Patent RU-2742771-C2 (RU)
Inventor: YAN Fanlun
IPC: C07D409/06
Filed: 2017-08-30
Granted: 2021-02-10
Abstract: 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   R 1  is -C(O)R 7 ; each R 2  is identical or different, and each is independently selected from a group consisting of hydrogen and halogen; R 3  is selected from a group consisting of C 1-6  alkoxy, where C 1-6  alkoxy, optionally substituted with one or more deuterium; R 4  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 R 9 ; each R 5  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)R 8 , -C(O)OR 8 , -NR 10 R 11 , -C(O)NR 10 R 11 , -CH 2 NR 10 R 11 , -C(O)OCH(R 10 )R 11  and -S(O) m R 8 , where C 1-6  alkyl is optionally substituted with one or more groups selected from a group consisting of halogen; R 7  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; R 8  is selected from a group consisting of hydrogen, C 1-6  alkyl, amino and 3–5-member cycloalkyl; R 9  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)R 12  and R 13 ; R 10  and R 11  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)OR 8  and -OC(O)OR 12 , where each 5-member heterocyclyl is optionally substituted with one or more C 1-6  alkyl and oxo; R 12  is selected from a group consisting of hydrogen, C 1-6  alkyl and 3–5-member cycloalkyl; R 13  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