hydrophobic frit and the organic phase concentrated in vacuo. The crude product was purified by column chromatography on silica (1% MeOH in DCM) to give the title compound as a white solid (95mg, 88%). SH (DMSO-(16) 7.69-7.61 (3H, m), 7.59-7.49 (3H, m), 7.45 (1H, d, J 9.6Hz), 7.44-7.42 (4H, m), 7.05 (1H, t, J 5.4Hz), 6.54 (1H, d, J 9.6Hz), 3.03 (2H, q, J 7.1 Hz), 0.84 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.33 minutes, 375.0 (M+H)+. The following compounds of Examples 62-74 were prepared from the compound of Example 59 and the appropriate amine or amine hydrochloride by the method of Example 61. Example 62 A/-(3-Hvdroxvpropvn-6-oxO"3,7-diphenyl-6,7-dihvdrothlenor2.3- /jlpyridine-2-carboxamide LCMS (ES+) RT 2.99 minutes, 405.0 (M+H)+ Example 63 6-Oxo-37-diphenvl"W2-(1-pvrrolidinvl>ethvn-6J-dihvdrothienor2.3- /j|pvridine-2-carboxamide LCMS (ES+) RT 2.29 minutes, 444.1 (M+H)+ Example 64 6-Oxo-3.7-diphenvl-/V-(2-piperidinoethvi)-6,7-dihvdrothienor2.3- b|pvr[dine-2-carboxarmde I.CMS (ES+) RT 2.33 minutes, 458.1 (M+H)+ Example 65 N-(3-Methoxvpropvi>-6-oxo-3.7-diphenvl-6J-dihvdrothienor2.3- blpyridine-2-carboxamide LCMS (ES+) RT 3.28 minutes, 419.0 (M+H)+ Example 66 A/- 2-carboxamide LCMS (ES1) RT 3.24 minutes, 405.0 (M+H)+ Example 67 3.7-Diphenvl-2-(1-pvrrolidinvlcarbonvnthienof2.3-blpyridin-6(7H)-one LCMS (ES^ RT 3.43 minutes, 401.0 (M+H)+ Example 68 A/-r3-(1H-lmidazol-1-vl)propvn-6-oxo-3.7-dlphenvl-6.7-dihvdrothienor2.3-dlpyridi ne-2-carboxam ide LCMS (ES+) RT2.28 minutes, 455.1 (M+H)+ Example 69 ^-(2-Morpholinoethvn-6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3- Olpyridine-2-carboxamide I.CMS (ES+) RT2.28 minutes, 460.1 (M+H)+ Example 70 A/-r3-(4-Methvlpiperazino)Dropvn-6-oxo-3.7-diphenvl-6.7- dihvdrothienor2.3-frlpyridine-2-carboxamlde LCMS (ES+) RT 2.16 minutes, 487.1 (M+H)+ Example 71 A/-(3-Morpholinopropvl)-6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3- &lPVrjdine-2-carboxamide LCMS (ES+) RT 2.26 minutes, 474.1 (M+H)+ Example 72 A/.A/-Diethvl-6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3-blpvridine-2- carboxamide LCMS (ES+) RT 3.62 minutes, 403.0 (M+H)+ Exampie73 A/.A/-Dimethvl-6-oxo-3.7-diphenvl-6,7-dlhvdrothienor2.3-blPvrldine-2- carboxamide LCMS (ES'1') RT 3.17 minutes, 375.0 (M+H)+ Example 74 A/-Methvl-6-oxo-3.7-diphenvl-6J-dihvdrothienor2.3-d1Pvridine-2- carboxamide LCMS (ES+) RT 3.15 minutes, 361.0 (M+H)+ Example 75 6-0x0-3.7-diphenvl-6.7-dihvdrothienor2.3-d1pvridine-2-carboxamide 1,1'-Carbonyldiimidazole (51 mg, 0.32mmol) was added to the compound of Example 59 (100mg, 0.29mmol) in DMF (2mL). After 15 min aq. ammonia (0.190 ml, 25% solution, 3.0mmol) was added and the solution stirred at r.t. overnight. The mixture was concentrated in vacuo and azeotroped twice with heptane. The crude product was purified by column chromatography on silica (3% MeOH in DCM) to give the title compound as a white solid (74mg, 74%). oH (DMSO-d6) 7.87-7.76 (3H, m), 7.75-7.68 (5H, m), 7.64-7.61 (2H, m), 7.54 f1H, d, J 9.6Hz), 6.69 (1H, d, J 9.6Hz), 6.25 (2H, br s). LCMS (ES+) RT 2.95 minutes, 347.0 (M+H)+. Example 76 A/-Methoxv-AA-methvl-6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3- fr]pvridine-2-carboxamide A/,O-Dimethylhydroxylamine hydrochloride (31 mg, 0.32mmol) was added to a mixture of the compound of Example 59 (101mg, 0.29mmol), HOBT (55mg, 0.41 mmol), EDO (78mg, 0.41 mmol) and NMM (0.090mL, 0.81 mmol) in DCM (3mL). The mixture was stirred for 6h at room temperature. DCM was added and the mixture washed with 2M HCI(aq). The organic phase was re-oxtracted with DCM. The combined organics were dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column nhromatography on silica (3.5% MeOH in DCM) to give the title compound as a white solid (95mg, 84%). 8H (DMSO-d6) 7.48-7.35 (3H, m), 7.34-7.30 (3H, in), 7.29-7.23 (3H, m), 7.16-7.13 (2H, m), 6.33 (1H, d, J 9.6Hz), 3.26 (3H, s), 2.79 (3H, s). LCMS (ES+) RT3.27 minutes, 391.0 (M+H)+. Example 77 B-Oxo-3.7-diDhenvl-6.7-dihvdrothienor2.3-dlDvridine-2-carbonitrile A mixture of cyanuric chloride (28mg, 0.15mmol) and the compound of Example 75 (52mg, 0.15mmol) in DMF (1.5mL) was heated at 110° for 18h. Two further portions of cyanuric chloride (14mg, 0.075mmol) were added and heating continued for a further 26h. Water was added and the precipitate filtered off, washed with water and dried. The crude product was purified by column chromatography on silica (1% THF in DCM) to give the title compound as a white solid (35rng, 71%). 8H (DMSO-d6) 7.78 (1H, d, J 9.6Hz), 7.71-7.67 (1H, m), 7.66-7.64 (1H, m), 7.64-7.59 (7H, m), 7.59-7.58 (1H, m), 6.67 (1H, d, J 9.6Hz). LCMS (ES+) RT 3.65 minutes, 329 (M+H)+. Example 78 2-(1-Hvdroxv-1-methvlethvn-3.7'diphenvlthienor2.3-f>lpyridin-6(7H^-one A solution of methyl magnesium iodide (0.084 mL of a 3M solution in ether, o,25mmol) was added drop-wise to a solution of the compound of Example 1 (47mg, 0.13mmol) in DCM (2ml_) at 0 °. The mixture was allowed to warm to i.t. and stirred for 18h. More methyl magnesium iodide (0.084 ml of a 3M solution in ether, 0.25mmol) was added at 0° and the mixture stirred at r.t. for In. DCM and NH4CI(aq) were added, the aqueous phase re-extracted with DCM and the combined organic extracts dried (NaaSCu) and concentrated in vacua. The crude product was purified by column chromatography on silica (1% MeOH in DCM) to give the title compound as a yellow solid (36mg, 80%). 5H (DMSO-d6) 7.74-7.64 (3H, m), 7.60-7.52 (5H, m), 7.39 (2H, dd, J 7.8, 1.6Hz), 7.10 (1H, d, J 9.5 Hz), 6.45 (1H, d, J 9.5Hz), 2.58 (6H, s). LCMS (ES1) RT 3.46 minutes, 362 (M+H)+. Example 79 2-(Hvdroxvmethvn-3.7-diphenvlthienor2.3-dlpyridin-6(7fn-one Lithium borohydride (O.IOOmL, 2M in THF, 0.2mmol) was added to a solution of the compound of Example 1 (75mg, 0.198mmol) in THF (2mL) and the reaction mixture was stirred at r.t. overnight. Two further portions of lithium borohydride (O.IOOmL, 2M in THF, 0.198mmol) were added and the mixture stirred for a further 6h. The reaction was quenched by the addition of 2M I-ICI(aq) and the mixture neutralised by the addition of Na2CO3 The resulting precipitate was filtered off, washed with water and dried to give the title compound as a white solid (55mg, 97%). 8H (DMSO-d6) 7.68-7.41 (11H, m), 6.49 (1H, d, J 9.5Hz), 5.57 (1H, br s), 4.50 (2H, br s). LCMS (ES+) RT 3.10 minutes, 334.0 (M+H)+. Example 80 tert-Butvl A/-(6-oxo-3.7-dlphenvt-6.7-d>hvdrothienof2.3-l)lDvridin-2- vDcarbamate Triethylamine (0.076mL, 0.55mmol) and diphenylphosphoryl azide (0.119ml_, d.55mmol) were added to a solution of the compound of Example 59 (174mg, o.Smmol) in dry terf-butanol (5mL) and the mixture heated under reflux under nitrogen for 6h. The cooled mixture was poured into saturated NaHCO3(aq) (20mL) and extracted with DCM (2 x 20mL). The combined organic fractions were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash column chromatography on silica (EtOAc) to give the title compound (196mg, 94%). 8H (CDCI3) 7.5-7.25 (11H, m), 6.70 (1H, br s), 6.46 (1H, d, J 9Hz), 1.29 (9H, s). m/z(ES+) 419 (M+H)+. Example 81 2-Amino-3.7-diPhenvlthienor2.3-dlPvridin-6f7H)-one Trifluoroacetic acid (2mL) was added to a solution of the compound of Example 80 (170mg, 0.406mmol) in DCM (2mL) and the reaction mixture stirred for 2h at r.t. The mixture was added to saturated NaHCOs(aq) (20mL) and the product extracted with DCM (2 x 20mL). The combined organic imotions were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash column chromatography on silica (EtOAc), followed by radial chromatography (20%EtOH in DCM) to give the title compound as a buff solid (30mg, 23%). 5H (CDCI3) 7.8-7.3 (13H, m), 6.58 (1H, d, J 9Hz). m/z(ES+) 319 (M+H)+. Example 82 terf-Butvl A/-methvlsulfonvl-/V-(6-oxo-3,7-diphenvl-6,7-dihvdrothienor2.3- fr|pvridin-2-vl)carbamate Sodium bis(trimethylsilyl) amide (0.25mL of a 1M solution in THF, 0.25mmol) was added to a solution of the compound of Example 80 (105mg, 0.25mmol) in dry THF (5mL) under a nitrogen atmosphere at 0°. After SOmin methane sulfonyl chloride (28.6mg, 0.25mmol) was added. The reaction mixture was allowed to warm to r.t. over 1h then poured into saturated NaHCO3(aq) (20mL) and the product extracted with DCM (2 x 20ml_). The combined organic fractions were dried (MgS04), filtered and concentrated in vacua. The crude product was purified by radial chromatography on silica (EtOAc) to give the title compound (115mg, 92%). 8H (CDCI3) 7.6-7.28 (11H, m), 6.55 (1H, d, J 9Hz), 2.68 (3H, s), 1.32 (9H, s). m/z (ES+) 497 (M+H)+. Example 83 A/-(6-Oxo-3,7-diphenvl-6.7-dihvdrothienor2.3-dlPvridin-2- vDmethanesulfonamide Trifluoroacetic acid (2.5mL) was added to a solution of the compound of EExample 82 (105mg, 0.212mmol) in DCM (2.5mL) and the reaction mixture stirred for 2h at r.t.. The mixture was added to Saturated NaHCO3 solution (20mL) arid the product extracted with DCM (2 x 20mL). The combined organic fractions were dried (MgSO4), filtered and concentrated in vacua. The crude product was purified by radial chromatography on silica (EtOAc) to give the title compound (62mg, 74%). 5H (CDCI3) 7.6-7.25 (11 H, m), 6.58 (I H, d, J 9Hz), 6.31 (1 H, br s), 2.53 (3H, s). m/z (ES+) 397 (M+H)+. Example 84 37-D[phenvlthienor2.3-dlPvrldin-6(7flV-one 2M HCI(aq) (10ml_) was added to a solution of the compound of Example 59 (300mg, 0.864mmol) in dioxane (30mL) and the mixture heated at reflux for 16h. The cooled reaction mixture was poured into 10% NaOH(aq) (50ml_) and extracted with DCM (2 x 50mL) The combined organic fractions were dried {Na2SO4), filtered and concentrated in vacua to give the title compound as a white solid in quantitative yield. 8H (CDCI3) 7.83 (1H, d, J 9Hz), 7.7-7.35 (10H, m), 6.80 (1H, s), 6.67 (1H, d, J 9Hz). m/z(ES+) 304 (M+H)+. Example 85 A/-(6-Oxo-3.7-diphenvl-6.7-dihvdrothienor2.3-blPvridin-2-vhacetamide Acetyl chloride (0.10ml) was added to a solution of the compound of [Example 81 (116mg, 0.38mmol) and pyridine (O.IOmL) in DCM (5mL) and the mixture stirred at r.t. overnight. The reaction was quenched with MeOH and partitioned between DCM and water. The organic phase was dried (MgSO4) and concentrated in vacua. The crude product was purified by column chromatography on silica (0-5% MeOH in EtOAc) to give the title compound (39mg, 21%). 5H(CDCI3) 7.65 (1H, br s), 7.63-7.39 (11H, m), 6.63 (1H, d, J 9.5Hz), 1.99 (3H, s). LCMS (ES4) RT 2.621 minutes, 361 (M+H)+. Example 86 1-Methvl-A/-f6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3-dlPvridin-2-vn-1H- imidazole-4-sulfonamide 1 -Methyl-1 H-imidazole-4-sulfonyl chloride (96mg, 0.53mmol) was added to a solution of the compound of Example 81 (136mg, 0.44mmol) and pyridine (52mg, 0.66mmol) in DCM (10ml_) and the reaction mixture stirred at r.t. overnight. The mixture was partitioned between DCM and NaHCO3(aq). The organic phase was dried (MgSO4) and concentrated in vacua. The crude product was purified by column chromatography on silica (10%MeOH in DCM) to give the title compound (75mg. 37%). 8H (MeOH-d4) 7.60-7.48 (5H, in), 7.38-7.25 (6H, m), 7.23 (1H, m), 7.13 (2H, m), 6.48 (1H, d, J 9.5Hz), 3.55 (3H, s). LCMS (ES+) RT2.90 minutes, 463 (M+H)+. Example 87 Ethyl 7-f4-(benzvloxv)phenvl1-^-oxo-3-phenvl-6.7-dihydrothienor2.3- dlpvridine-2-carboxvlate A mixture of Intermediate 4 (2.50g, 8,36mmol), 4-(benzyloxy)phenylboronic acid (2.86g, 12.5mmol), copper(ll) acetate (3.04g, 16.7mmol) and pyridine (2.7mL, 33.4mmol) in DCM (200mL) was stirred at r.t. for 5 days. The mixture was diluted with DCM (100ml_) and filtered through celite. The filtrate was washed with 2M HCI(aq) (2 x 200mL), dried (Na2SO4) and concentrated in vacua. The crude product was purified by column chromatography on silica (3% MeOH in DCM) to give the title compound as a white solid (1.35g, 34%). r>H (CDCI3) 7.52-7.35 (13H, m), 7.21-7.16 (2H, m), 6.60 (1H, d, J 9.6Hz), 5.15 (2H, s), 4.14 (2H, q, J 7.1Hz), 1.13 (3H, t, J 7.1 Hz), m/z (ES+) 482.1 (M+H)*. Example 88 Ethyl 7-r4-fhvdroxvmethvi>phenvn-6-oxo-3-phenvl-6.7- dihvdrothienof2.3-/?lpyridine-2-carboxvlate A mixture of Intermediate 4 (300mg, LOmmol), 4-(hydroxymethyl)phenyl horonic acid (304mg, 12.5mmol), copper(ll) acetate (913mg, 5.0mmol) and pyridine (0.404mL, 5.0mmol) in DCM (7mL) was stirred at r.t. for 3 days. The mixture was diluted with DCM, washed with HCI (2M), dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography on silica (50-100% EtOAc in isohexane) to give the title compound as a white solid (255mg, 63%). 5H (CDCI3) 7.54 (2H, d, J 8.9Hz), 7.44-7.28 (8H, m), 6.53 (1H, d, J 10.6Hz), 4.72 (2H, s), 4.06 (2H, q, J 7.1 Hz), 1.05 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.45 minutes, 406 (M+H)+. Exam pie 89 Ethyl 7-(4-hvdroxvphenvlV6-oxo-3-phenvl-6.7-dihvdrothienor2.3- b\ pyridi ne-2-carboxvlate A mixture of Intermediate 4 (554mg, 1.86mmol), 4-hydroxyphenyl boronic acid (511mg, 3,71mmol), copper(ll) acetate (37mg, 0.187mmol), pyridine-A/-oxide (350mg, 3.71 mmol) and pyridine (0.370mL, 3.71 mmol) in DCM (20mL) was stirred at r.t. overnight. The reaction mixture was diluted with DCM, washed with NH4CI(aq) and water, dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography on silica (5% MeOH in DCM) to give the title compound as a cream solid (484mg, 73%). i)H (DMSO-d6) 10.06 (1H, s), 7.54-7.50 (3H, m), 7.47-7.45 (3H, m), 7.37 (2H, (1 J 9Hz), 7.02 (2H, d, J 9Hz), 6.58 (1H, d, J 10Hz), 4.11 (2H, q, J 7Hz), 1.09 (3H, t, J 7Hz). LCMS (ES+) 392.1 (M+H)+. Example 90 Ethyi 7-f4"(2-hvdroxvethoxv)phenvn-6-oxo-3-phenvl-6.7- dihvdrothienof2.3-blPvridine-2-carboxvlate 2-Bromoethanol (0.148mL, 2.08mmol) was added to the compound of Example 89 (370mg, 0.95mmol) and Cs2CO3 (342mg, 1.04mmol) in DMF (5mL) and the mixture heated at 80° for 2 days. The solvent was removed in vacuo and the residue partitioned between EtOAc and HCI (10%). The aqueous phase was extracted with EtOAc (2 x 20ml_). The combined organics were washed with brine, dried (MgSCv) and concentrated in vacuo. The crude product was purified by column chromatography on silica (2% to 10% MeOH in DCM) to give the title compound (73mg, 18%). 8H (CDCI3) 7.44-7.28 (8H, m), 7.07 (2H, d, J 8Hz), 6.52 (1H. d, J 9.6Hz), 4.12-3.93 (6H, in), 1.06 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.42 minutes, 436 (M+H)+. Example 91 Ethyl 7-{4-r2-(2-methvl-1 tf-imldazol-1 -vnethoxvlphenvll-6-oxo-3-phenvl-6,7-dihydrothienof213-JblPvridine-2-carboxylate Pyridine (0.136mL, 1.68mmol) was added to a mixture of the compound of Example 90 (73mg, 0.168mmol) and tosylchloride (40mg, 0.21 mmol) in DCM (2mL) at 0°. The reaction mixture was stirred at 0° for 5h then allowed to warm to r.t. The mixture was diluted with DCM (20mL), washed with 2M HCI(aq), 10% NaOH(aq) and brine, dried (MgSCU) and concentrated in vacuo. The crude product was purified by column chromatography on silica (50 to 80% EtOAc in isohexane) to give the intermediate tosylate, ethyl 7-[4-{2-j(4-methylphenyl)sulfonyl]oxyethoxy)phenyl]-6-oxo-3-phenyl-6,7-dihydro-1-benzothiophene-2-carboxylate, as a solid (73mg, 12%). 8H(CDCI3) 7.78 (2H, (I, J 8.6Hz), 7.43-7.27 (10H, m), 6.93 (2H, d, J 8.6Hz), 6.52 (1H, d, J 9.6Hz), 4.38-4.35 (2H, m), 4.18-4.15 (2H, m), 4.07 (2H, q, J 7.1 Hz), 2.40 (3H, s), 1.06 (3H, t, J 7.1Hz). LCMS (ES+) RT4.15 minutes, 590 (M+H)+. A mixture of this tosylate (70mg, 0.12mmol), 2-methylimidazole (11mg, 0.13mmol) and Cs2CO3 (43mg, 0.13mmol) in DMF (1mL) was heated at 80° for 6h. The solvent was removed in vacuo and the residue partitioned between DCM (15mL) and NaHCO3(aq) (15mL). The organic phase was extracted with DCM (2 x 10mL). The combined organics were dried (MgSCU) and concentrated in vacuo. The crude product was purified by column chromatography on silica (10% MeOH in DCM) to give the title compound (20mg, 34%). 8H(CDCI3) 7.43-7,28 (8H, m), 7.19-7.15 (2H, m), 7.01-6.90 (2H, m), 6.51 (1H, d, J 9.6Hz), 4,25-4.20 (4H, br m), 4.06 (2H, q, J 7.1 Hz), :'.,43 (3H, s), 1.05 (3H, t, J 7.1 Hz). LCMS (ES+) RT 2.62 minutes, 500 (M+H)f. Example 92 Ethyl 7-r4-(2-morphormoethoxv)phenvn-6-oxo-3-phenvl-6.7- dihvdrothienor2.3-dlpyridine-2-carboxvlate To a mixture of the compound of Example 89 (100mg, 0.256mmol) and caesium carbonate (202mg, 0.62mmol) in dry DMF (5mL) was added 2-(chloroethyl)morpholine hydrochloride (58mg, 0.31 mmol) and the reaction heated at 60° under nitrogen for 48h. The reaction was partitioned between water and EtOAc, the EtOAc extracts dried (MgSCXj) and concentrated in vacuo. The crude product was then purified by column chromatography on silica eluting with 0-5% MeOH in DCM to give the title compound as a white solid (68mg). 5H (CDCI3) 7.44-7.20 (8H, m), 7.04 (2H, d, J 9Hz), 6.51 (1H, d, J 10Hz), 4.15-4.03 (4H, m), 3,68 (4H, m), 2.79 (2H, t, J 6Hz), 2.54 (4H, m), 1.05 (3H, t, J 7Hz). LCMS (ES+) RT 2.53 minutes, 505 (M+H)+. Example 93 Ethyl 6-oxo-3.7-dlphenvl-4.5.6.7-tetrahvdrothienor2.3-blpvridlne-2- carboxvlate Hydrogen at 20 to 25 bar was applied to a mixture of the compound of Example 1 (I85mg), 10% ruthenium on carbon (64mg) and EtOH (25mL) stirred at 60 to 90° for 30 hours. The mixture was filtered to remove the catalyst and the filter was washed with EtOH (70ml_). The solution was concentrated in vacuo to give a crude product. This was purified by preparative HPLC (0.08% formic acid in acetonitrile, pH2, Luna 2 C18 5|im 250 mm) to give the title compound as a white solid (48mg, 26%). 5H (CDCI3) 7.59-7.48 (3H, m), 7.47-7.36 (5H, m), 7.30 (2H, dd, J 8.5, 2.1 Hz), 4.10 (2H, q, J 7.3 Hz), 2.84 (2H, m), 2.75 (2H, m), 1.10 (3H, t, J 7.3 Hz). LCMS RT 4.1 minutes, 378 (M+H)+ Example 94 7 (4-Methoxvbenzvn-6-oxo-3-phenvl-6J-dihvdrothlenor2.3-blpvridine-2- carbonitrile Sodium hydride (24mg of 60% w/w dispersion in oil, 0.6mmol) was added to a solution of Intermediate 12 (126rng, O.Smmol) in dry DMF (4mL) and stirred at r.t. for 10 mins under nitrogen. 4-Methoxybenzyl chloride (68|nL, O.Smmol) was added and the reaction mixture heated to 60° for 2 hours. The reaction was allowed to cool to r.t. and was partitioned between EtOAc (75mL) and brine (50ml_). The organic layer was dried (Na2S04), concentrated in vacua arid the crude product purified by column chromatography (silica, 10% EtOAc in DCM) to give the title compound as a white solid (93mg, 50%). 6H (CDCI3) 7.48 (1H, d, J 9.6HZ), 7.42-7.33(5H, m), 7.26 (2H, d, J 8.8Hz), 6.77 (2H, d, J 8.8Hz), 6.55 (1H, d, J 9.6Hz), 5.19 (2H, s), 3.68 (3H, s). LCMS (ES+) 395 (M+H)H. Example 95 N-Allvl-6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3-Jb1pvridine-2- carboxamide To a stirred solution of the compound of Example 59 (174mg, O.Srnmol) in ciry DCM (5mL) was added allyl amine (29mg, O.Smmol), triethylamine (101mg, 1mmol), and a catalytic amount of 4-dimethylaminopyridine followed by EDC (96mg, O.Smmol). The reaction mixture was stirred at r.t. for 4h and then poured into 2M HCI(aq) (20mL). The product was extracted with DCM (2x20mL) and the combined organic fractions dried (MgSCU), filtered and the solvent removed in vacua. Purification by radial chromatography (silica, EtOAc) gave the title compound as a solid (70mg). 8H (CDCI3) 7,7-7.1 (11 H, m), 4.48 (1H, d, J 10Hz), 5.6-5.4 (1H, m), 5.28 (1H, bs), 4.84 (1H, dd, J 10, 1Hz), 4.69 (1H, dd, J 10, 1Hz), 3.8-3.6 (2H, m). LCMS (ES+) 387 (M+H)+. Example 96 N-(2.3-dihvdroxvpropvl)-6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3- /j|pvridine-2-carboxamide To a stirred solution of the compound of Example 95 (50mg) in 8:1 acetone-water (lOmL) was added 4-methyfmorpholine N-oxide (100mg) followed by a catalytic amount of OsCv The reaction mixture was stirred for 16h and then poured into saturated NaHCO3 solution (20mL).- The product was extracted with DCM (2x20mL) and the combined organic fractions dried over MgSO4, filtered and solvent removed in vacua. The crude product was purified by column chromatography (silica, 10% EtOH in DCM) to give the title compound as a solid (32mg). 8H (CDCI3) 7.8-7.1 (11H, m), 6.44 (1H, d, J 10Hz), 5.62 (1H, bs), 3.7-3.1 (5H, m). LCMS (ES+) 421 (M+H)+. Example 97 (6-Oxo-3,7-diphenvl-6.7-dihvdrothienor2.3-/?lpvridin-2"Vi)-urea To a stirred solution of the monohydrochloride salt of the compound of EExample 81 (0.177g, O.Smmol) in dry pyridine (5mL) was added excess trimethylsilyl isocyanate and the reaction stirred at r.t. for 16h. The reaction was poured onto 2M HCI(aq) (20mL) and extracted with DCM (2x20mL). The combined organic fractions were dried over MgSO4, filtered and solvent removed in vacua. The crude product was purified by radial chromatography (silica, EtOAc) to give the title compound as a solid (6mg). 8H (DMSO-d6) H.78 (1H, s), 7.8-7.55 (5H, m), 7.5-7.4 (6H, m), 6.48 (1H, d, J 10Hz), 6.32 (2H, bs). LCMS (ES+) 362 (M+H)+. Example 98 i-Ethvl-3-(6-oxo-3,7-diphenvl-6.7-dihvdrothienor2.3-blPvridin-2-vn-urea The title compound was prepared from the HCI salt of the compound of Example 81 and ethyl isocyanate following the method described for the compound of Example 97 to give the product as a solid (24mg). 5H (DMSO-ci6) 8.59 (1H,s). 7.8-7.4 (11H, m), 6.67 (1H, t, J 5Hz), 6.38 (1H, d, J 10Hz), 3.1-2.9 (2H, m), 0.97 (3H, t, J 7Hz). LCMS (ES+) 390 (M+H)+. Example 99 i-(2-Hvdroxvethvl)-3-(6-oxo-3.7-diphenvl-6.7-dihvdrothienor2.3- b1PVridin-2-vi)-urea To a stirred suspension of the monohydrochloride salt of the compound of Example 81 (177mg, O.Smmol) in dry DCM was added phosgene (0.26mL of 1.93M solution in toluene, O.Smmol), followed by triethylamine (101mg, l.Ommol). The reaction was stirred for 1h at r.t. before adding more triethylamine (51mg, O.Smmol) and ethanolamine (31 mg, O.Smmol). The reaction was stirred for a further hour and then poured into saturated NaHCO3(aq) (20ml_), The product was extracted with DCM (2x20ml_), the combined organic fractions dried over MgSO4, filtered and the solvent removed in vacua. The crude product was purified by radial chromatography (silica, EtOAc) to give the title compound as a solid (34mg). 8H (DMSO-d6) 8.84 (1H,s), 7.8-7.3 (11H, m), 6.85 (1H, t, J 5Hz), 6.41 (1H, d, J 10Hz), 4.69 (1H, t J 5Hz), 3.4-3.2 (2H, m), 3.1-2.9 (2H, m). LCMS (ES+) 406 (M+H)+. Example 100 6-Oxo-3.7-diphenvl-6.7-dihvdrothienor2.3-/7lpvridlne-2-sulfonic acid methylamide To a solution of Intermediate 13 (32mg, 0.085mmol) in DCM (5mL) was added methylamine (40% solution in water, 0.17mmol, 0.1 mL) and the reaction stirred at r.t. for 18h. The reaction was partitioned between DCM and saturated NaHCO3(aq) and the DCM layer dried over MgSO4, filtered and concentrated in vacua. The crude product was purified by column chromatography (silica, EtOAc) to give the title compound as an off-white solid (10mg). 8H (CDCI3) 7.71 (2H, dt, J 8.5, 1.8Hz), 7.73 (1H, d, J 9.6Hz), 7.48-7.82 (5H, m), 7.40 (2H, m), 6.86 (1 H, s), 6.63 (1 H, d, J 9.6Hz), 4.41 (1 H, • I, J 5.3Hz), 2.68 (3H, d, J 5.3Hz). LCMS (ES+) RT 3.14 minutes, 397 (M+H)+. Example 101 6-0x0-3 J-diphenvl-6.7-dihvdrothienor2.3-/JlPvridine--2-sulfonic acid pyrrolidine amide The title compound was prepared from Intermediate 13 (18mg) and pyrrolidine (0.1 ml) following the method described for the compound of Example 100 to give the product as an off-white solid (4mg). 8H (CDCI3) 7.89 (2H, m), 7.74 (1H, d, J 9.6Hz), 7.48-7.60 (5H, m), 7.40 (2H, m), 6.87 (1H, s), 6,64 (1H, d, J 9.6Hz), 3.24 (4H, m), 1.77 (4H, m). LCMS (ES+) RT 3.47 minutes, 437 (M+H)+. Example 102 7-r4-(2-Morpholinoethoxv)phenvn-6-oxo-3-phenvl-6.7-dihvdrothienor2,3- frlpyridine The compound of Example 92 (91 mg, 0.18mmol) was dissolved in dioxane (l ml) and 4M HCI(aq) (1mL) added and the mixture heated at reflux for 48h. The reaction was partitioned between 2M NaOH(aq) and THF and the combined THF layers were dried (MgSC>4), filtered and concentrated in vacua. The crude product was purified by column chromatography (silica, 0-10% MeOH in EtOAc) to give the title compound as an off-white solid (73mg, 04%). 6H (CDCI3) 7.74 (1H, d, J 9.6Hz), 7.33-7.28 (7H, m), 7.05-7.01 (2H, in), 6,75 (1H, s), 6.58 (1H, d, J 9.6Hz), 4.12 (2H, t, J 5.7Hz), 3.76-3.67 (4H, in), 2.78 (2H, t, J 5.7Hz), 2.56-2.52 (4H, m). LCMS (ES+) RT 2.46 minutes, 433 (M+H)1. Example 103 7-r4-(2-Morpholinoethoxv)phenvl1-6-oxo-3-phenvl-6.7-dlhvdrothienor2.3-blpyridine-2-carboxvlic acid A mixture of the compound of Example 92 (230mg, 0.46mmol), sodium hydroxide (91 mg, 2.28mmol) and EtOH (5mL) was heated at reflux for 18h. EtOH was removed in vacua and the residue treated with 2M HCI(aq) (2mL) to give a white solid. The reaction was diluted with water and then freeze dried. The resultant solid was extracted with isopropanol and the extracts concentrated in vacua to give the title compound as a white solid (97mg). 5H (DMSO-d6) 7.62-7.37 (8H, m), 7.21-7.16 (2H, m), 6.50 (1H, J 9.6Hz), 4.20 «2H, t, J 5JHz), 3.62-3.59 (4H, m), 2.76 (2H, t, J 5.7Hz), 2.54-2.51 (4H, m). LCMS (ES+) RT 2.35 minutes, 477 (M+H)+. Example 104 7-r4-(2-IVlorpholinoethoxv)phenvn-6-oxo-3-phenvl-6.7-dihvdrothienor2.3-b|pvridine-2-carboxamide To a suspension of the compound of Example 103 (120mg, 0.25mmol) in dry DMF (3mL) was added 1,1'-carbonyldiimidazole (41 mg) and the reaction stirred for 1h. A further portion of 1,1'-carbonyldiimidazole (5mg) was added and the reaction stirred for SOmins before adding aqueous ammonia (1.5ml_ of 25% solution). The reaction was stirred for 2h and then was diluted with water (20mL). The product was extracted with EtOAc (2x15ml_) and the combined organic extracts washed with water (x2), brine (x2) and dried over MgSO4, Solvent was removed in vacuo to give the title compound as a solid (128mg), SH (CDCI3) 7.52-7.49 (3H, m), 7.40-7.18 (5H, m), 7.10-7.00 (2H, in), 6.51 (1H, d, J 9.6Hz), 5.34 (2H, bs), 4.12 (2H, t, J 5.7Hz), 3.71-3.67 (4H, in), 2.79 (2H, t, J 5.7Hz), 2.56-2.53 (4H, m). LCMS (ES+) RT 2.28 minutes, 476 (M+H)+. Example 105 7-r4-(2-Morpholinoethoxv)phenvn-6-oxO"3-phenv[-6.7-dihvdrothienor2.3- frlpyridine-2-carbonitrHe To a solution of the compound of Example 104 (128mg, 0.27mmol) in dry DCM (1,5rnL) was added pyridine (44nL, 0.54mmol) followed by trifluoroacetic anhydride (46nL, 0.32mmol). TLC showed the reaction was complete after 5 minutes and the reaction was then diluted with DCM (20mL) and washed with 2M NaOH(aq) (20mL). The DCM layer was separated, dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was co-evaporated with toluene (2x15mL) to give the title compound as a solid (73mg). 8H (CDCI3) 7.62 (1H, d, J 9.7Hz), 7.51-7.45 (5H, m), 7.29-7.26 (2H, m), 7.08-7.04 (2H, m), 6.62 (1H, d, J 9.7Hz), 4.14 (2H, t, J 5.6Hz), 3.71-3.68 (4H, m), 2.81 (2H, t, J 5.6Hz), 2.58-2.54 (4H, m). LCMS (ES+) RT 2.47 minutes, 458 (M+H)+. Example 106 Ethyl _ 7-r4-(2.3-dihvdroxvpropoxv)phenvn-6-oxo-3-phenvl-6.7- dihvdrothienor2,3-fr|pvridlne-2-carboxvlate A mixture of the compound of Example 89 (680mg, 1.74mmol), 2,2-dimethyl-1 ,3-dioxalan-4-ylmethyl p-toluenesulfonate (600mg, 2.09mmol), and caesium carbonate (680mg, 2.09mmol) in DMF (3mL) was heated at 80° for 18h. The reaction mixture was cooled and then partitioned between DCM (30mL) and water (30mL). The aqueous layer was extracted with two further portions of DCM (10rnL) and the combined organic layers washed with brine, dried (MgSO4) and concentrated in vacua. The crude product was purified by column chromatography (silica, 10-15% EtOAc in DCM) to give ethyl 7-[4-(2,2-dimethyl-[1,3]dioxan-4-ylmethoxy)phenyl]-6-oxo-3-phenyl-6,7-i iihydrothieno[2,3-k]pyridine-2-carboxylate as a white solid (474mg, 54%). 8H (CDCI3) 7,52-7.43 (8H, m), 7.25-7.20 (2H, m), 6.67 (1H, d, J 9.6Hz), 4.66-4.58 (1H, m), 4.32-4.01 (5H, m), 1.58 (3H, s), 1.51 (3H, s), 1.22 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.99 minutes, 505 (M+H)+. This intermediate (450mg) was dissolved in EtOH (10mL) and a catalytic amount of Dowex® 50WX4-200 resin in H+ form was added followed by water (1mL). The reaction was heated at 50° overnight and then diluted with EtOH (1 OmL) and filtered hot to remove Dowex® resin. The filtrate was concentrated in vacua to give the title compound as an off-white solid (388mg). 8H (CDCI3) 7.60-7.38 (8H, m), 7.27-7.24 (2H, m), 6.72 (1H, d, J 9.6Hz), 6.30-4.23 (5H, m), 4.03-3.89 (2H, m), 1.26 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.18 minutes, 488 (M+Na)+, 466 Example 107 7-f4-r2-(2-MethvMH-imidazol-1-vnethoxvlPhenvl>-6-oxo-3-phenvl-6.7- dihvdrothienor2,3-/?lPvridine-2-carboxamide To a solution of the compound of Example 91 (134mg, 0.27mmol) in EtOH (O.SmL) and water (0.73mL) was added sodium hydroxide (0.27mL of a 1M solution, 0.27mmol) and the mixture heated at reflux for 5h. The reaction was (ieeze dried to give 7-{4-[2-(2-Methyl-1H-imidazol-1-yl)ethoxy]phenyl}-6-oxo-3-phenyl-6,7-dihydrothieno[2,3-£i]pyridine-2-carboxylic acid as a solid. LCMS (ES+) RT 2.34 minutes, 472 (M+H}+. This compound was dissolved in DMF (2mL) and thionyl chloride (SO^L, 0.405mmol) was added and the reaction stirred at r.t. for 5 mins. Aqueous ammonia (2mL of a 25% solution) was added and the reaction stirred for 30 mins. The reaction was diluted with water (20mL) and extracted with EtOAc (3x30ml_). The combined EtOAc extracts were washed with water (2x1 OmL), brine (20mL), dried (MgSO4) and concentrated in vacua to give the title compound as a solid (104mg, 82%). 8H (CDCI3) 7.52-7.48 (3H, m), 7.37-7.33 (2H, m), 7.29-7.26 (2H, m), 7.20-7.18 (1H, m), 7.01-6.96 (3H, m), 6.90-6.88 (2H, m), 6.50 (1H, d, J 9.6Hz), 4.23-4.20 (4H, m), 2.42 (3H, s). LCMS (ES+) RT 2.28 minutes, 471 (M+H)+. Example 108 7-f4-r2-(2-Methvl-1H-imida2ol-1-vnethoxvlphenvi>-6-oxo-3-phenvl-6.7- dihvdrothienof2,3-d1pyridine-2-carbonitrile To a suspension of the compound of Example 107 (93mg, 0.20mmol) and pyridine (32(u,L, 0.4mmol) in DCM (1 mL) was added trifluoroacetic anhydride (34|iL, 0.24mmol) and the reaction stirred at r.t. for 30 mins. A further SOpi. of trifluoroacetic anhydride was added and the reaction stirred for 18h before being diluted with DCM (10mL) and THF (5mL). The mixture was washed with 2M NaOH(aq), brine and the organic layer separated and dried over MgSCU. Solvent was removed in vacua and the residue purified by column ohromatography (silica, 2-5% MeOH in DCM) to give the title compound as a solid (GOrng, 67%). SH (CDCI3) 7.62 (1H, d, J 9.7Hz), 7.51-7.44 (5H, m), 7.30-7.27 (2H, m), 7.01-6.98 (2H, m), 6.89 (2H, d, J 0.9Hz), 6.61 (1H, d, J 9.7Hz), 4.30-4.20 (4H, m), 2.43 (3H, s). LCMS (ES+) RT 2.46 minutes, 453 Example 109 7-(4-r2-f 2-Meth vl-1 H-i midazo 1-1 -vhethox vlphen vl)-6-oxo-3-phen vl-6.7- dihvdrothlenor2.3-d1pvridine To a solution of the compound of Example 91 (60mg, 0.12mmol) in dioxane (1 ml) was added 4M HCI(aq) (1 mL) and the mixture heated at reflux for 48h. Reaction was diluted with 2M NaOH(aq) (5mL) and extracted with DCM (2x1 OrnL). The combined DCM extracts were dried (MgSO4), filtered and concentrated in vacuo. The resultant solid was dried at 60° in a vacuum oven (o afford the title compound (32mg, 62%). 8H (CDCI3) 7.76 (1H, d, J 9.6Hz), 7,42-7.30 (6H, m), 7.00-6.92 (4H, m), 6.76 (1H,-s), 6.58 (1H, d, J 9.6Hz), 4.26-4.20 (4H, m), 2.46 (3H, s). LCMS (ES+) RT 2.48 minutes, 428 (M+H)+. Example 110 Ethvl 7-r4-(2-methvl-1 tf-imidazol-1 -vlmethvnphenvi1-6-oxo-3-phenvl-6.7- ciihvdrothienof2.3-d1pyridine-2-carboxvlate To a suspension of the compound of Example 88 (130mg, 0.32mmol) in THF (2mL) was added NaH (14mg of 60% dispersion in oil, 0.35mmol). DMF (0.5ml) was added to aid solubility and the reaction was stirred for 1h. Thionyl chloride (25MJL, 0.35mmol) was added to the reaction mixture cooled in an ice-bath. The mixture was stirred in the ice-bath for 30 mins before quenching the reaction with water (20mL) and basifying with NaHCO3(aq). The product was extracted into DCM (2x1 5mL) and the combined DCM layers dried over MgSO4, filtered and concentrated in vacuo to give ethyl 7-(4-chloromethylphenyl)-6-oxo-3-phenyl-6,7-dihydrothieno[2,3-£>]pyridine-2-carboxylate LCMS (ES+) RT 3.97 minutes, 424 (M+H)"1". To a solution of this compound in DMF (1mL) was added 2-methylimidazole (13mg, 0.16mmol) and caesium carbonate (52mg, 0.16mmol) and the mixture heated at 80° for 3h. DMF was removed in vacua and the residue purified by column chromatography (silica, 40-100% EtOAc in isohexane followed by 5% MeOH in DCM) and also mass directed hplc to give the title compound as a solid (3mg). 6H (MeOH-d4) 7.47-7.27 (10H, m), 7.06 (1H, d, J_1.4Hz), 6.82 (1H, d, J 1,4Hz), 6.50 (1H, d, J 9.6Hz), 5.26 (2H, s), 4.00 (2H, q, J 7.1 Hz), 2.28 (3H, til, 0.99 (3H, t, J 7.1 Hz). LCMS (ES+) RT 2.53 minutes, 470 (M+H)+. Example 111 Ethyl 7-(4-bromophenvn-3-(2.4-difluorophenvl)-6-oxo-6.7- dihvdrothienof2.3-6lPvridirie-2-carboxvlate To an oven dried flask was added in sequence 4-bromophenylboronic acid (4.2g, 20.88mmol), DCM (100mL), pyridine (1.7mL), Intermediate 14 (3.5g, 10.44mmol), copper(ll) acetate (3.8g, 20.88mmol) and pyridine N-oxide (992mg). The reaction was stirred at room temperature for 7 days with the exclusion of moisture. A further equivalent each of Cu(OAc)2, pyridine N-oxide and pyridine was added and reaction stirred for 20h. The reaction was then diluted with DCM (100mL), washed with 2M HCI(aq), NaHCO3 (aq), dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica (0-3% THF in DCM) to give the title compound as an off-white solid (1.03g). LCMS (ES+) RT 4.13 minutes, 489 (M+H)+. Example 112 Ethyl 3-(2,4-difluorophenvn-7-r4-(4-methvlpiperazin-1-vl)phenvn-6-oxo- 6,7-dihvdrQthieno[2.3-blpvridine-2-carboxvlatehydrochloride The title compound was prepared from the compound of Example 111(1 .Og, 2.04mmol) and N-methylpiperazine (230^,1, 2.45mmol) following the analogous procedure described for the compound of Example 58. The crude product was purified by column chromatography (silica, 1% NH3(aq) 10%MeOH 90% DCM) to give the product as a yellow solid (320mg). This solid was dissolved in DCM and treated with 4M HCI(aq). Solvent was removed in vacua and the residue re-dissolved in hot DCM. The solution was allowed to cool and the resultant solid collected by filtration to give the title compound as an off-white solid (310mg). 8H (DMSO-d6) 7.66-7.52 (5H, m), 7.39-7.33 (3H, m), 6.67 (1H, d, J 9.6Hz), 4.10 (2H, q, J 3.1 Hz), 3.50-3.10 (8H, m), 2.94 (3H, s), 1.19 (3H, q, J 3.1 Hz). LCMS (ES+) RT 2.57 minutes, 510(M+H)+. Example 113 3-(2.4-Difluorophenvl)-7-r4-(4-methvlpiperazin-1-vnphenvn-6-oxo-6.7- dihvdrothienof2.3-f)1pvridine To a solution of the compound of Example 112 (310mg, 0.61 mmol) in dioxane (35mL) was added 4M HCI(aq) (20mL) and the mixture heated at reflux for 18h. Reaction had not reached completion and so a few drops of concentratedHCI were added and reflux continued for 5h. The reaction was quenched with saturated Na2CO3(aq) and extracted with DCM (x3). The combined DCM extracts were dried (Na2SC>4), filtered and concentrated in vacua. The crude product contained a small amount of residual ester starting material. The product was therefore dissolved in EtOH (15mL) and heated at reflux with NaOH (50mg) for 16h. Solvent was removed in vacua and the residue partitioned between DCM and saturated Na2CC>3(aq). The DCM layer was washed with Na2CC>3(aq) (x3), dried (Na2SC>4) and concentrated in vacua to give the pure title compound as an off-white solid (280mg). 5H (DMSO-d6) 8.10-7.95 (2H, m), 7.86 (1H, dt, J 9.5, 2.6Hz), 7.74-7.63 (4H, m), 7.55-7.52 (2H, m), 6.92 (1H, d, J 9.5Hz), 3.72-3.67 (8H, m), 2.67 (3H,s). LCMS (ES+) RT 2.47 minutes, 438 (M+H)+. Example 114 1.4-Diphenvl-1.4-dihvdro-pvrrolor3.2-6lpyridin-5-one Intermediate 17 (230mg, 1.1mmol) copper(ll) acetate (22mg, 0.11mmol), pyridine N-oxide (209mg, 3.3mrnol), and phenyl boronic acid (344mg, 2.2mmol) were suspended in DCM (5mL) and treated with pyridine (0.33mL, 3.3mmol). The reaction was stirred at r.t. for eighteen hours, further copper(li) acetate (415mg, 2.08mmol) was added and the reaction stirred for a further four hours. The reaction mixture was diluted with DCM, washed with ammonium chloride solution, separated, dried and concentrated in vacua. Chromatography (ethyl acetate-silica) gave the title compound. 8H (DMSO- Example 115 4-(4-Methoxvphenvl)-1-phenvl-1.4-dihvdro-pvrrolof3,2-6lpyridln-5-one The title compound was prepared from 4-methoxyphenylboronic acid and Intermediate 17 following the method described for the compound of Example 114. SH (DMSO-d6) 7.01 (1H, d, J 9.6Hz), 7.8-7.6 (6H, m), 7.49 (1H, d, J 8.9Hz), 7.27 (1H, d, J 8.9Hz), 6.42 (1H, d, J 9.6Hz), 5.91 (1H, d, J 2.8Hz), 4.01 (3H, s). LCMS (ES+) RT 3.299 minutes, 317(M+H)+ Example 116 Ethyl 6-Qxo-3-phenvt-7-pvrldln-3-vlmethvl-6.7-dihvdro-thienor2.3- frlpyridine-2-carboxvlate To a solution of intermediate 4 (200 mg, 0.67 mmol) in DMF (5 ml) at 0° was added sodium hydride (60 mg, 1.5 mmol, 60 % dispersion in mineral oil) and the solution stirred for 5 minutes. 3-(Bromomethyl)-pyridine (202 mg, 0.8 mmol) was added and the reaction heated at 65° for 18 hours. The reaction was poured into saturated ammonium chloride solution and the aqueous phase extracted with EtOAc (x3). The organic phases were dried (MgSO4), filtered and the solvents removed in vacuo. Column Chromatography (silica, 20 % THF in DCM) gave the title product as an off white solid (110 mg). 8H (CDCI3) 9.00 - 8.25 (2H, bm), 7.76 (1H, d, J 7.8 Hz), 7.40 - 7.35 (3H, m), 7.32 (1H,d, J9.2 Hz), 7.26-7.18 (3H, m), 6.51 (1H, d, J 9.2 Hz), 5.33 (2H, s), 4.11 (2H, q, J 7.1 Hz), 1.09 (3H, t, J 7.1 Hz). LCMS (ES+) RT 3.25 minutes, 391 (M+H)+ Example 117 Ethyl 7-{1-Benzvloxvcarbonvl-piperldin-4-vlmethvl)-6-oxo-3-phenvl-6.7- dihvdro-thienof2.3-/?1pvridine-2-carboxvlate To a solution of Intermediate 4 (1.0g, 3.35 mmol) in DMF (10ml_) at 0° was added sodium hydride (160mg, 4.0 mmol, 60 % dispersion in mineral oil) and the solution stirred for 5 minutes. A/-Benzyloxycarbonyl-4-bromomethylpiperidine (1g, 4 mmol) was added and the reaction heated at 65° for 18 hours. The reaction was poured into saturated ammonium chloride solution and the aqueous phase extracted with EtOAc (x3). The organic phases were dried (MgSO4), filtered and the solvents removed in vacua. Column chromatography (silica, 0-15% EtOAc in DCM) gave the title product as an off white solid (410 mg). 5H (CDCI3) 7.40 - 7.36 (3H, m), 7.30 - 7.23 (8H, m), 6.42 (1H, d, J 9.6 Hz), 5,06 (2H, s), 4.28 - 3.80 (4H, bm), 4.13 (2H, (|, J 7.0 Hz), 2.80 (2H, m), 2.26 (1H, m), 1.70 (2H, m), 1.42 (2H, m), 1.12 (3H, I, J 7.0 Hz). LCMS (ES+) RT 4.24 minutes, 531 (M+H)* Example 118 Ethyl 6-Oxo-3-phenvl-7-piperidin-4-vlmethvl-6.7-dlhvdro-thienor2.3- dlpyridine-2-carboxvlate The compound of Example 117 (400 mg) was dissolved in EtOH (20 ml_) and 10 % palladium on carbon (40 mg) added. A hydrogen atmosphere (1 atmosphere) was applied and the reaction aJlowed to stir at ambient temperature for 18 hours. The reaction was filtered and the solvents removed in vacua to give the title product as a white solid (210 mg). 8H (CDCI3) 7.50 -7.45 (3H, m), 7.28 - 7.20 (3H, m), 6.42 (1H, d, J 9.6Hz), 4.12 (2H, q, J 7.1 Hz), 3.98 (2H, d, J 7.4Hz), 3.05 (2H, m), 2.55 (2H, m), 2.18 (1H, m), 1.60 (2H, m), 1.30 (2H, m), 1.11 (3H, t, J 7.1 Hz). LCMS (ES+) RT 2.43 minutes, 397 (M+H)+ Example 119 Ethyl 7-(1-Methanesulfonvl-piperidin-4-vlmethyl)-6-oxo-3-phenvl-6.7- dihvdro-thienof2.3-fllpyridine-2-carpoxvlate The compound of Example 118 (104 mg, 0.26 mmol) was dissolved in DCM (5 ml) and triethylamine (73 jj,L) followed by methanesulphonylchloride (40 I.I.L, 0.28 mrnol) added. The reaction was allowed to stir at ambient temperature for 18 hours. The reaction was diluted with brine and extracted with DCM (x3). The organic phases were washed with saturated NaHCOs solution and dried (MgSCU). The reaction was filtered and the solvents removed in vacua to give the title product as a white solid (120mg). 8H (CDCI3) 7.45 - 7.30 (3H, m), 7.27 - 7.10 (3H, m), 6.43 (1H, d, J 9.4 Hz), 4.12 (2H, q, J 7.1 Hz), 4.02 (2H, d, J 7.2 Hz), 3.75 (2H, m), 2.70 (3H, s), 2.61 (2H, m), 2.20 (1H, m), 1.82 (2H, m), 1.55 (2H, m), 1.12 (3H, t, J 7.1 Hz). LCMS (ES') RT 3.55 minutes, 475 (M+H)+ Example 120 Ethyl 7-(2-njtrophenvl)-6-oxo-3-phenvi-6.7-dihvdrothienor2,3"felpvridine- 2-carboxvlate Sodium hydride (440mg of a 60% suspension in mineral oil, 11 mmol) was added portionwise to a suspension of Intermediate 4 (2.99g, 10mmol) in DMF (50mL) at r.t. 1 -Fluoro-2-nitrobenzene (1.48ml_, 15mmol) was added and the mixture heated at 80° for 4 days. The reaction was quenched with a few drops of water and the solvent removed in vacua. Purification by column ohromatography on silica (DCM to 5%MeOH in DCM then in 2%THF in DCM) gave the title compound (807mg, 19%) as a yellow solid. 5H (DMSO-d6) 8.44 (1H, dd, J 1.3, 8.2Hz), 8.17-8.08 (2H, m), 8.03-7.98 (1H, m), 7.61-7.57 (4H, m), 7,53-7.50 (2H, m), 6.62 (1H, d, J 9.7Hz), 4.14 (2H, q, J 7.1 Hz), 1.12 (3H, t, J, 7.1 Hz).). LCMS (ES+) RT 3.748 minutes, 421.0 (M+H)+. Example 121 Ethyl 7-(2-aminophenvl)-6-oxo-3-phenvl-6.7-dihvdrothlenor2.3- fr|pvridine-2-carboxvlate A mixture of the compound of Example 120 (455mg, 1.08mmol) and palladium on charcoal (10% Pd wt/wt, 90mg) in EtOH (20mL) was stirred under an atmosphere of hydrogen (balloon) for 45h. The catalyst was filtered off and the filtrate concentrated in vacua. Purification by column chromatography on silica (3% to 5%THF in DCM) gave the title compound as a pale yellow solid (257mg, 61%). 8H (DMSQ-d6) 7.59-7.52 (3H, m), 7.48-7.44 (3H, m), 7.33-7.28 (1H, m), 7.16 (1H, dd, J 1.5, 7.8Hz), 6.98 (1H, dd, J 1.2, 8.2Hz), 6.77-6.73 (1H, m), 6.59 (1H, d, J 9.6Hz), 5.33 (2H, br s), 4.12 (2H, q, J 7.1 Hz), 1.12 (3H, t, J 7.1 Hz). ). LCMS (ES+) RT 3.581 minutes, 391.0(M+H)+. Example 122 Ethyl 7-(2-ethvlaminophenvn-6-oxo-3-phenvl-6.7-dihvdrothienor2.3- /jlpyridine-2-carboxylate Obtained from the compound of Example 120 by the method of Example 121 using longer reaction times. White solid. 8H (DMSO-d6) 7.60-7.54 (3H, m), 7 50-7.45 (3H, m), 7.43-7.39 (1H, m), 7.18 (1H, dd, J 1.5, 7.7Hz), 6.93 (1H, U, J 7.7Hz), 6.79-6.75 (1H, m), 6.59 (1H, d, J 9.6Hz), 5.47 (1H, t, J 5.8Hz), 4.13 (2H, q, J 6.9HZ), 3.18 (2H, qn, J 6.7Hz), 1.13 (3H, t, J 7.0Hz), 1.11 (3H, 1, J 7.1 Hz). LCMS (ES+) RT 3.947 minutes, 419.1 (M+H)+. Example 123 7-(2-Nitrophenvl)-6-oxo-3-phenvl-6.7-dihvdrothlenor2.3-Jblpvridine-2- Garboxvlic acid A mixture of the compound of Example 120 (150mg, 0.357mmol) and lithium hydroxide monohydrate (30mg, 0.714mmol) in dioxane (3ml_) and water (3mL) was heated under reflux for 1.5h. The dioxane was removed in vacua, the aqueous residue acidified (2M HCI) and the precipitate filtered off and dried to give the title compound as a pale orange solid (112mg, 80%). 8H (DMSO-d6) 13.06 (1H, br s), 8.29 (1H, dd, J 1.3, 8.2Hz), 8.02-7.93 (2H, m), 7.88-7.84 (1H, m), 7.46-7.35 (6H, m), 6.46 (1H, d, J 9.7Hz). LCMS (ES+) RT 3.137 minutes, 393.0 (M+H)+. Example 124 7-(2-Nitrophenvl)-6-oxo-3-phenvl-6.7-dihvdrothienor2.3-£>lpvridine-2- carboxamide A mixture of the compound of Example 123 (105mg, 0.268mmol) and 1,1'-carbonyldiimidazoie (65mg, 0.40mmol) in DMF (3mL) was stirred at r.t. for 45min. Concentrated ammonia solution (1mL) was added and the mixture stirred overnight at r.t. Volatiles were removed in vacuo, the residue taken up in DCM, washed 2M HCI(aq), dried {NagSO^, and concentrated in vacuo. Purification by column chromatography on silica (4%MeOH in DCM) gave the title compound as a yellow solid (42mg). SH (DMSO-d6) 8.28 (1H, dd, J 1.3, 8.2Hz), 7.99 (1H, dt, J 1.4, 7.8Hz), 7.92 (1H, dd, J 1.4, 7.8Hz), 7.87-7.82 (1H, m), 7.54-7.47 (3H, m), 7.46-7.37 (3H, m), 6.44 (1H, d, J 9.7Hz), 6.21 (2H, v br). LCMS (ES+) RT 2.997 minutes, 392.0 (M+H)+. Example 125 Ethyl 7-(2"ChiorophenvlV6-oxo-3-phenvl-6.7-dihvdrothienor2.3- b|pvridine-2-carboxvlate iert-Butyl nitrite (0.145mL, 1.22mmol) was added to a suspension of copper ill) chloride (120mg, 0.894mmol) in acetonitrile (10ml_) at 0°C. After 10min, a solution of the compound of Example 121 (317mg, 0.813mmo!) in acetonitrile (5ml_) was added. The mixture was stirred at 0° for SOmin then warmed to r.t. The solvent was removed in vacuo, the residue dissolved in DCM, washed HCI (2M), dried (NaaSC^) and concentrated in vacuo. Purification by column chrornatography on silica (2% to 3% THF in DCM) gave the title compound as a yellow solid (163mg, 49%). 8H (DMSO-d6) 7.91 (1H, ddd, J 1.7, 7.7Hz), 7.86-7.83 (1H, m), 7.78-7.70 (2H, m), 7.60-7.57 (4H, m), 7.53-7.49 (2H, m), 6.66 (1H, d, J 9.7Hz), 4.13 (2H, q, J 7.1 Hz), 1.11 (3H, t, J 7.1 Hz). LCMS (ES') RT 3.944 minutes, 410.0 (M+H)+. Example 126 7-(2-Chlorophenvn-6-oxo-3-phenvl-6.7-dihvdrothienof2.3-/?lpvridme-2- carboxylic acid Obtained from the compound of Example 125 by the method of Example 123. Off-white solid. SH (DMSO-d6) 13.09 (1H, br s), 7.86-7.82 (1H, m), 7.78-7.76 (1H, m), 7.71-7.64 (2H, m), 7.52-7.41 (6H, m), 6.58 (1H, d, J, 9.7Hz). LCMS (ES+) RT 3.247 minutes, 381.9 (M+H)+. Example 127 7-(2-Chlorophenvl)-6-oxo-3-phenvl-6.7-dihvdrothienor2.3-d1pyridine-2- carboxamide A mixture of the compound of Example 126 (125mg, 0.328mmol) and 1,1'-carbonyldiimidazole (80mg, 0.49mmol) in DMF (3mL) was stirred at r.t. for oOrnin. Concentrated ammonia solution (0.5mL) was added and the mixture stirred for 1h. Volatiles were removed in vacua. The residue was treated with 2M HCI(aq) and the resulting solid filtered off and dried. Purification by column chromatography on silica (3% MeOH in DCM) gave the title compound as a pale brown solid (105mg, 84%). 6H (DMSO-d6) 7.91-7.89 (1H, m), 7.83-7.80 (1H, m), 7.76-7.69 (2H, m), 7.66-7.59 (3H, m), 7.56-7.53 (2H, m), 7.51 (1H, d, J 9.7Hz), 6.62 (1H, d, J 9.6Hz), 6.2 (2H, br s). LCMS (ES+) RT 3.120 minutes, 380.8 (M+H)+. Example 128 6-Oxo-3.7-diphenvl-6.7-dihvdrothienor2.3-dlPvridine-2-carbothioamide Hydrogen sulphide was bubbled through a solution of the compound of E:xample 77 (539mg, 1.64mmol) in pyridine (10mL) and triethylamine (0.5mL) for 30 minutes. The reaction was left to stand for 60h at r.t. and then nitrogen bubbled through the mixture to ensure the solution was purged of H2S. The solution was diluted with DCM and washed with water (x2), 2M HCI(aq) (x2) and brine. The organic layer was separated, dried (Na2SO4) and concentrated in vacua. The crude product was recrystallised from DCM-hexane to give the title compound as a solid (327mg, 40%). 5H (DMSO-d6) 9.70 (1H, s), 7.70-7.47 (9H, m), 7.45 (2H, m), 7.38 (1H, d J 9.6Hz), 6.52 (1H, d, J 9.6Hz). LCMS (ES+) RT 3.33 minutes, 385 (M+Na)+, 363 (M+H)+. Example 129 7-(2-chlorophenvl)-6-Oxo-3-phenvl-6.7-dlhvdrothienor2.3-dlDvridine-2- carbothioamide To a mixture of Lawesson's reagent (26.3mg, 0.065 mmol) and the compound of Example 127 (50mg, 0.13mmol) was added toluene (10ml_) and the reaction heated at 110° for 1h. A further portion of Lawesson's reagent (52.6mg, 0.13mmol) was added and reaction heated for 6.5h. The reaction was diluted with DCM, washed with water, dried (Na2SO4) and concentrated in vacua. The crude product was purified by column chromatography (silica, 5-10%EtOAc in DCM) to give the title compound as a yellow solid (10mg, 20%). 8H (MeOH-d4) 7.67 (1H, m), 7.58-7.46 (7H, m), 7.40 (3H, m), 6.48 (1H, d, J 9.6Hz). LCMS (ES+) RT 3.41 minutes, 397 The following assays and animal models can be used to demonstrate the potency and selectivity of the compounds according to the invention. In each assay an IC50 value was determined for each test compound and represents the concentration of compound necessary to achieve 50% inhibition. Preparation of activated human p38q for inhibitor assays. Purification of human p38a Human p38a, incorporating an N-terminal (His)6 tag, was expressed in baculovirus-infected High-Five™ cells (Invitrogen) according to the manufacturers instructions. The cells were harvested 72h post-infection and lysed in phosphate buffered saline (PBS) containing 1% (w/v) (3-octyiglucoside and Complete, EDTA-free™ protease inhibitors (Roche Molecular Biochemicals). The lysate was centrifuged at 35000xg for SOmin at 4oC and the supernatant applied to a NiNTA™ column (Qiagen). Bound protein was eluted by 150mM irnidazole in PBS (after a wash with 15mM imidazole in PBS) and directly applied to a HiTrap Q™ column (AP Biotech). Bound protein was eluted using a 20 column volume, 0 to 1M NaCI gradient. Fractions containing (His)6-p38 were aliquotted and stored at -70s prior to their activation. Preparation of GST-MKK6EE-containina Ivsates E. coli (BL21 pLysS) expressing the constituitively activated form of human MKK6 fused with an N-terminal glutathione^-S-transferase tag (GST-MKK6EE) were harvested by centrifugation and frozen at -709. Cells were lysed by resuspension in 1/1 Oth the culture volume of PBS containing Complete, EDTA-free™ protease inhibitors followed by sonication on ice for 4x15 sec. Cell debris was removed by centrifugation at 35,000xg and the resultant supernatant stored in aliquots at -70s. Activation of (His)6-p38 0.45mL of purified (His)6-p38 was incubated with 50uL of the GST-MKK6EE-containing lysate for SOmin at 23B in the presence of 1mM (3-glycerophosphate, 10mM MgCI2 and 9mM ATP. The extent of activation was monitored by mass spectrometric detection of the doubly-phosphorylated form of (His)6-p38, which routinely comprised greater than 90% of the final (His)6-p38 preparation. The activated (His)6-p38 was then diluted x10 in PBS and repurified using the method described above. The concentration of purified, activated (His)6-p38 was measured by UV absorbance at 280nm using A280,0.1%=1.2 and the preparation stored in aliquots at -70e prior to its use in inhibitor assays. p38 Inhibition Assays Inhibition of phosphorvlation of biotinvlated mvelin basic protein (MBP) The inhibition of p38 catalysed phosphorylation of biotinylated MBP is measured using a DELFIA based format. The assay was performed in a buffer comprising, 20mM HEPES (pH 7.4), 5mM MgCI2 and 3mM DTT. For a typical IC50 determination, biotinylated MBP (2.5u.M) was incubated at room temperature in a streptavidin-coated microtitre plate together with activated gst-p38 (10nM) and ATP (1(iM) in the presence of a range of inhibitor concentrations (final concentration of DMSO is 2 percent). After fifteen minutes the reaction was terminated by the addition of EDTA (75mM). The microtitre plate was then washed with Tris buffered saline (TBS), prior to the addition of 100uJ of anti-phospho MBP antibody (mouse) together with europium-labeled anti-mouse IgG antibody. After one hour at room temperature the plate was again washed in TBS followed by the addition of Enhancement solution (PerkinElmer Wallac). Fluorescence measurements were performed after a further fifteen minutes at room temperature. IC50 values are determined from the plot of Log™ inhibitor concentration (x-axis) versus percentage inhibition of the fluorescence generated by a control sample in the absence of inhibitor (y-axis). Purification of human Peripheral Bood Mononuclear Cells Peripheral blood mononuclear cells (PBMC) were isolated from normal healthy volunteers. Whole blood was taken by venous puncture using heparinised vacutainers (Becton Dickinson), diluted 1 in 4 in RPMI 1640 (Gibco. UK) and centrifuged at 400g for 35 min over a Ficoll-paque gradient (Amersham-Pharmacia Biotech, UK). Cells at the interface were removed and washed once followed by a low speed spin (250g) to remove platelets. Cells were then resuspended in DMEM containing 10% PCS, penicillin 100 units ml"1, streptomycin SOjig ml"1 and glutamine 2mM (Gibco, UK). Inhibitor dilutions Inhibitor stocks (20mM) were kept as a frozen solution (-20°C) in DMSO. Serial dilutions of inhibitors were performed in DMSO as 250-times concentrated stocks. Inhibitors were diluted 1 in 250 into tissue culture media, prewarmed to 37°C and transferred to plates containing PBMC. PBMC and inhibitors were incubated together for 30 mins prior to addition of LPS. Inhibitors used in whole blood assays were prepared according to a different regime. Using the same stock solution serial dilutions of inhibitors were performed in DMSO. Inhibitors were then diluted 1 in 500 straight into whole blood in a volume of 1)j,L. Inhibitor was incubated with whole blood for 30 mins prior to the addition of LPS. LPS stimulation of PBMC PBMC were resuspended at a density of 2x105 cells/well in flat bottomed 96 well tissue culture treated plates. After the addition of inhibitor cells were stimulated with an optimal dose of LPS (Eco//strain B5:055, Sigma, at a final concentration of 1^g ml"1) and incubated at 37°C in 5%CO2/95% air for 18 hours. TNF-cc levels were measured from cell free supernatants by sandwich ELISA (BioSource #CHC1751). LPS stimulation of whole blood Whole blood was taken by venous puncture using heparinised vacutainers (Becton Dickinson), and 500^,1 of blood aliquoted into each well of a 24 well tissue culture treated plate. After the addition of inhibitor cells were stimulated with an optimal dose of LPS (Econstrain 65:055, Sigma, at a final concentration of 1|Lig ml"1) and incubated at 37°C without CO2for 18 hours. TNF-a levels were measured from cell free supernatants by sandwich ELISA (BioSource#CHC1751). Rat LPS induced TNF release Male Lewis rats (180-200g) are anaesthetised with Isofluor and injected i.v. with LPS* in a volume of 0.5ml sterile saline. After 90minutes blood is collected into EDTA tubes for preparation of plasma samples. Plasma is stored at -70°C prior to assay for TNFcx by commercial ELISA. Rat CIA Female Lewis rats (180-200g) are anaesthetised with Isofluor and immunised i.cl. at the base of the tail with 2x100|u,l of emulsion containing 4mg/ml bovine collagen II in 0.01M acetic acid and Freund's Incomplete Adjuvant at a ratio i >t 1:1, A polyarthritis develops with onset from about 13 days post sensitisation. The disease is mainly confined to the ankles and is quantified by plethysmometry. Results are expressed as change in paw volume over time. In the p38 inhibitor assay compounds of the invention have IC5o values of around SOp-M and below. The more active compounds have IC50 values of around 500nM and below. The compounds of the invention are clearly potent inhibitors of p38 kinase, especially p38a kinase. CLAIMS i. A compound of formula (1a) or (1b): (Figure Remove) wherein: the dashed line represents an optional bond; A is a -N=: atom or a -N(Rb)-, -C(Rb)= or -C(Rb)(R°)- group; Ra, Rb and R° is each independently a hydrogen atom or an optionally substituted C^alkyl group; X is an -O- or -S- atom or -NH- group or substituted N atom; each Y is independently a N atom or CH group or substituted C atom; n is zero or the integer 1; Alk1 is an optionally substituted aliphatic or heteroaliphatic chain L' is a covalent bond or a linker atom or group; Cy'1 is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycioaliphatic, aromatic or heteroaromatic group; At is an optionally substituted aromatic or heteroaromatic group; and the salts, solvates, hydrates arid N-oxides thereof; for use in the prophylaxis or treatment of a p38 kinase mediated disease or disorder. 2. A compound according to claim 1 for use in the prophylaxis or treatment of a cytokine mediated disease or disorder. 3. A compound according to claim 1 for use in the prophylaxis or treatment of an immune or inflammatory disorder, 4. A compound according to claim 1 for use in the prophylaxis or treatment of rheumatoid arthritis. 5. The use of a compound according to Claim 1 for the manufacture of a medicament for the prophylaxis or treatment of a disease or disorder according to Claims 1 to 5. 6. A compound of formula (1 a): (Figure Remove) wherein: the dashed line represents an optional bond; A is a -N= atom or a -N(Rb)-, -C(Rb)= or -C(Rb)(R°)- group; Ra, Rb and R° is each independently a hydrogen atom or an optionally substituted Chalky! group; X is an -O- or -S- atom or -NH- group or substituted N atom; V is a N atom or CH group or substituted C atom; n is zero or the integer 1 ; Alk1 is an optionally substituted aliphatic or heteroaliphatic chain L ' is a covalent bond or a linker atom or group; Cy' is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group; Ar is an optionally substituted aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. '. A compound according to Claim 6 in which Cy1 is an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group. 8. A compound according to Claim 6 or Claim 7 in which X is an -O- or -S- atom, 9. A compound of formula (1 b): (Figure Remove) wherein: the dashed line represents an optional bond; A is a -N= atom or a -N(Rb)-, -C(Rb)= or -C(Rb)(Rc)- group; IT", Rl> and RG is each independently a hydrogen atom or an optionally substituted Ci-salkyl group; oach Y is independently a N atom or CH group or substituted C atom; n is zero or the integer 1; Alk1 is an optionally substituted aliphatic or heteroaliphatic chain I' is a covalent bond or a linker atom or group; Cy1 is a hydrogen atom or an optionally substituted cycloaliphatic, polycycioaliphatic, heterocycioaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group; Ar is an optionally substituted aromatic or heteroaromatic group; with the proviso that when the compound of formula (1b) is a compound of formula (1c): (Figure Remove) in which each Y is a N atom or a CH group, Ar is a 2,6-dichloro-4- trifluoromethylphenyl or 2-chloro-6-fluoro-4-trifluoromethylphenyl group, L1 is a covalent bond, n is the integer 1 and Alk1 is a -CH2-, -CH2CH2-, - CH2CH2CH2-, ~CH(CH3)CH2-, -CH2CH=CH-, -CH2CH=CCI-, -CH2CC- or - CF;r chain then Cy1 is other than a hydrogen atom; or in which each Y is a N atom or a CH group, Ar is a 3-chloro-5-trifluoromethylpyridin-2- vl group, L1 is a covalent bond, n is the integer 1 and Alk1 is a -CHa-, - OHpCHa- or -CH2CH2CH2- chain then Cy1 is other than a hydrogen atom; or in which each Y is a N atom or a CH group, Ar is a 2,6-dichloro-4- Irifluoromethylphenyl or 2-chloro-6-f!uoro-4-trifluoromethylphenyl group, L1 is a covaient bond and n is zero then Cy1 is other than a cyclopropyl group; or in which oach Y is a N atom or a CH group, Ar is a 2,6-dichloro-4- (rifluoromethylphenyl, 2-chloro-6-fluoro-4-trifluoromethylphenyl or 3-chloro-5- iritluoromethylpyridin-2-yl group, L1 is a covalent bond and n is zero then Cy1 is other than a hydrogen atom; and with the further proviso that when the compound of formula (1b) is a compound of formula (1d): (Figure Remove) in which: i ' is a covalent bond, n is the integer 1 and Alk1 is a -CH2- chain then Ar is other than a 3-rnethyl-5-trifluoromethylpyridin-2-yl, 5-trifluoromethylpyridin-2-'I, 3-trifluoromethylpyridin-2-yl, 3,5-difluoropyridin-2-yl, 3,5-dichloropyridin-2-y! or 2-chloro-4-trifluoromethylphenyl group; and the salts, solvates, hydrates and N-oxides thereof; 10. A compound according to any one of Claims 6 to 9 in which Cy1 is an optionally substituted cycloaliphatic, aromatic or heteroaromatic group. 11. A compound according to Claim 10 in which Cy1 is an optionally substituted phenyl group. \2. A compound according to any one of Claims 6 to 11 in which Ar is an optionally substituted phenyl or monocyclic five- or six-membered heteroaromatic group. 13. A compound according to Claim 12 in which Ar is an optionally substituted phenyl group. 14. A compound according to any one of Claims 6 to 13 in which Ra is a hydrogen atom or methyl group. 15. A compound according to any one of Claims 6 to 14 in which L1 is a covalent bond or an -O- or -S- atom or an -N(R2)- [where R2 is a hydrogen atom or a straight or branched alkyl group], -C(O)-, -C(S)-, - S(O)- or -S(O)2- group. 16. A compound according to Claim 15 in which L1 is a covalent bond. 17. A compound according to any one of Claims 6 to 16 in which n is zero. 18. A compound according to any one of Claims 6 to 17 in which each Y is a CH group or a substituted C atom. 19. A compound according to any one of claims 6 to 18 in which the dashed line represents a bond and A is a -C(Rb)= group. 20. A compound according to Claim 19 in which Rb is a hydrogen atom. 21. A compound which is: Ethyl 6-oxo-3,7-diphenyl-6,7-dihydrothieno[2,3-£)]pyridine-2-carboxylate; Ethyl 7-cyclopropylmethyl-6-oxo-3»phenyl -6,7-dihydrothieno[2,3-£>]pyridine-2- carboxylate; Ethyl 6-oxo-3-phenyl-7-(3-thienyl)-6,7-dihydrothieno[2,3-d]pyridine-2- carboxylate; Ethyl 3-(4-fluorophenyl)-6-oxo-7-phenyl-6,7-dihydrothieno[2,3-fa]pyridine-2- carboxylate; Ethyl 3-(2-methoxyphenyl)-6-oxo-7-phenyl-6,7-dihydrothieno[2,3-jb]pyridine- 2-carboxylate; Ethyl 6-oxo-7-phenyl-3-(4-tolyI)-6,7-dihydrothieno[2,3-i)]pyridine-2- carboxylate; Ethyl 3-(3-rnethoxyphenyl)-6-oxo-7-phenyl-6,7-dihydrothieno[2,3-i)]pyridine- 2-carboxylate; 6-Oxo-3,7-diphenyl-A/-(2-piperidinoethyl)-6,7-dihydrothieno[2,3-fci]pyridine-2- carboxamide; 6-Oxo-3,7-diphenyl-6(7-dihydrothieno[2,3-i)]pyridine-2-carbonitrile; 3,7-Diphenylthieno[2,3-£>]pyridin-6(7H)-one; Ethyl 3-(2,4-difluorophenyl)-7-[4-(4-methylpiperazin-1-yl)phenyl]-6-oxo-6,7- ciihydrothieno[2,3-/?]pyridine-2-carboxylate; 1,4-Diphenyl-1,4-dihydro-pyrrolo[3,2-b]pyridin-5-one; Ethyl 7-(2-chlorophenyl)-6-oxo-3-phenyl-6,7-dihydrothieno[2,3-fe]pyridine-2- carboxylate; and the salts, solvates, hydrates and N-oxides thereof. 22. A pharmaceutical composition comprising a compound according to any one of Claims 6 to 21 together with one or more pharmaceutically acceptable carriers, excipients or diluents.

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