Patent RU-2746129-C2 (RU)
Inventor: TANG HAIFENG
IPC: C07D417/14
Filed: 2016-12-12
Granted: 2021-04-07
Abstract: FIELD: pharmaceuticals. 
     SUBSTANCE: invention relates to biaryl monobactam compounds of Formula I and their pharmaceutically acceptable salts, where W is a bond or O; R x  and R z  independently represent hydrogen, C 1 -C 3 alkyl; X represents N or CR 1 ; R 1  represents hydrogen, C 1- C 3 alkyl or halogen; in each case R a  independently represents hydrogen, halogen, C 1 -C 3 alkyl or -OR e ; Z represents C 1 -C 3 alkylene, optionally substituted with 1-3 R b ; in each case R b  independently represents -C 1 -C 8 alkyl, -C 3 -C 7 cycloalkyl, -C(O)OR e , -C(O)NR c R d , tetrazolyl or -P(O)(R e ) p , wherein the specified -C 1 -C 8 alkyl and the specified -C 3 -C 7 cycloalkyl are optionally substituted with 1-3 R a ; AryA is a 5-6 membered monocyclic aromatic ring with 0, 1, 2 or 3 ring atoms independently selected from N, N as a quaternary salt, optionally substituted with 1-4 R 4 ; Y represents O; R 2  represents hydrogen or -C 1 -C 3 alkyl, wherein the above -C 1 -C 3 alkyl  is optionally substituted with 1-3 R a ; A 1  represents AryA; A 2  represents the groups of pyrazole, imidazole and pyridine (given in the claims), where * indicates attachment to Q and ** indicates attachment to M; in each case R 4  represents halogen; HetB it is a 3-6-membered saturated or monounsaturated monocyclic ring with 1, 2, or 3 heteroatoms in the ring, independently selected from N, N as a quaternary salt, and O, optionally substituted with 1-3 R a ; Q represents bond, CH 2 , O, S, -(CH 2 ) n NR 3 - or -NR 3 (CH 2 ) n -, wherein each CH 2  is unsubstituted, or substituted by 1-2 substituents selected from halogen, -C 1 -C 6 alkyl, OR e  and -(CH 2 ) n NR c R d ; R 3  represents hydrogen or -C 1 -C 3 alkyl, wherein the -C 1 -C 3 alkyl is optionally substituted with 1-3 R a ; M represents -(CH 2 ) n R 5  or R 5 ; R 5  is H, C 2 -C 10 alkyl, C 3 -C 7 cycloalkyl, HetB or -NH(C 1 -C 6 alkyl), wherein the specified C 2 -C 10 alkyl and the above C 3 -C 7 cycloalkyl are optionally substituted with 1-4 R 6 ; in each case R 6   is independently selected from a group consisting of halogen, -OR e , -NR c R d , -(CH 2 ) n NR c R d  and HetB; in each case R c  and R d  independently represent hydrogen, -C 1 -C 10 alkyl or -C 1 -C 10 alkylene-HetB and wherein each R c  and R d  is optionally substituted with 1-3 R f ; in each case R e  independently represents hydrogen, -C 1 -C 10 alkyl, -OH or -OC 1 -C 4 alkyl, wherein each R e   is optionally substituted with 1-3 R h ; in each case R f  independently represents halogen, -C 1 -C 10 alkyl, -OH, -OC 1 -C 4 alkyl or NH 2 , wherein the specified -C 1 -C 10 alkyl is optionally substituted with 1-3 substituents independently selected from -OH, halogen, cyano and -S(O) 2 CH 3 ; every n is independently equal to 0, 1, 2, 3, or 4; every m is independently equal to 0, 1, or 2, and every p is independently equal to 1 or 2. The invention also relates to the salt of trifluoroacetic acid of the compound of Formula I, as well as to specific biaryl compounds.  
     EFFECT: technical result is biaryl compounds exhibiting antibacterial activity.  
     16 cl, 7 tbl, 126 ex