IMIDAZOLE DERIVATIVES AS TAFIa INHIBITORS Russian patent published in 2009 - IPC C07D401/06 C07D401/14 C07D409/14 A61K31/4427 A61K31/4178 A61K31/4196 A61P7/00 

FIELD: medicine.

SUBSTANCE: invention refers to imidazole derivatives of formula (1a): and/or to stereoisomeric forms of compound of formula (1a) and/or to physiologically acceptable salt of compound of formula (1a), and U means 1) hydrogen atom; X means the remaining formula (II): -(A1)_m-A2 (II), where m means an integer 1; A1 means 1) -(CH₂)_n- where n means an integer 1; A2 means 1) aminopyridyl; Y means 1) the remaining formula (III): A3-(A4)_o-(A5)_p (III), and A3 means (C₃-C₈)-cycloalkyl or (C₂-C₆)-alkinylene wherein cycloalkyl or alkinylene is unsubstituted or independently one-, two- or three-substituted with R1, A4 is absent, A5 is absent; b) A3 means -(C₃-C₈)-cycloalkyl wherein cycloalkyl is unsubstituted or independently one-, two- or three-substituted with R1, A4 means -N(R2)- and A5 means a)1) -C(O)-R3; a)2) -C(O)-N(R4)-R5; a)3) -(SO₂)-R6; O stands for an integer 1, and p stands for an integer 1; A3 means cyclic amine with 3-8 atoms in cycle where cyclic amine is unsubstituted, A4 is absent; and A5 has value specified in cl. b), and A5 is connected with N-atom A3, o means an integer zero and p means an integer zero or 1; or d) A3 means -(CH₂)_q-phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted with R1, A4 is absent; and A5 has value specified in cl. b), p means an integer 1 and q means integer zero or 1;) A3 means -(CH₂)_rHet wherein Het stands for benzothiophene or piperidine which is unsubstituted or independently one-, two- or three-substituted by =0 or R1, A4 is absent; and A5 has value specified cl. b), p means an integer 1 and r means an integer 1 or 2; f) A3 means -(CH₂)_q-phenyl wherein phenyl is unsubstituted, A4 means -O- A5 means phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted by R1, o and p mean an integer 1, and q means an integer zero, 1; g) -CH(-phenyl)-phenyl; and R1 means phenyl, and phenyl is unsubstituted or independently one-, two- or three-substituted by -(C₁-C₆)alkyl, b) triazolyl,) c) - (C₁-C₆)-alkyl, d) - (C₀-C₄)-alkyl - (C₃-C₈) a-cycloalkyl, e) -O-CF₃ or g) halogen; and R2 means: a) hydrogen atom; and R3 and R6 are identical or different and independently mean: a) -(C₁-C₆)-alkyl wherein alkyl is unsubstituted or independently one-, two- or three-substituted by R1, b) -phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted by R1, while R4 and R5 are identical or different and independently mean: a) -(C₁-C₆)-alkyl or -(C₂-C₁₀)-alkenyl wherein alkyl or alkenyl is unsubstituted, b) -phenyl wherein phenyl is unsubstituted, c) hydrogen atom; Y means 2) the remaining formula (IV): , and R8 means a) -phenyl where phenyl is unsubstituted; Z means 1) hydrogen atom, 2) -(C₁-C₆)-alkyl, 3) -(C₁-C₆)-alkyl, 4) -(C₀-C₄)-alkyl-(C₃-C₆)-cycloalkyl, 5) -(C₁-C₁₀)-alkyl-O-C(O)-O-R1. Besides the invention concerns the method for making the compound of formula (1a) and the based medicinal agent for inhibition of TAFIa enzyme.

EFFECT: production of new compounds and the based medicinal agent to be used in medicine to prevent and treat the conditions accompanied with thromboses, embolism, hypercoagulation or fibrotic changes.

8 cl, 1 tbl, 47 ex