NEW ANTI-DIABETIC AGENTS Russian patent published in 2005 - IPC

FIELD: organic chemistry, medicine, endocrinology, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (1) or its pharmaceutical salts wherein A means

R¹ means hydrogen atom (H), (C₁-C₆)-alkyl (including branched alkyl and cycloalkyl), -(CH₂)_aNHW¹, -(CH₂)_bCOW², -(CH₂)_cOW³, -CH(Me)OW⁴, -(CH₂)_d-C₆H₄-W⁵, -(CH₂)_eSW⁶ wherein a = 2-5; b = 1-4; c = 1-2; d = 1-2; e = 1-3; W¹ means -COW⁶, -CO₂W⁶, -SO₂W⁶; W² means -OH, -NH₂, -OW⁶, -NHW⁶; W³ means hydrogen atom (H), W^6; W⁴ means H, W⁶; W⁵ means H, -OH, -OMe; W⁶ means (C₁-C₆)-alkyl, benzyl, optionally substituted phenyl wherein optional substitutes (up to two groups) are taken among (C₁-C₃)-alkyl, (C₁-C₃)-alkoxy-group, fluorine (F) and/or chloride (Cl) atoms; R² means H, -(CH₂)_nNH-C₅H₃N-Y wherein n = 2-4; Y means H, F, Cl atoms, -NO₂ and -CN; or R¹ and R² represent in common -(CH₂)_p- wherein p = 3 or 4; X is taken among: (i) one L-alpha-aminoacyl group taken among Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr and Val, or two such groups that represent Arg and Ile; (ii) groups -R³CO wherein R³ represents H, (C₁-C₆)-alkyl (including branched alkyl and cycloalkyl) or phenyl; (iii) groups -R⁴COOC, -(R⁵)(R⁶)OCO wherein R⁴ means H, (C₁-C₆)-alkyl (including branched alkyl and cycloalkyl), benzyl or optionally substituted phenyl wherein substituted (up to two groups) are taken among (C₁-C₃)-alkyl, (C₁-C₃)-alkoxy-group, F and Cl atoms; each R⁵ and R⁶ means independently H or (C₁-C₆)-alkyl; or R⁵ and R⁶ mean in common -(CH₂)_m- wherein m means a whole number 4-6; and (iv) methoxycarbonyl, ethoxycarbonyl and benzyloxycarbonyl groups; R⁷ is taken among pyridyl and optionally substituted phenyl wherein substitutes (up to two groups) are taken among (C₁-C₃)-alkyl, (C₁-C₃)-alkoxy-group, F, Cl atoms, -NO₂, -CN and -CO₂H; R⁸ means H or (C₁-C₃)-alkyl; R⁹ means H, (C₁-C₆)-alkyl, phenyl or (C₁-C₆)-alkoxy-group and under condition that indicated compound doesn't represent N(Z-Val)-2-cyanopyrrolidine. Compounds of the formula (1) are inhibitors of DP-IV and can be used in pharmaceutical compositions in treatment of the tolerance disturbances to glucose and diabetes mellitus of type 2.

EFFECT: valuable medicinal properties of compounds and compositions.

26 cl, 2 tbl, 19 ex