OXOPICOLINAMIDE DERIVATIVE, A METHOD FOR PRODUCTION THEREOF AND PHARMACEUTICAL USE THEREOF Russian patent published in 2021 - IPC C07D213/64 C07D401/12 C07D401/14 C07D405/06 C07D409/06 C07D413/06 A61K31/4439 A61P7/02 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a compound of formula (AI):

or a pharmaceutically acceptable salt thereof, in which: ring A is 6-member aryl or 5–10-member heteroaryl, having 1–3 heteroatoms, selected from a group consisting of S and N as ring atoms, wherein said 6-member aryl is optionally condensed with ring of 5- or 6-member heteroaryl having 1–2 heteroatoms selected from a group, consisting of S and N as ring atoms, or 3–8-member heterocyclyl, having 1–2 heteroatoms selected from a group consisting of O and N as ring atoms; or is R¹ is -C(O)R⁷; each R² is identical or different, and each is independently selected from a group consisting of hydrogen and halogen; R³ is selected from a group consisting of C_1-6 alkoxy, where C_1-6 alkoxy, optionally substituted with one or more deuterium; R⁴ is selected from a group consisting of hydrogen, C_1-6 alkyl and C_1-6 alkoxy, where C_1-6 alkyl, optionally substituted with one or more groups R⁹; each R⁵ is identical or different, and each is independently selected from a group, consisting of hydrogen, C_1-6 alkyl, C_1-6 alkoxy, oxo, halogen, C_1-6 haloalkyl, cyano, -C(O)R⁸, -C(O)OR⁸, -NR¹⁰R¹¹, -C(O)NR¹⁰R¹¹, -CH₂NR¹⁰R¹¹, -C(O)OCH(R¹⁰)R¹¹ and -S(O)_mR⁸, where C_1-6 alkyl is optionally substituted with one or more groups selected from a group consisting of halogen; R⁷ is selected from a group consisting of hydrogen, C_1-6 alkyl, C_1-6 haloalkyl and 3–5-member cycloalkyl, where C_1-6 alkyl optionally substituted by one or more than one group selected from the group consisting of hydrogen, deuterium, and 3–5-membered cycloalkyl; R⁸ is selected from a group consisting of hydrogen, C_1-6 alkyl, amino and 3–5-member cycloalkyl; R⁹ is selected from a group consisting of hydrogen, deuterium, C_1-6 alkoxy, 3–8-member cycloalkyl, 3–5-member cycloalkyloxy, 3–8-member heterocyclyl, having one oxygen atom as a heteroatom, 6-member aryl and 5-6-member heteroaryl, having 1–2 heteroatoms selected from a group consisting of O, S and N as ring atoms, where each 3–8-member cycloalkyl, 3–8-member heterocyclyl, 6-member aryl and 5–6-member heteroaryl is optionally substituted with one or more groups selected from a group consisting of deuterium, halogen, C_1-6 alkyl, C_1-6 alkoxy, cyano, hydroxy, 3–5-member cycloalkyl, -NHC(O)R¹² and R¹³; R¹⁰ and R¹¹ are identical or different and each is independently selected from a group consisting of hydrogen, C_1-6 alkyl of 3–5-member cycloalkyl, 5-member heterocyclyl, having two oxygen atoms as heteroatoms, -C(O)OR⁸ and -OC(O)OR¹², where each 5-member heterocyclyl is optionally substituted with one or more C_1-6 alkyl and oxo; R¹² is selected from a group consisting of hydrogen, C_1-6 alkyl and 3–5-member cycloalkyl; R¹³ is 6-member aryl, where each 6-member aryl and heteroaryl is optionally substituted with one or more groups selected from a group consisting of hydrogen, C_1-6 alkyl, and cyano; n is equal to 0, 1, 2, 3 or 4; m is 0, 1 or 2; and s is equal to 0.1, 2, 3 or 4. As well as to a method for production thereof and to a pharmaceutical composition containing said derivative, and to use thereof as a therapeutic agent, in particular as a blood coagulation factor inhibitor XIa (Factor XIa, abbreviated—FXIa), and its use in preparing a drug for treating diseases such as thromboembolism.

EFFECT: disclosed is an oxopicolinamide derivative, a method for production thereof and pharmaceutical use thereof.

28 cl, 5 tbl, 186 ex