| 摘要 |
Heterocyclic amides possessing glycogen phosphorylase inhibitory activity of formula 1 are described wherein: Z is CH or nitrogen; R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S-; R6 and R7 are independently selected from hydrogen, halo, nitro, cyano, hydroxy,fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, carboxy, carbamoyl, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy and C1-4alkanoyl; A is phenylene or heteroarylene; n is 0, 1or 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 wherein 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 -NHC(O)heterocycle ringR4R5 is a substituent on carbon (2) and when the r is 2(hereby forming a six membered ring) the group is substituent on carbon (2) or (3); Y is-NR2R3 or -OR3; wherein R2 and R3 are as herein defined. with the proviso that the compound of formula (1) is not: i) 2,3-dichloro-5-(N-{l-[N-(1,1-dimethylethoxy) carbonylamino]indan-2-yl}carbamoyl)-4H-thieno[3,2-b]pyrrole; ii) 5-[N(1-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]pyrrole; v) 2,3-dichloro-5-{N-[1-(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-b]pyrrole; vii) 2,3-dichloro-5-[N-(l-hydroxyindan-2-yl)carbamoyl]-4H-thieno[3,2-b]pyrrole; viii) 2-chloro-5-[N-(1-hydroxindan-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(1-methoxyindan-2-yl)carbamoyl-4H-thieno[3,2-b]pyrrole; xi) 2,3-dichlor9o-5-[N-(1-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)carbamoyl]-4H-thieno[3,2-b]pyrrole. Pharmaceutical compositions comprising the compound are useful for treating type 2 diabetes, insulin resistance, syndrome X, hyperinsulinaenia, hyperglucagonaemia, cardiac ischemia and obesity
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