| abstract |
FIELD: pharmacology. n SUBSTANCE: invention relates to a heterocyclic derivative or a pharmaceutically acceptable salt thereof, of the general formula n , wherein ring A is a group represented by the general formulas , or , where X 1 is NH, NC 1 - 6 alkyl or O; A 1 is hydrogen; A 2 is i) hydrogen; ii) halogen; iii) C 1 - 6 alkyl optionally substituted by one to three groups selected from a group consisting of halogen, amino, mono(C 1 - 6 alkyl)amino, di(C 1 - 6 alkyl)amino, carbamoyl, mono(C 1 - 6 alkyl)aminocarbonyl, di(C 1 - 6 alkyl)aminocarbonyl, saturated cyclic aminocarbonyl, wherein the "saturated cyclic amino group" of the "saturated cyclic aminocarbonyl" part is 1-pyrrolidinyl, C 1 - 6 alkoxy and C 1 - 6 alkoxy-C 1 - 6 alkoxy; iv) C 3 - 6 cycloalkyl, optionally substituted by C 1 - 6 alkyl optionally substituted by one to three halogens; vi) a 4 to 5-membered saturated heterocyclic group containing one nitrogen or oxygen atom in the ring, optionally substituted by C 1 - 6 alkyl, (C 1 - 6 alkyloxy)carbonyl, (C 1 - 6 alkyl)carbonyl or hydroxy; (vii) C 1 - 6 alkylthio; (viii) C 1 - 6 alkylsulfonyl; ix) C 1 - 6 alkylsulfinyl; x) -NR 3 R 4 , where R 3 and R 4 are the same or different groups selected from a) hydrogen, b) optionally substituted C 1 - 6 alkyl, or c) C 3 - 6 cycloalkyl; or xi) saturated cyclic amino, wherein the "saturated cyclic amino" is piperidino, 1-piperazinyl or 4-morpholino, optionally substituted by C 1 - 6 alkyl, amino, mono(C 1 - 6 alkyl)amino, di(C 1 - 6 alkyl)amino, C 1 - 6 alkoxy or hydroxyl; R 1 is phenyl, benzyl, naphthyl, C 3 - 6 cycloalkyl, C 3 - 6 cycloalkylmethyl, heteroaryl wherein heteroaryl is benzothiadiazolyl, benzothiazolyl, indolyl, 1,1-dioxobenzothiophenyl, quinolyl or 1,3-benzoxazol-2-yl, 1,2,3,4-tetrahydronaphthalen-5-yl, 1,2, 3,4-tetrahydronaphthalen-6-yl, 2,3-dihydro-1H-inden-4-yl, 2,3-dihydro-1H-inden-5-yl or C 1 - 6 alkyl, wherein the said phenyl, benzyl, cycloalkyl, cycloalkylmethyl and heteroaryl are optionally substituted; R 2 is phenyl or pyridyl, wherein the said phenyl and pyridyl are optionally substituted. The invention also relates to a pharmaceutical composition and to an agent having the ability to inhibit mPGES-1 comprising a compound selected from the group consisting of a heterocyclic derivative of formula 1 and a pharmaceutically acceptable salt thereof as an active ingredient. n EFFECT: heterocyclic derivatives possessing the inhibitory activity of mPGES-1. n 10 cl, 18 tbl, 257 ex |