Derivatives of 1-(2 -aminoacyl)-2-cyanpyrrolidine, pharmaceutical preparation, method for treating disorder of glucose tolerance or diabetes mellitus of type 2 and use of these derivatives

摘要

Compounds which are 1-(2'-aminoacyl)-2-cyanopyrrolidine derivatives according to general formula (1) are DP-IV inhibitors for treatment of impaired glucose tolerance or type 2 diabetes; wherein A is selected from groups (2, 3 and 4); X is selected from aminoacyl groups corresponding to the natural amino acids, acyl groups R³CO, groups R⁴COOC(R⁵)(R⁶)OCO, methoxycarbonyl, ethoxycarbonyl and benzyloxycarbonyl; R¹ is selected from H, C₁-C₆alkyl residues, (CH₂)_aNHW¹, (CH₂)_bCOW², (CH₂)_cOW³, CH(Me)OW⁴, (CH₂)_d-C₆H₄-W⁵ and (CH₂)_eSW⁶, where a is 2-5, b is 1-4, c is 1-2, d is 1-2, e is 1-3, W¹ is COW⁶, CO₂W⁶ or SO₂W⁶, W² is OH, NH₂, OW⁶ or NHW⁶, W³ is H or W⁶, W⁴ is H or W⁶, W⁵ is H, OH or OMe, and W⁶ is C₁-C₆ alkyl, optionally substituted phenyl, optionally substituted heteroaryl or benzyl and R² is selected from H and (CH₂)_n-C₅H₃N-Y, where n is 2-4 and Y is H, F, Cl, NO₂ or CN, or R¹ and R² together are -(CH₂)_p- where p is 3 or 4; R³ is selected from H, C₁-C₆ alkyl and phenyl; R⁴ is selected from H, C₁-C₆ alkyl, benzyl and optionally substitued phenyl; R⁵ and R⁶ are each independently selected from H and C₁-C₆ alkyl or together are -(CH₂)_m-, where m is 4-6; R⁷ is selected from pyridyl and optionally substituted phenyl; R⁸ is selected from H and C₁-C₃ alkyl; and R⁹ is selected from H, C₁-C₆ alkyl, C₁-C₆ alkoxy and phenyl.