| 摘要 |
Dipeptidyl peptidase IV inhibitors of formula 1 are described wherein: R1 is H or CN, R2 is selected from CH2R5, CH2CH2R5 and C(R3)(R4)-X2-(CH2)aR5, R3 and R4 are each independently selected from H and Me; R5 is selected from CON(R6)(R7), N(R8)C(=O)R9, N(R8)C(=S)R9, N(R8)SO2R10 and N (R8)R10; R6 and R7 are each independently R11(CH2)b or together they are -(CH2)2-Z-(CH2)2- or -CH2-o-C6H4-Z-CH2-; R8 is H or Me; R9 is selected from R11(CH2) b, R11(CH2)bO and N(R6)(R7); R10 is R11(CH2)b; R11 is selected from H, alkyl, optionally substituted aryl, optionally substituted aroyl, optionally substituted arylsulphonyl and optionally substituted heteroaryl; R12 is selected from H2NCH(R13)CO, H2NCH(R14)CONHCH(R15)CO, C(R16)=C(R17)COR18 andR19OCO; R13, R14 and R15 are selected from the side chains of the proteinaceous amino acids; R16 is selected from H, lower alkyl(C1-C6) and phenyl; R17 is selected from H and lower alkyl(C1-C6); R18 is selected from H, lower alkyl(C1-C6), OH, O-(lower alkyl(C1-C6)) and phenyl; R19 is selected from lower alkyl(C1-C6), optionally substituted phenyl and R20C(=O)OC(R21)(R22); R20, R21 and R22 are each independently selected from H and lower alkyl(C1-C6); Z is selected from a covalent bond, -(CH2)c-, -O-, -SO-- and -N(R10)-; X1 is S or CH2; X2 is O, S or CH2; a is 1, 2 or 3; b is 0-3 ; c is 1 or 2; and d is 0-2; with the proviso that if R1 is CN and X1 is CH2, R12 is selected form C(R16)=C(R17)COR18 and R19OCO only wherein R16, R17 and R18 area as defined above and R19 is lower alkyl(C1-C6); the compounds can be used in pharmaceutical compositions for treating impaired glucose tolerance, type II diabetes or hyperglycemia.
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