Title of Invention	"HETEROCYCLIC AMIDE DERIVATIVE HAVING GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY"
Abstract	The present invention relates to heterocyclic amide compound of formula (I): or a pharmaceutically acceptable salt or pro-drug thereof

Full Text

The present invention relates to a heterocyclic amide derivative having glycogen phosphorylase inhibitory activity The present invention relates to hetcrcc)chc amide denvatives, pharmaceutic ally acceptable salts and in vivo hydrolysable esters thereof. These heterocyclic airudes possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity and thus are potentially useful in methods of treatment of a warm-blooded ariirrial such as man. The invention also relates to processes for the manufacture of said heterocyclic amide denvatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments to inhibit glycogen phosphorylase activity ui a warm-blooded animal such as man The hver is the major organ regulating glycaemia in the post-absorptive state Additionally, although having a smaller role in the contnbution to post-prandial blood glucose levels, the response of the hver to exogenous sources of plasma glucose is key to an ability to maintain euglycaemia. An increased hepatic glucose output (HGO) is considered to play an important role in maintaining the elevated fasting plasma glucose (FPG) levels seen in type 2 diabetics; particularly those with a FPG >140mg/dl (7 8mM). (Weyer et al, (1999), J Chn Invest 104- 787-794; Clore & Blackgard (1994), Diabetes 43 256-262, De Fronzo, R. A., et al, (1992) Diabetes Care 15, 318 - 355; Reaven, GM. (1995) Diabetologia 38, 3-13). Since current oral, anti-diabetic therapies fail to bnng FPG levels to within die normal, non-diabetic range and since raised FPG (and glycFlbAlc) levels are nsk factors for both macro- (Charles, in A. et al (1996) Lancet 348, 1657-1658, Coutinho, in et al (1999) Diabetes Care 22, 233-240, Shaw, J.E et al (2000) Diabetes Care 23, 34-39) and micro-vascular disease (DCCT Research Group (1993) New Eng J. Med. 329, 977-986), the reduction and normalisation of elevated FPG levels remains a treatment goal in type 2 DM It has been estimated that, after an overnight fast, 74% of HGO was denved from glycogenolysis with the remainder denved from gluconeogenic precursors (Hellerstem et al (1997) Am J Physiol, 272. E163) Glycogen phosphorylase is a key enzyme in the generation by glycogenolysis of glucose-1-phosphate, and hence glucose in hver and also in other tissues such as muscle and neuronal tissue Liver glycogen phosphorylase a activity is elevated in diabetic animal models including the db/db mouse and the fa/fa rat (Alston S et al (2000). Diabetalogia 43, 589-597) Inhibition of hepatic glycogen phosphorylase with chloroindole inhibitors (CP91149 and CP320626) has been shown to reduce both glucagon stimulated glycogenolysis and glucose output in hepatocytes (Hoover et al (1998) J Med Chem 41, 2934-8; Martin et al (1998) PNAS 95, 1776-81). Additionally, plasma glucose concentration is reduced, in a dose related manner, db/db and ob/ob mice following treatment with these compounds. Studies in conscious dogs with glucagon C1-4allenge in the absence and presence of another glycogen phosphorylase inhibitor, Bay K 3401, also show the potential utility of such agents where there is elevated circulating levels of glucagon, as in both Type 1 and Type 2 diabetes. In the presence of Bay R 3401, hepatic glucose output and arterial plasma glucose following a glucagon C1-4allenge were reduced significantly (Shiota et al, (1997), Am J Physiol, 273 E868). The heterocyclic amides of the present invention possess glycogen phosphorylase inhibitory activity and accordingly are expected to be of use in the treatment of type 2 diabetes, insulin resistance, syndrome X, hypennsulinaemia, hyperglucagonaemia, cardiac ischaemia and obesity, particularly type 2 diabetes According to the present invention there is prodded a heterocyclic amide compound (Formula Removed) wherein1 Z is CH or nitrogen; R4 and R5 together are either -3-C(R6)=C(R7)- or -C(R7)=C(R6)-S-; R6 and R7 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, fluoromethyl, difluoromethyl, tnfluoromethyl, tnfluoromethoxy, carboxy, carbamoyl, C1-4alkyl, C2Jtalkenyl, C2.4alkynyl, C1-4alkoxy and C1-4alkanoyl; A is phenylene or heteroarylene; nis 0, 1 or 2, R1 is independently selected from halo, nitio, cyano, hydroxy, carboxy, carbamoyl, N C1-4alkylcarbamoyl, iV//-(C1-4allcyl)2carbamoyl, sulphamoyl, N-C1-4alkylsulphamoyl, N,N-(C1-4alkyl)2sulphamoyl, -S(O)bC1-4alkyl (wherein b is 0,1,or 2), C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, hydroxyCj^alkyl, fluoromethyl, difluoromethyl, trifluoromethyl and tnfluoromethoxy; or, when n is 2, the two R1 groups, together with the carbon atoms of A to which they are attached, may form a 4 to 7 membered nng, optionally containing 1 or 2 heteroatoms independently selected from O, S and N, and optionally being substituted by one or two methyl groups, r is 1 or 2; and when r is 1 the group (Formula Removed) is a substituent on carbon (2) and when r is 2 (hereby forming a six membered nng) the same group is a substituent on carbon (2) or on carbon (3), y is -NR2R3 or -OR3; R2andR3 are independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkanoyl, carbamoyl, C3-7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups), cyano(C1-4)alkyl, heterocyclyl, aryl, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8, -SObR8 (wherein b is 0, 1 or 2) and groups of the formulae B and B' (Formula Removed) wherein y is 0 or 1, t is 0, 1, 2 or 3 and u is 1 or 2, provided that the hydroxy group is not a substituent on the nng carbon adjacent to the nng oxygen, or wherein NR2R3 may form a 4 to 7 membered saturated, partially saturated or unsaturated nng, optionally containing 1, 2 or 3 additional heteroatoms independently selected from N, O and S, wherein any -CH2- may optionally be replaced by -C(=O)-, and any N or S atom may optionally be oxidised to form an N-oxide or SO or SO2 group respectively, and wherein the is optionally substituted by 1 or 2 substituents independently selected from halo, cyano, C1-4alkyl, hydroxy, C1-4alkoxy and C1-4alkylS(O)b- (wherein b is 0, I or 2); R is independently selected from hydrogen, hydroxy, C1-4alkyl, C2-4alkenyl, C1-4alkoxy, cyano(C1-4)alkyl, ammo(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], halo(Cw)alkyl, dihalo(C1-4)alkyl, tnhalo(C1.4)aikyl, hydroxy(C1- 4)alkyl, dihydroxy(C]ut)alkyl, C1-4alkoxyC1-4alkoxy, C1-4alkoxyC1-4aikyl, hydroxyC1-4alkoxy, 5- and 6-membered cychc acetals and mono- and di-methyl derivatives thereof, aryl, heterocyclyl, (heterocyclyl)C1-4alkyl, C3.7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups, C1-4alkyl or -C(O)OC1-4alkyl), C1-4alkanoyl, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3.6cycloalkylS(O)b- (wherein b is 0, l or 2), arylS(O)b- (wherein b is 0, l or 2), heterocyclylS(O)b- (wherein b is 0, 1 or 2), benzylS(O)b- (wherem b is 0, l or 2), Q. 4alkylS(O)c(C1_4)alkyl (wherein c is 0, l or 2), -N(OH)CHO, -C(=N-OH)NH2, -C(=N- OH)NHC1-4alkyl, -C(=N-OH)N(C1-4alkyl)2, -C(=N-OH)NHC3^cycloalkyl, -C(=N-OH)N(C3.6cycloalkyl)2, -COCOOR9, -C(O)N(R9)(R10)f -NHC(O)R9, -C(O)NHSO2(C1-4alkyl), -NHSO2R9, (R9)(R10)NSO2-, -COCH2ORn, (R9)(RI0)N- and -COOR9, -CH2OR9, -CH2COOR9, -CH2OCOR9, -CH2CH(CO2R9)OH, -CH2C(O)NR9R10, -(CH2)wCH(NR9R10)CO2R9' (wherein w is 1, 2 or 3), and -(CH2)wCH(NR9R1())CO(NR9'R10') (wherein w is 1, 2 or 3), R9 , R9', R10 and R10' are independently selected from hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13), C2-4alkenyl, C3.7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups), cyano(C1-4)alkyl, tnhaloalkyl, aryl, heterocyclyl, heterocyclyl(C1-4.alkyl), and -C(=O)O(Cw)alkyl; or R9 and R10 together with the nitrogen to which they are attached, and/or R9 and R10 together with the nitrogen to which they are attached, form a 4- to 6-membered nng where the nng is optionally substituted on carbon by 1 or 2 substituents independently selected from oxo, hydroxy, carboxy, halo, nitro, cyano, carbonyl, C1-4alkoxy and heterocyclyl, or the nng may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cyclic acetal wherem one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl, R13 is selected from halo, tnhalomethyl, and C1-4alkoxy, R11 is independently selected from hydrogen, C1-4alkyl, and hydroxyC1-4alkyl, or a pharmaceutically acceptable salt or pro-drug thereof, with the proviso that the compound of formula (1) is not- l) 2,3-dichloro-5-(Af-{ 1-[7V-(1 ,l-dimethylethoxy)carbonylammo]indan-2- yl }carbamoyl)-4R-thieno[3,2-b]pyrrole, n) 5-[N-(l-aniinoindan-2-yl)carbamoyl]-2,3-diQhloro-4H-thieno[3,2-i]pyrrole 111) 5-[N-(l-acetarmdoindan-2-yl)carbamoyl]-2,3-dichloro-4flr-thieno[3,2-b]pyrrole IV) 2,3-dichloro-5-{N-[l-(methanesulphonamido)mdan-2-yl]carbamoyl}-4H- thieno [3,2-£]pyrrole v) 2,3-dichloro-5-{N-[l-(methylamino)mdan-2-yl]carbamoyl}-4-ff-thieno[3)2- b]pyrrole; vi) 23-dicUorcn5-{N-[l-(methylacetarriido)indan-2-yl]carbanioyl}-4H-thieno[3,2- t]pyrrole; vn) 2,3-dichloro-5-[?/-(l-hydroxyindan-2-yl)carbamoyl]-4H-thieno[3,2-b]pyrrole, vm) 2-chloro-5-[N-(l-hydroxymdan-2-yl)carbamoyl-6H-thieno[2,3-6]pyrrole; IX) 2,3-dichlorx>-5-[//-(6-fluoro-l-hydroxyindan-2-yl)carbamoyl-4H-thieno[3,2- &]pyrrole x) 23-dichloro-5-[A'r-(l-methoxymdan-2-yl)carbamoyl-4ii/-tnieno[3,2-i>]pyrrole, xi) 2,3-dichloro-5-[N-(l-hydroxy-l,2,3,4-tetrahydronaphth-2-yl)carbamoyl]-4-R- thieno[3,2-Zj]pyrrole. According to another aspect of the present invention there is provided a compound of formula (1): (Formula Removed) wherein Z is CH or nitrogen, R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S- , R°andR' are independently selected from hydrogen, halo, nitro, cyano, hydroxy, fluoiomethyl, difluoromethyl, tnfluoromethyl, tafluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, ureido, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkanoyl, C1-ealkanoyloxy, N-(C1-6aikyl)amino, N-(C1-6alkyl)2amino, Q.galkanoylamino, N-C1-6alkyl)carbamoyl, iV,N-(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a wherein a is O to 2, C1-4alkoxycarbonyl, C1-6alkoxycarbonylarmno, N-(C1-4alkyl)sulphamoyl, N,N-(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino and C1-6alkylsulphonyl-N-(C1-6alkyl)amino; A is phenylene or heteroarylene; nis 0, 1 or 2, R1 is independently selected from hydrogen, halo, mtro, cyano, hydroxy, amino, carboxy, carbamoyl, N-C1-4alkylcarbamoyl, N,N-(C1-4alkyl)2carbamoyl, sulphamoyl, N-C1-4alkylsulphamoyl, 7V^V-(C1-4alkyl)2Sulphamoyl, sulfmo, sulfo, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-4aIkanoyloxy, N-(C1-4alkyl)amino, N,NC1-4alkyl)2amino, hydroxyC1-4alkyl, fluoromethyl, difluoromethyl, tnfluoromethyl, tnfluoromethoxy, C1-4alkoxy and R1 is of the formula A' or A": (Formula Removed) wherein x is 0 or 1, p is 0, 1, 2 or 3 and s is 1 or 2; provided that the hydroxy group is not a substituent on the ring carbon adjacent to the ring oxygen; r is 1 or 2, and when r is 1 the group (Formula Removed) is a substituent on carbon (2) and when r is 2 (hereby forming a six membered ring) the same group is a substituent on carbon (2) or on carbon (3), y is -NR2R3 or -OR3, R2 and R3 are independently selected from hydrogen, hydroxy, C1-4alkyl (substituted by 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), C5-7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), cyano(C1-4)alkyl, 4-butanohdyl, 5-pentanolidyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranylgroup, 1,1-dioxotetrahydrothiopyranyl, fluoromethylcarbonyl, difluoromethylcarbonyl, tnfluoromethylcarbonyl, C1-4alkyl [substituted by 1 or 2 R8 groups provided that when there are 2 R8 groups they are not substituents on the same carbon)], -COR8, -SObR8 (wherein b is 0,1 or 2) and groups of the formulae B and B'. (Formula Removed) wherem y is 0 or 1, t is 0, 1, 2 or 3 and u is 1 or 2; provided that the hydroxy group is not a substituent on the nng carbon adjacent to the ring oxygen); {wherein R8 is independently selected from hydrogen, hydroxy, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, 2,2-dimethyl-l,3-dioxolan-4-yl, heterocyclyl (optionally substituted on carbon or nitrogen by 1 or 2 groups selected from hydrogen, rutro, halo, cyano, hydroxy and C1-4alkyl), (heterocyclyl)C1-4alkyl (wherein the heterocyclyl is optionally substituted on carbon or nitrogen by 1 or 2 groups selected from hydrogen, nitro, halo, cyano, hydroxy and C1-4alkyl), aryl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), C1-4alkyl, C2-4alkenyl, cyclo(C3-8)alkyl, C1-4alkoxy, cyano(C1-4)alkyl, ammo(C1-4)alkyl (optionally substituted on nitrogen by 1 or 2 groups selected from hydrogen, C1-4alkyl, hydroxy, hydroxy(C1-4)alkyl, dihydroxy(C1-4.)alkyl, aryl and aryKC1-4afkyl), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0,-1 or 2), -N(OH)CHO, -CH2CH(CO2R9)N(R9R10)) -CH2OR9, (R9)^10)^, -COOR9 and -CH2COOR9 , -CH2CONR9R10, -(CH2)uCH(NR9R10)CO2R9 (wherein u is 1, 2 or 3), [wherein R9 and R10 are independently selected from hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), C5_7cycloalky] (optionally substituted by 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), C2-4alkenyl, cyano(C1-4)alkyl, 4-butanolidyl, 5-pentanohdyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranylgroup, 1,1-dioxotetrahydrothiopyranyl, 2,2-dimethyl-l,3-dioxolan-4-yl, aryl (optionally substituted by 1 or 2 substituents selected from hydrogen, nitro, halo, hydroxy and C1-4alkyl) and C1-4alkyl substituted by R13 , (wherein R13 is selected from hydroxy, C1-4alkoxy, heterocyclyl, C1-4alkanoyl, C1-4alkylS(O)d (wherem d is 0, 1 or 2)1, -N(OH)CHO, (Rn)(R12)NCO-, (Ru)(R12)NSO2-, -COCH2OR11nd (Rn)(R12)N-; {wherein R11 and R12 are mdependently selected from hydrogen, C1-4alkyl, C1-4alkoxy, hydroxyC1-4alkyl, C1-4alkylS(O)e (wherein e is 0, 1 or 2)}), and R and R can together with the nitrogen to which they are attached form 4- to 6-membered nng where the ring is optionally substituted on carbon by 1 or 2 substituents selected from oxo, hydroxy, carboxy, halo, nitro, nitroso, cyano, isocyano, ammo, N-C1-talkylammo, N,N-(C1-4)2alkylamrno, carbonyl, sulfo, C1-4alkoxy, heterocyclyl, C1-4alkanoyl, C1-4alkylS(O)f(C1-4)arkyl (wherein f is 0, 1 or 2), -N(OH)CHO, (Rn)(RI2)NCO-, (Rn)(R12)NSO2-, -COCH2ORn, (R11)(R12)N-, wherein Ru and R12 are as defined above]}, provided that when R1 is of the formula A' or A' then R2 and R3 do not contain a group of the formula B or B' and when R2 or R3 is of the formula B or B' then R1 does not contain a group of the formula A' or A" such that a compound of formula (1) can contain only one of A', A", B andB', or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof; with the proviso that the compound of formula (1) is not I) 2,3-dichloro-5-(/\f-{ l-[AT-(l,l-dmiethylethoxy)carbonylamino]mdan-2- yl} carbamoyl)-4H-thieno [3,2-fr]pyrrole; II) 5-[^ III) 5-[N-(l-acetamidoindan-2-yl)carbamoyl]-2,3-dichloro-4H-thieno[3,2- frjpyrrole 1 v) 2,3 -dichloro-5-{ N-[ 1 -(methanesulphonamido)indan-2-yl] carb amoyl} -4H- thieno[3,2-b]pyrrole v) 2,3 -dichloro-5- {N-[l -(methylammo)mdan-2-yl] carbamoyl} -4H-thieno [3,2- b]pyrrole, vi) 2,3-dichloro-5-{Af-[l-(mediylacetamido)indan-2-yl]carbamoyl}-4i^- thieno [3,2-b]pyrrole; vn) 2,3-dicrdoro-5-[N-(l-hyNoxyindan-2-yl)carbamoyl]-4^-thieno[3,2-6]pyrrole, vm) 2-chloro-5-[N-(l-hydroxymdan-2-yl)carbamoyl-6^-thienot2,3-6]pyrrole; IX) 2,3-dichloro-5-[7V-(6-fluoro-l-hydroxyindan-2-yl)carbamoyl-4H-thieno[3,2- 6]pyrrole x) 2,3-dichloro-5-[Af-(l-methoxyindan-2-yl)carbamoyl-4H-thieno[3,2-fo]pyrrole, xi) 2,3-dichloro-5-[N-(l-hydroxy-l,2,3,4-tetrahydronaphth-2-yl)carbamoyl]-4-H'- thieno [3,2-b]pyrrole. It is to be understood that when A is heteroarylene, the bridgehead atoms joining ring A to the pipendinone nng may be heteroatoms Therefore, for example, the definition of (Formula Removed) when A is heteroarylene encompasses the structures y (Formula Removed) It is to be understood that, where optional substitution on alkyl or cycloalkyl groups in R3, R9 and R10 (as defined hereinbefore or hereinafter) allows two hydroxy substituents on the alkyl or cycloalkyl group, or one hydroxy substituent and a second substituent linked by a heteroatom (for example alkoxy), then these two substituents are not substituents on the same carbon atom of the alkyl or cycloalkyl group In another aspect, the invention relates to compounds of formula (1) as hereinabove defined or to a pharmaceutically acceptable salt In another aspect, the invention relates to compounds of formula (1) as hereinabove defined or to a pro-drug thereof. Suitable examples of pro-drugs of compounds of formula (1) are m-vivo hydrolysable esters of compounds of formula (1) Therefore in another aspect, the invention relates to compounds of formula (1) as hereinabove defined or to an in-vivo hydrolysable ester thereof It is to be understood that, insofar as certain of the compounds of formula (1) defined above may exist in optically active or racemic forms by virtue of one or more asymmetric carbon atoms, the invention includes in its definition any such optically active or racemic form which possesses glycogen phosphorylase inhibition activity The synthesis of optically active forms may be carried out by standard techmques of organic chemistry well known in the art, for example by synthesis from optically active starting materials or by resolution of a racemic form Similarly, the above-mentioned activity may be evaluated usmg the standard laboratory techmques referred to hereinafter Within the present invention it is to be understood that a compound of the formula (1) -r a salt thereof may exhibit the phenomenon of tautomensm and that the formulae drawings within this specification can represent only one of the possible tautomeric forms. It is to be understood that the invention encompasses any tautomeric form which has glycogen phosphorylase inhibition activity and is not to be limited merely to any one tautomeric form utilised within the formulae drawings. The formulae drawings within this specification can represent only one of the possible tautomenc forms and it is to be understood that the specification encompasses all possible tautomenc forms of the compounds drawn not just those forms which it has been possible to show graphically herein It is also to be understood that certain compounds of the formula (1) and salts thereof can exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention encompasses all such solvated forms which have glycogen phosphorylase inhibition activity. It is also to be understood that certain compounds of the formula (1) may exhibit polymorphism, and that the invention encompasses all such forms which possess glycogen phosphorylase inhibition activity. The present invention relates to the compounds of formula (1) as hereinbefore defined as well as to the salts thereof Salts for use in pharmaceutical compositions will be pharmaceutically acceptable salts, but other salts may be useful in the production of the compounds of formula (1) and their pharmaceutically acceptable salts Pharmaceutically acceptable salts of the invention may, for example, include acid addition salts of the compounds of formula (1) as hereinbefore defined which are sufficiently basic to form such salts Such acid addition salts include for example salts with inorganic or organic acids affording pharmaceutically acceptable anions such as with hydrogen halides (especially hydrochloric or hydrobromic acid of which hydrochlonc acid is particularly prefened) or with sulphunc or phosphonc acid, or with tnfluoroacetic, citnc or maleic acid Suitable salts include hydrochlondes, hydrobromides, phosphates, sulphates, hydrogen sulphates, alkylsulphonates, arylsulphonates, acetates, benzoates, citrates, maleates, fumarates, succinates, lactates and tartrates. In addition where the compounds of formula (1) are sufficiently acidic, pharmaceutically acceptable salts may be formed with an inorganic or organic base which affords a pharmaceutically acceptable cation Such salts with inorganic or organic bases include for example an alkali metal salt, such as a sodium or potassium salt, an alkaline earth metal salt such as a calcium or magnesium salt, an ammonium salt or for example a salt with methylamme, dimethylamine, tnmethylamine, pipendme, morphohne or wiS-(2-hydroxyethyl)amine The compounds of the mvention may be administered in the form of a pro-drug which is broken down in the human or animal body to give a compound of the invention. A prodrug may be used to alter or improve the physical and/or pharmacokinetic profile of the parent compound and can be formed when the parent compound contains a suitable group or substituent which can be denvatised to form a prodrug. Examples of pro-drugs include m-vivo hydrolysable esters of a compound of the invention or a pharmaceutically-acceptable salt thereof Various forms of prodrugs are known in the art, for examples see. a) Design of Prodrugs, edited by H Bundgaard, (Elsevier, 1985) and Methods in ^nzymology, Vol. 42, p 309-396, edited by K Widder, et al (Academic Press, 1985), t() A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and M Bundgaard, Chapter 5 "Design and Application of Prodrugs", by H. Bundgaard p 113-191 01991), £1) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77, 285 (1988), and e) N Kakeya, et al, Chem Pharm Bull, 32, 692 (1984) An in vivo hydrolysable ester of a compound of formula (1) containing carboxy or hydroxy group is, for example A pharmaceutically acceptable ester which is cleaved in the human or animal body to produce the parent acid or alcohol Suitable pharmaceutically acceptable esters for carboxy include C1-6alkoxymethyl esters for example methoxymethyl, C1-6alkanoyloxymethyl esters for example pivaloyloxymethyl, phthalidyl esters, C3.8cycloalkoxycarbonyloxyC1-4alkyl esters for example 1-cyclohexylcarbonyloxyethyl, l,3-dioxolen-2-onylmethyl esters for example 5-methyl-l,3-dioxolen-2-onylmethyl, and C1-6alkoxycarbonyloxyethyl esters for example 1-methoxycarbonyloxyethyl and may be formed at any carboxy group in the compounds of this mvention Suitable pharmaceutically-acceptable esters for hydroxy mclude inorganic esters such as phosphate esters (including phosphoramidic cyclic esters) and oc-acyloxyalkyl ethers and related compounds which as a result of the in-vivo hydrolysis of the ester breakdown to give the parent hydroxy group/s Examples of a-acyloxyalkyl ethers mclude acetoxymethoxy and 2-4-dimethylpropionyloxymethoxy A selection of in-vivo hydrolysable ester forming groups for hydroxy include C1-10alkanoyl, for example acetyl, benzoyl, phenylacetyl, substituted benzoyl and phenylacetyl, C1-10alkoxycarbonyl (to give alkyl carbonate esters), for example ethoxycarbonyl; di-(C1-4)alkylcarbamoyl and AKm-(C1-4)alkylaminoethyl)-N-(C1-4)alkylcarbamoyl (to give carbamates), di-(C1-4)alkylammoacetyl and carboxyacetyl. Examples of ring substituents on phenylacetyl and benzoyl include ammomethyl, (Cj. 4)alkylammomethyl and di-((C1-4)alkyl)aminomethyl, and morpholmo or piperazino linked from a nng nitrogen atom via a methylene linking group to the 3- or 4- position of the benzoyl ring Other interesting in-vivo hyrolysable esters include, for example, RAC(O)O(C1-6)alkyl-CO-, wherein R is for example, benzyloxy-(C1-4)alkyl, or phenyl) Suitable substituents on a phenyl group in such esters include, for example, 4-(C1-4)piperazrno-(C1-4)alkyl, piperazmo-(C1-4)alkyl and morpholino-(C1-C4)alkyl In this specification the generic term "alkyl" includes both straight-chain and branched-chain alkyl groups. However references to individual alkyl groups such as "propyl" are specific for the straight chain version only and references to individual branched-chain alkyl groups such as Nbutyl are specific for the branched chain version only. For example, "C1-4alkyl" includes methyl, ethyl, propyl, isopropyl and r-butyl and examples of "C1-4alky1" include the examples of "C1-4alkyl"and additionally pentyl, 2,3-dunethylpropyl, 3-methylbutyl and hexyl. An analogous conyention applies to other generic terms, for example "C2-4alkenyl" includes vinyl, allyl and 1-propenyl and examples of "C2-4alkenyl" include the examples of "C2-4alkenyl" and additionally 1-butenyl, 2-butenyl, 3-butenyl, 2-methylbut-2-enyl, 3-methylbut-1-enyl, 1-pentenyl, 3-pentenyl and 4-hexenyl Examples of "C2-4alkynyl" includes ethynyl, 1-propynyl and 2-propynyl and examples of "C2-6alkynyr'include the examples of "C2-4alkynyl" and additionally 3-butynyl, 2-pentynyl and l-methylpent-2-ynyl The term "hydroxyC1-4alkyl" includes hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxyisopropyl and hydroxybutyl The term "hydroxyethyl" includes 1-hydroxyethyl and 2-hydroxyethyl The term "hydroxypropyl" includes 1-hydroxypropyl, 2-hydroxypropyl and 3-hydroxypropyl and an analogous conyention applies to terms such as hydroxybutyl The term "dihydroxyC1-4alkyl" mcludes dihydroxyethyl, dihydroxypropyl, dihydroxyisopropyl and dihydroxyburyl The term "dihydroxypropyl" includes 1,2-dihydroxypropyl and 1,3-dihydroxypropyl. An analogous conyention applies to terms such as dihydroxyisopropyl and dihydroxybutyl The term "halo" refers to fluoro, chloro, bromo and lodo The term "dihaloC1-4alkyl" cludes difluoromethyl and dichloromethyl The term "tnhaloC1-4alkyl" mcludes tnfluoromethyl Examples of "5- and 6-membered cychc acetals and mono- and di-methyl derivatives thereof are. l,3-dioxolan-4-yl, 2-methyl-l,3-dioxolan-4-yl, 2,2-dimethyl-l,3-dioxolan-4-yl; 2,2-drmethyl-l,3-dioxan-4-yl, 2,2-dimethyl-l,3-dioxan-5-yl, l,3-dioxan-2-yl. Examples of "C1-4alkoxy" mclude methoxy, ethoxy, propoxy and isopropoxy. Examples of "C1-4alkoxy" include the examples of "C1-4alkoxy" and additionally butyloxy, t-butyloxy, pentoxy and l,2-(methyl)2propoxy Examples of "C1-4alkanoyl" mclude formyl, acetyl and propionyl. Examples of "C1-4alkanoyl" include the example of "C1-4alkanoyl" and additionally butanoyl, pentanoyl, hexanoyl and l,2-(methyl)2propionyl. Examples of "C1-4alkanoyloxy" are formyloxy, acetoxy and propionoxy Examples of "C1-6alkanoyloxy" mclude the examples of "C1-4alkanoyloxy" and additionally butanoyloxy, pentanoyloxy, hexanoyloxy and 1,2-(methyl)2propionyloxy Examples of 'W-(C1-4alkyl)aimno" mclude methylammo and ethylammo. Examples of 'W-(C1-6aIkyl)ammo" include the examples of "N-(C1-4alkyl)ammo" and additionally pentylamino, hexylammo and 3-methylbutylammo Examples of 'W,N-(C1-4alkyl)2amino" include N-AHmetiiyl^ammo, N-AKethyl^ammo and N-ethyl-AT-methylamino. Examples of 'W,N-(C1-6alkyl)2amino" include the example of "iV,N-(C1-4alkyl)2amino" and additionally N-methyl-A7-pentylamino and Af,iy"-(pentyl)2amino Examples of 'W-(C1-4alkyl)carbamoyl" are methylcarbamoyl and ethylcarbamoyl Examples of "N-CC1-4alkyl^arbamoyl" are the examples of 'W-(C1-4alkyl)carbamoyl"and additionally pentylcarbamoyl, hexylcarbamoyl and 1,2-(methyi)2propylcarbamoyl Examples of 'W,Af-(C1-4alkyl)2carbamoyl" are A',N-(methyl)2carbamoyl, A7',A?-(ethyl)2carbamoyl and N-methyl-N-ethylcarbamoyl. Examples of "NJV-CC1-4aikyl^carbamoyl" are the examples of 'W,A/-(C1-4alkyl)2carbamoyl" and additionally Af,A7-(pentyl)2carbamoyl, A'-methyl-N-pentylcarbamoyl and N-ethyl-TV-hexylcarbamoyl Examples of "N-(C1-4alkyl)sulphamoyl" are ^-(methy^sulphamoyl and ^-(ethy^sulphamoyl Examples of W-(C1-6alkyl)sulphamoyl" are the examples of 'W-CC1-4alky^sulphamoyl" and additionally N-pentylsulphamoyl, N-hexylsulphamoyl and 1,2-(methyl)2propylsulphamoyl. Examples of "^^-(C1-4alkyl^sulphamoyl" are A7,N-(methyl)2Sulphamoyl, N,N-(ethyl)2Sulphamoyl and N-(methyl)-iV'-(ethyl)sulphamoyl Examples of "A7,A7-(C1.6alkyl)2Sulphamoyl" are the examples of "N,N-(C1-4alkyl)2Sulphamoyl" and additionally N,N-(pentyl)2Sulphamoyl, N-rnethyl-.N-pentylsulphamoyl and N-ethyl-N-hexylsulphamoyl Examples of "cyano(C1-4)alkyl" are cyanometfvyl, cyanoethyl and cyanopropyl. Examples of "C5-7cycloalkyl" are cyclopentyl, cyclohexyl and cycloheptyl. Examples of "C3-scycloalkyl" and "C3-7cycloalkyl" include "C5-7cycloalkyl", cyclopropyl, cyclobutyl and cyclooctyl. Examples of "C3.6cycloalkyl" inclulde cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl The term "aminoC1-4alkyl" includes aminomethyl, aminoethyl, ammopropyl, aminoisopropyl and aminobutyl The term "aminoethyl" mcludes 1-ammoethyl and 2-ammoethyl The term "aminopropyl" includes 1-ammopropyl, 2-aminopropyl and 3-aminopropyl and an analogous conyention applies to terms such as aminoethyl and aminobutyl Examples of "C1-4alkoxyC1-4alkoxy" are methoxymethoxy, ethoxymethoxy, ethoxyedioxy and methoxyethoxy. Examples of "hydroxyC1-4alkoxy" are hydroxyethoxy and hydroxypropoxy. Examples of "hydroxypropoxy" are 1-hydroxypropoxy, 2-hydroxypropoxy and 3-hydroxypropoxy. Examples of "C1-4alkylS(O)b (wherein b is 0,1 or 2)", "C1-4aIkylS(O)c (wherein c is 0 to 2)", "C1-4alkylS(O)d (wherein d is 0 to 2)", "C1-4alkylS(O)e (wherein e is 0 to 2)", and "C1-4alkylS(O)f (wherein f is 0 to 2)" independently include methylthio, ethylthio, propylthio, methanesulphinyl, ethanesulphrnyl, propanesulphinyl, mesyl, ethanesulphonyl, propanesulphonyl and isopropanesulphonyl Examples of "C3-6cycloalkylS(O)b (wherein b is 0,1 or 2)" include cyclopropylthio, cyclopropylsulphmyl, cyclopropylsulphonyl, cyclobutylthio, cyclobutylsulphinyl, cyclobutylsulphonyl, cyclopentylthio, cyclopentylsulphmyl and cyclopentylsulphonyl. Examples of "arylS(O)b (wherem b is 0,1 or 2)" include phenylthio, phenylsulphinyl and phenylsulfonyl. Examples of "benzylS(O)b (wherein b is 0,1 or 2)" mculde benzylthio, benzylsulfinyl and benzylsulfonyl Examples of "heterocyclylS(O)b (wherein b is 0,1 or 2)" include pyndylthio, pyndylsulfmyl, pyndylsulfonyl, lmidazolylmio, imidazolylsulfmyl, lmidazolylsulfonyl, pynmidinylthio, pynmidinylsufinyl, pynmidinylsulfonyl, pipendylthio, pipendylsulfmyl and pipendylsulfonyl Examples of "C1-6alkoxycarbonyl" include methoxycarbonyl, ethoxycarbonyl, N- and f-butoxycarbonyl. Examples of "C1-6aIkoxycarbonylarnino" mclude methoxycarbonylammo, ethoxycarbonylamino, n- and t-butoxycarbonylammo Examples of 'C1.6aLkylsulphonyl-N-(C1-4alkyl)amino' include methylsulphonyl-N-methylarnmo, wthylsulphonyl-N-methylamino and propylsulphonyl-N-ethylamino Examples of "C1-4alkylsulphonylamino" include methylsulphonylamino, ethylsulphonylammo and propylsulphonylammo Examples of "C1-4alkanoylamino" include formamido, acetamido and propionylamino. Where optional substituents are chosen from "0, 1, 2 or 3" groups it is to be understood that this definition includes all substituents being chosen from one of the specified groups or the substituents being chosen from two or more of the specified groups An analogous conyention applies to substituents chose from "0, 1 or 2" groups and "1 or 2" groups "Heterocyclyl" is a saturated, partially saturated or unsaturated, optionally substituted monocyclic rmg containing 5 to 7 atoms of which 1, 2, 3 or 4 ring atoms are chosen from nitrogen, sulphur or oxygen, which may, unless otherwise specified, be carbon or nitrogen linked, wherein a -CH2- group can optionally be replaced by a -C(O)-and a ring sulphur atom may be optionally oxidised to form the S-oxide(s). Examples and suitable values of the term "heterocyclyl" are morpholmo, morpholinyl, pipendino, pipendyl, pyndyl, pyranyl, pyrrolyl, lmidazolyl, thiazolyl, thienyl, dioxolanyl, thiadiazolyl, piperazmyl, isothiazolidinyl, tnazolyl, tetrazolyl, pyrrolidinyl, 2-oxazokdmonyl, 5-isoxazolonyl, thiomorpholino, pyrrohnyl, homopiperazmyl, 3,5-dioxapiperidinyl, 3-oxopyrazokn-5-yl, tetrahydropyranyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, pynmidyl, pyrazinyl, pyndazinyl, pyrazolyl, pyrazohnyl, isoxazolyl, 4-oxopydndyl, 2-oxopyrrohdyl, 4-oxothiazohdyl, furyl, thienyl, oxazolyl, and oxadiazolyl. Suitably a "heterocyclyl" is morphokno, morphohnyl, pipendino, pipendyl, pyndyl, pyranyl, pyrrolyl, lmidazolyl, thiazolyl, thienyl, thiadiazolyl, piperazmyl, isothiazolidinyl, 1,3,4-tnazolyl, tetrazolyl, pyrrohdmyl, thiomorphohno, pyrrohnyl, homopiperazmyl, 3,5-dioxapipendmyl, pynmidyl, pyrazinyl, pyndazinyl, pyrazolyl, pyrazohnyl, isoxazolyl, 4-oxopydndyl, 2-oxopyrrolidyl, 4-oxothiazohdyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, and 1,2,4-oxadiazolyl. Conyemently "heterocyclyl" is oxazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, tetrazolyl, thizoyl, thiadiazolyl, pyndyl, lmidazolyl, furyl, thienyl, morpholme, pynmidyl, pyrazinyl, pyndazinyl, pyrazolyl, pyrazohnyl, and piperazmyl Suitable optional substituents for "heterocyclyl" as a saturated or partially saturated nng are 1, 2 or 3 substituents independently selected from halo, cyano, hydroxy, C1-4alkyl, C1- alkoxy and C1-4alkylS(O)b (wherein b is 0, I or 2) Further suitable substituents for "heterocyclyl" as a saturated or partially saturated nng are 1, 2 or 3 substituents independently selected from fluoro, chloro, cyano, hydroxy, methyl, ethyl, methoxy, methylthio, methylsulfmyl and methylsulfonyl. Suitable optional susbtituents for "heterocyclyl" as an unsaturated ring are 1, 2 or 3 substituents independently selected from halo, cyano, rutro, amino, hydroxy, C1-*alkyl, C1-4alkoxy, C1-4alkylS(O)b (wherein b is 0, I or 2), JV-(C1-4alkyl)amrno and AfN-(C1-4alkyl)2amino Further suitable optional susbtituents for "heterocyclyl" as an unsaturated nng are 1, 2 or 3 substituents independently selected from fluoro, chloro, cyano, nitro, ammo, methylamino, dimethylamino, hydroxy, methyl, ethyl, methoxy, methylthio, methylsulfmyl and methylsulfonyl Examples of "(heterocyclyl)C1-4alkyl" are morpholmomethyl, morpholinethyl, morphohnylmethyl, morpholmylethyl, pipendinomethyl, pipendmoethyl, pipendylxnethyl, pipendylethyl, lmidazolylrnethyl, lmidazolyletliyl, oxazolylmethyl, oxazolylethyl, 1,3,4-oxadiazolylmethyl, 1,2,4-oxadiazolylmethyl, 1,2,4-oxadiazolylethyl, pyndylmethyl, pyndylethyl, furylmethyl, furylethyl, (thienyl)methyl, (thienyl)ethyl, pyrazrnylmethyl, pyrazmylethyl, piperazmylmethyl and piperazinylethyl Examples of "aryl" are optionally substituted phenyl andnaphthyl Examples of "aryl(C1-4)alkyl" are benzyl, phenethyl, naphthylmethyl and naphthylethyl. Suitable optional substituents for "aryl" groups are 1, 2 or 3 substituents independently selected from halo, cyano, nitro, ammo, hydroxy, C1-4alkyl, C1-4alkoxy, C1-4alkylS(O)b (wherein b is 0, 1 or 2), ^-(Cj^alky^amino and N,N-(C1-4alkyl)2ammo Further suitable optional susbtituents for "aryl" groups are 1, 2 or 3 substituents independently selected from fluoro, chloro, cyano, nitro, amino, methylamino, dimethylamino, hydroxy, methyl, ethyl, methoxy, methylthio, methylsulfmyl and methylsulfonyl. "Heteroarylene" is a diradical of a heteroaryl group. A heteroaryl group is an aryl, monocyclic nng containing 5 to 7 atoms of which 1, 2, 3 or 4 nng atoms are chosen from nitrogen, sulphur or oxygen. Examples of heteroarylene are oxazolylene, oxadiazolylene, pyndylene, pynmidinylene, lrxudazolylene, tnazolylene, tetrazolylene, pyrazmylene, pyndazmylene, pyrrolylene, thienylene and furylene Suitable optional substituents for heteroaryl groups, unless otherwise defined, are 1, 2 or 3 substituents independently selected from halo, cyano, rutro, amino, hydroxy, C1-4alkyl, C1-4alkoxy, C1-4alkylS(O)b (wherein b is 0, 1 oi 2), N-(C1-4arkyl)armno and N,N-(C1-4aIkyl)2amino Further suitable optional susbtituents for "heteroaryl" groups are 1, 2 or 3 substituents independently selected from fluoro, chloro, cyano, rutro, amino, methylamino, dimethylamino, hydroxy, methyl, ethyl, methoxy, methylthio, methylsulfinyl and methylsulfonyl. Preferred values of A, y, R1, R4, R5, r and n are as follows. Such values may be used where appropriate with any of the definitions, claims, aspects or embodiments defined hereinbefore or hereinafter. In one embodiment of the invention are provided compounds of formula (1), in an alternative embodiment are provided pharmaceutically-acceptable salts of compounds of formula (1), in a further alternative embodiment are provided m-vivo hydrolysable esters of compounds of formula (1), and in a further alternative embodiment are provided pharmaceutically-acceptable salts of m-vivo hydrolysable esters of compounds of formula (1) Particular examples of in-vivo hydrolysable esters of compounds of the formula (1) are such esters of compounds of the formula (1) wherein y comprises a group containing a carboxy group Suitable esters are those hereinbefore descnbed for carboxy groups In one aspect of the present invention there is provided a compound of formula (1) as depicted above wherein z is CH In another aspect of the invention Z is nitrogen In one aspect of the present invention diere is provided a compound of formula (1) as depicted above wherein R4 and R5 are together -S-C(R6)=C(R7)- In another aspect of the invention R4 and R5 are together -C(R7)=C(R5)-S-. In a further aspect of the invention, R6 and R7 are mdependentiy selected from hydrogen, halo or C1-4alkyl. Preferably R6 and R7 are independently selected from hydrogen, chloro, bromo or methyl Particularly R6 and R7 are independently selected from hydrogen or chloro More particularly one of R6 and R7 is chloro In one embodiment, one of R6 and R7 is chloro and the other is hydrogen In another embodiment, both R and R are chloro. In one aspect of the invention A is phenylene In another aspect of the invention A is heteroarylene Preferably A is selected from phenylene, pyndylene, pynmidmylene, pyrrolylene, lmidazolylene, tnazolylene, tetrazolylene, oxazolylene, oxadiazolylene, thienylene and furylene In one embodiment, when A is heteroarylene, there is a nitrogen in a bndgehead position In another embodiment, when A is heteroarylene, the heteroatoms are not in bndgehead positions It will be appreciated that the preferred (more stable) bndgehead position is as shown below (Formula Removed) In one aspect of the invention n is 0 or 1 In one aspect preferably n is 1 In another aspect, preferably n is 0 When n is 2, and the two R1 groups, together with the carbon atoms of A to which they are attached, form a 4 to 7 membered nng, optionally containing 1 or 2 heteroatoms independently selected from O, S and N, conyeniently such a nng is a 5 or 6 membered nng containing two O atoms (le a cychc acetal) When the two R1 groups together form such a cychc acetal, preferably it is not substituted Most preferably the two R1 groups together are the group -O-CH2-O- In another aspect of the present invention R1 is selected from halo, nitro, cyano, hydroxy, fluoromemyl, difluoromethyl, tnfluoromethyl and C1-4alkoxy In a further aspect R1 is selected from halo, nitro, cyano, hydroxy, fluoromethyl, difluoromethyl, tnfluoromethyl, -S(O)bC1-4aTkyl (wherein b is 0, 1 or 2), C1-4alkyl and Q. 4alkoxy In a further aspect R1 is selected from halo, nitro, cyano, hydroxy, fluoromethyl, difluoromethyl, tnfluoromethyl, -S(O)bMe (wherein b is 0, 1 or 2), methyl and methoxy In a further aspect, R1 is C1-4alkyl Preferably R1 is selected from halo and C1-4alkoxy In another embodiment preferably R1 is selected from fluoro, chloro, methyl, ethyl, methoxy and -O-CH2-O-. In one aspect of the invention r is 1 and when r is 1 the group (Formula Removed) is a subsutuent on carbon (2) such that an example of when r is 1 is. (Formula Removed) In another aspect of the invention r is 2 and when r is 2 the group R4(Formula Removed) is a subsutuent on carbon (2) such that an example of when r is 2 is R4- (Formula Removed) In another aspect of the invention r is 2 and when r is 2 the group R4^ is a subsutuent on carbon (3) such that an example of when r is 2 is (Formula Removed) In one aspect of the invention y is -NR R In another aspect of the invention y is -OR3 Suitable values for R2 and R3 as heterocyclyl axe morphohno, morphoknyl, pipendmo, pipendyl, pyndyl, pyranyl, pyrrolyl, lmidazolyl, thiazolyl, thienyl, thiadiazolyl, piperazinyl, isothiazolidmyl, 1,3,4-tnazolyl, tetrazolyl, pyrrolidinyl, thiomorpholino, pyrrolmyl, homopiperazinyl, 3,5-dioxapipendinyl, pynmidyl, pyrazmyl, pyndazinyl, pyrazolyl, pyrazohnyl, isoxazolyl, 4-oxopydndyl, 2-oxopyrrohdyl, 4-oxothiazolidyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, and 1,2,4-oxadiazolyl, tetrahydrothiopyranyl, 1- oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl. More suitable values for R2 and R3 as heterocyclyl are pyndyl, pynrmdinyl and rmidazolyl Further suitable values for R2 and R3 as heterocyclyl are tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl. In one aspect of the invention, R2 and R3 are independently selected from groups of the formulae B and B' as hereinbefore described In one aspect of the invention R2 and R3 are independently selected from hydrogen, hydroxy, C1_4alkyl [optionally substituted by 1 or 2 R8 groups], C3_7cycloaLky] (optionally substituted with 1 or 2 hydroxy groups), cyano(C1-4)alkyl, phenyl, morphohno, morpholinyl, pipendino, pipendyl, pyndyl, pyranyl, pyrrolyl, lmidazolyl, thiazolyl, thienyl, thiadiazolyl, piperazmyl, isothiazolidinyl, 1,3,4-tnazolyl, tetrazolyl, pyrrohdmyl, thiomorphohno, pyrrohnyl, homopiperazinyl, 3,5-dioxapipendrnyl, pynmidyl, pyrazinyl, pyndazinyl, pyrazolyl, pyrazohnyl, isoxazolyl, 4-oxopydndyl, 2-oxopynohdyl, 4-oxothiazohdyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, and 1,2,4-oxadiazolyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, -COR8 and-SObR8 (wherein b is 0, 1 or 2), R is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, Q. 4alkoxyC1-4talkoxy, IiydroxyC1-4aLkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-t)alkyl], C2-4alkenyl, C3-7cycloalkyl (optionally substituted by -C(O)0C1-4alkyl), 5- and 6-membered cychc acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4l)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, heterocyclyl, heterocyclylC1-4alkyl, aryl, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3^cycloalkylS(O)b- (wherem b is 0, l or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2), benzylS(O)b-(wherem b is 0, 1 or 2), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0, l or 2), -CH2CH(NR9R10)CO(NR9'R10,)) -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)NCR9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9RI0)CO2R9' and- C12OCOR9, R'^R^andR10 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), C3-7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups), -C(=O)OtBu, C2-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), or R and R10 together with the nitrogen to which they are attached, and/or R9 and R10 together with the nitrogen to which they are attached, form a 4- to 6-membered ring where the ring is optionally substituted on carbon by 1 or 2 substituents independently selected from oxo, hydroxy, carboxy, halo, nitro, cyano, carbonyl and C1-4alkoxy; or the ring may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cyclic acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl, R13 is selected from halo, tnhalomethyl and C1-4alkoxy In a further aspect of the invention R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], C3-7cycloaLkyl (optionally substituted with 1 or 2 hydroxy groups), -COR8 and -SObR8 (wherein b is 0, 1 oi 2), R is independently selected from hydrogen, hydroxy, C1-4aLkoxy, C1-4alkoxyC1-4alkyl, Cj. 4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, armno(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryKC1-4alkyl], C2-4alkenyl, C3.7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)aTkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholino, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lrmdazolyl, pyrrohdmyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and Cj^alkyl), pyrazinyl, piperazinyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherein b is 0, I or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherem b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, 1 or 2), benzylS(O)b- (wherem b is 0, I or 2), C1-4alkylS(O)c(Cw)alkyl (wherein c is 0, 1 or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, ^9)(R10)N-> -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, - CH2CONRV0, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9, R9, R , R1 and R10 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), -C(=O)O(Bu, C1-4alkenyl, cyano(C1-4)alkyl, phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, hydroxy and cyano), or R9andR together with the nitrogen to which they are attached, and/or R9 andR10 together with the nitrogen to which they are attached, form a 4- to 6-membered nng where the ring is optionally substituted on carbon by 1 or 2 substituents independently selected from oxo, hydroxy, carboxy, halo, mtro, cyano, carbonyl and C1-4alkoxy, or the nng may be optionally substituted on two adjacent carbons by -O-CH2-O to form a cyclic acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl, R13 is selected from halo, tnhalomethyl and C1-4alkoxy In another aspect of the invention R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally subsUtuted by 1 or 2 R8 groups], -COR8 and -SObR8 (wherein b is 0, 1 or 2), R8 is mdependentiy selected from hydrogen, hydroxy, C1-4alkoxy, C1-4arkoxyC1-4alkyl, Cj, 4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4arkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, phenyl and aryKC1-4alkyl], C1-4alkenyl, C3-7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 mtro groups), thienyl (optionally substituted on carbon by 1 or 2 mtro groups), morphohno, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 mtro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 mtro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrohdmyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazmyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherein b is 0, l or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2 -CH2CH(NR9R10)CO(NR9'R10'), -CH20R9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, - CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9; R9,R9',R10andR10, are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups), C2-4alkenyl, and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano) In one aspect, one of R9 and R10 is hydrogen and the other is selected from heterocyclyl and heterocyclyl(C1-4alkyl) Conyeniently R9 or R10 as heterocyclyl and heterocyclyl(C]_ 4alkyl) is selected from oxazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, tetrazolyl, thiazoyl, thiadiazolyl, pyndyl, lmidazolyl, furyl, thienyl, morphohne, pynmidyl, pyrazinyl, pyndazmyl, pyrazolyl, pyrazohnyl, piperazmyl. morphohnomethyl, morphohnethyl, morpholinylmethyl, morphohnylethyl, pipendmomethyl, pipendinoethyl, pipendylmethyl, pipendylethyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, lmidazolylmethyl, lmidazolylethyl, oxazolylmethyl, oxazolylethyl, 1,3,4-oxadiazolylmethyl, 1,2,4-oxadiazolylmethyl, 1,2,4-oxadiazolylethyl, pyndylmethyl, pyndylethyl, furylmethyl, furylethyl, (thienyl)methyl, (thienyl)ethyl, pyrazinylmethyl, pyrazinylethyl, piperazinylmethyl and piperazmylethyl, wherein the heterocylic nng is optional substituted on any available atom by 1, 2 or 3 substituents independently selected from halo, cyano, hydroxy, C1-4alkyl, C1-4alkoxy and C1-4alkylS(O)b (wherein b is 0, 1 or 2), and additionally when the heterocyclyl nng is a heteroaryl ring, further suitable optional substituents are selected from mtro, amino, AHC1-4alky^amino and /^//-(C1-4alkyl^amino, and/or wherein any heterocyclic nng is optionally oxidised such that a -CH2- group is replaced by a -C(O)-and/or a nng sulphur atom is oxidised to form the S-oxide(s) In another aspect of the invention R2 is selected from hydrogen, acetyl and C1-4alkyl In a further aspect of the invention, y is NR2R3 and NR2R3 forms a 4 to 7 membered saturated, partially saturated or unsaturated nng, optionally containing 1, 2 or 3 additional heteroatoms independently selected from N, O and S, wherein any -CH2- may optionally be replaced by -C(=O)-, and any N or S atom may optionally be oxidised to form an N-oxide or SO or SO2 group respectively, and wherein the nng is optionally substituted by 1 or 2 substituents independently selected from halo, cyano, C1-4alkyl, hydroxy, C1-4alkoxy and C1-4alkylS(O)b- (wherein b is 0, 1 or 2) Suitable values for NR2R3 as a 4 to 7 membered rmg are morpholino, 2,5- dioxomorphohno, pipendmyl, pyrrohdinyl, pyrazolyl, pyrrolyl, lmidazolyl, piperazinyl and thiomorpholinyl. In yet a further aspect of the inventions R3 is selected from hydrogen, 1,3-dihydroxyisopropyl, 1,2-dihydroxypropyl, cyanomethyl, tnfluoromethylcaxbonyl, carboxyacetyl, carboxymethyl, formyl, acetyl, carbamoylacetyl, carbamoylmethyl, methoxyacetyl, methoxypropanoyl, acetoxyacetyl, methanesulfonyl, chloromethylsulfonyl, tnfluoromethylsulfonyl, morpholinomethylcarbonyl, furylcarbonyl, thienylcarbonyl, mtrofurylcarbonyl, AyV-dimethylcarbamoyl, 4-methylpiperazinocarbonyl, N-ethylcarbamoyl, N-allylcarbamoyl, N-dinitrophenylcarbamoyl, pyndinylcarbonyl, tetrahydrofuran-2-on-5-ylcarbonyl, hydroxyphenylcarbonyl, acryloyl, 2-(tert-butoxycarbonyl)methylcarbonyl, aminoacetyl, 1-armno-l-carboxypropanoyl, chloroacetyl, hydroxyacetyl, carbamoylacetyl, carbamoylmethyl, methoxyacetyl, methoxypropanoyl, acetoxyacetyl, hydroxypipendinoammoacetyl, hydroxypyrrolidinylammoacetyl, N-methyl-N-hydroxyethyl aminoacetyl, N-benzyl-N-hydroxyethylammoacetyl, N-(2,3-dihydroxypropyl)-N-methylammoacetyl, Af//-bis(hydroxyethyl)aminoacetyl, 7V,N-bis(hydroxypropyl)aminoacetyl, (l-amino-l-carbonylammo)ethylcarbonyl, 1-hydroxy-1-carboxyethylcarbonyl, tert-butoxycarbonylmethyl, l,3-dihydroxyisoprop-2-ylcarbonyl, l-(tert-butoxycarbonylarnmo)-l-(carbamoyl)propanoyl, N-ethyl-N-(2-hydroxyethyl)arninoacetyl, thienylmethyl, tetxazolylmethyl, [2-(ethoxycarbonyl)cyclopropyl]methyl, N-(tert-butoxycarbonyl)aminoacetyl andA(-(aminocarbonyl)-N-(tert-butoxycarbonyl)aminoacetyl. In yet a further aspect of the inventions R3 is selected from tnfluoromethylcarbonyl, carboxyacetyl, formyl, acetyl, , methanesulfonyl, morpholinomethylcarbonyl, furylcarbonyl, thienylcarbonyl, mtrofurylcarbonyl, Ar,N-dimethylcarbamoyl, 4-methylpiperazinocarbonyl, N-ethylcarbamoyl, N-allylcarbamoyl, N-dmitrophenylcarbamoyl, pyndinylcarbonyl, tetrahydrofuran-2-on-5-ylcarbonyl, hydroxyphenylcarbonyl, acryloyl, 2-(tert-butoxycarbonyl)methylcarbonyl, aminoacetyl, 1-amino-l-carboxypropanoyl, chloroacetyl, hydroxyacetyl, carbamoylacetyl, carbamoylmethyl, methoxyacetyl, methoxypropanoyl, acetoxyacetyl, N-methyl-N-hydroxyethylammoacetyl, TV-benzyl-W-hydroxyethylaminoacetyl, N-(2,3-dihydroxypropyl)-Af-me1xiylaminoacetyl, iV,//-bis(hydroxyethyl)aminoacetyl, N,N-bis(hydroxypropyl)aminoacetyl, (l-amino-l-carbonylanTino)ethylcarbonyl, 1-hydroxy-l-carboxyethylcarbonyl, tert-butoxycarbonylmethyl, l,3-dihydroxyisoprop-2-ylcarbonyl, l-(tert-butoxycarbonylamino)-l-(carbamoyl)propanoyl and N-ethyl-N-(2-hydjoxyethyl)arninoacetyl A preferred class of compound is of the formula (1) wherein; Z is CH, R4 and R5 are together -S-C(R6)=C(R7)-, R6 is halo or hydrogen; R is halo or hydrogen, A is phenylene; n is 0, 1 or 2; R1 is independently selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) memylenedioxy, r is 1 or 2; yis-NR2R3or-OR3, R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], C3-7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups), phenyl, morphobno, morphobnyl, pipendino, pipendyl, pyndyl, pyranyl, pyrrolyl, imidazolyl, thiazolyl, thienyl, thiadiazolyl, piperazinyl, isothiazobdmyl, 1,3,4-tnazolyl, tetrazolyl, pyrrobdinyl, thiomorphobno, pyrrobnyl, homopiperazmyl, 3,5-dioxapipendinyl, pynmidyl, pyrazinyl, pyndazinyl, pyrazolyl, pyrazobnyl, isoxazolyl, 4-oxopydndyl, 2-oxopyrrobdyl, 4-oxothiazobdyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, Q tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, -COR and -SObR8 (wherein b is 0, 1 or 2), R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, aminotC1-4alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CC1-4C1-4alkyl, aryl and aryl(C1-4)alkyl], C2.4alkenyl, C3.7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1.4)aIkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, heterocyclyl, heterocyclylC1-4aTkyl, aryl, C1-4alkylS(O)b- (wherem b is 0, 1 or 2), C3.6cycloalkylS(O)b- (wherein b is 0, l or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherem b is 0, I or 2), benzylS(O)b-(wherein b is 0, 1 or 2), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0, 1 or 2), - \C H2CH(NR9R1D)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9, -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and-CH2OCOR9, R9,R9',R10andR10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), C3-7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups), -C(=O)OtBu, C24alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), or R9 and R10 together with the nitrogen to which they are attached, and/or R9 and R10 together with the nitrogen to which they are attached, form a 4- to 6-membered nng where the nng is optionally substituted on carbon by 1 or 2 substituents independently selected from oxo, hydroxy, carboxy, halo, nitro, cyano, caxbonyl and C1-4alkoxy, or the nng may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cychc acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl, R1 is selected from halo, tnhalomethyl and C1-4alkoxy, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, [with the proviso that the compound of formula (1) is not. I) 2,3-dichloro-5-(N-{ l-[N-(l,l-dimethylethoxy)carbonylarmno]mdan-2-yl}carbamoyl)-4H-thieno[3,2-b]pyrrole, II) 5-[N-(l-aminoindan-2-yl)carbamoyl]-2,3-dichloro-4H-thieno[3,2-i']pyrrole III) 5-[7^-(l-acetarmdoindan-2-yl)carbamoyl]-2,3-dicMoro-4H-thieno[3,2-ft]pyrrole IV) 2,3-dichloro-5-{N-[l-(methanesulphonamido)mdan-2-yl]carbamoyl}-4Jcir- thieno[3,2-£>]pyrrole v) 2,3-dichloro-5-{N-[l-(methylamino)indan-2-yl]carbamoyl}-4H-thieno[3,2- b]pyrrole, vi) 2,3-dichloro-5-{N-[l-(methylacetamido)indan-2-yl]carbamoyl}-4H-thieno[3,2- fr]pyrrole, vii) 2,3-dichloro-5-[N-(l-hydroxymdan-2-yl)carbamoyl]-4if-thieno[3,2-b]pyrrole, vui) 2,3-dichloro-5-[N-(6-fluoro-l-hydroxymdan-2-yl)carbamoyl-4H-thieno[3,2- fr]pyrrole; IX) 2,3-dichloro-5-[^-(l-methoxyindan-2-yl)carbamoyl-4R-thieno[3,2-i>]pyrrole x) 2,3-dichloro-5-[N-(l-hydroxy-l,2,3,4-tetrahydronaphth-2-yl)carbamoyl]-47f- thieno [3,2-b] pyrrole Another preferred class of compounds is of formula (1) wherein Z is CH, R4 and R5 are together-C(R7)=C(R6)-S-, R6 is chloro; R7 is hydrogen; A is phenylene, n is 0, 1 or 2; R1 is independently selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenediQxy, r is 1 or 2, y is -NR2R3 or -OR3, R2 and R3 are independently selected from hydrogen, Cj^alkyl [optionally substituted by 1 or 2 R8 groups], C3-7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups), phenyl, morphobno, morpholmyl, pipendmo, pipendyl, pyndyl, pyranyl, pyrrolyl, lmidazolyl, thiazolyl, thienyl, thiadiazolyl, piperazinyl, lsothiazohdmyl, 1,3,4-tnazolyl, tetrazolyl, pynohdmyl, thiomorpholino, pyrrolmyl, homopiperazmyl, 3,5-dioxapipendmyl, pynmidyl, pyrazinyl, pyridazmyl, pyrazolyl, pyrazohnyl, isoxazolyl, 4-oxopydndyl, 2-oxopyrrolidyl, 4-oxothiazohdyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, and 1,2,4-oxadiazolyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, -COR and -SObR8 (wherein b is 0, 1 or 2), R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1.4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3.7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cychc acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, heterocyclyl, heterocyclylC1-4alkyl, aryl, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3.6cycloalkylS(O)b- (wherein b is 0, I or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2), benzylS(O)b-(wherein b is 0, 1 or 2), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0, l or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2CO0R9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2COMR9R10, -CH2CH(NR9R10)CO2R9' and-CH2OCOR9, R9,R9',R1QandR10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), C3.7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups), -C(=O)0'Bu, C2-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), or R9 and R10 together with the nitrogen to which they are attached, and/or R9 and R10 together with the nitrogen to which they are attached, form a 4- to 6-membered ring where the nng is optionally substituted on carbon by 1 or 2 substituents mdependently selected from oxo, hydroxy, carboxy, halo, nitro, cyano, carbonyl and C1-4alkoxy; or the nng may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cychc acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl, R13 is selected from halo, tnhalomethyl and C1-4alkoxy, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof; with the proviso that the compound of formula (1) is not l) 2-chloro-5-[N-(l-hydroxyindan-2-yl)carbamoyl-6H-thieno[2,3-6Jpyrrole, \nother preferred class of compound is of the formula (1) wherein: Z is CH; R4 and R5 are together -S-C(R6)=C(R7)-, R is chloro, R7 is hydrogen or chloro, A is phenylene, nis 0, 1 or 2, R1 is independently selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy, r is 1 or 2, yis-NR2R3; R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R3 groups], -COR8 and -SObR8 (wherein b is 0, 1 or 2), R8 is independently selected from hydrogen, hydroxy, C1-4aLkoxy, C1-4alkoxyCj^alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)aTkyl, dihydroxytC1-4alkyl, -CO2C1-4aIkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3-7cycloalkyl (optionally substituted by O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)allcyl, dihydroxy(C1-4)alkyl, cyano(Ci4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholmo, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrohdinyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazinyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherein b is 0, I or 2), C3.6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2), benzylS(O)b- (wherein b is 0, 1 or 2), C1-4alkylS^MC1-4alkyl (wherein c is 0, 1 or 2), -CH2CH(NR9R10)CO(NR9,R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, - CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9, R9 , R9 , R10 and R10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), -C(=O)0'Bu, C2-4alkenyl, cyano(C1-4)alkyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), R13 is selected from halo, tnhalomethyl and C1-4alkoxy; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, with the proviso that the compound of formula (1) is not- I) 2,3-dichloro-5-(N-{ l-[Af-(l,l-dimemylethoxy)carbonylamino]indan-2- yl}carbamoyl)-4fl-thieno[3,2-i]pyiTole, II) 5-[7^-(l-ammoindan-2-yl)carbamoyl]-2,3-dichloro-4H-thieno[3,2-b]pyrrole m) 5-[N-(l-acetamidoindan-2-yl)carbamoyl]-2,3-dichloro-4H-thieno[3,2-b]pyrrole IV) 2,3-dichloro-5-{N-[l-(methanesulphonamido)indan-2-yl]carbamoyl}-4H- thieno [3,2-6]pyrrole v) 2,3-dichloro-5-{^-[l-(methylamino)indan-2-yl]carbamoyl}-4H-thieno[3,2- b] pyrrole; vi) 2,3-dichloro-5-{N-[l-(methylacetamido)indan-2-yl]carbamoyl}-4if-thieno[3,2- &]pyrrole. Another preferred class of compound is of the formula (1) wherein. Z is CH, R4 and R5 are together -S-C(R6)=C(R7)-, R6 is hydrogen or halo, R7 is hydrogen or halo, A is phenylene, n is 0, 1 or 2, R1 is independently selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy, r is 1 or 2, yis-OR3, R3 is selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and -SObR8 (wherein b is 0, 1 or 2), wherein R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)allcyl, dihydroxy(C1-4)alkyl, -CO2C1-4aTkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3-7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, fuiyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholino, furyl(C]^j)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrokdinyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazmyl, 4-methylpiperazmo, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS((D)b- (wherem b is 0, 1 or 2), benzylS(O)b- (wherein b is 0, 1 or 2), C1-4alkylS(O)c(C1-4)alkyl (wherem c is 0,1 or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, - C.\2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9; R9, R9 R10 and R10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), -C(=O)0'Bu, C2-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from rutro, halo, hydroxy and cyano); R13 is selected from halo, tnhalomethyl and C1-4alkoxy, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof; with the proviso that the compound of formula (1) is not. I) 2,3-mcMoro-5-[Af-(l-hydroxymdan-2-yl)carbamoyl]^H-thieno[3,2-6]pyrrole, II) 2,3-dichloro-5-[N-(6-fluoro-l-hydroxyindan-2-yl)carbamoyl-4R-thieno[3,2-6]pyrrole, III) 2,3-dichloro-5-[N-(l-methoxymdan-2-yl)carbamoyl-4H-thieno[3,2-i>]pyrroIe IV) 2,3-dichloro-5-[N-(l-hydroxy-l,2,3,4-tetrahydronaphth-2-yl)carbamoyl]-4iir- thieno [3,2-b] pyrrole A further preferred class of compound is of the formula (1) wherein, ZisCH, R4 and R5 are together -C(R7)=C(R6)-S-, R6 is halo, R7 is hydrogen, A is phenylene; n is 0, 1 or 2, R1 is independently selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy; r is 1 or 2, y is -NR2R3, R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally substituted 1 by 1 or 2 R8 groups], -COR8 and -SObR8 (wherein b is 0, 1 or 2), R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4aikoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4t)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy^.^alkyl, CO2C1-4.alkyl, aryl and aryl(C1-4)alkyl], C1-4alkenyl, C3-7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C].4)alkyl, dihydrox.y(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 rutro groups), thienyl (optionally substituted on carbon by 1 or 2 mtro groups), morphohno, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 mtro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 mtro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrolidmyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazmyl, 4-methylpiperazmo, C1-4alkylS(O)b- (wherem b is 0, 1 or 2), C3_6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2), benz.ylS(O)b- (wherein b is 0, l or 2), C1-4allcylS(O)c(C1-4)alkyl (wherein c is 0, I or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9, -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, - CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9, R9,R9',R10andR10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), -C(=O)OlBu, C2-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, hydroxy and cyano); R13 is selected from halo, tnhalomethyl and C1-4alkoxy; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. Another preferred class of compound is of the formula (1) wherein: Z is CH, R4 and R5 are together -C(R7)=C(R6)-S-, R6 is hydrogen or halo, R is hydrogen or halo; A is phenylene, n is 0, 1 or 2, R is independently selected from halo, cyano, mtro, hydroxy, methyl, fluoromethyl, drfluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy; r is 1 or 2; yis-OR3; R3 is selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and -SObR8 (wherein b is 0, 1 or 2), R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from Cj^alkyl, hydroxy(C14)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3_7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C]^)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyanofC1-4alkyl, furyl (optionally substituted on carbon by 1 or 2 rutro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morphohno, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, rmidazolyl, pyrrohdinyl, pipendyl, pyridyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazmyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, 1 or 2), benzylS(O)b- (wherein b is 0, l or 2), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0, l or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9, R9, R9 , R10 and R10 are mdependenUy selected from hydrogen, Cj^alkyl (optionally substituted by 1 or 2 R13), -C(=O)0'BU, C2.4alkenyl, cyano(C1-4)alkyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano); or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof; provided that the compound of formula (1) is not 2-chloro-5-(l-hydroxyindan-2-yl)carbamoyl-6H-thieno[2,3-b]pyrrole. A. further preferred class of compound is of the formula (1) wherein, Z is CH; R4 and R5 are together -C(R7)=C(R6)-S-, R6 is halo, R7 is hydrogen, A is phenylene, nis 0 yis-NR2R3, R2 is hydrogen or C1-4alkyl, R3 is selected from C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and -SObR8 (wherein b is 0, 1 or 2), R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl> -CO2C1-4alkyl, phenyl and aryl(C1-4)alkyl], C2-4alkenyl, C3.7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholino, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyKC1-4alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrohdmyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazmyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherem b is 0, l or 2), C3_6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherem b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, I or 2 -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9RI0)CO2R9' and -CH2OCOR9, R9, R9', R10 and R10' are independently selected from hydrogen, C1-4alkyl (optionally abstituted by 1 or 2 hydroxy groups), C2-4alkenyl, and phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, hydroxy and cyano), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof A further preferred class of compound is of the formula (1) wherein, Z is CH, R4 and R5 are together -S-C(R6)=C(R7)-, R6 is halo, R is hydrogen, A is phenylene; nis 0, r is 1, yis-NR2R3, R2 is hydrogen or C1-4alkyl, R3 is selected from C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and -SObR8 (wherein b is 0,1 or 2), R8 is mdependently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)aikyl, -CO2C1-4alkyl, phenyl and aryl(C1-4)alkyl], C2-4alkenyl, C3-7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cychc acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C]^)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 mtro groups), morpholino, furyl(C1-4)a1kyl (wherein furyl is optionally substituted on carbon by 1 or 2 mtro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 mtro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrolidmyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazinyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherein b is 0, I or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2 -CH2CH(NR9R10)CO(NR9'R10'), -CH20R9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and-CH2OCOR9, R9, R9 , R10 and R10 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups), C2-4alkenyl, and phenyl (optionally substituted by 1 or 2 groups selected from rutro, halo, hydroxy and cyano), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof; Drovided that the compound of formula (1) is not (l) 2,3-dichloro-5-(N-{ l-[N-(l,l-dimethylethoxy)carbonylammo]indan-2- yl }carbamoyl)-4H-thieno [3,2-b]pyrrole, (u) 5-[^/-(l-arrunomdan-2-yl)carbamoyl]-2,3-dichloro-4H-thieno[3,2-6]pyrrole (m) 5-[N-(l-acetarmdoindan-2-yl)carbamoyl]-2,3-dichloro-4iir-thieno[3,2-fe]pyrrole (IV) 2,3-dichloro-5-{N-[l-(methanesulphonamido)indan-2-yl]carbamoyl}-4i/- thieno[3,2-6]pyrrole (v) 2,3-dichloro-5-{N-[l-(methylamino)indan-2-yl]carbamoyl}-4H-tlneno[3,2- bjpyrrole; (vi) 2,3-dichloro-5-{N-[l-(methylacetamido)indan-2-yl]carbamoyl}^l-i/-thieno[3,2- £>]pyrrole, A preferred class of compound is of the formula (1) wherein; Z is nitrogen; R4 and R5 are together -S-C(R6)=C(R7)-, R6 is halo or hydrogen; R7 is halo or hydrogen; A is phenylene; n is 0, 1 or 2, R1 is independently selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, mefhoxy, -SMe, -SOMe, -SdMe and, (when n is 2) methylenedioxy; ris 1 or 2, yis-NR2R3or-OR3, R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], C3.7cycloaIkyl (optionally substituted with 1 or 2 hydroxy groups), phenyl, morphobno, morphobnyl, pipendino, pipendyl, pyndyl, pyranyl, pyrrolyl, imidazolyl, tfuazolyl, thienyl, thiadiazolyl, piperazinyl, lsothiazohdinyl, 1,3,4-tnazolyl, tetrazolyl, pyrrohdmyl, thiomoiphobno, pyrrobnyl, homopiperazmyl, 3,5-dioxapipendmyl, pynmidyl, pyrazmyl, pyndazmyl, pyrazolyl, pyrazolmyl, isoxazolyl, 4-oxopydndyl, 2-oxopyrrohdyl, 4- o. .ihiazolidyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, and 1,2,4-oxadiazolyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, -COR8 and -SObR8 (wherem b is 0, 1 or 2); Q R is independendy selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4.alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, ammo(C1-4)aIky] [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(Ciut)alkyl, dihydroxy(C1.4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3-7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhakKQ-^alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, heterocyclyl, heterocyclylC1-4alkyl, aryl, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3^cycloalkylS(O)b- (wherein b is 0, l or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherem b is 0, I or 2), benzylS(O)b-(wherem b is 0, 1 or 2), C1-4alkylS^^C1-4alkyl (wherein c is 0, 1 or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10); -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9, R9 , R9 , R10 and R10 are independendy selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), C3.7cycloaikyl (optionally substituted by 1 or 2 hydroxy groups), -C(=O)0'Bu, C2-4alkenyl, cyano(C1-4)alkyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), or R9 and R10 together with the mtrogen to which they are attached, and/or R9 and R10 together with the mtrogen to which they are attached, form a 4- to 6-membered nng where the nng is optionally substituted on carbon by 1 or 2 subsutuents independently selected from oxo, hydroxy, carboxy, halo, nitro, cyano, carbonyl and C1-4alkoxy, or the nng may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cyclic acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl, R is selected from halo, tnhalomethyl and C1-4alkoxy; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, with the proviso that the compound of formula (1) is not: (i) 2,3-dichloro-5-(N-{ l-[N-(l,l-dimethylethoxy)carbonylammo]indan-2-yl }carbamoyi)-4H-thieno [3,2-fe]pyrrole, (u) 5-[N-(l-aminoindan-2-yl)carbamoyl]-2,3-dichloro-4H-thieno[3,2-i]pyrrole (ui) 5-[N-(l-acetamidoindan-2-yl)carbamoyl]-2,3-dichloro-4H-thieno[3,2-b]pyrrole (IV) 2,3-dichloro-5-{N-[l-(rDethanesulphonamido)indan-2-yl]carbamoyl}-4H- thieno [3,2-fe]pyrrole (v) 23-dichloro-5-{^-[l-(methylainino)indan-2-yl]carbamoyl}-4H-thieno[3,2- b]pyrro1e, (vi) 2,3-dichloro-5-{N-[l-(methylacetamido)indan-2-yl]carbamoyl}-4H-thieno[3,2- £]pyrrole, (vn) 2,3 -dichloro-5- [N- (1 -hydroxyindan-2-yl)carbamoyl] -4H-thieno [3,2-i]pyrrole, (vm) 2,3-dichloro-5-[Af-(6-fluoro-l-hydroxyindan-2-yl)carbamoyl-4H-tliieno[3,2- fc]pyrrole; (ix) 2,3-dicUoro-5-[N-(l-methoxyindan-2-yl)carbamoyl-47f-thieno[3,2-i']pyrrole (x) 2,3-dichloro-5-[N-(l-hydroxy-l,2,3,4-tetrahydronaphth-2-yl)carbamoyl]-4i/- thieno [3,2-b]pyrrole. Another preferred class of compounds is of formula (1) wherein: Z is nitrogen, R4 and R5 are together -C(R7)=C(R6)-S-, R6 is chloro, R7 is hydrogen, A is phenylene, n is 0, 1 or 2, R1 is independentiy selected from halo, cyano, mtro, hydroxy, methyl, fiuoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SC1-4Me and, (when n is 2) methylenedioxy, r is 1 or 2, yis-NR2R3or-OR3, R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], C3-7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups), phenyl, morphohno, morpholinyl, pipendino, pipendyl, pyndyl, pyranyl, pyrrolyl, imidazolyl, thiazolyl, thienyl, thiadiazolyl, piperazmyl, lsothiazohdmyl, 1,3,4-tnazolyl, tetrazolyl, pyrrohdmyl, truomorpholino, pyrrohnyl, homopiperazinyl, 3,5-dioxapipendinyl, pynmidyl, pyrazmyl, pyndazmyl, pyrazolyl, pyrazohnyl, isoxazolyl, 4-oxopydndyl, 2-oxopyrrolidyl, 4- oxothiazolidyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, and 1,2,4-oxadiazolyl, tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, -COR8 and -SObR8 (wherem b is 0, 1 or 2), Q R is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, ammo(C1-4)aIkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3.7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, txihaloCC1-4alkyl, hydroxy(C1-4t)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, heterocyclyl, heterocyclylC1-4alkyl, aryl, C1-4alkylS(O)b- (wherem b is 0, 1 or 2), C3^cycloalkylS(O)b- (wherem b is 0, l or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2), benzylS(O)b-(wherem b is 0, 1 or 2), C1-4alkylS(O)c(C1-4)alkyl (wherem c is 0, l or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9RI0)CO2R9' and -CH2OCOR9, R9 , R9 , R10 and R10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), C3-7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups), -C(=O)OlBu, C1-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, hydroxy and cyano), or R9 and R10 together with the nitrogen to which they are attached, and/or R and R together with the nitrogen to which they are attached, form a 4- to 6-membered nng where the nng is optionally substituted on carbon by 1 or 2 substttuents independently selected from oxo, hydroxy, carboxy, halo, nitro, cyano, carbonyl and C1-4alkoxy, or die nng may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cychc acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl; R13 is selected from halo, tnhalomethyl, and C1-4alkoxy, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, with the proviso that the compound of formula (1) is not n) 2-cMoro-5-[N-(l-hydroxyindan-2-yl)carbamoyl-6i^-thieno[2,3-b]pyrrole, Another preferred class of compound is of the formula (1) wherein-Z is nitrogen, R4 and R5 are together -S-C(R6)=C(R7)-, R6 is chloro, R7 is hydrogen or chloro; A is phenylene, n is 0, 1 or 2, R1 is independently selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy; r is 1 or 2; y is -NR2R3; R2andR3 are independently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and-SObR8 (wherein b is 0, 1 or 2), o R is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3_7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cychc acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, dihalo(C14)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morphohno, furyl(C1-4t)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherem thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lrnidazolyl, pyrrohdinyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazmyl, 4-methylpiperazmo, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3^cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2), benzylS(O)b- (wherein b is 0, l or 2), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0, 1 or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9, -C(O)N(R9)(R10); -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9, R9,R9',R10andR10, are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), -C(=O)OtBu, C2-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), R is selected from halo, tnhalomethyl, and C1-4alkoxy, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. Another preferred class of compound is of the formula (1) wherein Z is nitrogen; R4 and R5 are together -S-C(R6)=C(R7)-, R6 is hydrogen or halo, R is hydrogen or halo, A is phenylene, n is 0, 1 or 2, R1 is independently selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy; r is 1 or 2, y is -OR3; R is selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R groups], -COR8 and -SObR8 (wherein b is 0, 1 or 2), R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], d^alkenyl, C3_7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)aTkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholmo, furyl(Cj-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4t)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrohdmyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazmyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherein b is 0,1 or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, l or 2), heterocyclylS(O)b- (wherein b is 0, 1 or 2), benzylS(O)b- (wherein b is 0, l or 2), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0, l or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9, -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, - CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9; R9, R9 , R10 andR10 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), -C(=O)0LBu, C2-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), R13 is selected from halo, tnhalomethyl, and C1-4alkoxy, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. A further preferred class of compound is of the formula (1) wherein, Z is nitrogen; R4 and R5 are together -C(R7)=C(R6)-S-, R6 is halo; R7 is hydrogen, A is phenylene, n is 0,1 or 2, R1 is independently selected from halo, cyano, rutro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy, r is 1 or 2, yis-NR2R3, R2 and R3 are mdependently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and -SObR8 (wherein b is 0,1 or 2); R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4arkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3.7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cychc acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)aIkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholino, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lnaidazolyl, pyrrolidmyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazinyl, 4-methylpiperazrno, C1-*alkylS(O)b- (wherein b is 0, I or 2), C3.6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, 1 or 2), benzylS(O)b- (wherein b is 0, I or 2), C1.4alkylS(O)c(C1-4)alkyl (wherein c is 0, I or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, - CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9; R9 , R9', R10 and R10' are independently selected from hydrogen, C1-4alkyl (optionally subsUtuted by 1 or 2 R13), -C(=O)O(Bu, C1-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano); R13 is selected from halo, tnhalomethyl, and C1-4alkoxy, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof Another preferred class of compound is of the formula (1) wherein Z is nitrogen, R4 and R5 are together -C(R7)=C(R6)-S-, R6 is hydrogen or halo; R7 is hydrogen or halo; A is phenylene, n is 0, 1 or 2, R1 is independentiy selected from halo, cyano, nitro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy; r is 1 or 2; yrs-OR3, R is selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and-SOtR8 (wherem b is 0, 1 or 2), Q R is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyCi4aIkoxy, hydroxyC1-4alkoxy, C1-4alltyl, armnoCC1-4alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3.7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholmo, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrohdinyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazinyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherem b is 0, l or 2), C3^cycloalkylS(O)b- (wherem b is 0, 1 or 2), arylS(O)b- (wherem b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2), benzylS(O)b- (wherem b is 0, l or 2), C1-4alkylS(O)c(C1-0alkyl (wherein c is 0, 1 or 2), -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9; R9, R9 , R10 and R10 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), -C(=O)O(Bu, C1-4alkenyl, cyano(C1-4)alkyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), R13 is selected from halo, tnhalomethyl, and C1-4alkoxy, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, A further preferred class of compound is of the formula (1) wherein; Z is nitrogen, R4 and R5 are together -C(R7)=C(R6)-S-, R6 is halo, R7 is hydrogen; A is phenylene, nisO, ris 1, yis-NR2R3; R2 is hydrogen or d^alkyl, R3 is selected from Cj^alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and - SObR8 (wherein b is 0,1 or 2); o R is independently selected from hydrogen, hydroxy, C1-4alkoxy, Cj^alkoxyC1-4alkyl, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4aLkyl, phenyl and aryl(C1-4)alkyl], C2-*alkenyI, C3-7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)aTkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 mtro groups), thienyl (optionally substituted on carbon by 1 or 2 mtro groups), morpholino, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 mtro groups), tmenyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 mtro groups), 1,2,4-oxadiazolyl, tetrazolyl, imidazolyl, pyrrohdinyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrotruopyranyl, tetrahydroduenyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazinyl, 4-methylpiperazino, C1^alkylS(O)b- (wherein b is 0,1 or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2 -CH2CH(NRV°)CO(NR9'R10'), -CH20R9, (R9)(R,0)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9; R9, R9, R10 and R10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups), C2-ialkenyl, and phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, hydroxy and cyano), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. A further preferred class of compound is of the formula (1) wherein, Z is nitrogen, R4 andR5 are together-S-C(R6)=C(R7)-, R6 is halo; R7 is hydrogen, A is phenylene; nis 0 r is 1, yis-NR2R3, R2 is hydrogen or C1-4alkyl, R3 is selected from C1-4alkyl [optionally substituted by 1 or 2 Rs groups], -COR8 and -SOhR8 (wherein b is 0, 1 or 2); R is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkyl, arnino(C1-4)alkyl [optionally substituted on mtrogen by 1 or 2 groups selected from Cj^alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, phenyl and aryl(C1-4)alkyl], C1-4alkenyl, C3_7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cychc acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 mtro groups), thienyl (optionally substituted on carbon by 1 or 2 mtro groups), morphohno, furyl(C1-4)aIkyl (wherein furyl is optionally substituted on carbon by 1 or 2 mtro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 mtro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrohdinyl, piperidyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazmyl, 4-methylpiperazmo, C1-4alkylS(O)b- (wherein b is 0, l or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, l or 2 -CH2CH(NR9R10)CO(NR9'R10'), -CH20R9, (R9)(RI0)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and-CH2OCOR9, R9, R9 , R10 and R10' are mdependently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups), C2-4alkenyl, and phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, hydroxy and cyano), or a pharmaceutical^ acceptable salt or in vivo hydrolysable ester thereof In a further preferred aspect of the invention is provided a compound of the formula (1A) (Formula Removed) wherein Z is CH, R4 and R5 are together-S-C(R6)=C(R7)- or -C(R7)=C(R6)-S-, R6 is hydrogen or halo, R7 is hydrogen or halo, A is phenylene; n is 0, 1 or 2; R1 is independently selected from halo, cyano, mtro, hydroxy, methyl, fluoromethyl, difluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy, yis-NR2R3or OR3; R2 is hydrogen or C1-4alkyl, R3 is selected from C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and -SObRs (wherein b is 0, 1 or 2); R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on mtrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, phenyl and aryl(C1-4)alkyl], C2-4alkenyl, C3.7cycloalkyl (optionally substituted by -C(O)OC1-4talkyl), 5- and 6-membered cychc acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 mtro groups), thienyl (optionally substituted on carbon by 1 or 2 mtro groups), morpholmo, furyl(C1-4)alkyl (wherein furyl is optionally substtuted on carbon by 1 or 2 mtro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 mtro groups), 1,2,4-oxadiazolyl, tetrazolyl, miidazolyl, pyrrohdinyl, pipendyl, pyndyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrotmopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazinyl, 4-methylpiperazmo, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3.6cycloarkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, l or 2), heterocyclylS(O)b- (wherein b is 0, l or 2 -CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, - CH2CONR9R10, -CH2CH(NR9R10)CO2R9' and -CH2OCOR9, R , R9 , R10 and R10 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups), C2-4alkenyl, and phenyl (optionally substituted by 1 or 2 groups selected from mtro, halo, hydroxy and cyano), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. A further preferred class of compound is of the formula (1) wherein, ZisCH, R4 and R5 are together -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S-; R is halo or hydrogen, R7 is halo or hydrogen, A is heteroarylene, n is 0, 1 or 2, R1 is independently selected from halo, cyano, mtro, hydroxy, methyl, fluoromethyl, drfluoromethyl, tnfluoromethyl, methoxy, -SMe, -SOMe, -SO2Me and, (when n is 2) methylenedioxy; r is 1 or 2; yis-NR2R3or-OR3, R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], C3.7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups), phenyl, morpholmo, morphohnyl, pipendino, pipendyl, pyndyl, pyranyl, pynolyl, imidazolyl, thiazolyl, fhienyl, thiadiazolyl, piperazmyl, lsothiazohdinyl, 1,3,4-tnazolyl, tetrazolyl, pyrrohdmyl, thiomorphohno, pyrrohnyl, homopiperazmyl, 3,5-dioxapipendinyl, pynmidyl, pyrazinyl, pyndazmyl, pyrazolyl, pyrazolinyl, isoxazolyl, 4-oxopydndyl, 2-oxopyrrohdyl, 4-oxothiazolidyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, and 1,2,4-oxadiazolyl, g tetrahydrothiopyranyl, 1-oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, -COR and -SObR8 (wherein b is 0, 1 or 2), R8 is mdependentiy selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyCj^alkoxy, hydroxyC].4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -CO2C1-4alkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3.7cycloaikyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl denvatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, tnhalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, heterocyclyl, heterocyclylC1-4alkyl, aryl, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3.6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherern b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, I or 2), benzylS(O)b- (wherem b is 0, 1 or 2), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0, l or 2), - CH2CH(NR9R10)CO(NR9'R10'), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9, -C(O)N(R9)(R10), -CH2CH(CO2R9)OH, -CH2CONRV0, -CH2CH(NR9R10)CO2R9' and- CH2OCOR9. R9, R9 , R10 and R10 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), C3.7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups), -C(=O)0'Bu, C2-4alkenyl, cyano(C1-4)alkyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano), or R and R10 together with the nitrogen to which they are attached, and/or R9 and R1 together with the nitrogen to which tiiey are attached, form a 4- to 6-membered ring where the ring is optionally substituted on carbon by 1 or 2 substituents independently selected from oxo, hydroxy, carboxy, halo, nitro, cyano, carbonyl andC1-4alkoxy, or the ring may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cyclic acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl, R13 is selected from halo, trihalomethyl, and C1-4alkoxy; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. A preferred class of compound is of the formula (1) wherein; Z is CH; R4 and R5 are together-S-C(R6)=C(R/)-, R6 is halo or hydrogen; R is halo or hydrogen, A is phenylene, n is 1 or 2, R1 is independently selected from hydrogen, halo, cyano, nitro, hydroxy, fluoromethyl, difluoromethyl, tnfluoromethyl, C1-4alkoxy and and R1 is of the formula A' or A' (Formula Removed) wherein x is 0 or 1, p is 0, 1, 2 or 3 and s is 1 or 2, provided that the hydroxy group is not a substituent on the ring carbon adjacent to the ring oxygen, r is 1 or 2, yis-NR2R3or-OR3; R2 and R3 are independently selected from hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), Cs.ycycloalkyl (optionally substituted with 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), cyano(C1-4)alkyl, fluoromethylcarbonyl, difluoromethylcarbonyl, tnfluoromethylcarbonyl, C1-4alkyl [substituted by 1 or 2 R8 groups (provided that when there are2R groups they are not substituents on the same carbon)],-COR and-SObR (wherem b is 0, 1 or 2), (wherein R8 is independently selected from hydrogen, hydroxy, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morphobno, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C]^)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrolidinyl, pipendyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, morphokno, pyndyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazrnyl, 4-methylpiperazmo, C1-4alkyl, C2-4alkenyl, cyclo(C3.g)alkyl, C1-4aIkoxy, cyano(C1-4j)alkyl, ammo(C1-4)alkyl (optionally substituted on nitrogen by 1 or 2 groups selected from hydrogen, C1-4alkyl, hydroxy, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, aryl and aryl(C1-4t)alkyl), C1.4alkylS(O)c(C1-4)alkyl (wherem c is 0, I or 2), -CH2CH(CO2R9)N(R9R10), -CH2OR9, (R9)(R10)N-, -COOR9, -CH2COOR9, -CH2CONR9R10, and -CH2CH2CH(NR9R10)CO2R9, [wherein R and R ° are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), C5-7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same caioon), C2-4alkenyl, cyano(C1-4)alkyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano) and C1-4alkyl substituted by R13; (wherein R13 is selected from C1-4afkoxy, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholmo, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrohdmyl, pipendyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazrnyl, piperazmyl, ClJtalkylS(O)d(C1-4)alkyl (wherein d is 0, I or 2)), and R9andR10 can together with the nitrogen to which they are attached form 4- to 6-membered ring where the nng is optionally substituted on carbon by 1 or 2 substituents selected from oxo, hydroxy, carboxy, halo, nitro, nitroso, cyano, isocyano, amino, N-C\. 4alkylamino, /^//-(C1-4alkylamino, carbonyl, sulfo, C1-4alkoxy, heterocyclyl, C1-4alkanoyl, and C1-4alkylS(O)f(C1-4)alkyl (wherein f is 0, l or 2)]}, or a pharmaceutic ally acceptable salt or in vivo hydrolysable ester thereof, with the proviso that die compound of formula (1) is not l) 2,3-dichloro-5-(AT-{ l-[AHl,l-dimethylethoxy)carbonylarnmo]indan-2- yl}carbamoyl)^#-thieno[3,2-bJpyrrole, n) 5-[N-( 1 -aminomdan-2-yl)c arbamoyl] -2,3- dichloro-4H-thieno [3,2-b] pyrrole ui) 5-[N-(l-acetanaidomdan-2-yl)carbamoyl]-2,3-dichloro-4H-thieno[3,2-£>]pyrrole IV) 2,3-dichloro-5-{N-[l-(methanesulphonamido)indan-2-yl]carbamoyl}-4H-thieno[3,2-b]pyrrole v) 2,3-dichloro-5-{N-[l-(methylamino)indan-2-yl]carbamoyl}-4i^-thieno[3,2- b]pyrrole, vi) 2,3-dacUoro-5-{N-[l-(memylacetamido)indan-2-yl]carbamoyl}-4H-thieno[3,2- 6]pyrrole, vn) 2,3-dichloro-5-[Af-(l-hydroxyindan-2-yl)carbamoyl]-4H-thieno[3,2-6]pyrrole; vm) 2,3-dichloro-5-[N-(6-fluoro-l-hydroxyindan-2-yl)carbamoyl-4H-thieno[3,2- i]pyrrole; rx) 2,3-dichloro-5-[N-(l-methoxymdan-2-yl)carbamoyl-4fl'-thieno[3,2-b]pyrrole x) 2,3-dichloro-5-[N-(l-hydroxy-l,2,3,4-tetrahydronaphth-2-yl)carbamoyl]-4H- ttueno [3,2-6]pyrrole. Another preferred class of compounds is of formula (1) wherein- Z is CH, R4 and R5 are together -C(R7)=C(R6)-S-, R6 is chloro, R7 is hydrogen, A is phenylene, n is 1 or 2; R1 is independently selected from hydrogen, halo, nitro, hydroxy, C1-4alkyl, C1-4alkoxy and and R1 is of the formula A' or A" -(CH2)p (Formula Removed) wherein x is 0 or 1, p is 0, 1, 2 or 3 and s is 1 or 2, provided that the hydroxy group is not a substituent on the ring carbon adjacent to the ring oxygen, r is 1 or 2, y is -NR2R3 or -OR3, R2 and R3 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups piovided that when there are 2 hydroxy groups they are not substituents on the same carbon), C5-7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), cyano(C1-4t)alkyl, fluoromethylcarbonyl, difluoromethylcarbonyl, tnfluoromethylcarbonyl, C1-4alkyl [substituted by 1 or 2 R8 groups (provided that when there are 2 R8 groups they are not substituents on the same carbon)], -COR8 and -SObR3 (wherein b is 0, 1 or 2), {wherein R8 is mdependentiy selected from hydrogen, hydroxy, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 mtro groups), morpholmo, furyl(C 1.4) alky 1 (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, nmdazolyl, pyrrohdinyl, pipendyl, turahydrofuryl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazmyl, piperazinyl, C1-4alkyl, C2-4alkenyl, cyclo(C3-8)alkyl, C1-4alkoxy, cyano(C1-4)alkyl, amino(C1-4)alkyl (optionally substituted on nitrogen by 1 or 2 groups selected from hydrogen, C1-4alkyl, hydroxy, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, aryl and aryl(C1-4)alkyl), C1- 4alkylS(O)c(C1-4)alkyl (wherein c is 0, 1 or 2), -CH2CH(CO2R9)N(R9R10), -CH2OR9, (R9)(R10)N-, -COOR9 and-CH2COOR9 , -CH2CONR9R10, - CH2CH2CH(NR9R10)CO2R9, [wherein R9 and R10 are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), C5-7cycloalk:yl (optionally substituted by 1 or 2 hydroxy groups provided that when there are 2 hydroxy groups they are not substituents on the same carbon), C2-4aTkenyl, cyano(C1-4)alkyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano) and C1-4alkyl substituted by R13; (wherein R13 is selected from C1-4alkoxy, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morphohno, furyl(C1-4)alkyl (wherem furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, lmidazolyl, pyrrolidmyl, pipendyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazinyl, C1-4alkylS(O)d(C1-4)arkyl (wherein d is 0, I or 2)); and R9 and R10 can together with the nitrogen to which they are attached form 4- to 6-membered ring where the ring is optionally substituted on carbon by 1 or 2 substituents selected from oxo, hydroxy, carboxy, halo, nitro, mtroso, cyano, isocyano, amino, N-Cu 4alkylammo, iV.NC1-4alkylamino, carbonyl, sulfo, C1-4alkoxy, heterocyclyl, C1-4alkanoyl, and C1-4alkylS(O)f l) 2-chloro-5-[N-(l-hydroxyindan-2-yl)carbamoyl-67/-thieno[2,3-ii]pyrrole, In another aspect of the invention, preferred compounds of the invention are any one - 2,3-dichloro-N-[(lR,2R)- l-(foimylamino)-2,3-dihydro- lH-inden-2-yl]-4H-thieno[3,2- b]pyrrole-5-carboxamide, 2,3-dichloro-N-((lR,2R)-l-{[(methyloxy)acetyl]amino}-2,3-dihydro-lR-inden-2-yl)-4H- thieno[3,2-b]pyrrole-5-carboxamide; N-((15,2S)-l-{[(3(R)-3-(tert-butoxycarbonylamino)-3-carbamoylpropanoyl]amino}-2,3- dihydro-lH-inden-2-yl)-2,3-dichloro-4H-thieno[3,2-i']pyrrole-5-carboxamide; 2,3-dichloro-N-[(lR,2R)-l-({[(4R)-2,2-dimethyl-5-oxo-l,3-dioxolan-4-yl]acetyl}amino)-2,3- dihydro-lH-inden-2-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide, 2,3-dichloro-N-{(lR,2R)-l-[(3-methoxypropanoyl)arnino]-2,3-dihydro-lH-inden-2-yl}-4H- thieno[3,2-b]pyrrole-5-carboxamide; N-{(lR,2R)-l-[(2-acetoxyacetyl)amino]-2,3-dihydro-m-inden-2-yl}-2,3-dichloro-4H- thieno[3,2-b]pyrrole-5-carboxamide, N-{(lR,2R)-l-[(2-carbamoylacetyl)amino]-2,3-dihydro-lH-mden-2-yl}-2,3-dichloro-4H- thieno[3,2-Z7]pyrrol-5-carboxamide; 2,3-dichloro-N-{(lR,2R)-l-[(tnfluoroacetyl)amino]-2,3-dihydro-lH-mden-2-yl}-4H- thieno [3,2-b]pyrrole-5-carboxamide; 23-dicmoro-N-{(15,25)-l-[(furan-2-ylcarbonyl)amino]-2,3-dihydro-1H-inden-2-yl}-4H- thieno[3,2-b]pyrrole-5-carboxamide; 23-dichloro-N-{(15,2-4-l-[(furan-3-ylcarbonyl)amino]-2,3-dihydro-lH-inden-2-yl}-4H- thieno[3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-{(15,25)-l-[(3-thienylcarbonyl)amino]-2,3-dihydro-lH-inden-2-yl}-4H- thieno [3,2-b]pyirole-5-carboxanude, 2,3-dichloro-N-((15,21S')-l-{[(5-nitrofuran-2-yl)carbonyl]amino}-2,3-dihydro-lH-inden-2-yl)- 4H-thieno[3,2-b]pyirole-5-carboxamide, 2,3-dichloro-N-{(lS,2S)-l-[(pynd]n-3-ylcarbonyl)amino]-2,3-dihydro-1H-inden-2-yl}-4H- ttueno[3,2-b]pyrrole-5-carboxamide, N-[(15,25)-l-(acryloylamino)-2,3-dihydro-m-mden-2-yl]-2,3-dichloro-4H-thieno[3,2- b]pyrrole-5-carboxamide, 2,3-dichloro-N-((15,25)-l-{[(3-hydroxyphenyl)carbonyl]amino}-2,3-dihydro-m-inden-2-yl)- 4H-thieno[3,2-b]pyrrole-5-carboxamide, N-[(1S,2S)-l-(acetylamino)-2,3-dihydro-lH-inden-2-yl]-2,3-dichloro-4H-thaeno[3,2- b]pyrrole-5-carboxamide, N-[(lS,2S)-l-[(2-carboxyacetyl)amino]-2,3-dihydro-m-mden-2-yl]-2,3-dichloro-4if- amino[3,2-b]pyrrole-5-carboxamide; 2-4-dichloro-N-((15,21S)-l-{[(dimethylammo)carbonyl]amino}-2,3-dihydro-lH-inden-2-yl)- 4H-thieno[3,2-b]pyrrole-5-carboxamide, 2,3-dichloro-N-((l,S,2,S)-l-{[(4-methylpiperazin-l-yl)carbonyl]arDino}-2,3-dihydro-lH-inden- 2-yl)-4H-thienot3,2-b]pyrrole-5-carboxannde, 2,3-dichloro-N-((15,2-4-l-{[(ethylaimno)carbonyl]amino}-2,3-dihydro-lH-inden-2-yl)-4H- thieno[3,2-Z>]pyrrole-5-carboxamide, 23-dichloro-N-((l1S,21S)-l-{[(prop-2-en-l-ylamino)carbonyl]amino}-2,3-dihydro-lR-inden-2- yl)-4#-tfaeno[3,2-Z?]pyrrole-5-carboxamide, 2,3-dicWoro-N-[(l1S,25)-l-({[(3,5-dirutrophenyl)arruno]carbonyl}amino)-2,3-dihydro-m- inden-2-yl]-4H-thieno[3,2-Z?]pyirole-5-carboxamide, 23-dichloro-N-[(15,21S)-l-(formylamino)-2,3-dihydro-liJ-inden-2-yl]-4Jy-thieno[3,2- fc]pyrrole-5-carboxamide; N-{(lR,2-4)-14((3R)-3-arnino-3-carbamoylpropanoyl)airiino]-2,3-dihydro-l//-inden-2-yl}-2,3- dichloro-4R-thieno[3,2-b]pyrrole-5-carboxamide, 7V-(lR,2R)-l-[((3R)-3-carboxy-3-hydroxypropanoyl)anuno]-2,3-dihydro-l//-inden-2-yl}-2,3- dichloro-4R-thieno [3,2-£>]pyrrole-5-carboxamide, 2,3-dicWoro-^-{(lR,2R)-14(^yckoxyacetyl)amino]-2,3-dihydro-lJy-inden-2-yl}-4JHr- thieno[3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-{(15,25)-l-[(methylsulfonyl)amino]-2,3-dihydro-m-mden-2-yl}-4i/- thieno[3,2-d]pyrrole-5-carboxarmde, 2,3-dichloro-1H-{(15, 25)-l-[methyl(morpholin-4-ylacetyl)amino]-2,3-dihydro-li^-inden-2- yl}-4H-thieno[3,2-b]pyrrole-5-carboxamide, N-{(lR,2R)-l-[(2-amino-2-oxoethyl)amino]-2,3-dihydro-lH-inden-2-yl}-2,3-dichloro-4H- thieno[3,2-b]pyrrole-5-carboxamide, N-(lR,2R)-l-[(tert-butoxycarbonylmethyl)amino]-2,3-dihydro-lH-mden-2-yl}-2,3-dichloro- 4H-thieno[3,2-b]pyrrole-5-carboxamide, N-4(lR,2R)-lKcarboxymethylaimno)-23-dihydro-lH-mden-2-yl]-2,3-dichloro-4H-thieno[3,2- &]pyrrole-5-carboxamide, N-(lR,2ii)-l-[N-acetyl-N-(carboxymethyl)amino]-2,3-dihydro-l^-mden-2-yl}-2,3-dichloro- 4H-thieno[3,2-b]pyrrole-5-carboxamide, N- {(1R, 2R)-1 -[acetyl(2-amino-2-oxoethyl)amino]-2,3-dihydro-lH-mden-2-yl }-2,3-dichloro- 4H-tmeno[3,2-b]pyrrole-5-carboxamide, N-{(lR,2R)-l-[N-(carboxymethyl)-N-(hydroxyacetyl)aminol-3-dihydro-m-inden-2-yl}-2,3- dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide, 2-chloro-N-[( 1 R,2R)-1 -({[(25)-5-oxotetrahydrofuran-2-yl]carbonyl} amino)-2,3-dihydro-1H- inden-2-yl]-6H-tmeno[2,3-b]pyrrole-5-carboxamide, 2-chloro-N4(lR,2R)-l-(formylanuno)-2,3-dihydro-lH-inden-2-yl]-6if-thieno[2,3-i]pyrrole-5- carboxamide, 2-chloro-Af-{(1R,2R)-l-[(methoxyacetyl)amino]-2,3-dihydro-lH-inden-2-yl}-6ff-thieno[2,3- £>]pyrrole-5-carboxamide, Af-[(lJR,2R)-l-(acetylamino)-2,3-dihydro-m-inden-2-yl]-2-chloro-6^-thieno[2>3-b]pyn:ole-5- carboxamide; 2-chloro-N-{(lR,2R)-l-[(3-methoxypropanoyl)amino]-2,3-dihydro-lH-inden-2-yl}-6H- thieno[2,3-£>]pyrrole-5-carboxamide, N-{(lR,2R)-l-[(2-acetoxyacettyl)amino]-2,3-dihydro-m-iiideri-2-yl}-2-chloro-6H-thieno[2,3- &]pyrrole-5-carboxamide, N-((15,25)-l-{[(2(1S')-2-(rerf-butoxycarbonylairiino)-2-carbamoylacetyl]anuno}-2,3-dihydro- lH-inden-2-yl)-2-chloro-6H-thieno[2,3-^]pyn"ole-5-carboxamide; N-{(l1S,2-4-l-[(2-(rert-butoxycarbonylamino)acetylamino]-2,3-dihydro-lH-inden-2-yl}-2- chloro-6H-thieno [2,3 - b] pyrrole- 5 -carboxamide, N-{(lR,2R)-l-[2-carbamoylacetyl)amino]-2,3-dihydro-1H-mden-2-yl}-2-chloro-6Jff- thieno[2,3,5]pyrrole-5-carboxamide; N-{(l^,2R)-l-[2-(tert-butoxycarbonyl)acetylammo]-2,3-dihydro-lH-mden-2-yl}-2-chloro-6H- thieno[2,3,i]pyrrole-5-carboxamide, 2-chloro-N-(( IR,2R)-1 - {[3 -hydroxy-2-(hydroxymethyl)propanoyl] ammo} -2,3 -dihydro- IH- inden-2-yl)-6if-tmenot2,3-b]pyrrole-5-carboxamide, N-{(12?,2R)-l-[((3R)-3-armno-3-carbamoylpropaiioyl)amiiio]-2,3-dihydro-li^-inden-2-yl}-2- chloro-6i/-thieno[2,3-t]pynrole-5-carboxamide, N-{(lR12R)-l-[(arninoacety])amino]-2,3-dihydro-li^-inden-2-yl}-2-chloro-6i/-thieno[2,3- b]pyrrole-5-carboxamide, 2-cUoro-N-[(lR,2R)-l-({[(2-hydroxyethyl)(phenylmethyl)amirio]acetyl} amino)-2,3-dihydro- lK-mden-2-yl)-6H-thieno[2,3-6]pyrrole-5-carboxarmde, 2-chloro-N-{(lR,2R)-l-[(morpholin-4-ylacetyl)amino]-2,3-dihydro-lH-inden-2-yl}-6H- amino[2,3-b]pyrrole-5-carboxamide, 2-chloro-N-((lR,2R)-l-({[(2-hydroxyethyl)(methyl)amino]acetyl}araino)-2,3-dihydro-lH- mden-2-yl)-6H-thieno[2,3-b]pyrrole-5-carboxamide, N-((1R,2R)-l-({ [bis(2-hydroxyethyl)amino]acetyl} amino)-2,3-dihydro-lH-mden-2-yl)-2- chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide, 2-chloro-N-((lR,2R)-l-({[ethyl(2-hydroxyethyl)amino]acetyl}amino)-2,3-dihydro-lH-inden- 2-yl)-6i^-thieno[2,3-6]pyrrole-5-carboxairude, 2-chloro-N-((lR,2R)-l-({[(2,3-dihydroxypropyl)(methyl)amino]acetyl}amino)-2,3-dihydro- 1H-mden-2-yl)-6H-thieno[2,3-£]pyrrole-5-carboxamide, N-((lR,2R)-l-({ [bis(2-hydroxypropyl)ammo]acetyl} amino)-2,3-dihydro-1H-inden-2-yl)-2- chloro-6H-thieno[2,3-i]pyrrole-5-carboxamide; N- {(1R,2R)- l-[(2-amino-2-oxoethyl)amino] -2,3-dihydro-lH-inden-2-yl} -2-chloro-6H- thieno[2,3-b]pyrrole-5-carboxamide, N-[(lR,2R)-l-[(tert-butoxycarbonylmethyl)amino]-2,3-dihydro-lH-inden-2-yl}-2-chloro-6if- thieno[2,3-b]pyrrole-5-carboxamide, N- {(1R,2R)- l-(carboxymethylamino)-2,3 -dihydro-1H-inden-2-yl} -2-chloro-6H- thieno(3,2,&]pyrrole-5-carboxarnide, 2-chloro-N-{(12?,2R)-l-[(hydroxyacetylanuno]-2,3-dihydro-ljyr-inden-2-yl}-6R-thieno[2>3- &]pyrrole-5-carboxamide, 2,3-dichloro-N-{(lR,2R)-l-[(chloroacetyl)anuno]-2,3-dihydro-lH-inden-2-yl}-4H-thieno[3,2- b]pyrrole-5-carboxamide, N-{(lR,2R)-l-[((3S)-3-airano-3-carboxypropanoyl)amino]-2,3-dihydro-lR-inden-2-yl}-2,3- dichloro-4H-thieno(3,2,b]pyrro]e-5-carboxamide, N-{(lR,2R)-l-[(2-carboxyacetyl)amino]-2,3-dihydro-m-inden-2-yl}-2,3-dichloro-4H- thieno(3,2,b]pyrrole-5-carboxamide, N-{(lR,2R)-l-[(2-carboxyacetyl)amino]-2,3-dihydro-lH-inden-2-yl}-2-chloro-6H- trueno(3,2,b]pyrrole-5-carboxamide, N-{(lR,2R)-l-[((3S)-3-anuno-3-carboxypropanoyl)amino]-2,3-dihydro-lH-inden-2-yl}-2- chloro-6R-thieno(3,2,i]pyrrole-5-carboxamide, 2,3-dichloro-N-{(lR,2R)-l-[(methylsulfonyl)amino]-2,3-dihydro-lH-inden-2-yl}-4H- trueno[3,2-b]pyrrole-5-carboxamide, or a pharmaceuticaily acceptable salt or an in vivo hydrolysable ester thereof In another aspect of the invention, further preferred compounds of the invention are any one of. 2-chloro-N-{(1R,2R)-l-[(hydroxyacetylamino]-2,3-dihydro-lR-inden-2-yl}-6H-thieno[2,3-b]pyrrole-5-carboxamide, N-{(1R,2R)-l-[(2-arrnno-2-oxoethyl)amino]-2,3-dihydro-lH-rnden-2-yl}-2,3-dichloro-4H-thieno [3,2-b]pyrrole-5-carboxamide, 2,3-dichloro-N-{(lR,2-4)-l-[(hydroxyacetyl)arruno]-2,3-dihydro-lH-inden-2-yl}-4H-thieno[3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-[(lR,2R)-l-(formylarmino)-2,3-dihydro-1H-inden-2-yl]-4H-thieno[3,2- b]pyrrole-5-carboxamide, or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof Another aspect of the present invention provides a process for preparing a compound of formula (1) or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof which process (wherein A, y, R1, R4, R5, r and n are, unless otherwise specified, as defined in formula (1)) comprises of a) reacting an acid of the formula (2): (Formula Removed) (2) or an activated derivative thereof; with an amine of formula (3). (Formula Removed) and thereafter if necessary- i) conyerting a compound of the formula (1) into another compound of the formula (1), u) removing any protecting groups, iii) forming a pharmaceutically acceptable salt or in vivo hydrolysable ester. Specific reaction conditions for the above reaction are as follows Process a) Acids of formula (2) and amines of formula (3) may be coupled together in the presence of a suitable coupling reagent Standard peptide coupling reagents known in the art can be employed as suitable coupling reagents, or for example carbonyldiimidazole, l-ethyl-3-(3-dimethylaminopropyl)carbodi-imide hydrochlonde (EDCI) and dicyclohexyl-carbodumide (DCCI), optionally in the presence of a catalyst such as 1-hydroxybenzotnazole, dimethylaminopyndme or 4-pyrrolidinopyndine, optionally in the presence of a base for example tnethylamme, di-isopropylethylamine, pyridine, or 2,6-d1-alkyl-pyndmes such as 2,6-lutidme or 2,6-di-terr-butylpyndme Suitable solvents include dimethylacetamide, dichloromethane, benzene, tetrahydrofuran and dimethylfonnamide The coupling reaction may conyemently be performed at a temperature in the range of -40 to 40°C Suitable activated acid denvatives include acid halides, for example acid chlondes, and active esters, for example pentafluorophenyl esters The reaction of these types of compounds with amines is well known in the art, for example they may be reacted in the presence of a base, such as those descnbed above, and in a suitable solvent, such as those descnbed above The reaction may conyemently be performed at a temperature in the range of -40 to 40°C A compounds of formula (2) where Z is CH may be prepared according to Scheme 1 (Scheme Removed) Scheme 1 Compounds of formula (2a) are commercially available or they are known compounds or they are prepared by processes known in the art A compound of the formula (2) wherein X is nitrogen, can be prepared from a compound of the formula (4) (Formula Removed) by firstly conyertmg the oxo group to chlonne or bromine with a halogenatmg agent such as POCI3 or POBr3, in an inert organic solvent such as dichloromethane in a temperature range of ambient temperature to reflux (for example see Nucleic Acid Chem 1991, 4, 24-6), then displacing the chlorine or bromine group with cyamde using a cyamde salt such as potassium cyamde, in an inert organic solvent such as toluene, benzene or xylene, optionally in the presence of a catalyst such as 18-crown-6 (for example see J Heterocycl Chem 2000, 37(1), 119-126) and finally hydrolysing the cyano group to a carboxy group, with for example, an aqueous acid such as aqueous hydrogen chloride (for example see Chem Pharm Bull 1986, 34(9). 3635-13). Alternatively, a compound of the formula (2) wherein X is nitrogen may be formed by reacting the compound of the formula (4) with (Cl3CCO)20 and C13CCO2H in the presence of magnesium chlonde using CI3CCO2H as solvent, to form a compound of the formula (5) (Formula Removed) and then hydrolyismg the compound of the formula (5), using, for example, aqueous sodium hydroxide, at a temperature range of ambient temperature to reflux (for example see J Heterocycl Chem 1980, 17(2), 381-2) The compound of formula (4) may be prepared from a compound of formula (6) and (7) using conditions known for the Curtius rearrangement {Tetrahedron 1999, 55_, 6167) (Formula Removed) (6) The compounds of the formula (8) and (9) (Formula Removed) transform into compounds of the formula (6) and (7) respectively This transformation either occurs spontaneously or may be induced with acid or base Compounds of the formula (8) and (9) may be prepared by introducing a carboxy group into a compound of the formula (10) or (11) (Formula Removed) wherein P' is an amino protecting group such as butoxycarbonyl A carboxy group is introduced into the compound of the formula (10) or (11) by reacting an alkyl hthium reagent such as n-butyl hthium, in an inert orgamc solvent such as THF, at low temperature, for example in the range -10°C to -78°C and then forming the compound of the formula (8) or (9) as appropriate by either a) reacting the resulting compound with carbon dioxide, or b) by reacting with DMF in the temperature range of -10°C to ambient temperature to form the corresponding aldehyde and oxidizing the aldehyde to carboxy with standard reagents to give the compound of the formula (8) or (9) Compounds of the formula (10) and (11) may be prepared from a compound of the formula (12) and (13) (Formula Removed) using conditions known for the Curtius reaction (12) Compounds of the formula (12) and (13) may be prepared by oxidizing the corresponding aldehyde using standard oxidizing reagents such as potassium manganate or sodium penodate. The aldehyde precursor of a compound of the formula (12) or (13) can be prepared using standard techmques known in the art For example, many compounds of the formula (12) or (13) may be prepared by introducing the appropriate R5 and R7 mto a compound of the formula (14) or (15) as appropnate (Formula Removed) For example, when R6 and R7 are both chloro a compound of the formula (14) or (15) may be chlorinated with a chlorinating agent such as chlorine in the presence of aluminium chloride or iron (HI) chloride, in an inert organic chlorinated solvent such as dichloromethane or 1,2-dichloroethane, followed by treatment with an aqueous base, such as, aqueous sodium hydroxide The mono chlorinated compound can be formed in the same way Compounds of formula (2b) may also be prepared as illustrated in Scheme 2 (Scheme Removed) Scheme 2 The conyersion of compounds of formula (10) into compounds of formula (16) may be earned out by directed ortho lithiation reactions (J. Org Chem, 2001, volume 66, 3662-3670), for example with n-butyl lithium and (CHO)N(alkyl)2. The protecting group P' in compounds of formula (10) must be suitable directing group for this reaction and may be for example - CChtBu Reaction of compounds of formula (16) with LCH2CO2R where L is a leaving group, and replacement of the protecting group P' with an alternative P" (for example - COalkyl) according to standard processes, gives a compound of formula (17) This may be cychsed using a base, for example potassium carbonate or sodium methoxide Compounds of formula (3) where y is OR3 are commercially available or they are iiown compounds or they are prepared by processes known in the art When y is NR R , the amines of formula (3) may be prepared according to Scheme 3: (Scheme Removed) Scheme 3 Compounds of formula (3a) are commercially available or they are known compounds or they are prepared by processes known in the art For example, starting from primary amines of formula (4), in which R is H or a suitable protecting group, one or both of R and/or R2 may be introduced by acylation, (for example reacting with acetoxyaceuc acid and l-(3-dimethylaminopropyl)-3-ethyl-carbodiirnide hydrochloride -EDAC), alkylation, reductive alkylation, sulphonation or related processes, followed by O-deprotection when appropriate Alternatively, one or both of R1 and/or R2 may be obtained by modification of functionabty in groups previously thus introduced, by reduction, oxidation, hydrolysis (for example the conyersion of an acetoxy group to a hydroxy group), nucleophihc displacement, amidation, or a related process, or a combination of these processes, followed by O-deprotection when appropriate It will be appreciated that such modifications may include modifications which conyert one compound of the formula (1) mto another compound of the formula (1) (Formula Removed) Armnes of formula (3) may alternatively be obtained by applying the processes descnbed for the preparation of compounds of formula (3a) to compounds of formula (20) in which W is NH2 or a nitrogen atom with one or two suitable protecting groups (Formula Removed) Compounds of the formula (3) where r = 1 and wherein A is heteroarylene can be prepared from suitably functionalised cycloalkyl fused heterocycles. For example, when A is pyridine, (Formula Removed) compounds of formula (3b) and (3c) may be prepared from the corresponding pynndmone regioisomer according to Scheme 4 – (Scheme Removed) Step 1 is performed on a compound known in the literature (Jpn. Kokai Tokkyo Koho, 1995, 14 JP 07070136) Steps 2, 3, 4, 5, 6, 7 and 8 are performed using standard techniques known in the art. It will be appreciated that the bromopynndinone isomers (21a, 21b and 21c) could (Formula Removed) be conyerted to the corresponding heterocyhc version of (3) by the means described in Scheme 4. The bromopyndinones can be prepared from the corresponding pynndmone by standard techniques known in the art The pyrrndmones (22a, 22b, 22c) are known in the literature or they are prepared by processes known in the art (Formula Removed) The process described above and shown in Scheme 4 may also be applied to other six membered heterocycles containing more than one nitrogen It will be appreciated that, in a similar manner, compounds of the formula (3) wherein A is heteroarylene containing a bridgehead nitrogen can be prepared from the appropnate suitably functionalised cycloalkyl fused heterocycles It will be appreciated that the processes described above for formation and modification of y as NR'R2 may be applied similarly whether to make the compound of formula (3) before coupling to the acid of formula (2) or whether to the product of such a coupling It will be appreciated that certain of the various ring substituents in the compounds of the present invention, for example R1 may be introduced by standard aromatic substitution reactions or generated by conyentional functional group modifications either prior to or immediately following the processes mentioned above, and as such are included in the process aspect of the invention Such reactions may conyert one compound of the formula (1) into another compound of the formula (1) Such reactions and modifications include, for example, introduction of a substituent by means of an aromatic substitution reaction, reduction of substituents, alkylation of substituents and oxidation of substituents The reagents and reaction conditions for such procedures are well known in the chemical art. Particular examples of aromatic substitution reactions include the introduction of a mtro group using concentrated nitnc acid, the introduction of an acyl group using, for example, an acyl hahde and Lewis acid (such as aluminium trichloride) under Fnedel Crafts conditions, the introduction of an alkyl group using an alkyl halide and Lewis acid (such as aluminium trichloride) under Fnedel Crafts conditions, and the introduction of a halogen group Particular examples of modifications mclude the reduction of a mtro group to an ammo group by for example, catalytic hydrogenation with a nickel catalyst or treatment with iron in the presence of hydrochloric acid with heating, oxidation of alkylthio to alkylsulphmyl or alkylsulphonyl. It will also be appreciated that in some of the reactions mentioned herein it may be necessary/desirable to protect any sensitive groups in the compounds The instances where protection is necessary or desirable and suitable methods for protection are known to those skilled in the art. Conyentional protecting groups may be used in accordance with standard practice (for illustration see T.W. Green, Protective Groups in Orgamc Synthesis, John Wiley and Sons, 1991). Thus, if reactants include groups such as amino, carboxy or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein A suitable protecting group for an amino or alkylammo group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl, ethoxycarbonyl or f-butoxycarbonyl group, an arylmethoxycarbonyl group, for example benzyloxycarbonyl, or an aroyl group, for example benzoyl The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group may be removed for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide Alternatively an acyl group such as a r-butoxycarbonyl group may be removed, for example, by treatment with a suitable acid as hydrochloric, sulphuric or phosphoric acid or tnfluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example boron tns(tnfluoroacetate) A suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group which may be removed by treatment With an alkylamine, for example dimethylammopropylamme, or with hydrazine A suitable protecting group for a hydroxy group is, for example, an acyl group, for imple an alkanoyl group such as acetyl, an aroyl group, for example benzoyl, or an arylmethyl group, for example benzyl. The deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or an aroyl group may be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide Alternatively an arylmethyl group such as a benzyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon A suitable protecting group for a carboxy group is, for example, an estenfying group, for example a methyl or an ethyl group which may be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a r-butyl group which may be removed, for example, by treatment with an acid, for example an organic acid such as tnfluoroacetic acid, or for example a benzyl group which may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon The protecting groups may be removed at any conyenient stage in the synthesis using conyentional techniques well known in the chemical art Certain intermediates in the preparation of a compound of the formula (1) are novel and form another aspect of the invention As stated hereinbefore the compounds defined in the present invention possesses glycogen phosphorylase inhibitory activity This property may be assessed, for example, using the procedure set out below. Assay The activity of the compounds is determined by measuring the inhibitory effect of the compounds in the direction of glycogen synthesis, the conyersion of glucose-1-phosphate into glycogen with the release of inorganic phosphate, as described in EP 0 846 464 A2 The reactions were in 96well microplate format in a volume of lOOu.1. The change in optical density due to morgamc phosphate formation was measured at 620nM in a Labsystems lEMS Reader MF by the general method of (Nordhe R C and Anon W.J, Methods of Enzymology, 1966, 619-625) The reaction is in 50mMHEPES (N-(2-Hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid),4-(2-Hydroxyethyl)piperazme-l-ethanesulfomc acid), 2.5mMMgCl2, 2 25mM ethylene glycol-bis(b-aminoethyl ether) N,N,N',N'-te,tcaacetic acid, lOOmM KC1, 2mM D-(+)-glucose pH7 2, containing 0 5mM dithiothreitol, the assay buffer solution, with lmg type HI glycogen, 0 15ug glycogen phosphorylase a (GPa) from rabbit muscle and 0.5mM glucose-1-phosphate. GPa is pre-mcubated in the assay buffer solution with the type m glycogen at 2 5 mg ml"] for 30 minutes. 40u,l of the enzyme solution is added to 25ul assay buffer solution and the reaction started with the addition of 25jal 2mM glucose-1-phosphate Compounds to be tested are prepared in lOjo.110% DMSO in assay buffer solution, with final concentration of 1% DMSO in the assay The non-inhibited activity of GPa is measured in the presence of 10JJ.1 10% DMSO in assay buffer solution and maximum inhibition measured in the presence of 30uJVl CP320626 (Hoover et al (1998) J Med Chem 41, 2934-8, Martin et al (1998) PNAS 95, 1776-81). The reaction is stopped after 30min with the addition of 50ui acidic ammonium molybdate solution, 12ug ml"1 in 3 48% H2SO4 with 1% sodium lauryl sulphate and lOug ml'1 ascorbic acid After 30 minutes at room temperature the absorbency at 620nm is measured The assay is performed at a test concentration of inhibitor of lOuM or lOOuM. Compounds demonstrating sigmficant inhibition at one or both of these concentrations may be further evaluated using a range of test concentrations of inhibitor to determine an IC50, a concentration predicted to inhibit the enzyme reaction by 50% Activity is calculated as follows.-% inhibition = (1 - (compound OD620 - fully inhibited OD620)/ (non-inhibited rate OD620 -fully inhibited OD620)) * 100 OD620 = optical density at 620nM Typical IC50 values for compounds of the invention when tested in the above assay are in the range IOOJJM to InM. The activity of the compounds is alternatively determined by measuring the inhibitory effect of the compounds on glycogen degradation, the production of glucose-1-phosphate from glycogen is momtored by the multienzyme coupled assay, as described in EP 0 846 464 A2, general method of Pesce et al (Pesce, in A, Bodounan, S H, Hams, R C, and Nicholson, J F (1977) Clinical Chemistry 23, 1171 - 1717) The reactions were in 384well microplate format in a volume of 50jil. The change in fluorescence due to the conyersion of the co-factor NAD to NADH is measured at 340nM excitation, 465nm emission in a Tecan Ultra Multifunctional Microplate Reader The reaction is in 50mM HEPES, 3 5mM KH2P04, 2 5mM MgCl2, 2 5mM ethylene glycol-bis(b-arninoethyl ether) AT,N,iV'.W-terraacetic acid, lOOmM KCl, 8mM D-(+)-glucose pH7 2, containing 0 5mM dithiothreitol, the assay buffer solution Human recombmant hver glycogen phosphorylase a (hrl GPa) 20nM is pre-incubated in assay buffer lution with 6 25mM NAD, 1 25mg type EI glycogen at 1 25 mg ml"1 the reagent buffer, for 30 minutes. The coupling enzymes, phosphoglucomutase and glucose-6-phosphate dehydrogenase ( Sigma) are prepared in reagent buffer, final concentration 0 25Units per well. 20(ol of the hrl GPa solution is added to 10(0,1 compound solution and the reaction started with the addition of 20ul coupling enzyme solution Compounds to be tested are prepared in 10jj.l 5% DMSO in assay buffer solution, with final concentration of 1% DMSO in the assay The non-inhibited activity of GPa is measured in the presence of lOui 5% DMSO in assay buffer solution and maximum inhibition measured in the presence of 5mgs ml"1 N- sthylmaleumide After 6 hours at 30°C Relative Fluoresence Units (RFUs) are measured at 340nM excitation, 465nm emission The assay is performed at a test concentration of inhibitor of lOuM or lOOuM Compounds demonstrating significant inhibition at one or both of these concentrations may be further evaluated using a range of test concentrations of inhibitor to determine an IC50, a concentration predicted to inhibit the enzyme reaction by 50%. Activity is calculated as follows -% inhibition = (1 - (compound RFUs - fully inhibited RFUs)/ (non-inhibited rate RFUs - fully inhibited RFUs))* 100. Typical 1C50 values for compounds of the invention when tested in the above assay are in the range IOOJAM to InM. For example, Example 10 was found to have an IC50 of 4 5|im The inhibitory activity of compounds was further tested in rat primary hepatocytes. Rat hepatocytes were isolated by the collagenase perfusion technique, general method of Seglen (P.O Seglen, Methods Cell Biology (1976) 13 29-83). Cells were cultured on Nunclon six well culture plates in DMEM (Dulbeco's Modified Eagle's Medium) with high level of glucose containing 10% foetal calf serum, NEAA (non essential amino acids), Glutamrne, penicillin /streptomycin ((100units/100ug)/ml) for 4 to 6 hours. The hepatocytes were then cultured in the DMEM solution without foetal calf serum and with lOnM insulin and lOnM dexamethasone. Expenments were initiated after 18-20 hours culture by washing the cells and adding Krebs-Henseleit bicarbonate buffer containing 2.5mM CaCl2 and 1% gelatin The test compound was added and 5 minutes later the cells were C1-4allenged with 25nM glucagon. The Krebs-Henseleit solution was removed after 60 mm incubation at 37°C , 95%02/5%CO2 and the glucose concentration of the Krebs-Henseleit solution measured. Accordmg to a further aspect of the invention there is provided a pharmaceutical composition which comprises a compound of the formula (1), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, as defined hereinbefore in association with a pharmaceutically-acceptable diluent or earner The compositions of the invention may be in a form suitable for oral use (for example as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for topical use (for example as creams, ointments, gels, or aqueous or oily solutions or suspensions), for administration by inhalation (for example as a finely divided powder or a liquid aerosol), for administration by msufflation (for example as a finely divided powder) or for parenteral administration (for example as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular or intramuscular dosing or as a suppository for rectal dosing). The compositions of the invention may be obtained by conyentional procedures using conyentional pharmaceutical excipients, well known in the art Thus, compositions intended for oral use may contain, for example, one or more colouring, sweetening, flavouring and/or preservative agents. Suitable pharmaceutically acceptable excipients for a tablet formulation include, for example, inert diluents such as lactose, sodium carbonate, calcium phosphate or calcium carbonate, granulating and disintegrating agents such as corn starch or algemc acid; binding agents such as starch, lubricating agents such as magnesium stearate, stearic acid or talc, preservative agents such as ethyl or propyl p_-hydroxybenzoate, and anti-oxidants, such as ascorbic acid. Tablet formulations may be uncoated or coated either to modify their disintegration and the subsequent absorption of the active ingredient within the gastrointestinal tract, or to improve their stability and/or appearance, in either case, using conyentional coating agents and procedures well known in the art Compositions for oral use may be in the form of hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules in which the active ingredient is mixed with water or an oil such as peanut oil, liquid paraffin, or olive oil. Aqueous suspensions generally contain the active ingredient in finely powdered form together with one or more suspending agents, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvmyl-pyrrolidone, gum tragacanth and gum acacia, dispersing or wetting agents such as lecithin or condensation products of an alkylene oxide with fatty acids (for example polyoxethylene stearate), or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate The aqueous suspensions may also contain one or more preservatives (such as ethyl or propyl p_-hydroxybenzoate, antioxidants (such as ascorbic acid), colouring agents, flavouring agents, and/or sweetening agents (such as sucrose, saccharine or aspartame) Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil (such as arachis oil, olive oil, sesame oil or coconut oil) or in a mineral oil (such as liquid paraffin) The oily suspensions may also contain a thickening agent such as beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as those set out above, and flavouring agents may be added to provide a palatable oral preparation These compositions may be preserved by the addition of an anti-oxidant such as ascorbic acid Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water generally contain the active ingredient together with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above Additional excipients such as sweetening, flavouring and colouring agents, may also be present. The pharmaceutical compositions of the invention may also be in the form of oil-m-water emulsions The oily phase may be a vegetable oil, such as olive oil or arachis oil, or a mineral oil, such as for example liquid paraffin or a mixture of any of these. Suitable emulsifying agents may be, for example, naturally-occurring gums such as gum acacia or gum tragacanth, naturally-occurring phosphatides such as soya bean, lecithin, an esters or partial esters derived from fatty acids and hexitol anhydrides (for example sorbitan monooleate) and condensation products of the said partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening, flavouring and preservative agents. Syrups and elixirs may be formulated with sweetening agents such as glycerol, propylene glycol, sorbitol, aspartame or sucrose, and may also contain a demulcent, preservative, flavouring and/or colouring agent The pharmaceutical compositions may also be in the form of a sterile injectable aqueous or oily suspension, which may be formulated according to known procedures using one or more of the appropriate dispersing or wetting agents and suspendmg agents, which have been mentioned above. A sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenteraUy-acceptable diluent or solvent, for example a solution in 1,3-butanediol Compositions for administration by inhalation may be in the form of a conyentional pressurised aerosol arranged to dispense the active ingredient either as an aerosol containing finely divided solid or liquid droplets Conyentional aerosol propellants such as volatile fluonnated hydrocarbons or hydrocarbons may be used and the aerosol device is conyeniently arranged to dispense a metered quantity of active ingredient For further information on formulation the reader is referred to Chapter 25 2 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansen, Chairman of Editorial Board), Pergamon Press 1990 The amount of active ingredient that is combined with one or more excipients to produce a single dosage form will necessarily vary depending upon the host treated and the particular route of adrnimstration. For example, a formulation intended for oral administration to humans will generally contain, for example, from 0 5 mg to 2 g of active agent compounded with an appropriate and conyement amount of excipients which may vary from about 5 to about 98 percent by weight of the total composition. Dosage unit forms will generally contain about 1 mg to about 500 mg of an active ingredient. For further information on Routes of Administration and Dosage Regimes the reader is referred to Chapter 25.3 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansen; Chairman of Editorial Board), Pergamon Press 1990. The compound of formula (1) will normally be administered to a warm-blooded animal at a unit dose withm the range 5-5000 mg per square meter body area of the animal, l e. approximately 0.1-100 mg/kg, and this normally provides a therapeutically-effective dose A unit dose form such as a tablet or capsule will usually contain, for example 1-250 mg of active ingredient. Preferably a daily dose in the range of 1-50 mg/kg is employed However the daily dose will necessarily be varied depending upon the host treated, the particular route of administration, and the seventy of the illness being treated Accordingly the optimum osage may be determined by the practitioner who is treating any particular patient. The inhibition of glycogen phosphorylase activity described herem may be applied as a sole therapy or may involve, in addition to the subject of the present invention, one or more other substances and/or treatments. Such conjoint treatment may be achieved by way of the simultaneous, sequential or separate administration of the individual components of the treatment Simultaneous treatment may be in a single tablet or in separate tablets For example in the treatment of diabetes mellitus chemotherapy may include the following main categories of treatment 1) Insulin and insulin analogues, 2) Insulin secretogogues including sulphonylureas (for example ghbenclamide, glipizide) and prandial glucose regulators (for example repaglinide, nateghnide), 3) Insulin sensitising agents including PPARg agonists (for example pioglitazone and rosightazone), 4) Agents that suppress hepatic glucose output (for example metformin) 5) Agents designed to reduce the absorption of glucose from the intestine (for example acarbose), 6) Agents designed to treat the complications of prolonged hyperglycaemia, 7) Anti-obesity agents (for example sibutramme and orlistat), 8) Anti- dyshpidaemia agents such as, HMG-CoA reductase inhibitors (statins, eg pravastatin), PPARoc agonists (fibrates, eg gemfibrozil), bile acid sequestrants (cholestyramine); cholesterol absorption inhibitors (plant stands, synthetic inhibitors); bile acid absorption inhibitors (IBATi) and nicotinic acid and analogues (niacin and slow release formulations), 9) Antihypertensive agents such as, P blockers (eg atenolol, Inderal); ACE inhibitors (eg lismopnl); Calcium antagonists (eg nifedipine), Angiotensin receptor antagonists (eg candesartan), a antagonists and diuretic agents (eg furosemide, benzthiazide); 10)Haemostasis modulators such as, antithrombotics, activators of fibrinolysis and antiplatelet agents, thrombin antagonists, factor Xa inhibitors; factor Vila inhibitors), antiplatelet agents (eg. aspirin, clopidogrel), anticoagulants (heparin and Low molecular weight analogues, hirudin) and warfarin, and 11) Anti-inflammatory agents, such as non-steroidal anti-inflammatory drugs (eg aspirin) and steroidal anti-inflammatory agents (eg cortisone) According to a further aspect of the present invention there is provided a compound of the formula (1), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, as defined herembefore, for use in a method of treatment of a warm-blooded animal such as man by therapy. According to an additional aspect of the mvention there is provided a compound of the formula (1), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, as defined herembefore, for use as a medicament According to an additional aspect of the invention there is provided a compound of the formula (1), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, as defined hereinbefore, for use as a medicament in the treatment of type 2 diabetes, insulin resistance, syndrome X, hypennsulinaemia, hyperglucagonaerma, cardiac ischaemia or obesity in a warm-blooded animal such as man. According to this another aspect of the invention there is provided the use of a compound of the formula (1), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, as defined hereinbefore in the manufacture of a medicament for use in the treatment of type 2 diabetes, insulin resistance, syndrome X, hypennsulinaemia, hyperglucagonaerma, cardiac ischaemia or obesity in a warm-blooded animal such as man According to this another aspect of the invention there is provided the use of a compound of the formula (1), or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, as defined herembefore in the manufacture of a medicament for use in the treatment of type 2 diabetes in a warm-blooded animal such as man. According to a further feature of this aspect of the invention there is provided a method of producing a glycogen phosphorylase inhibitory effect in a warm-blooded animal, such as man, in need of such treatment which compnses admimstenng to said animal an sffective amount of a compound of formula (1) According to this further feature of this aspect of the invention there is provided a method of treating type 2 diabetes, msuhn resistance, syndrome X, hypennsulinaemia, tiyperglucagonaemia, cardiac ischaemia or obesity in a warm-blooded animal, such as man, in need of such treatment which compnses admimstenng to said animal an effective amount of a compound of formula (1). Accordmg to this further feature of this aspect of the invention there is provided a lethod of treating type 2 diabetes in a warm-blooded animal, such as man, in need of such treatment which comprises administering to said animal an effective amount of a compound of formula (1). As stated above the size of the dose required for the therapeutic or prophylactic treatment of a particular cell-proliferation disease will necessarily be varied depending on the host treated, the route of administration and the seventy of the illness being treated A unit dose in the range, for example, 1-100 mg/kg, preferably 1-50 mg/kg is envisaged In addition to their use in therapeutic medicine, the compounds of formula (1) and then pharmaceutically acceptable salts are also useful as pharmacological tools in the development and standardisation of in vitro and in vivo test systems for the evaluation of the effects of inhibitors of cell cycle activity in laboratory animals such as cats, dogs, rabbits, monkeys, rats and mice, as part of the search for new therapeutic agents In the above other pharmaceutical composition, process, method, use and medicament manufacture features, the alternative and preferred embodiments of the compounds of the invention described herein also apply Examples The invention will now be illustrated by the following non-limiting examples in which, unless stated otherwise: (l) temperatures are given in degrees Celsius (°C), operations were earned out at room or ambient temperature, that is, at a temperature in the range of 18-25°C and under an atmosphere of an inert gas such as argon; (n) organic solutions were dned over anhydrous magnesium sulphate, evaporation of solvent was earned out using a rotary evaporator under reduced pressure (600-4000 Pascals; 4 5-30 rnmHg) with a bath temperature of up to 60°C, (in) chromatography means flash chromatography on silica gel, thin layer chromatography (TLC) was earned out on silica gel plates, where a Bond Elut column is referred to, this means a column contaimng 10 g or 20 g or 50 g of silica of 40 micron particle size, the silica being contained in a 60 ml disposable synnge and supported by a porous disc, obtained from Vanan, Harbor City, California, USA under the name "Mega Bond Elut SI", "Mega Bond Elut" is a trademark; where a Biotage cartndge is referred to this means a cartridge containing KP-SIL™ silica, 60µ, particle size 32-63mM, supplied by Biotage, a division of Dyax Corp , 1500 Avon Street Extended, Charlottesville, VA 22902, USA, (IV) in general, the course of reactions was followed by TLC and reaction times are given for illustration only; (v) yields are given for illustration only and are not necessarily those which can be obtained by diligent process development; preparations were repeated if more material was required, (vi) where given, NMR data is in the form of delta values for major diagnostic protons, given m parts per million (ppm) relative to tetramethylsilane (TMS) as an internal standard, determined at 300 MHz using perdeuteno dimethyl sulphoxide (DMSO-Sg) as solvent unless otherwise indicated, other solvents (where indicated in the text) include deuterated chloroform CDC13, (vu) chemical symbols have their usual meamngs, SI units and symbols are used, (vm) reduced pressures are given as absolute pressures in Pascals (Pa); elevated pressures are given as gauge pressures in bars; (rx) solvent ratios are given in volume volume (vN) terms, (x) mass spectra (MS) were run with an electron energy of 70 electron volts in the chemical ionisation (CI) mode usmg a direct exposure probe, where indicated ionisation was effected by electron impact (EI), fast atom bombardment (FAB) or electrospray (ESP), values for m/z are given, generally, only ions which indicate the parent mass are reported and unless otherwise stated the value quoted is (M-H)", (xi) The following abbreviations are used- SM starting material, EtOAc ethyl acetate, MeOH methanol, EtOH ethanol, DCM dichloromethane, HOBT 1 -hydroxybenzotnazole, DIPEA di-isopropylethylamine, EDCI l-ethyl-3-(3-dimethylarmnopropyl)carbodiimide hydrochloride, Et20 diethyl ether, THF tetrahydrofuran, DMF N, N-dimemylformarnide; HATU O-(7-Azabenzotnazol-l-yl)-N,N,N',N- tetxamethyluromumhexafluorophosphate EDAC l-(3-dirnethylaminopropyl)-3-ethyl-carbodiimide hydrochlonde TFA Tnfluoroacetic acid DMTMM 4-(4,6-Dimethoxy-l,3,5-tnazm-2-yl)-4-methylmorpholimuin chlonde DMA N, N-dimethylacetamide Example 1: 2,3-Dichloro-N-[(1R,2R)-l-(formylamino)-2,3-dihydro-1H-inden-2-yl]-4H-thieno[3,2-61pyrrole-5-carboxamide (Formula Removed) N-[(lRl2R)-l-Anuno-2,3-dihydro-lH-inden-2-yl]-2,3-dichloio-4fl-thieno[312-£>]pyrrole-5-carboxamide tnfluoroacetic acid salt (Method 8, 240 mg, 0 5 mmol), formic acid (50 \xL, 1 4 mmol), DIPEA (174 uL, 1 0 mmol) and HOBT (67 mg, 0 5 mmol) were dissolved in DCM (5 ml), stirred for 5 mins, EDCI (120 mg, 0 625 mmol) added and the reaction stirred for lhr Formic acid (50 |iL, 1.4 mmol) and EDCI (240 mg, 1 25 mmol) were added, the reaction stirred for 2 hours and the volatiles removed by evaporation under reduced pressure The residue was dissolved in EtOAc (20 mL), washed with water (2 x 10 mL), bnne (10 mL), dried (MgSCu) and the volatiles removed by evaporation under reduced pressure The residue was purified by column chromatography (2 1 EtOAc.Hexane) to afford the title compound (175mg, 89%) as a white foam 'HNMR 2.86 (dd, 1H), 3.23 (dd, 1H), 4 6 (m, 1H), 5.53 (m, 1H), 7.12 (m, 2H), 7 25 (m, 1H), 8 2 (s, 111), 8 55 (d, 1H), 8.63 (d, 1H), 12 36 (s, 1H), MS m/z 394 Example2 2,3-Dichloro-N-((1R,2R)-l-{r(methyIoxv)acetvllamino[2,3-dihvdro-1H- en-2-yl)-4H-thieno[3,2-blpvrrole-5-carboxamide (Formula Removed) DIPEA (180 µL, 1.05 mmol), HOBT (68 mg, 0 5 mmol), methoxyacetic acid (0 5 mrnol, 38 µL) and ED AC (120 mg, 0.63 mmol) were added to a suspension of N-[(lR,2R)-l-armno-23-dmydro-lH-mden-2-yl]-2,3-dicmoro-4H-tineno[3,2-fe]pyrTole-5-carboxarnide (Method 8,240 mg, 0 5 mmol) in anhydrous DCM (7 mL) The reaction was stirred at ambient temperature for approximately 16 h The volatiles were removed by evaporation under reduced pressure, the residue dissolved in EtOAc (10 mL), washed with water (2 x 10 mL), bnne (10 mL) and dried (MgSO4) The volatiles were removed by evaporation under reduced pressure and the residue was punfied by flash column chromatography on S1O2 (1 1 EtOAc.isohexane), the solvent removed by evaporation under reduced presssure and dned to give the title compound (44 mg, 20%) as a white solid 1H NMR 2 88 (dd, 1H), 3 26 (dd, 1H), 3 87 (dd, 2H), 4 73 (m 1H), 5.51 (t, 1H), 7 17 (m, 5H), 8 26 (d, 1H), 8 59 (d, 1H), 12.36 (s, 1H), MS m/z 439 The following examples were made by the process similar to Example 2 using N-[(lR,2R)-l-aimno-2,3-dmydro-lH inden-2-yl]-2,3-dichloro-4H-tnieno[3,2-6]pyrrole-5-carboxamide (Method 8) and the appropnate commercially available carboxyhc acid Example 3: N-((1S,2S)-l-{r(3(R)-3-(tert-Butoxycarbonylamino)-3-carbamovlpropanoyllamino}-2,3-dihydro-lH-mden-2-vl)-2,3-dichloro-4H-thieno[3,2-b]pvrrole-5-carboxamide Example 4: 2,3-Dichloro-N-[(lR,2R)-l-({[(4R)-2,2-dimethyl-5-oxo-l,3-dioxolan-4-yl]acetyl}armno)-2,3-dihydro-lH-mden-2-yl]-4R-thieno[3,2-b]pvnole-5-carboxamide Example 5: 2,3-Dichloro-N-{(lR,2R)-l-r(3-methoxypropanoyl)aminol-2,3-dihydro-lH-inden-2-yl}-4H-thieno[3,2-b]pyrrole-5-carboxamide Example 6: N-{(lR,2R)-l-[(2-Acetoxyacetyl)aminol-2,3-dihydro-1H-inden-2-yl}-2,3-dichloro-4ff-thieno[3,2-blpyrcole-5-carboxamide Example7:N-f(lR,2R)-l-r(2-Carbamoylacetyl)anuno1-2,3-dihydro-lH-inden-2-yl}-2,3- dichloro-4H-thieno[3,2-b]pvrrol-5-carboxamide Example 55: 2,3-Dichloro-N-f (lR,2R)-l-F(tnfluoroacetyl)aminol-2,3-dihydro-lH-mden-2-yl}-4H-thieno[3,2-b]pyrrole-5-carboxamide (Table Removed) The following examples were made by the process of Example 2 using N-[(15,25)-l-armno-2,3-dmydro-lH-mden-2-yl]-2,3-ojchloro^H-thieno[3,2-Z)]pyaole-5-carboxamide (Method 9) and the appropriate commercially available carboxylic acid ExampleS: 2,3-Dichloro-N-{ClS,25)-l-r(furan-2-vlcarbonyl)aminol-2,3-dihydro-m-inden-2-yl} -4H-thieno[3,2-blpyttole-5-carboxamide Example 9: 2,3-Dichloro-N-{(lS,25)-l-rffuran-3-ylcarbonyl)aminol-2,3-dihydro-1H-mden-2-yl}-4H-thienor312-fclpyrrole-5-carboxamide Example 10: 2,3-Dichloro-AM (15,25')-l-r(3-thienylcarbonyl)aminol-2,3-dihvdro-lH-inden-2-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide Example 11: 2,3-Dichloro-N-(( 15,25)-1 - f [(5-nitrofuran-2-yl)carbonyllamino}-2,3-dihydro-lH-inden-2-yl]-4H-trneno[3,2-b]pyrrole-5<:arboxarnide> Example 12: 2,3-Dichloro-AM(lS,2SVl-r(pyndm-3-ylcarbonyl)aminol-2,3--dihydro-lH-inden-2-yl}-4R-thieno[3,2-61pyrrole-5-carboxamide Example 13: ^-rC15,25)-l-(Acryloylamino)-2,3-dihydro-m-inden-2-yll-2,3-dichloro-4H-thieno[3,2-&lpyrrole-5-carboxamide Example 14: 2,3-Dichloro-N-('(15,25)-l-{[(34iydroxyphenyl)carbonyllarmno}-2,3-&hydro-lJftr-inden-2-yl)-4H-thieno T3,2-Z7]pyrrole-5-carboxamide Example 15: N-[(15,25)-l-fAcetyIarmno)-2,3-dihydro-lR-inden-2-yl]-2,3-dichloro-4H-thieno[3,2-61pyrrole-5-carboxamide Example 16:N-[(15,25)-l-r(2-Carboxyacetyl)aminol-2,3-dihydro-m-inden-2-yl]-2,3-dJchloro^ZZ-thienoP^-blpyrrole-S-carboxamide (Formula Removed) Example 17: 2,3-Dichloro-N-((lS,2S)-14[(dimethylarnino)carbonyllamino}-23-dihvdro-1H-inden-2-yl)-4H-thieno[3,2-61pyrrole-5-carboxamide (Formula Removed) To a solution of N-[(1S,2S)-l-amino-2,3-dihydro-lH-mden-2-yl]-2,3-dichloro-4R-thieno[3,2-b]pyrrole-5-carboxamide (Method 9, 240 mg, 0 5 mmol) and Et3N (101 mg, 1 0 mmol) in DCM (4 mL) was added a solution of dimethylcarbamoyl chlonde (54 mg, 0 5 mmol) in DCM (1 mL) The reaction was stirred at ambient temperature for 2 hours, washed with saturated NaHCO3 (1 mL), water (1 mL), brme (1 mL) and dried (MgSO4) The volatiles were removed by evaporation under reduced pressure to give the title compound (50 mg, 23%) as a foam 1H NMR 2.81 (s, 6H), 2.83 (m, 1H), 3 25 (m, 1H), 4.61 (m, 1H), 5 33 (m, 1H), 7.16 (m, 5H), 8 6 (d, 1H), 12.37 (s, 1H), MS m/z 437 Example 18: 23-Dichloro-N-((15,25)-l-{r(4-methylpiperazin-l-yl)carbonyllamino}-2,3-dihydro-lH-inden-2-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide (Formula Removed) To a solution of N-[(lS,2-4-l-amino-2,3-mhydro-1H-mden-2-yl]-2,3-dichloro-4H-thieno[3,2-i]pyrrole-5-carboxamide (Method 9, 240 mg, 0 5 mmol) and Et3N (101 mg, 1.0 mmol) in DCM (4 mL) was added a solution of 4-methyl-l-piperazine carbonyl chlonde (100 mg, 0.5 mmol) in DCM (1 mL) The reaction was stirred at ambient temperature for 2 hours, washed with saturated NaHCO3 (1 mL), water (1 mL), brme (1 mL) and dned (MgSO4). The volatiles were removed by evaporation under reduced pressure to give the title compound (110 mg, 45%) as a foam MSm/z(M-H)"491. The following examples were made by the method below using yV-[(liS,2iS)-l-ammo-23-dihydro-lH-mden-2-yl]-2-4-oUcUoro^i^-thieno[3,2-b]pyrrole-5-carboxamide tnfluoroacetic acid salt (Method 9) and the appropriate commercially available isocyanate N-[(15,25)-l-armno-23-Nydro-li/-mden-2-yl]-2,3-dicMoro-4H-thieno[3,2-b]pyrrole-5-carboxamide tnfluoroacetic acid salt (0.5 mmol) and Et3N (1.0 mmol) were dissolved in dry THF (5 mL), the appropriate isocyanate (1.0 mmol) was added and the reaction stirred at ambient temperature for 20 hours. EtOAc (15 mL) was added and the mixture washed with water (2x5 mL) bnne (5 mL), dned (MgSO^t) and the volatiles removed by evaporation under reduced pressure to give the title compound as a foam. Example 19: 2,3-Dichloro-N-((LS,25>l-{[(ethylamino)carbonyllamino}-2,3-dihvdro-lH-inden-2-vl)-4H-thieno[3,2-&lpyrrole-5-carboxamide Example 20: 23-Dichloro-N-((15,2S)-l-{r(prop-2-en-l-vlamino)carbonyllamino}-23-dihydro-lflr-inden-2-yl)-4H-thieno[3,2-&lpvrrole-5-carboxamide Example 21: 2,3-Dichloro-N-r(lS,2S)-l-({r(3^-dinitrophenyl)aininolcarbonyl}aniino)-2,3-dihydro-lJfif-inden-2-vll-4flr-thieno[3,2-&lPyTrole-5-carboxamide (Formula Removed) Example 22: 2,3-Dichloro-N-[(15,25)-l-(formylamino)-2,3-dihvdro-lH-inden-2-vll-4H-thieno [3,2-blp vrrole-5-carboxamide (Formula Removed) [(15,25)-l-Armno-2,3-dihydro-m-inden-2-yl]-2,3-dichloro-4H-thieno[3,2-&]pyrrole-5-carboxamide tnfluoroacetic acid salt (Method 9, 240 mg, 0.5mmol), formic acid (50 uL, 1 4 mmol), DEPEA (174 pE, 1.0 mmol) and HOBT (67 mg, 0 5 mmol) were dissolved in DCM (5 ml), stirred for 5 mins, EDCI (120 mg, 0 625 mmol) added and the reaction stirred for lhr Formic acid (50 pJL, 1 4 mmol) and EDCI (240 mg, 1 25 mmol) were added, the reaction stirred for 2 hours and the volatiles removed by evaporation under reduced pressure. The residue was dissolved in EtOAc (20 mL), washed with water (2 x 10 mL), brme (10 mL), dried (MgSCv) and the volatiles removed by evaporation under reduced pressure. The residue was purified by column chromatography (2.1 EtOAc Hexane) to afford the title compound (180mg, 97%) as a white foam JHNMR 2.86 (dd, 1H), 3.23 (dd, 1H), 4.6 (m, 1H), 5 53 (m, 1H), 7.12 (m, 2H), 7.25 (m, 1H), 8 2 (s, 1H), 8.55 (d, 1H), 8.63 (d, 1H), 12.36 (s, 1H), MS m/z 394. Example 23: N-{(lif,2R)-l-F((3R)-3-Ammo-3-carbamoylpropanoyl)aminol-2,3-dihydro-li/-inden-2-vl}-23-dichloro-4H-thienor-3-yrrole-5-carboxamide (Formula Removed) N-((IS,2S)-1 - {[(3 (R)-3-(tert-Butoxycarbonylamino)-3-carbamoylpropanoyl] amino} -2,3-cahydro-lH-inden-2-yl)-2,3-dicUoro-4H-thieno[3,2-b]pyrrole-5-carboxamide (Example 3, 290 mg, 0.5 mmol) was dissolved in TFA (3 mL) and the reaction stirred at ambient mperature for 1 hour. The volaules were evaporated under reduced pressure and the crude matenal was azeotroped with chloroform (3x5 mL) to afford a gum. The gum was tnturated with ether (5 mL), the solid collected by filtration, washed with ether (2x5 mL) and dried to give the tnfluoroacetate salt of the title compound (270 mg, 91%) as a yellow solid 1H NMR 1.24 (m, 1H), 2.72 (m, 1H), 2.90 (dd, 1H), 3.26 (dd, 1H), 4.04 (m, 1H), 4.61 (m, 1H), 5.50 (t, 1H), 7 12 (s, 1H), 7.24 (m, 4H), 7.55 (s, 1H), 7.74 (s, 1H), 8.06 (br, 3H), 8 66 (d, 1H), 8 72 (d, 1H), 12.36 (s, 1H); MS m/z 502 (M+Na)+ Example 24: N-(1R,R)-l-[((3R)-3-Carboxy-3-hydroxypropanoyl)amino]-2,3-dihydro-lH-inden-2-yl)-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide (Formula Removed) 2,3-Dichloro-N-[(lR,2R)-l-({[(4R)-2,2-dimethyl-5-oxo-l,3-dioxolan-4-yl]acetyl}amino)-2,3-C1-4ydro-lH-mden-2-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide (Example 4, 200 mg, 0.4 mmole) was dissolved in THF (2 mL) and water (2 mL) and NaOH (100 mg) were added and the suspension stirred at ambient temperature for 48 hours. 2N HCl was added until pH 1 and the aqueous phase was extracted witfi EtOAc (3x5 mL). The combined orgamc phases were washed with water (10 mL), brine (10 mL) and dried (MgSO4) The solvent was evaporated under reduced pressure and the reisdue was tnturated with Et20, filtered and dned to give the title compound (133 mg, 69%) as a brown solid. 'H NMR 2.45 (obs m, 2H), 2.87 (dd, 1H), 3 26 (obs dd, 1H), 4.39 (m, 1H), 4.57 (m, 1H), 5.52 (t, 1H), 7.18 (m, 5H), 8.43 (d, 1H), 6.63 (d, 1H), 12 39 (s, 1H); MS m/z 483 Example25: 2,3-DichIoro-N-{(LR,2R)-l-r(hydroxvacetvl)amlnol-2,3-dihydro-1H-inden- 2-yl}-4H-thieno[3,2-b]pyrrole-5-carboxamide (Formula Removed) N-{(lR,2R)-l-[(2-Acetoxyacetyl)amino]-2,3-dihydro-1H-mden-2-yl}-2,3--dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide (Example 6; 632 mg, 1 36 mmol) was dissolved in THF (10 mL), MeOH (10 mL) and K2CO3 (100 mg) were then added and the suspension stirred at ambient temperature for 16 hours. Water (50 mL) was added and the aqueous phase was jxtracted with EtOAc (3 x 30 mL) The combmed organic phases were washed with water (2 x. 50 mL), bnne (50 mL) and dned (MgSCU) The solvent was removed by evaporation under reduced pressure, the crude product was tnturated (EtOAc:isohexane, 1:10), filtered, washed with isohexane (5 mL) and dned to give the title compound (428 mg, 74%) as a white solid. 'H NMR 2 86 (dd, 1H), 3 25 (obs dd, 1H), 3.89 (m, 2H), 4.72 (m, 1H), 5.39 (t, 1H), 5.51 (t, 1H), 7.17 (m, 5H), 8.13 (d, 1H), 8.59 (d, 1H), 12 35 (s, 1H); MS m/z 424. Example 26: 2,3-Dichloro-N-{(15v25)-l-[(methylsulfonyl)aminol-2,3-dihydro-lff-inden-2-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide (Formula Removed) 5-Carboxy-2,3-dichloro-4tf-thieno[3,2-fo]pyrrole (Method 4, 236 mg, 1.0 mmol), N-[(15,2-4-2-armno-2,3-dihydro-lH-inden-l-yl]methanesulfonarmde (226 mg, 1 0 mmol), } DIPEA (174 uL, 1 0 mmol) and HOBT (135 mg, 1.0 mmol) were dissolved in DCM (10 mL) and stirred for approximately 5 mins. EDCI (240 mg, 1.25 mmol) was added and the reaction stirred for 20 hours. The volatiles were removed by evaporation, EtOAc (25mL) added, the mixture washed with water (2 x 10 mL) and brine (10 mL) and dried (MgSO4) The volatiles /ere removed by evaporation under reduced pressure to give the tide compound (430mg, 97%) as a foam. 'HNMR 2.83 (m, 1H), 2.99 (s, 3H), 3.23 (m, 1H), 4 57 (m, 1H), 4.95 (m, 1H), 7.13 (s, 1H), 7.21-7.34 (m, 4H), 7.87 (d, 1H), 8.66 (d, 1H), 12.41 (s, 1H); MS m/z (M-H)" 442 Example 27: 2,3-Dichloro-iy-{(lS, 25)-l-rmethyl(morpholin-4-ylacetvl)aminol-2,3-dihvdro-LHr-inden-2-yl)-4flr-thieno[3,2-61pvrrole-5-carboxamide (Formula Removed) 23-DicWoro-N-{(lJ?,2R)-l-[(chloroacetyl)(methyl)amino]-2,3-dmydro-li^-mden-2-yl}-4H-thieno[3^-i]pyrrole-5-carboxamide (Method 10,100 mg, 0 22 mol) and morphohne (100 mg, 12 6 mmol) were dissolved in DCM, stirred at ambient temperature for 20hours and the volatiles removed by evaporation under reduced pressure. EtOAc (10 mL) was added and the mixture washed with water (2x5 mL), brine (5 mL), dried (MgSO4) and the volatiles removed by evaporation under reduced pressure to give the title compound (60 mg, 54%) as a buff coloured powder. 'H NMR 2 36 (m, 4H), 2 74 (d, 3H), 2.9-3.55 (m, 7H), 4.8 (m, 1H), 5.96 (dd, 1H), 7.0 (m, 1H), 7 09 (d, 1H), 7.26 (m, 3H), 8.62 (dd, 1H), MS m/z 507. Example 28: N-[(lR,2R)-l-r(2-Amino-2-oxoethyl)aminol-2,3-dihydro-1H-inden-2-yl}-2,3-dichloro-4H-thieno-3-61pyrrole-5-carboxamide (Formula Removed) Prepared in a similar manner to Example 29 using -y-{(lR,2R)-l-ammo-2,3-dihydro- if-inden-2-yl}-2,3-dichloro-1H-thieno[3,2-i]pyrrol-5-yl-2-carboxamide (Method 8) and bromoacetamide. XH NMR 2.69 (s, 1H), 2.8 (dd, 1H), 3.16 (m, 2H), 3 24 (m, 1H), 4.21 (m, 1H), 4 44 (m, 1H), 7 03 (s, 1H), 7.12 (s, 1H), 7.23 (m, 3H), 7 28 (s, 1H), 7 37 (s, 1H), 8.49 (d, 1H), 12.36 (s, 1H), MSm/z(M-H)"422. Example 29: 7y-(lR^K)-l-r(tert-Butoxycarbonylmethyl)aminol-2,3-dihvdro-lff-iriden-2-yl}-2,3-dichloro-4H-thieno[3,2-61pvrrole-5-carboxamide (Formula Removed) DIPEA (520 µL, 3 0 mmol) and f-butyl bromoacetate (150 µL, 1.0 mmol) were added to a solution of N-{(lR,2R)-l-amino-2,3-dihydro-lH-mden-2-yl}-2,3-dichloro-4H-thieno[3,2-b]pyirol-5-yl-2-carboxamide (Method 8, 479 mg, 1.0 mmol) in CH3CN (15 mL) The resulting suspension was stirred at 60°C for approximately 2 h. Upon cooling the volatiles were removed by evaporation under reduced pressure, the residue dissolved in EtOAc (20 mL), washed with water (2 x 20 mL), brine (20 mL) and dried (MgSO4). The volatiles were removed by evaporation under reduced pressure and the residue purified by column chromatography (EtOAc-isohexane 1 1) to afford the title compound (100 mg, 21%) as a white sokd- JH NMR 1.49 (s, 9H), 1.87 (bra, 1H), 2.75 (dd, 1H), 3 62 (d, 2H), 3.65 (dd, 1H), 4.15 (d, 1H), 4 40 (m, 1H), 6.82 (s, 1H), 7.10 (d, 1H), 7 25 (s, 2H), 7.40 (d, 1H), 9 80 (s, 1H), MS m/z 480 Example 30: N-r(lR,2R)-l-(Carboxyniethylamino)-2,3-dihvdro-lH-inden-2-yl]-2,3- chloro-4H-thieno[3,2-b]pvrroIe-5-carboxamide (Formula Removed) N-(lR,2R)-l-[(tert-Butoxycarbonylmethyl)amino]-2,3-dihydro-lH-inden-2-yl}-2,3-dichloro-4H-thieno[3,2-i]pyrrole-5-carboxamide (Example 29; 100 mg, 0.21 mmol) dissolved in DCM (10 mL). TFA (1 mL) added and the reaction stirred at ambient temperature for 6 hours Evaporation under reduced pressure, co-evaporation with CHCI3 (2 x 10 mL) and drying gave the title compound (85mg, 36%) as a white powder. 1H NMR 2 71 (dd, 1H), 3.16 (dd, 1H), 3 29 (m, 2H), 4 25 (m, 1H), 4 39 (m, 1H), 6 97 (m, 2H), 7.08 (m, 3H), 7 24 (m, 2H), 7.48 (d, 1H), 8.63 (d, 1H), 11 62 (s, 1H), MS m/z (M-H)" 422. Example 31: N-(1R,2R)-l-[N-Acetyl-N-(carboxymethyl)aminol-2,3-dihvdro-1H-inden-2-yl}-2,3-dichloro-4H-thienor3,2-61pyrrole-5-carboxamide (Formula Removed) TFA (1 mL) was added to a solution of 1,1-dimeuiylethyl [acetyl((l.R,2R)-2-{[(2,3-dicnloro-4H-tmeno [3,2-d]pyrrol-5 -yl)carbonyl] ammo} -2,3 -dihydro- lH-inden-1 -yl)ammo]acetate (Method 18, 40 mg, 0.08 mmol) in DCM (5 mL) and the reaction was stirred at ambient temperature for 1 h The volatiles were removed by evaporation under reduced pressure to afford the tide compound (35 mg, 94%) as a white solid. 1HNMR2 49 (s, 3H), 2 97 (dd, 1H), 3.20 (dd, 1H), 3 90 (m, 2H), 4.70 (m, 1H), 5.50 (d, 1H), 7 25 (m, 5H), 8 60 (d, 1H), 12.43, (s, 1H), MS m/z 466, 349. Example32: N-{(1R,2R)-1-[Acetyl(2-amino-2-oxoethy])aminol-2,3-dihydro-1H-inden-2- l}-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide (Formula Removed) Acetyl chloride (17 µL, 0.24 mmol) was added to a solution of N-{(lR,2R)-l-[(2-armno-2-oxOemyl)armno]-2,3-dmydro-lR-inden-2-yl}-23-dicMoro-4i/-1±iieno[3,2-6]pyrrole-5-carboxamide (Example 28, 100 mg, 0.24 mmol) in THF (10 mL). The reaction was stirred at ambient temperature for 1 h. The volatiles were removed by evaporation under reduced pressure, the residue dissolved in EtOAc (50 mL), washed with water (2 x 10 mL), brme (10 mL) and dried (MgSO4). The volatiles were removed by evaporation under reduced pressure and the residue purified by column chromatography (EtOAc :isohexane 1:2) to afford the title compound (50 mg, 45%) as a white solid 'H NMR 2.49 (s, 3H), 2.98 (dd, 1H), 3.20 (dd, 1H), 3 29 (brs, 2H), 4.0 (m, 2H), 4 65 (m, 1H), 5-70 (d, 1H), 7 25 (m, 5H), 8 30 (d, 1H), 12 10, (s, 1H), MS m/z 487. Example 33: N-{(lR,2R)-l-rAir-(Carboxymethyl)-N-(liydroxyacetvl)aminol-2,3-dihydro-1H-inden-2-yl)-2,3-dichloro-4#-tMenor3^-61pyrrole-5-carboxamide (Formula Removed) Potassium carbonate (20 mg) and MeOH (1 mL) were added to a solution of [[(acetyloxy)acetyl]((lR,2R)-2-{[(2,3-dichloro-4J^-tmeno[3,2-b]pyrrol-5-yl)carbonyl]amino}-2,3-dihydro-lH-inden-l-yl)armno]acetic acid (Method 19, 120 mg, 0 23 mmol) in THF (5 mL) and the reaction was stirred at ambient temperature for 24 h. The volatiles were removed by evaporation under reduced pressure, the residue dissolved in water and acidified to pH 2 0 and then extracted into EtOAc (3 x 10 mL) The volatiles were removed by evaporation under reduced pressure to afford the title compound (110 mg, 100%) as a white solid (Formula Removed) 1HNMR 3.07 (dd, 1H), 3.18 (dd, 1H), 3 92 (d, 1H), 4 35 (d, 1H), 4 82 (m, 3H), 5.96 (d, 1H), 5 (m, 5H), 8 67 (d, 1H), 12.40 (s, 1H); MS m/z 482 Example 34: 2-ChIoro-N-[(lR,2R)-l-({r(25)-5-oxotetrahvdrofuran-2-yl]carbonyl)amino)-2,3-dihvdro-lH-inden-2-yl]-6H-thienor2,3-b]pvrrole-5-carboxamide (Formula Removed) DEPEA (180 uL, 1.05 mmol), HOBT (68 mg, 0 5 mmol), (2S)-5-oxotetrahydrofuran-2-carboxyhc acid (CAS Reg. No: [21461-84-7], 0 5 mmol, 65 mg) and EDAC (120 mg, 0.63 mmol) were added to a suspension of N-[(1R,2R)-l-amino-2,3-dihydro-lR-mden-2-yl]-2-chloro-6i/-thieno[2,3-b]pyrrole-5-carboxamide (Method 21, 223 mg, 0.5 mmol) in anhydrous DCM (7 mL). The reaction was stirred at ambient temperature for approximately 16 h. The volatiles were removed by evaporation under reduced pressure, the residue dissolved in EtOAc (5 mL), washed with water (2x5 mL), brine (10 mL) and dried (MgSO4) The volatiles were removed by evaporation under reduced pressure and the residue triturated (EtOAc hexane, 110), collected by filtration, washed with hexane (2x5 mL) and dried to give the title compound (112 mg, 56%) as a brown solid lH NMR 2.15 (m, 1H), 2 43 (m, 3H), 2.91 (dd, 1H), 3.25 (dd, 1H), 4 70 (m, 1H), 4.92 (m, 1H), 5 46 (t, 1H), 7.03 (s, 1H), 7.13 (m, 1H), 7 18 (s, 1H), 7.25 (m, 3H), 8.55 (d, 1H), 8.75 (s, 1H), 11.85 (s, 1H), MS m/z 444, 446 The following examples were made by a similar process to Example 34 using N-[(lR,2R)-l-ammo-2,3-dihydro-lH-mden-2-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide (Method 21) and the appropriate commercially available carboxyhc acid: Example35:2-Chloro-N-[(lR,2R)-l-(formylamino)-23"dihydro-li7-inden-2-yl]-6H- thienor2,3-61Pyrrole-5-carboxamide Example 36: 2-Chloro-N-{(lJR,2R)-l-r(methoxyacetvl)aminol-2,3-dihydro-1H-inden-2- yl}-6/T-thienor2,3-ilPyrrole-5-carboxamide Example 37: N-f(lR,2R)-l-(Acetylamino)-23-dihydro-1H-inden-2-yl]-2.chloro-6H- thienor2,3-&lpvrrole-5-carboxamide Example 38: 2-Chloro-N-{(LR,2S)-l-r(3-methoxyPropanoyl)aminol-2,3-dihydro-lS- inden-2-yl)-6flr-thienor2,3-61Pyrrole-5-carboxamide Example 39: Af-{(LR,22?)-l-r(2-Acetoxyacetyl)aminol-2J-dihydro-LHr-inden-2-vlV2- chloro-6fl-thienor2,3-£lpyrrole-5-carboxainide Example 40: N-((LS,2S)-l-{r(2(5)-2-(tert-ButoxvcarbonyIamino)-2- carbamoylacetyllamino)-2,3-dihydro-lH-inden-2-yl)-2-chloro-6Jy-thieno[2,3-&lPyrrole- 5-carboxamide Example 41: N-(lR,2K)-l-[(2-(^ert-Butoxycarbonylainino)acetylaminol-2,3-dihydro-lH- inden-2-vl)-2-chloro-6Jff-thienor2,3-61Pyrrole-5-carboxamide Example 42: N-i(lR,2R)-l- r2-Carbamoylacetyl)aminol-23-dib.ydro-lH-inden-2-yl]-2-chloro-6H- thienor23^1Pvrrole-5-carboxamide Example 56: N-{(lR,2R)-l-r2-(terf-Butoxycarbonyl)acetylaminol-2,3-dihydro-lHr-inden- 2-yl}-2-chloro-6flr-thienor2,3^1pyrrole-5-carboxamide Example 57: 2-Chloro-N-((lR,2R)-l-{r3-hydroxy-2-(hydroxymethyl)propanoyl]amino}- 2,3-dihydro-LHr-mden-2-vD-6flr-thieno[2,3-b]Pyrrole-5-carboxamide (Formula Removed) inden-2-yH-2-chloro-6/f-thienor2,3-ilPyrrole-5-carboxamide (Formula Removed) N-((15,25)-l-{[(2(S)-2-(ferr-Butoxycarbonylarrmio>2K;arbamoylacetyl]amino}-2,3-Nydro-1H-inden-2-yl)-2-cUorcH6if-trueno[23-b]pyrrole-5-carboxarnide (Example 40, 251 mg, 0 46 mmol) was dissolved in tnfluoroacetic acid (4 mL) and stirred at ambient temperature for 24 hours. The volatiles were evaporated under reduced pressure and the crude matenal was azeotroped with chloroform (3x5 mL) to afford a gum. The gum was tnturated with ether (5 mL), the solid collected by filtration, washed with ether (2x5 mL) and dned to give the tnfluoroacetate salt of the title compound (239 mg, 93%) as a brown solid 1H NMR 2.75 (m, 2H), 2.90 (dd, 1H), 3 23 (dd, 1H), 4.04 (m, 1H), 4.59 (m, 1H), 5.50 (t, 1H), 7 00 (s, 1H), 7 19 (m, 5H), 7 54 (s, 1H), 7 74 (s, 1H), 8 05 (br s, 3H), 8.56 (d, 1H), 8 70 (d, 1H), 11.83 (s, 1H), MS m/z 468, 469. Example 44: N-{(lR,2/f)-l-r(Aniirioacetyl)aminol-2,3-dihydro-l^-ixideri-2-yl}-2-chloro-6H-thienor2,3-ilPyrrole-5-carboxamide (Formula Removed) -{(liS,2iS)-l-[(2-(fert-Butoxycarbonylarmno)acetylamino]-2,3-dihydro-LH-inden-2- 2-chloro-6H-thieno[2,3-fe]pvrrole-5-carboxamide (Example 41; 366 mg, 0 75 mmol) was dissolved in dichloromethane (10 mL) and tnfluoroacetic acid (0.5 mL) was added and the reaction stirred at ambient temperature for 7 hours. The volatiles were evaporated under reduced pressure and the crude solid was azeotroped with chloroform (3x5 mL), triturated with ether (5 mL), collected by filtration, washed with ether (2x5 mL) and dned to give the tnfluoroacetate salt of the title compound (200 mg, 53%) as a brown solid. 'H NMR 2.90 (dd, 1H), 3.21 (m, 1H), 3.65 (m, 2H), 4.59 (m, 1H), 5.51 (t, 1H), 6.99 (s, 1H), 7 19 (m, 5H), 8.08 (br, 3H), 8.58 (d, 1H), 8 84 (d, 1H), MS m/z 389, 391. Example 45 : 2-Chloro-N-[(lR,2R)-l-({r(2-hydroxvethyl)(phenvlmethyl)aminolacetyl} amino)-2,3-dihvdro-lfiT-inden-2-yl)-6H-thienor2,3-61pyrrole-5-carboxamide (Formula Removed) 2-(Benzylamino)ethanol (160 mg, 1 06 mmol) was added to a solution of 2-chloro-N-{(1R,2-4)-l-[(cMoroacetyl)ammo]-2,3-dmydro-lH-inden-2-yl}-6^-thieno[2,3-ft]pyrrole-5-carboxarmde (Method 23, 216 mg, 0.53 mmol) and Et3N (500 uL, 3 60 mmol) in anhydrous THF (5 mL) and the reaction stirred for approximately 16 hours at room temperature then for a further 16 h at 50 °C The volatiles were removed under reduced pressure, the residue dissolved in EtOAc (10 mL), washed with H20 (2 x 10 mL) and dned (MgSO4) The solvent was removed under reduced pressure, the residue tnturated (EtOAc:isohexane, 1:5), collected by filtration, washed with isohexane (10 mL) and dned to give the title compound (100 mg, 36%) as a brown solid XH NMR 2.58 (t, 2H), 2.90 (dd, 1H), 3 09 (dd, 2H), 3 18 (dd, 1H), 3.50 (dd, 2H), 3.68 (dd, 2H), 4 55 (t, 1H), 4 65 (m, 1H), 5.46 (t, 1H), 6.99 (s, 1H), 7.04 (d, 1H), 7.23 (m, 9H), 8.38 (d, 1H), 8 53 (d, 1H), 11 81 (s, IH); MS m/z 523, 525 The following examples were made by the process of Example 45 using 2-chloro-N- lJR,2R)-l-[(cUoroacetyl)airiino]-23-dihydro-lH-mden-2-yl}-6R-thieno[2,3-fe]pyrrole-5-- carboxamide and the appropnate commercially available amine Example 46: 2-Chloro-N-{(lR,2R)-l-r(morpholin-4-vlacetvl)aminol-2,3-dihydro-lff- inden-2-yl>-6flr-thienor2,3-Jlpvrrole-5-carboxamide Example 47: 2-Chloro-N-((LR,2R)-l-({r(2-hvdroxyethyl)(methyl)aminolacetyl>amino)- 2,3-dihvdro-1H-inden-2-vl)-6/f-thienor2,3-ilPyrroIe-5-carboxamide Example 48: N-((lR^27f)-l-({|^is(2-hydroxyethyl)aniinolacetyl)amino)-2,3-dihvdro-lff- inden-2-yl)-2-chloro-6ff-thienor2,3-61Pyrrole-5-carboxamide Example 49: 2-Chloro-N-((lR,2-4)-l-({rethyl(2-hydroxvethyl)aminolacetyl}amino)-2,3- dihydro-ltT-inden-2-yl)-6f?-thienor2,3-61pyrrole-5-carboxamide Example 50: 2-Chloro-AT-((lR,2R)-l-({r(2,3- dihydroxypropyl)(methyl)aminolacetyl)amino)-2v3-dihydro-LHr-inden-2-vl)-6/f- thienor2,3-61PVrrole-5-carboxamide Example 51: ^V-((lJ?,2R)-l-({rBis(2-hydroxyPropvl)arm^olacetyl>amino)-23-dihydro-li/- inden-2-vl)-2-chloro-6flr-thienof2,3-61pyrrole-5-carboxamide (Formula Removed) Example52: N-{(lR,2R)-l-r(2-Ajnmo-2-oxoethyl)aminol-2,3-dihydro-lff-iiiden-2-yl}-2- ^nloro-6ff-thienor2,3-61pyrroIe-5-carboxamide (Formula Removed) {(lR,2R)-l-Amino-2,3-dihydro-l^-mden-2-yl}-2-chloro-6^-thieno[2,3-b]pyrrol-5-yl)-2-carboxamide tnfluoroacetic acid salt (Method 21, 225 mg, 0.5 mmol), DIPEA (216 uJL, 1 5 mmol) and bromoacetamide (70 mg, 0 5 mmol) heated in a microwave at 180°C for 3 mins EtOAc (30 mL) was added and the mixture washed with water (2 x 10 mL), bnne (10 mL), dned (MgSO4) and evaporated The residue was purified by column chromatography (EtOAc:MeOH 19:1) to afford the title compound (52 mg, 27%) as a white foam 'HNMR 2.68 (s, 1H), 2.79 (dd, 1H), 3 24 (m, 3H), 4 21 (m, 1H), 4.41 (m, 1H), 7 02 (m, 2H), 7 14 (s, 1H), 7.21 (m, 3H), 7.28 (m, 1H), 7 36 (m, 1H), 8 42 (d, 1H), 11 83 (s, 1H), MS m/z 389,391 Example 53: N-(lR,2R)a4(tert-Butoxycarbonylmethyl)aminol-2,3-dihydro-lH-inden-2-yl}-2-chloro-6H-thienor2,3-&lpyrrole-5-carboxarnide (Formula Removed) DIPEA (350 µL, 2.0 mmol) and r-butyl bromoacetate (90 µL, 0.7 mmol) were added to a solution of N-{(lR,2R)-l-ammo-2,3-dihydro-1H-inden-2-yl}-2-chloro-6flr-thieno[2,3-b]pyrrol-5-yl)-2-carboxamide (Method 21, 300 mg, 0.7 mmol) in CH3CN (10 mL) The resulting suspension was stirred at 60°C for approximately 2 h. Upon cooling the volables were removed by evaporation under reduced pressure, the residue dissolved in EtOAc (10 mL), washed with water (2 x 10 mL), bnne (10 mL) and dried (MgSC1-4). The volatiles were removed by evaporation under reduced pressure and die residue purified by column chromatography (EtOAc:isohexane 1.1) to afford the title compound (30 mg, 10%) as a white Aid. 1H NMR 1.45 (s, 9H), 2.11 (br s, 1H), 2.80 (dd, 1H), 3 60 (m, 3H), 4.27 (d, 1H), 4.46 (m, 1H), 6.8 (d, 2H), 7.10 (d, 1H), 7.30 (m, 4H), 11.35 (s, 1H), MS m/z 446, 448. Example54: N-{(lR,2R)-l-(Carboxymethylamino)-2,3-dihvdro-1H-inden-2-yl}-2-chloro-6H-thieno(3,2,b]pyrro]e-5-carboxarnide (Formula Removed) N-4(lH,2J0-H(tert-Butoxycarbonymiemyl)ammo]-2,3-d thieno[2,3-fe]pvrrole-5-carboxamide (Example 53, 100 mg, 0 22 mmol), dissolved in DCM (5mL). TFA (1 mL) added and the reaction stirred at ambient temperature for 20 hours. Evaporation under reduced pressure, co-evaporation with CHCI3 (2 x 10 mL) and drying gave the tnfluoroacetic acid salt of the title compound (110 mg, 99%) as a grey powder. JH NMR 3 1 (dd, 1H), 3.52 (dd, 1H), 4 2 (m, 2H), 4 9 (m, 2H), 7.05 (s, 1H), 7.2 (s, 1H), 7 4 (m, 3H), 7.7 (d, 1H), 8.76 (d, 1H), 9.73 (s, 2H), 12.02 (s, 1H), 13.9 (s, 1H); MS m/z (M-H)" 388,390 Example 58: 2-Chloro-N-{(lR,2R)-l-r(hydroxyacetvlaminol-2,3-dihvdro-LN-inden-2-ylj-6H-thienor2,3-61pvrrole-5-carboxamide (Formula Removed) N-{(lR,2R)-l-[(2-Acetoxyacetyl)amlno]-2)3-dlhydro-lJf/-lnden-2-yl}-2-cllloro-6JH,-tiueno[2,3-b]pyrrole-5-carboxamide (Example 39; 393 mg, 0.92 mmol) was dissolved in THF (5 mL), MeOH (5 mL) and K2CO3 (50 mg) were then added and the suspension stirred at ambient temperature for 4 hours. Water (10 mL) was added and the aqueous phase was extracted with EtOAc (3 x 10 mL) The combined orgamc phases were washed with water (50 mL), bnne (50 mL) and dned (MgSO4) The solvent was removed by evaporation under -•educed pressure, the crude product was triturated (EtOAcisohexane, 1:5), filtered, washed with isohexane (5 mL) and dned to give the title compound (257 mg, 72%) as a white solid LHNMR 2.86 (dd, 1H), 3.23 (dd, 1H), 3.88 (dd, 2H), 4 70 (m, 1H), 5.39 (t, 1H), 5 50 (t, 1H), 7.00 (s, 1H), 7.18 (m, 5H), 8.10 (d, 1H), 8.51 (d, 1H), 11 81 (s, 1H); MS m/z 391, 393 Example 59: 23-Dichloro-N-{(lR,2R)-l-r(chloroacetyl)arninol-2,3-dihydro-1H-inden-2-yl}-4H-thieno[3,2-ftlpyrrole-5-carboxaniide (Formula Removed) N-[(lR,2R)-l-Amino-2,3-dihydro-lH-inden-2-yl]-2,3-dichloro-4R-thieno[3,2-b]pyrrole-5-carboxamide (Method 8, 602 mg, 1 6 mmol) was dissolved in dichloromethane (30 mL), to this was added tnethylanune (0.25 mL, 1 8 mmol) and chloroacetyl chlonde (0 14 mL, 1.8 mmol) The solution was stirred at ambient temperature for 16 hours, after which triethylamrae (0.25ml, 1.8mmol) and chloroacetyl chlonde (0.14ml, 1 8mmol) were added before staring for 1 hour To the resulting slurry, water (15 mL) was added before filtenng to give the title product (532 mg, 73%) as a cream solid. JH NMR 2.88 (m, 1H), 3.25 (m, 1H), 4.11 (s, 2H), 4 63 (m, 1H), 5.47 (t, 1H), 7 13 (m, 2H), 7.23 (m, 3H), 8.63 (d, 1H), 8.73 (d, 1H), 12 38 (s, 1H); MS m/z 442 Example 60: N-{(lR,2K)-l-r((35)-3-Amino-3-carboxvpropanovl)aminol-2,3-dihvdro-lH-inden-2-yl}-2,3-dichloro-4H-thieno(3,2-b]pyrrole-5-carboxamide (Formula Removed) N-[(lR,2R)-l-Arriino-2,3-dihydro-m-inden-2-yl]-2,3-dichloro-4H-thieno[3,2- lpyrrole-5-carboxamide (Method 8, 350 mg, 0 73 mmol) was added to a solution of N- alpha-t-Boc-L^aspaxtic acid alpha-t- butyl ester (232 mg, 0 80 mmol), 1-hydroxybenzotnazole monohydrate (123 mg, 0.80 mmol), l-ethyl-3-(3-dimethylaminopropyl)carbodumide hydrochloride (154 mg, 0.80 mmol), 4-methylmorpholine (0.18 mL, 1.6 mmol) in N,N- dimethylformamide (20 mL). The mixture was stirred at ambient temperature for 16 hours The volatiles were removed by evaporation and the residue was dissolved in ethyl acetate (20 mL) and water (10 mL), the layers were separated before washing with 2MHC1 then saturated NaHCO3 Evaporation afforded a white solid which was redissolved in dichloromethane (5 mL) and tnfmoroacetic acid (5 mL), the solution was allowed to stir at ambient temperature for 2 hours The volatiles were removed by evaporation and the residue triturated with ether, collected by filtration, washed with ether (2x10 ml) and dried to give the title compound (210 mg, 48%) as a white solid 1HNMR 2.85 (m, 2H), 3.25 (m, 2H), 3 94 (t, 1H), 4 56 (m, 1H), 5.45 (t, 1H), 7 11 (s, 1H), 7 23 (m, 4H), 8 64 (d, 1H), 8.73 (d, 1H), MS m/z 481. The following examples were prepared in a similar manner to Example 60 using N-[(lR,2R)-l-amino-2,3-dmydro-lH-inden-2-yl]-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide (Method 8) or N-{(lR,2R)-l-amino-2,3-dihydro-lH-inden-2-yl}-2-chloro-6H-thieno[2,3-b]pyrrol-5-yl)-2-carboxamide (Method 21) as the amine component and the appropriately protected carboxyhc acid as starting material, prior to deprotecuon. Example 61: N-{(LR,2-4)-l-r(2-Carboxvacetvl)aminol-2-4-dihvdro-Lff-inden-2-vH-2,3-dichloro-4H-thieno(3,2,b]pyrrole-5-carboxamide (Formula Removed) :HNMR 2 84 (m, 1H), 3.25 (m, 3H), 4 56 (m, 1H), 5 47 (t, 1H), 7.11 (s, 1H), 7.20 (m, 4H), 8 59 (m, 1H), 12.36 (s, 1H); MS m/z 452 Example62:N-{(1R,2R)-l-[(2-Carboxyacetyl)aminol-2,3-dihydro-1H-inden-2-yl}-2- chloro-6H-thieno(3,2,b]pyrroIe-5-carboxamide Example 63: N-{(lR,2R)-l-[((3S)-3-Amino-3-carboxypropanoyl)aminol-2,3-dihydro-1H- inden-2-yl}-2-chloro-6R-thieno(3,2-4b]pyrrole-5-carboxamide (Formula Removed) Example 64: 2,3-Dichloro-N-{(1R,2R)-l-[(methylsulfonyl)aminol-2,3-dihydro-lH-inden-2-yl}-4H-thieno[3,2-b]pyirole-5-carboxamide (Formula Removed) N-[(lR,2R-l-Amino-2,3-dihydro-lH-mderi-2-yl]-2,3-dichloro-4R-th]eno[3,2-b]pyrrole-5-carboxamide tnfluoroacetate salt (Method 8, 223 mg, 0.5 mmol) was dissolved in THF (4 mL) and the solution cooled to 0 °C. Et3N (223 µL, 1.6 mmol) then methanesulfonyl chlonde (43 µX,, 0 55 mmol) were added and the reaction was stirred 0 °C for 5 mins. Saturated aqueous NaHCO3 (5 mL) was added, the phases separated and the aqueous phase extracted with EtOAc (3 x 10 mL) The combined organic fractions were washed with H2O (20 mL), dned (MgSO4) and the solvent removed under reduced pressure. The residue was bjected to purification by reverse phase preparative HPLC to afford the title compound (30 mg, 15%) as a white solid 1H NMR 2.83 (dd, 1H), 2.98 (s, 3H), 3.22 (dd, 1H), 4 55 (m ,1H), 4 96 (t, 1H), 7.01 (s, 1H), 7.23 (m, 5H), 7 87 (d, 1H), 8.57 (d, 1H), 11 90 (s, 1H), MS m/z 410, 412. Method 1 3-Chloro-5-methoxvcarbonyl-4H-thieno[3,2-61pyrrole (Formula Removed) Methanohc sodium methoxide solution (28%) (5 ml, 25.9 mmol) was diluted with MeOH (5 ml) and was cooled to -25°C under nitrogen. A solution of 4-chloro-2-thiophenecarboxaldehyde (J Heterocyclic Chem, 1976, 13, 393; 1.1 g, 7.5 mmol) and methyl azidoacetate (3.0 g, 26 1 mmol) in MeOH (20 ml) was added dropwise, maintaining the temperature at -25°C On completion of addition the solution was allowed to warm to 5°C over a period of approximately 16 hours The solution was added to saturated aqueous ammonium chloride (250 ml) and the mixture was extracted using DCM. The combined organic layers were concentrated at 0°C The residue was taken up in xylene (30 ml) and this solution was added dropwise to xylene (120 ml) under reflux The solution was heated under reflux for 30 minutes before being cooled and concentrated. The title compound was purified by a mixture of crystallisation (EtOAc/isohexane) and chromatography on a Bond Elut column elutmg with a graduated solvent of 5-50% EtOAc in isohexane (640 mg, 40%). NMR (CDC13) 9 1 (1H, br), 7 1 (2H, s), 3 9 (3H, s), m/z 214.3. Method 2 and 2a The following compounds were made by the process of Method 1 using the appropriate starting materials Method 2. 2,3-Dichloro-5-memoxycarbonyl-4H-thieno[3,2-b]rrole Method 2a: : 2-Chloro-5-methoxvcarbonyl-6H-thieno[2,3-blpyrrole (Formula Removed) 1 Aldehyde: DE 2814798 2 Aldehyde: Gronowitz et al. Tetrahedron Vol 32 1976 p 1403 Method 3 5-Carboxy-3-chloro-4H-thieno[3,2-b]pvrrole (Formula Removed) 3-Chloro-5-methoxycarbonyl-4H-thieno[3,2-b]pyrrole (Method 1, 0 61 g, 2 83 mmol) was taken up in MeOH (10 ml) and was heated under reflux. Aqueous lithium hydroxide (2 0 M, 3 0 ml, 6.0 mmol) was added portionwise over 45 minutes. The mixture was heated under reflux for 30 minutes before being cooled and concentrated Water (20 ml) was added and the solution was neutralised using aqueous hydrochloric acid (2.0 M, 3.0 ml). The solution was extracted using EtOAc, and the combined organic layers were concentrated to afford the title compound as a yellow solid (0 57 g, 100%). NMR. 12.4 (1H, br), 7.4 (1H, s), 7.0 (1H, s), m/z 200.3 Method 4 and 4a The following compounds were made by the process of Method 3 using Methods 2 and 2a as starting materials Method 4. 5-Carboxy-2,3-dichloro-4H-thieno[3,2-b]pyrrole Method 4a. 5-Carboxy-2-chloro-6H-thieno[2,3-b]pyrrole (Formula Removed) Method 5 C1s-1 -[(1,l-Dimethylethoxy)carbonylaminol-2 hydroxyindan (Formula Removed) C1s-l-Amino-2-hydroxyindan (12 Og, 80 5mmol) was dissolved in DCM (500 ml) and taethylamine (22.4 ml, 161mmol). D1-tert-butyl dicarbonate (22 Og, lOOmmol) in DCM (50 ml) was added and the mixture stirred at room temperature for 20 hours then evaporated. EtOAc (200 ml) was added, the solution washed with water, dried over magnesium sulphate and evaporated. The crude product was purified by chromatography on silica with 4 1 iso-hexane:EtOAc as eluent to give the title compound (17.9 g, 90%) as a white solid 'H NMR 1.42 (s, 9H), 2.78 (dd, 1H), 3 00 (dd, 1H), 4.40 (m, 1H), 4.85 (m, 1H), 4.95 (m, 1H), 6 30(d, lH),7.10(m,4H). Method 6 Trans-2- Ammo-1 - \( 1,1 -drmethylethoxy)carbonylarrunolmdan (Formula Removed) Dimethylemoxy)carbonylamino]-2-hydroxymdan (Method 5, 14.0g, 56 2mmol) was dissolved in DCM (200 ml) and tnethylamine (11.8 ml, 84.3mmol). Methanesulfonyl chloride (7.1g, 61.9mmol) dissolved in DCM (20 ml) was added and the mixture stirred at room temperature for 3 hours. The mixture was evaporated and EtOAc (250 ml) added After washing with water and drying over magnesium sulphate the organic solution was evaporated to yield C1S-l-[(l,l-dimethylethoxy)carbonylarmno]-2- methanesulphonyloxyindan (9.7g, 98%) as a white solid 1HNMR 1.45 (s, 9H), 3 15 (m, 2H), 3 18 (s, 3H), 5 20 (m, 1H), 5.35 (m, 1H), 7 15 (m, 4H), 7 45 (d, IH). C1s-1 -[(1,1 -dimethylethoxy)carbonylamino]-2-methanesulphonyloxyindan (18.1 g, 55 3mmol) was dissolved in dry dimethyl acetamide (100 ml). Sodium azide (5 4g, 830mmol) was added and the mixture heated to 90°C for 6 hours. The reaction was cooled, diluted with ethyl acetate (150 ml), washed with water (6 x 200 ml) and dried over magnesium sulphate. 10% Palladium on activated carbon was added and the mixture stirred under a hydrogen atmosphere for 24 hours Filtration through celite followed by evaporation gave the title compound (2 6g, 98%) as a white solid 1H NMR: 1.45 (s, 9H), 2.50 (dd, 1H), 3 05 (dd, 1H), 3.30 (m, 3H), 4.55 (m, 1H), 7 1 (m, 5H). Method 7 2,3-Dichloro-5-(N-{(lR,2K)-l-[N-(l,l-dimethylethoxy)carbonylaminolindan-2-yl}carbamoyl)-4R-thieno[3,2-b]pvrrole (Formula Removed) 5-Carboxy-2,3-dichloro-4H-thieno[3,2-b]pyrrole (Method 4; 2 36g, 100mmol), trans-2-amino-l-{N-[(l,l-dimethylethoxy)]carbonylarmno}indan (Method 6, 2.5g, l0.0mmol), DIPEA (1.7 ml, l0.0mmol) and HOBT (1 35g, 100mmol) was stirred in DCM (75 ml) at room temperature for 2 minutes EDCI (2.4g, 12.5mmol) was added and the mixture stirred at room temperature for 20 hours during which time the product precipitated The reaction was filtered, washed with DCM (2 x 25 ml) and dned to give the title compound (3 7 g, 80%) as a file green powder. 1H NMR 1.40 (s, 9H), 2.81 (dd, 1H), 3 20 (dd, 1H), 4 55 (m, 1H), 5 15 (m, 1H), 7 15 (m, 5H), 7 35 (d, 1H), 8.55 (d, 1H), 12.36 (broad s, 1H); m/z 463 7/465-7 Method 8 N-[(lR,2R)-Amino-2,3-dmydro-1H-mden-2-yl]-2,3-dichloro-4H-tmeno[3,2-b]pyrrole-5-carboxamide (Formula Removed) 2,3-Dichloro-5-(N-{l-[(l)l-dimethylethoxy)carbonylarmno]mdan-2-yl}carbamoyl)-4H-thieno[3,2-b]pyrrole (Method 7, 3 7g, 7 9mmol) was dissolved in DCM (75 ml) Trifluoroacetic acid (10 ml) was added and the mixture stirred at room temperature for 24 hours. The reaction was filtered and the isolated solid washed with DCM to give the tnfluoroacetic acid salt of the tide compound (3.1g, 82%) as a pale green powder. 1H NMR 3.05 (dd, 1H), 3.42 (d, 1H), 4 7 (m, 2H), 7 20(d, 1H), 7.35 (m, 3H), 7.55 (d, 1H), 8.60 (broad s, 3H), 8.80 (d, 1H), 12 5 (broad s, 1H) Method 9 N-[(1S,2S)-l-Armno-2,3-dihydro-1H-mden-2-yl]-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide (Formula Removed) The tide compound was prepared in an analogous fashion to Method 8. 1H NMR 3.05 (dd, 1H), 3 42 (d, 1H), 4 7 (m, 2H), 7 20(d, 1H), 7 35 (m, 3H), 7 55 (d, 1H), 8 60 (broad s, 3H), 8.80 (d, 1H), 12 5 (broad s, IH) Method 10 2,3-Dichloro-N-{(1R,2R)-l-r(chloroacetyl)(methyl)amino]2,3-dihydro-lH-mden-2-yl}-4H- thieno[3,2-b]pyrrole-5-carboxamide (Formula Removed) 2,3-Dichloro-N-[(1R,2-4)-l-(methylamino)-2,3-dihydro-m-mden-2-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide (Method 11, 300 mg, 0 79 mmol) and tnethylamme (167 µL, 1 2 mmol) was dissolved in DCM (5 mL), chloroacetyl chlonde (73 µL, 0.9 mmol) added and the reaction stirred at ambient temperature for 2 hours The volatiles were removed by evaporation under reduced pressure and EtOAc (15 mL) added The mixture was washed with water (10 mL), brine (10 ml), dried (MgSO4) and the volatiles were removed by evaporation under reduced pressure to give the title compound (310 mg, 86%) as a pale brown foam lH NMR 2.73 (d, 3H), 2.98 (m, 1H), 3.24 (m, 1H), 4 45 (m, 2H), 4 82 (m, 1H), 5 77 (dd, 1H), 7.05 (m, 2H), 7.28 (m, 3H), 8 65 (m, 1H); MS m/z 456. Method 11 23-Dichloro-W'-r(lR,2JR)-l-(methylamino)-2,3-dihydro-1H-inden-2-yll-477-thieno[3,2-Z?lpyrrole-5-carboxamide ^rr-Butyl((lR,2R)-2-{[(2,3-dichloro-4H-thieno[3,2-b]pyrrol-5-yl)carbonyl]ammo}-2,3-dihydro-1H-mden-l-yl)methylcarbamate (Method 12, 900 mg, 1.87 mmol) was dissolved in DCM (20 mL), TFA (2 mL) added and the reaction stirred at ambient temperature for 1 hour. The volatiles were removed by evaporation under reduced pressure and the residue purified by ion exchange chromatography (MeOH'Water 1 1 then MeOH:Water NH4OH 1.1.0 05) to afford, after evaporation, the title compound (300 mg, 32%) as an off white powder (Formula Removed) 1H NMR 2.75 (s, 3H), 3.01 (dd, 1H), 3 49 (dd, 1H), 4.75 (m, 1H), 4.86 (m, 1H), 7 11 (d, 1H), 35 (m, 3H), 7 58 (d, 1H), 8.74 (d, 1H), 9 04 (m, 1H), 12.37 (s, 1H); MS m/z 380 Method 12 tert-Butyl((1R,2R)-2-{[(2,3-dichloro-4H-thieno[3,2-b]pyrrol-5-yl)carbonyllarnino}-2,3-dihydro-lH-mden-1-yl)methylcarbamate (Formula Removed) 5-Carboxy-2,3-dichloro-4H-thieno[3,2-b]pyrrole (Method 4, 472 mg, 2 0 mmol), tert-butyl [(lR,2R)-2-ammo-2,3-dmydro-1H-inden-l-yl]memylcarbamate (Method 13, 524 mg, 2 0 mmol), DIPEA (348 µL, 2 0 mmol), HOBT (270 mg, 2 0 mmol) and EDCI (480 mg, 2 5 mmol) were dissolved in DCM (10 mL) and stirred at ambient temperature for 20 hours The volatiles were removed by evaporation under reduced pressure, the residue dissolved in EtOAc (50 mL), washed with water (3 x 25 mL), brine (25 mL) and dried (MgSO4). The volatiles were removed by evaporation under reduced pressure to give the title compound (900 mg, 93%) as a pale brown foam. 1H NMR 1.29 (m, 9H), 2.66 (s, 3H), 2 9-3 25 (m, 2H), 4.8 (m, 1H), 5 64 (m, 1H), 6 23-7 34 (m, 4H), 8 65 (m, 1H), MS m/z 480 Method 13 terf-Butyl r(1R,2R)-2-amino-2,3-dihydro-li/-inden-l-vllmethylcarbamate (Formula Removed) (lR,2lS)-l-[(rerf-Butoxycarbonyl)(methyl)amino]-2,3-dihydro-l^-inden-2-yl methanesulfonate (Method 14, 3 Og, 8 8mmol) and sodium azide (2 3 g, 35.2 mmol) in dry DMA (30 mL) was heated to 90°C for 7 hours The reaction was cooled and ethyl acetate (100 mL) added. The mixture was washed with water (6 x 25 mL), bnne (50 mL) and dried (MgSd) 10% Palladium on carbon (400 mg) was added to the organic solution which was stirred under a hydrogen atmosphere for 4h, filtered through Cekte and evaporated The residue was purified by column chromatography (EtOAc and then DCM:MeOH 9.1) to afford die title compound (1.2 g, 55%) as a pale brown oil. 1H NMR 1.45 (m, 9H), 2.6 (s, 3H), 2.8 (m, 1H), 3.3 (m, 1H), 4.45 (m, 1H), 5.55 (dd, 1H), 7 26 (m, 4H), MS m/z 264. Method 14 (lR,2S)-l-[(tert-Butoxycarbonyl)(methyl)aminol-2,3-dihydro-lH-inden-2-yl methanesulfonate (Formula Removed) tert-Butyl [(lR,21S)-2-hydroxy-2,3-dihydro-lR-mden-l-yl]methylcarbamate (Method 15, 3.0 g, 11 4 mmol) was dissolved in dry THF (40 mL) at 10°C A solution of methane sulphonyl chloride (1.44 g, 12 55 mmol) in dry THF (10 mL) was added, the reaction allowed to warm to ambient temperature and stirred for 30 mins. The volatiles were removed by evaporation under reduced pressure and ethyl acetate (100 mL) added The mixture was washed with water (2 x 50 mL), brine (50 mL) and the organic phase was dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (EtOAc:Hexane) to afford the title compound (3.1g, 80%)as a colourless syrup 'H NMR 1.46 (s, 9H), 2.61 (s, 3H), 3.12 (m, 1H), 3.18 (s, 3H), 3 32 (m, 1H), 5 45 (m, 1H), 5 68 (m, 1H), 7.28 (m, 4H); MS m/z 342 Method 15 tert-Butyl r(lR,21Sr)-2-hydroxy-2,3-dihydro-lff-inden-l-yllmethylcarbamate (Formula Removed) tert-Butyl methyl[(12?,25)-2-(tetrahydro-2H-pyran-2-yloxy)-2,3-dihydro-lR-inden-1 -yl]carbamate (Method 16, 4.0 g, 11.5 mmol) was dissolved in methanol (50 mL), 4-toluene sulphomc acid added and the reaction stirred at ambient temperature for 2 hours. Saturated NaHCO3 (50 mL), water (100 mL) was added and ethyl acetate (100 mL) was added and the mixture stirred for 30 mms The organic phase was separated, washed with water (50 mL), brine (50 mL) and dried (MgSO4). The volatiles were removed by evaporation under reduced pressure to give the title compound (3.0 g, 99%) as an oil 1HNMR 1 45 (s, 9H), 2 6 (s, 3H), 2.75 (m, 1H), 3 05 (m, 1H), 4.5 (m, 1H), 5.05 (m, 1H), 5 34 (m, 1H), 7.03-7.3 (m, 4H). Method 16 tert-Butyl methyl [(lR,2S)-2-(tetrahvdro-2H-pyran-2-yloxy)-2,3-dihydro-lR-inden-l-yl] carbamate (Formula Removed) tert-Butyl[(1R,2-4)-2-(tetrahydro-2H-pyran-2-yloxy)-2,3-dihydro-1H-inden-l-yl]carbamate (Method 17, 4.0 g, 12.0 mmol) was dissolved in dry DMA (25 mL) at 5°C 60% Sodium hydride (575 mg, 14.4 mmol) was added, the reaction stirred at 5°C for 30 mms, allowed to warm to ambient temperature and stirred for a further 30 mms Methyl iodide (896 µL, 14.4 mmol) was added and the reaction stirred at ambient temperature for 3 hours The reaction was poured into water (100 mL) and extracted with ethyl acetate (2 x 50ml) The organic extracts were washed with waiter (6 x 25 mL), brine (50 mL) and dried (MgSO4) The volatiles were removed by evaporation under reduced pressure to give the title compound (4 1 g, 97%) as an oil. 1HNMR 1.4-1 9 (m, 6H), 1.5 (s, 9H), 2.7 (dd, 3H), 2.85-3.3 (m, 2H), 3.5 (m, 1H), 3.7-4 0 (m, 1H), 4 6-4.9 (m, 2H), 5.5-5.85 (m, 1H), 7 2 (s, 4H) Method 17 tert-Butyl [(lR,2S)-2-(tetrahydro-2H-pyran-2-yloxy)-2,3-dihydro-lH-mden-l-yl]carbamate (Formula Removed) tert-Butyl [(1R,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl]carbamate (Method 15, 7 0 g, 28.1 mmol) and 3,4-dihydro-2H-pyran (4 7 g, 56 2 mmol) dissolved in DCM (50 mL) 4-Toluene sulphonic acid pyndrmum salt (100 mg) was added and the reaction stirred for 4 hours at ambient temperature. The reaction was diluted with ethyl acetate (100 mL), washed with water (2 x 50 mL), bnne (50 mL) and dried (MgSO4). The volatiles were removed by evaporation under reduced pressure to give the title compound (8 9 g, 95%) as an oil. 1HNMR 1 25-1.85 (m, 6H), 1 45 (s, 9H), 2 85-3.1 (m, 2H), 3.4 (m, 1H), 3.8 (m, 1H), 4.35-5.1 (m, 3H), 6.8 (dd, 1H), 7 2(s, 1H). Method 18 1,1-Drmethylethyl racetyl((lR,2R)-2- {[(2,3-dichloro-4H-thieno[3,2-b]pyrrol-5-yl)carbonyll amino} -2,3-dihydro-1H-inden-1-yl)ammol acetate (Formula Removed) Acetyl chloride (7 uL, 0.1 mmol) was added to a solution of N-(lR,2R)-l-[(^ert-butoxycarbonylmemyl)arnino]-2,3-dihydro-l-mden-2-yl}-2,3-dichloro-4H-thieno[3,2-&]pyrrole-5-carboxamide (Example 29, 50 mg, 0 1 mmol) in THF (5 mL) The reaction was stirred at ambient temperature for 1 h. The volatiles were removed by evaporation under reduced pressure, the residue dissolved in EtOAc (5 mL), washed with water (2x5 mL), bnne (10 mL) and dned (MgSCU). The volatiles were removed by evaporation under reduced pressure and the residue purified by column chromatography (EtOAc isohexane 1-1) to afford the title compound (168 mg, 76%) as a white solid JH NMR 1 40 (s, 9H), 2 75 (dd, 1H), 3.42 (m, 2H), 3.60 (dd, 1H), 3 90 (s, 3H), 4 15 (d, 1H), 4.45 (m, 1H), 6.83 (d, 1H), 7.20 (m, 4H), 7 70 (d, 1H), 9.70 (s, 1H), MS m/z 522. Method 19 [[(Acetyloxy)acetyll((lR,2R)-2-([(2,3-dichloro-4H-thieno[3,2-b]pyrrol-5-yl)carbonyllammo)-2,3-dihydro-1H-mden-l-yl)aminolacetic acid (Formula Removed) TFA (3 mL) was added to a solution of 1,1-dimethylethyl [[(acetyloxy)acetyl]((lR,2R)-2- {[(2,3-dichloro-4H-thieno[3,2-b]yrrol-5-yl)carbonyl]amino} -2,3-dihydro-lH-inden-l-yl)amino]acetate (Method 20, 130 mg, 0 25 mmol) in DCM (10 mL) and the reaction was stirred at ambient temperature for 2 h. The volatiles were removed by evaporation under reduced pressure to afford the title compound (130 mg, 99%) as a white solid. 1HNMR 2.20 (s, 3H), 2 78 (dd, 1H), 3 32 (dd, 1H), 3 97 (m, 2H), 4.35 (d, 1H), 4 68 (m, 2H), 4 90 (d, 1H), 6.42 (d, 1H), 6.83 (s, 1H), 7 25 (m, 4H), 11.14, (s, 1H); MS m/z 524 Method 20 l,l-Dimemylemyl[r(acetyloxy)acetyll((lR,2R)-2-{r(2,3-dichloro-4H-thieno[3,2-ftlpyrrol-5-yl)carbonyn amino) -2,3-dihydro- lH-inden-1-yl)aminol acetate (Formula Removed) Acetoxyacetic acid (34 mg, 0.3 mmol) and DMTMM (81 mg, 0.3 mmol) were added to a solution of N-(lR,2-4)-l-[(rert-butoxycarbonylmethyl)amino]-2,3-dihydro-1H-mden-2-yl}-2,3-dichloro-4^-thieno[3,2-6]pyrrole-5-carboxarmde (Example 29,140 mg, 0 3 mmol) in THF (10 mL) The reaction was stirred at ambient temperature for 7 h The volatiles were removed by evaporation under reduced pressure, the residue dissolved in EtOAc (10 mL), washed with water (2x5 mL), bnne (10 mL) and dried (MgSO4) The volatiles were removed by evaporation under reduced pressure to afford the title compound (145 mg, 83%) as a white solid 1H NMR 1.45 (s, 9H), 2.10 (s, 3H), 2.75 (dd, 1H), 3.50 (m, 3H), 3.90 (m, 2H), 4 15 (d, 1H), 4 50 (m, 1H), 6.83 (s, 1H), 7.20 (m, 4H), 7.70 (d, 1H), 9 70 (s, 1H); MS m/z 580 Method 21 N-(lR,2R)-l-Armno-2,3-dihydro-lR-inden-2-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide (Formula Removed) tert-Butyl ((lR,2R)-2-{ [(2-CWoro-6H-thieno[2,3-fr]pyrrol-5-yl)carbonyl]arriino}-2,3-dihydro-lH-inden-l-yl)carbamate (Method 22, 10 6 g, 24 5 mmol) was suspended in DCM (200 mL), TFA (20 mL) added and the reaction stirred at ambient temperature for 20 hours The volatiles were removed by evaporation under reduced pressure and the residue tnturated with DCM (50 mL) then filtered and dried to give the title compound (10.9 g, 100 %) as the tnfluoroacetic acid salt. 1H NMR 3.03 (dd, 1H), 3.38 (dd, 1H), 4 7 (m, 2H), 7 06 (d, 1H), 7 17 (s, 1H), 7.35 (m, 3H), 7 55 (m, 1H), 8 55 (s, 3H), 8.68 (d, 1H), 11 9 (s, 1H), MS m/z (M-NH3)+315, 317. Method 22 rerr-Butyl((lR,2R)-2-{r(2-cWoro-6H-thieno[2,3-61pyrrol-5-yl)carbonyllamino}-2,3-dihydro-1H-mden-1 -yl)carbamate (Formula Removed) 2-Chloro-5-carboxy-6H-thieno[3,2-b]pyrrole (Method 4a, 5.0 g, 25.0 mmol), trans-2-miino-l-[(l,l-dimethylethoxy)carbonylammo]indan (Method 6, 6 25 g, 25.0 mmol), DIPEA (4 35 mL, 25.0 mmol) and HOBT (3.4 g, 25.0 mmol) were dissolved in DCM (200 mL) and stirred for 5 mms. EDCI (6.0 g, 31.0 mmol) was added, the reaction stirred for 24 hours and evaporated under reduced pressure. EtOAc (150 mL) was added and the mixture filtered, washed with water (2 x 200 mL), brine (200 mL), dried (MgSO4) and the volatiles removed by evaporation under reduced pressure to give the title compound (10.6g, 98%) as a brown solid 1H NMR 1 38 (s, 9H), 2 81 (dd, 1H), 3.17 (dd, 1H), 4 56 (m, 1H), 5 14 (m, 1H), 7 01 (s, 1H), 7.16 (m, 5H), 7 32 (d, 1H), 8.47 (d, 1H), 11 82 (s, 1H) Method 23 2-Chloro-N-{(lR,2R)-l-[(chloroacetyl)aminol-2,3-dihydro-1H-mden-2-yl}-6H-thienor2,3- b]pyrrole-5-carboxamide (Formula Removed) Et3N (3 mL, 21.6 mmol) was added to a suspension of N-[(lR,2R)-l-amino-2,3-dihydro-lH-inden-2-yl]-2-chloro-6H-thieno[2,3-t]pyrrole-5-carboxamide (Method 21, 3 11 g, 6.98 mmol) in anhydrous dichloromemane (55 mL) and stirred at ambient temperature for 5 miuntes The suspension was cooled to -78 °C and chloroacetylchlonde (611 uL, 7 68 mmol) was added and die reaction was warmed to 0 °C and starred at this temperature for 3 hours NaHCO3 (50 mL) was added, the phases were separated and the aqueous phase was extracted with THF (2 x 50 mL) The combined organic fractions were washed with water (100 mL), dried (MgSO^ and the solvent removed under reduced pressure The residue was triturated (THF-isohexane, 1:5), collected by filtration, washed with hexane (20 mL) and dried to give the tide compound (1.92 mg, 68%) as a brown solid. 'HNMR2 88 (dd, 1H), 3 24 (dd, 1H), 4 11 (dd, 2H), 4.61 (m, 1H), 5.46 (t, 1H), 6.99 (s, 1H), 7 20 (m ,5H), 8 55 (d, 2H), 8.73 (d, 1H), 11.84 (s, 1H); MS m/z 408, 410. WE CLAIM: 1. Heterocyclic amide derivative having glycogen phosphorylase inhibitory activity of formula (I): (Formula Removed) and pharmaceutically acceptable salts or prodrugs thereof wherein: Z is CH or nitrogen; R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S- ; either one of R6 and R7 is chloro and the other is hydrogen, or both R6 and R7 are chloro; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is independently selected from halo, nitro, cyano, hydroxy, carboxy, carbamoyl, N-C1-4alkylcarbamoyl, N,N-(C1-4alkyl)2carbamoyl, sulphamoyl, N-C1-4alkylsulphamoyl, N,N-(C1-4alkyl)2Sulphamoyl, S(O)bC1-4alkyl (wherein b is 0,1,or 2), C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkanoyloxy, hydroxyC1-4alkyl, fluoromethyl, difluoromethyl, trifluoromethyl and trifluoromethoxy; or, when n is 2, the two R1 groups, together with the carbon atoms of A to which they are attached, may form a 4 to 7 membered ring, optionally containing 1 or 2 heteroatoms independently selected from O, S and N, and optionally being substituted by one or two methyl groups; r is 1 or 2; and when r is 1 the group is a substituent on carbon (2) and when r is 2 (hereby forming a six membered ring) the same group is a substituent on carbon (2) or on carbon (3); Y is -NR2R3 or -OR3; R2 and R3 are independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkanoyl, carbamoyl, C3-7 cycloalkyl (optionally substituted with 1 or 2 hydroxy groups), cyano(C1-4)alkyl, heterocyclyl, aryl, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8, -SObR8 (wherein b is 0,1 or 2) and groups of the formulae B and B': (Formula Removed) wherein y is 0 or 1, t is 0, 1, 2 or 3 and u is 1 or 2; provided that the hydroxy group is not a substituent on the ring carbon adjacent to the ring oxygen; or wherein NR2R3 may form a 4 to 7 membered saturated, partially saturated or unsaturated ring, optionally containing 1, 2 or 3 additional heteroatoms independently selected from N, O and S, wherein any -CH2- may optionally be replaced by -C( =O )-, and any N or S atom may optionally be oxidised to form an N-oxide or SO or SO2 group respectively, and wherein the ring is optionally substituted by 1 or 2 substituents independently selected from halo, cyano, C1-4alkyl, hydroxy, C1-4alkoxy and C1-4 alkylS(O)b- (wherein b is 0, 1 or 2); R8 is independently selected from hydrogen, hydroxy, C1-4alkyl, C2-4alkenyl, C1-4alkoxy, cyano(C1-4)alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -C02(C1-4)alkyl, aryl and aryl(C1-4)alkyl], halo(C1-4)alkyl, dihalo(C1-4)alkyl, trihalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, C1-4alkoxyC1-4alkoxy, C1-4 alkoxyC1-4alkyl, hydroxyC1-4alkoxy, 5- and 6-membered cyclic acetals and mono- and dimethyl derivatives thereof, aryl, heterocyclyl, (heterocyclyl)C1-4alkyl, C3-7cycloalkyl [optionally substituted with 1 or 2 hydroxy groups, C1-4alkyl or -C(O)0 C1-4alkyl], C1-4alkanoyl, C1-4alkyl S(O)b- (wherein b is 0, 1 or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), aryl S(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, I or 2), benzyl S(O)b- (wherein b is 0, 1 or 2), C1-4alkyl S(O)c C1-4alkyl (wherein c is 0, 1 or 2), -N(OH)CHO, -C(=N-OH)NH2, -C( =N-OH)NH C1-4alkyl, -C( =N -OH)N (C1-4alkyl)2, -C( =N-OH)NHC3-6cycloalkyl, -C(=N-OH)N(C3-6cycloalkyl)2, COCOOR9, -C(O)N(R9)(R10), -NHC(O)R9, -C(O)NHS02 (C1-4alkyl), -NHSO2R9, (R9)(R10) NSO2-, -COCH2ORI1, (R9)(RiO)N- and -COOR9, CH2OR9, -CH2COOR9, -CH2OCOR9, -CH2CH(C02R9)OH, -CH2C(O)NR9R10, - (CH2)w CH(NR9R10)CO2R9' (wherein w is 1, 2 or 3), and -(CH2)wCH(NR9R10)CO(NR9'R10') (wherein w is 1, 2 or 3) ; R9, R9', R10 and R10' are independently selected from hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13), C2-4alkenyl, C3-7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups), cyano(C1-4)alkyl, trihaloalkyl, aryl, heterocyclyl, heterocyclyl(C1-4)alkyl, and -C(=O)O(C1-4)alkyl or R9 and R10 together with the nitrogen to which they are attached, and/or R9' and R10' together with the nitrogen to which they are attached, form a 4- to 6-membered ring where the ring is optionally substituted on carbon by 1 or 2 substituents independently selected from oxo, hydroxy, carboxy, halo, nitro, cyano, carbonyl, C1-4alkoxy and heterocyclyl; or the ring may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cyclic acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl; R13 is selected from halo, trihalomethyl, and Cwalkoxy; R11 is independently selected from hydrogen, C1-4alkyl, and hydroxyl C1-4alkyl; or a pharmaceutically acceptable salt or pro-drug thereof; with the proviso that the compound of formula (1) is not: i) 2,3-dichloro-5-(N-{ l-[N-(l,l-dimethylethoxy)carbonylamino ]indan-2- yl }carbamoyl)-4Jf thieno [3 ,2-b Jpyrrole; ii) 5- [N-(l-aminoindan- 2- yl)carbamoyl]- 2,3-dichloro-4H -thieno[3,2-b ] pyrrole iii) 5- [N -(1-acetamidoindan- 2- yl)carbamoyl]- 2,3-dichloro-4H -thieno[3 ,2-b ]pyrrole iv) 2,3-dichloro-5-{N-[1-(methanesulphonamido )indan-2-yl]carbamoyl }-4H-thieno[3 ,2-b Jpyrrole v) 2,3-dichloro- 5-{ N -[l-(methylamino )indan- 2- yl]carbamoyl} -4H -thieno [3 ,2- b]pyrrole; vi) 2,3-dichloro-5- {N-[ l-(methylacetamido )indan- 2- yljcarbamoyl }-4H-thieno[3 ,2-b]pyrrole; vii) 2,3-dichloro- 5- [N-(l-hydroxyindan- 2- yljcarbamoyl]-4H -thieno[3 ,2-b ]pyrrole; viii) 2-chloro- 5- [N-(l-hydroxyindan- 2- yl)carbamoyl-6H -thieno[2,3-b ]pyrrole; ix) 2,3-dichloro- 5- [N-{ 6-fluoro-1 -hydroxyindan- 2- yl)carbamoyl-4H -thieno [3 ,2-b ]pyrrole x) 2,3-dichloro- 5- [N-(l-methoxyindan- 2- yl)carbamoyl-4H-thieno[3 ,2-b ]pyrrole; xi) 2,3-dichloro-5-[N-(1-hydroxy-1,2,3,4-tetrahydronaphth- 2-yl)carbamoyl]-4Hthieno[3,2-b]pyrrole. 2. A compound of the formula (1) as claimed in claim 1, wherein: R2 and R3 are independently selected from hydrogen, hydroxy, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], C3-7cycloalkyl (optionally substituted with 1 or 2 hydroxy groups), cyano(C1-4)alkyl, phenyl,morpholino, morpholinyl, piperidino, piperidyl, pyridyl, pyranyl, pyrrolyl, imidazolyl, thiazolyl, thienyl, thiadiazolyl, piperazinyl, isothiazolidinyl, 1,3,4-triazolyl, tetrazolyl, pyrrolidinyl, thiomorpholino, pyrrolinyl, homopiperazinyl, 3,5-dioxapiperidinyl, pyrimidyl, pyrazinyl,pyridazinyl, pyrazolyl, pyrazolinyl, isoxazolyl, 4-oxopydridyl, 2- oxopyrrolidyl, 4-oxothiazolidyl, furyl, thienyl, oxazolyl, 1,3,4-oxadiazolyl, and 1,2,4-oxadiazolyl, tetrahydrothiopyranyl, 1- oxotetrahydrothiopyranyl, 1,1-dioxotetrahydrothiopyranyl, -COR8 and -SObR8 (wherein b is 0, 1 or 2); R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkoxyC1-4alkoxy, hydroxyC1-4alkoxy, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, C02C1-4alkyl, aryl and aryl(C1-4)alkyl], C2-4alkenyl, C3-7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, dihalo(C1-4)alkyl, trihalo(C1-4)alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, heterocyclyl, heterocyclylC1-4alkyl, aryl, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3-6cycloalkylS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, 1 or 2), benzylS(O)b- wherein b is 0, 1 or 2), C1-4alkylS(O)c(C1-4)alkyl (wherein c is 0, 1 or 2), - CH2CH(NR9R10)CO(NR9R10), -CH2OR9, (R9)(Rio)N-, -COOR9,-CH2COOR9, C(O)N(R9)(R10), -CH2CH(C02R9)OH, -CH2CONR9R10, -CH2CH(NR9R 10)CO2R9 and -CH2OCOR9; R9, R9', R10 and R10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 R13), C3-7cycloalkyl (optionally substituted by 1 or 2 hydroxy groups), C(=O)OtBu, C2-4alkenyl, cyano(C1-4)alkyl and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano); or R9 and R10 together with the nitrogen to which they are attached, and/orR9' and R10' together with the nitrogen to which they are attached, form a 4- to 6-membered ring where the ring is optionally substituted on carbon by 1 or 2 substituents independently selected from oxo, hydroxy, car boxy, halo, nitro, cyano, carbonyl and C1-4alkoxy; or the ring may be optionally substituted on two adjacent carbons by -O-CH2-O- to form a cyclic acetal wherein one or both of the hydrogens of the -O-CH2-O- group may be replaced by a methyl; R13 is selected from halo, trihalomethyl and C1-4alkoxy. 3. A compound of the formula (1) as claimed in claim 1 or claim 2, wherein: R2 and R3 are independently selected from hydrogen, C1-4alkyl [optionally substituted by 1 or 2 R8 groups], -COR8 and-SObR8 (wherein b is 0,1 or 2); R8 is independently selected from hydrogen, hydroxy, C1-4alkoxy, C1- 4alkoxyC1-4alkyl, C1-4alkyl, amino(C1-4)alkyl [optionally substituted on nitrogen by 1 or 2 groups selected from C1-4alkyl, hydroxy(C1-4)alkyl, dihydroxy(C1-4)alkyl, -C02C1-4alkyl, phenyl and aryl(C1-4)alkyl], C2 4alkenyl, C3-7cycloalkyl (optionally substituted by -C(O)OC1-4alkyl), 5- and 6-membered cyclic acetals and mono- and di-methyl derivatives thereof, halo(C1-4)alkyl, trihalo(C1-4)alkyl, hydroxy(C 1-4) alky 1, dihydroxy(C1-4)alkyl, cyano(C1-4)alkyl, furyl (optionally substituted on carbon by 1 or 2 nitro groups), thienyl (optionally substituted on carbon by 1 or 2 nitro groups), morpholino, furyl(C1-4)alkyl (wherein furyl is optionally substituted on carbon by 1 or 2 nitro groups), thienyl(C1-4)alkyl (wherein thienyl is optionally substituted on carbon by 1 or 2 nitro groups), 1,2,4-oxadiazolyl, tetrazolyl, imidazolyl, pyrrolidinyl, piperidyl, pyridyl, tetrahydrofuryl, tetrahydropyranyl, 1-oxo-tetrahydrothiopyranyl, tetrahydrothienyl, phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, cyano, hydroxy and C1-4alkyl), pyrazinyl, piperazinyl, 4-methylpiperazino, C1-4alkylS(O)b- (wherein b is 0, 1 or 2), C3-6cycloalkyIS(O)b- (wherein b is 0, 1 or 2), arylS(O)b- (wherein b is 0, 1 or 2), heterocyclylS(O)b- (wherein b is 0, I or 2 - CH2CH(NR9R10)CO(NR9'Rio), -CH2OR9, (R9)(RiO)N-, -COOR9, -CH2COOR9 , -C(O)N(R9)(Ri0), -CH2CH(C02R9)OH, -CH2CONR9Rio, CH2CH(NR9R10)CO2R9' and-CH2OCOR9; R9, R9', R10 and R10' are independently selected from hydrogen, C1-4alkyl (optionally substituted by 1 or 2 hydroxy groups), C2-4alkenyl, and phenyl (optionally substituted by 1 or 2 groups selected from nitro, halo, hydroxy and cyano); 4. A compound as claimed in any preceding claim wherein Y is NR2R3. 5. A compound as claimed in anyone of claims 1 to 3 wherein Y is OR3. 6. A compound as claimed in any preceding claim wherein R4 and R5 together are -S-C(R6)=C(R7)-. 7. A compound as claimed in anyone of claims 1 to 5 wherein R4 and R5 together are -C(R7)=C(R6)-S-. 8. A compound as claimed in any preceding claim wherein A is phenylene. 9. A compound as claimed in anyone of claims 1 to 7 wherein A is heteroarylene. 10. A compound as claimed in any preceding claim wherein Z is CH. 11. A compound of the formula (1) as claimed in any preceding claim, which is a compound of formula (IB): (Formula Removed) 12. A compound of the formula (1) as claimed in claim 1, which is any one of: 2,3-dichloro-JV-[ (lR,2R)-l-(formylamino )-2,3-dihydro-lH -inden-2- yl]-4H-thieno[3 ,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-( (lR,2R)-l-{ [(methyloxy)acetyl] amino }-2,3-dihydro-LH-inden-2-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-{ (IS ,2S)-1- { [(3 (R)-3-(teri-butoxycarbonylamino )-3-carbamoylpropanoyl] amino }-2,3-dihydro-lH-inden-2-yl)-2,3-dichloro-4H-thieno[3,2-fa ]pyrrole-5-carboxamide; 2,3 dichloro-JV-[(lR,2R)-l-({[(4R)-2,2-dimethyl-5-oxo-l,3-dioxolan-4- yl]acetyl}amino)-2,3-dihydro-lH-inden-2-yl]-4H-thieno[3,2-b]pyrrole-5- carboxamide; 2,3 dichloro-N-[(lR,2R)-l-[(3-methoxypropanoyl)amino]-2,3-dihydro-lH-inden-2-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-{ {lR,2R)-l-[ (2-acetoxyacetyl)amino]- 2,3-dihydro-lH-inden- 2- yl}-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-{ (lR,2R)-l-[ (2-carbamoylacetyl)amino]-2,3-dihydro-lH -inden-2-yl}-2,3-dichloro-4H-thieno[3,2-b]pyrrol-5-carboxamide; 2,3-dichloro-N -{ {lR,2R)-l-[ (trifluoroacetyl)amino]- 2,3-dihydro-lH-inden-2-yl} -4H-thieno[3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-{ (lS,2S)-l-[ (furan-2-ylcarbonyl)amino ]-2,3-dihydro-lH-inden-2-yl }-4H-thieno [3 ,2-b]pyrrole- 5-carboxamide; 2,3-dichloro-N-{ (IS,2S)-l-[(furan-3-ylcarbonyI)amino ]-2,3-dihydro- 1H-inden-2-yl }-4H-thieno[3 ,2-b]pyrrole- 5-carboxamide; 2,3-dichloro-N-{ (IS,2S)-1-[ (3-thienylcarbonyl)amino]-2,3-dihydro- 1H-inden-2-yl }-4H-thieno[3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-{ (IS,2S)-1-{[ (5-nitrofuran-2-yl)carbonyl]amino}-2,3-dihydro-lH-inden-2-yl }-4H-thieno[3,2-b ]pycrole-5-carboxamide; 2,3-dichloro-N-{ (1S,2S)-1 -[ (pyridin-3-ylcarbonyl)amino]-2,3-dihydro-lH-inden-2- yl }-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-[ (IS,2S)-l-( acryloylamino)- 2,3-dihydro-lH-inden-2-yl]-2,3-dichloro-4H-thieno[3,2-b]pyirole-5-carboxamide; 2,3-dichloro-N-{ (lS,2S)-l-{[ (3-hydroxyphenyl)carbonyl]amino}-2,3-dihydro-lH-inden-2-yl }-4H -thieno [3 ,2-b ]pyrrole-5-carboxamide; N-[ (IS ,2S)-l-( acetylamino)- 2,3-dihydro-lH-inden-2-yl]- -2,3 -dichloro-4H-thieno [3 ,2-b]pyrrole-5-carboxamide; N-[{1S, 2S)-l-[(2-carboxyacetyl)amino]- 2,3-dihydro-lH-inden-2-yl]- 2,3 -dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-((lS ,2S)-l-{ [(dimethylamino)carbonyl]amino}-2,3-dihydro-lH-inden-2-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-((lS ,2S)-l-{ [( 4-methylpiperazin-l-yl)carbonyl]amino}-2,3-dihydro-lH-inden-2-yl)-4H-thieno [3 ,2-b]pyrrole- 5 -carboxamide; 2,3-dichloro-N-((lS ,2S)-l-{ [(ethylamino)carbonyl] amino}-2,3-dihydro-lH-inden-2-yl)-4H-thieno [3 ,2-b]pyrrole- 5 -carboxamide; 2,3-dichloro-N-((lS,2S)-l-{ [(prop-2-en-l-ylamino)carbonyl]amino}-2,3-dihydro-lH-inden-2-yl)-4H-thieno [3 ,2-b]pyrrole- 5-carboxamide; 2,3-dichloro-N-[( 1 S,2S)-1 -({[(3 ,5-dinitrophenyl)amino]carbonyl}amino)-2,3-dihydro-lH-inden-2-yl]-4H-thieno [3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-[ (1S ,2S)-l-(formylamino)-2,3-dihydro-lH-inden-2-yl]-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-{(lR,2R)-l-[((3R)-3-amino-3-carbamoylpropanoyl)amino] -2,3-dihydro-lH-inden- 2-yl}- 2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-{1R,2R)-1-[((3R)- 3:-carboxy-3-hydroxypropanoyl)amino]-2,3-dihydro-lH-inden-2-yl }-2,3-dichloro-4H-thieno[3,2-b]pyrrole- 5 -carboxamide; 2,3-dichloro-N-{ (lR,2R)-l-[(hydroxyacetyl)amino]-2,3-dihydro-lH-inden-2-yl }-4H-thieno[3,2-b]pyrrole- 5-carboxamide; 2,3-dichloro-N-{ (1S ,2S)- l-[(methylsulfonyl)amino]-2,3-dihydro- 1H-inden-2-yl}-4H-thienof[3,2-b]pyrrole-5-carboxamide; 2,3-dichloro-N-{ (1S, 2S)-l-[methyl(morpholin-4-ylacetyl)amino]- 2,3-dihydro- lH-inden-2-yl }-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-{{lR,2R)-l-[ (2-amino- 2-oxoethyl)amino]- 2,3-dihydro-lH-inden-2-yl} -2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-(lR,2R)-l-[(tert -butoxycarbonylmethyl)amino]-2,3-dihydro- 1H -inden-2-yl}-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-[ {lR,2R)-l-{ carboxymethylamino )-2,3-dihydro-lH-inden-2-yl]-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-(lR,2R)-l-[ N-acetyl-N-(carboxymethyl)amino] -2,3-dihydro-lH-inden-2-yl} -2,3-dichloro- 4H-thieno[3,2-b]pyrrole-5-carboxamide; N-{(lR,2R)-l-[acetyl(2-amino-2-oxoethyl)amino]- 2,3-dihydro-lH-inden-2-yl}- 2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide; N-{(1R,2R)- l-[N-(carboxymethyl)-N-(hydroxyacetyl)amino] -2,3-dihydro-lH-inden-2-yl}-2,3-dichloro-4H-thieno[3 ,2-b]pyrrole- 5 carboxamide; 2-chloro-N-[(lR,2R)-l-({ [(2S)-5-oxotetrahydrofuran-2-yl]carbonyl}amino)-2,3-dihydro-lH-inden-2-yl]-6H-thieno[2,3-b]pyirole-5-carboxamide; 2-chloro-N-[ (lR,2R)-l-(formylamino)- 2,3-dihydro-lH -inden-2-yl]-6H-thieno[2,3-b]pyrrole- 5-carboxamide; 2-chloro-N-{(lR,2R)-l-[(methoxyacetyl)amino]-2,3-dihydro-lH-inden-2-yl }-6H-thieno[2,3-b]pyrrole-5-carboxamide; N-[(lR,2R)-l-(acetylamino)-2,3-dihydro-lH-inden-2-yl]-2-chloro-6H-thieno[2,3- b]pyrrole-5-carboxamide; 2-chloro-N-{(lR,2R)- l-[(3-methoxypropanoyl)amino]-2,3-dihydro- 1H-inden-2-yl}-6H-thieno[2,3-b]pyrrole-5-carboxamide; N-{{lR,2R)-l-[ (2-acetoxyacetyl)amino]-2,3-dihydro-lH-inden-2-yl}-2- chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide; N-(( 1 S,2 S)-1 -{[(3(S)-3-(tert-butoxycarbonylamino)-3-carbamoylpropanoyl] amino}-2,3-dihydro-lH-inden-2- yl)- 2-chloro-6H-thieno[2,3 -b]pyrrole-5-carboxamide; N-{(lS ,2S)-l-[(2-(tert-butoxycarbonylamino)acetylamino ]-2,3-dihydro-lH-inden-2-yl}-2-chloro-6H-thieno [2,3-b]pyrrole- 5-carboxamide; N-{(1R,2R)- l-[2-carbamoylacetyl)amino]- 2,3-dihydro- lH-inden-2-yl} -2-chloro-6H-thieno[2,3-b ]pyTrole-5-carboxamide; N-{(1R,2R)-1 -[2-(tert-butoxycarbonyl)acetylamino ]-2,3-dihydro-1H- inden- 2-yl }-2-chloro-6H-thieno[2,3-b ]pyrrole-5-carboxamide; 2-chloro-N-( (1 R,2R)-l-{[3-hydroxy-2-(hydroxyniethyl)propanoyl]amino}-2,3-dihydro-lH-inden- 2-yl)-6H-thieno[2,3-b]pyirole-5-carboxamide; N-{ (lR,2R)-l-[((3R)-3-amino-3-carbamoylpropanoyl)amino]-2,3-dihydro-lH-inden-2-yl }-2-chloro-6H-thieno [2,3-b]pyrrole-5-carboxamide; N-{ (lR,2R)-l-[(aminoacetyl)amino]-2>3-dihydro-lH-inden-2-yl}- 2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide; 2-chloro-N-[(lR,2R)-l-({[(2-hydroxyethyl)(phenylmethyl)amino]acetyl} amino)-2,3-dihydro-lH -inden-2-yl )-6H -thieno [2,3-b]pyrrole-5-carboxamide; 2-chloro-N-{(lR,2R)-l-[(morpholin-4-ylacetyl)amino]- 2,3-dihydro-1H- inden-2-yl }-6H-thieno [2,3-b]pyrrole-5-carboxamide; 2-chloro-N-((lR,2R-l-({[(2-hydroxyethyl)(methyl)amino]acetyl}amino)-2,3-dihydro-lH-inden-2-yl )-6H -thieno[2,3-b]pyrrole-5-carboxamide; N-{ (lR,2R)-l-({[bis(2-hrdroxyethyl)amino]acetyl}amino)-2,3-dihydro-lH-inden-2-yl}- 2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide; 2-chloro-N-((lR,2R)-l-({[ethyl(2-hydroxyethyl)amino]acetyl}amino)-2,3- dihydro- lH-inden-2-yl)-6H -thieno[2,3-b]pyrrole-5-carboxamide; 2-chloro-N-((lR,2R)-l-({[(2,3- dihydroxypropyl) (methyl)amino]acetyl}amino) -2,3-dihydro-1 H-inden-2 - yl)-6H-thieno[2,3-b]pyrrole-5-carboxamide; N-((lR,2R)-l-({[bis(2-hydroxypropyl)amino]acetyl}amino)-2,3-dihydro-lH-inden-2-yl)-2-chloro-6H -thieno [2,3-b]pyrrole-5-carboxamide; N-{(lR,2R)-l-[(2-amino-2-oxoethyl)amino]-2,3-dihydro-lH-inden-2-yl }-2-chloro-6H-thieno [2,3-b]pyrrole-5-carboxamide; N-[ (lR,2R)-l-[tert-butoxycarbonylmethyl)amino]-2,3-dihydro-lH-inden-2-yl}-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide; N-{(1R,2R)- l-(carboxymethylamino)-2,3-dihydro- lH-inden-2-yl }-2- chloro-6H-thieno(3,2-b ]pyirole-5-carboxamide; 2-chloro-N-{(lR,2R)-l-[(hydroxyacetylamino]-2,3-dihydro-lH-inden-2-yl }-6H-thieno[2,3-b]pyrrole-5-carboxamide; 2,3-dichloro-N-{(lR,2R)-l-[(chloroacetyl)amino]-2,3-dihydro-lH-inden-2-yl} -4H -thieno[3,2-b]pyrrole-5-carboxamide; N-{(lR,2R)-l-[((3S)-3-amino-3-carboxypropanoyl)amino]-2,3-dihydro-lH-inden-2-yl }-2,3-dichloro-4H-thieno(3,2-b]pyrrole- 5-carboxamide; N-{(lR,2R)-l-K2-carboxyacetyl)amino]-2,3-dihydro-lH -inden-2-yl }-2,3-dichloro-4H-thieno(3,2-b]pyrrole-5-carboxamide; N-{(lR,2R)-l-[(2-carboxyacetyl)amino]-2,3-dihydro-lH-inden-2-yl}-2- chloro-6H-thieno(3,2-b ]pyrrole-5-carboxamide; N-{(1 R,2R)-1 -[((3 S)-3-amino-3-carboxypropanoyl)amino]-2,3-dihydro-1H-inden-2-yl}-2-chloro-6H-thieno(3 ,2-b] pyrrole-5-carboxamide; 2,3-dichloro-N-{(lR,2R)-1-[ (methylsulfonyl)amino]-2,3-dihydro- IH inden-2-yl}-4H-thieno[3,2-b]pyrrole-5-carboxamide; 13. A pharmaceutical composition which comprises therapeutically effective amount of a compound of the formula (1), or a pharmaceutically acceptable salt thereof, as claimed in anyone of claims 1 to 12 in association with a pharmaceutically-acceptable diluent or carrier. 14. A compound of the formula (1), or a pharmaceutically acceptable salt, as claimed in anyone of claims 1 to 12, as a medicament in the treatment of type 2 diabetes, insulin resistance, syndrome X, hyperinsulinaemia, hyperglucagonaemia, cardiac is chaemia or obesity in a warm-blooded animal such as man. 15. Heterocyclic amide derivative compound as claimed in claim 1, wherein the compound is N-[(lR,2R)-l-amino-2,3-dihydro-lH-inden-2-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide; or tert-butyl(( 1 R,2R)-2-{[2-chloro-6H-thieno[2,3-b]pyrrol-5-yl)carbonyl] amino]-2,3-dihydro-1 H-inden-1 -yl) carbamate.

Documents:

2325-delnp-2004-abstract.pdf

2325-delnp-2004-claims.pdf

2325-delnp-2004-complete specification (granted).pdf

2325-delnp-2004-correspondence-others.pdf

2325-delnp-2004-correspondence-po.pdf

2325-delnp-2004-description (complete).pdf

2325-delnp-2004-form-1.pdf

2325-delnp-2004-form-13.pdf

2325-delnp-2004-form-18.pdf

2325-delnp-2004-form-2.pdf

2325-delnp-2004-form-3.pdf

2325-delnp-2004-form-5.pdf

2325-delnp-2004-gpa.pdf

2325-delnp-2004-pct-210.pdf

2325-delnp-2004-pct-304.pdf

2325-delnp-2004-pct-409.pdf

2325-delnp-2004-pct-416.pdf

2325-delnp-2004-petition-137.pdf

2325-delnp-2004-petition-138.pdf

abstract.jpg