Patent RU-2315746-C2 (RU)
IPC: C07C311/08
Filed: 2002-08-08
Granted: 2008-01-27
Abstract: FIELD: organic chemistry, medicine, pharmacy. 
     SUBSTANCE: invention relates to derivatives of carboxylic acids of the formula (I):   wherein R 1  means -COOH, -COOR 4 , -CH 2 OH, -CONR 5 SO 2 R 6 , -CONR 7 R 8 , -CH 2 NR 5 SO 2 R 6 , -CH 2 NR 9 COR 10 , -CH 2 NR 9 CONR 5 SO 2 R 6 , -CH 2 SO 2 NR 9 COR 10 , tetrazole, 1,2,4-oxasizol-5-one, 1,2,4-oxadiazol-5-thione, 1,2,4-thiadiazol-5-one or 1,2,3,5-oxathiadiazol-2-one; A means: (ii) (C 1 -C 6 )_alkylene; (iii) (C 2 -C 6 )-alkenylene; (iv) (C 2 -C 6 )-alkynylene; (v) -O-(C 1 -C 3 )-alkylene; (vii) -NR 20 -(C 1 -C 3 )-alkylene; (viii) -CONR 21 -(C 1 -C 3 )-alkylene; (ix) (C 1 -C 3 )-alkylene-O-(C 1 -C 3 )-alkylene; (xi) (C 1 -C 3 )-alkylene-NR 20 -(C 1 -C 3 )-alkylene; (xiv) -(C 1 -C 4 )-alkylene-Cyc1; cycle B means (C 6 -C 10 )-unsaturated mono- or bicarbocyclic fragment or 5-10-membered saturated, partially saturated or unsaturated mono- or biheterocyclic fragment comprising 1 atom of sulfur, nitrogen or oxygen; R 2  means (C 1 -C 6 )-alkoxy-group, halogen atom; m = 0, 1; n = 1 if -D-R 3  is added to B cycle in ortho-position with respect to -A-R; n = 0 if -D-R 3  is added to B cycle in position distinct from ortho-position with respect to -A-R 1 ; Q mans (1) (i) -(C 1 -C 4 )-alkylene, (C 2 -C 4 )-alkenylene-Cyc2; (ii0 -(C 1 -C 4 )-alkylene-Z-Cyc3; (iii) (C 1 -C 4 )-alkyl substituted with substitute(s) chosen from -NR 24 R 25 , -S(O) p R 26 , cyano-group, -NR 23 COR 27 , -NR 23 SO 2 R 28  and -NR 23 CONR 24 R 25 ; (iv) (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkoxy-group, -NR 23 COR 27 , -COR 28 , -OSO 2 R 28 , -NR 23 SO 2 R 28 ; (v) C 6 -unsaturated monocarbocyclic fragment or 6-membered fully saturated monoheterocyclic fragment comprising 1 atom of nitrogen that is substituted with 1-5 R 30  wherein one of R 30  is bound with a cycle by position distinct from position 1; (vi) 9-membered fully saturated, partially saturated or unsaturated biheterocyclic fragment comprising 2 atoms chosen from nitrogen, sulfur and oxygen that can be unsubstituted or substituted with 1-5 R 30 ; (vii) -T-Cyc5; (viii) -L-Cyc 6-1 , -L-(C 3 -C 6 )-cycloalkyl, -L-(C 2 -C 4 -alkylene)-Cyc 6-2 , or -L-(C 1 -C 4 -alkylene) q -Cyc 6-3  wherein cycloalkyl is unsubstituted; (2) (i) phenoxy-group; (ii) benzyloxy-group; (iii) hydroxy-(C 1 -C 4 )-alkyl; (iv) (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl, or (iv) (C 1 -C 4 )-alkylene-O-benzyl, or (v) cyano-group; (vi) -NR 33 R 34 ; (vii) -CONR 33 R 34 ; D means (1) -CH 2 -, -O-CH 2 -, -CONH-, -NHSO 2 -, -NHCO- or -CO-CH(CH 3 )-,; (2) -(CH 2 ) 3 -, -(CH 2 ) 5 -, -CH=CH-(CH 2 ) 3 - and so on; R 3  means (1) (C 1 -C 6 )-alkyl or (2) (C 6 -C 10 ) fully or partially saturated or unsaturated mono- bicarbocyclic fragment, or 5-15-membered partially or fully saturated or unsaturated mono-, bi- or triheterocyclic fragment comprising 1-3 atoms of nitrogen, oxygen or sulfur and substituted with 1-5 R 42  or unsubstituted fragment, or its nontoxic salt. Also, invention relates to a pharmaceutical composition possessing antagonistic activity to EP 3  and/or EP 4  and comprising the effective amount of compound of the formula (I), or its nontoxic salt and a pharmaceutically acceptable carrier, and to using these compounds in treatment of diseases mediated by activity of EP 3  and/or EP 4 . Invention proposes derivatives of carbocyclic acids possessing antagonistic activity to EP 3  and/or EP 4 . 
     EFFECT: valuable medicinal properties of compounds and pharmaceutical composition. 
     17 cl, 1369 ex