| abstract |
FIELD: medicine; pharmaceuticals. n SUBSTANCE: invention relates to a compound of formula I having the properties of a coagulation factor inhibitor XIa, a pharmaceutical composition based thereon, a method of inhibiting and preventing the formation of a blood thrombosis, method of treating and using for treating venous thromboembolism and pulmonary embolism, deep vein thrombosis, thrombotic stroke. In general formula I is phenyl or 5–10-member heteroaryl with 1–2 nitrogen atoms, which is optionally substituted with one or two groups independently selected from a group, consisting of halogen, oxo, cyano, R 6 , OR 6 , C(O)OR 6 , NR 6 R 7 , NHC(O)O-C 1-3 alkyl-OR 7 ; is phenyl or 5–6 membered heteroaryl with 1–2 nitrogen atoms, which is optionally substituted with one or two groups independently selected from a group consisting of halogen, oxide, cyclopropyl, R 6 ; W is N or N + O - ; YX is -CHC(O)OR 7 -NR 6 -, -CR 6 R 7 -C(O)NR 6 -, -CHC(O)R 7 -NR 6 -; Z is C 3-4 alkylene; R 1 is phenyl, optionally substituted with one to four substitutes, independently selected from a group consisting of halogen, cyano, R 6 , OR 6 , C(O)R 6 , NR 6 R 7 , and 5-member heteroaryl with 2–4 heteroatoms selected from nitrogen and oxygen (which is optionally substituted with halogen, cyano, cyclopropyl, C(O)OH, or R 6 ); R 2 denotes hydrogen or OR 6 ; R 3 denotes hydrogen; each R 4 independently represents C 1-6 alkyl; R 5 denotes hydrogen, halogen or C 1-6 alkyl; or one of R 4 and R 5 can be taken together with atoms between them to form 3–6-member alkyl ring; each R 6 independently represents hydrogen or C 1-6 alkyl, which is optionally substituted with one to three groups independently selected from a group consisting of halogen; each R 7 independently represents hydrogen, C 1-6 alkyl, 6-member heteroaryl with 1 to 2 nitrogen atoms or 5-member heterocyclyl with 1 nitrogen atom, wherein said alkyl group is optionally substituted with one to three groups independently selected from a group consisting of halogen; R a is hydrogen or hydroxy; n is an integer from zero to one. n n n n EFFECT: inhibitors of factor XIa are offered. n 15 cl, 172 ex |