THIENOTRIAZOLODIAZEPINE COMPOUNDS AND PHARMACEUTICAL USES THEREOF

摘要

A thienotriazolodiazepine compound of the formula: <IMG> or a pharmaceutically acceptable salt thereof, wherein R1 is alkyl; R2 is methyl or trifluoromethyl; R3 is phenyl or phenyl substituted by one substituent selected from the group consisting of halogen, alkyl and alkoxy; R4 is -B1R3 In the formula -B1R5, when ? > O, R3 is hydroxy; halogen; a group represented by -N(R11)(R12), wherein R11 and R12 are the same or different and each is a hydrogen; straight or branched chain alkyl having 1 to 10 carbon atoms, which may be substituted by amino, alkylamino, dialkylamino or cyclic amino; or R11 and R12 together with the adjacent nitrogen atom form a saturated 5- to 7-membered heterocycle selected from the group consisting of 1-pyrrolidinyl, piperidino, 1-piperazinyl, 1-perhydroazepinyl, morpholino, thiomorpholino, 4-methyl-1-piperazinyl and 2,6-dimethyl-morpholino; arylsulfonyloxy which may be mono- or polysubstituted by straight or branched chain alkyl and/or alkoxy having 1 to 4 carbon atoms; straight or branched chain alkylsulfonyloxy having 1 to 4 carbon atoms; or straight or branched chain alkylcarbonyloxy having 2 to 12 carbon atoms; and when ? ? 0, R5 is -COOH; cyano; straight or branched chain alkoxycarbonyl having 1 to 4 carbon atoms; or a group represented by (Rl7)(R18)NCO-, wherein R17 and R18 are the same or different and each is hydrogen, phenyl, substituted phenyl, aralkyl or straight or branched chain alkyl, alkenyl or alkynyl having 1 to 10 carbon atoms, or R17 and R18 together with the adjacent nitrogen atom form a 5- to 7membered heterocycle selected from the group consisting of 1pyrrolidinyl, piperidino, 1-piperazinyl, 1-perhydroazepinyl, morpholino, thiomorpholino, 4-methyl-1-piperazinyl, 4isobutyl-1-piperazinyl and 3-thiazolidinyl; B is straight or branched chain alkylene having ? carbon atoms, which may be di-substituted by R5 wherein R5 is the same or different; and ? is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and ring A is thiophene ring, tetrahydrobenzothiophene ring or 4,5-dihydro-6H-cyclopenta¢b!thiophene ring, which compounds exhibit PAF-antagonistic activity and are useful for the prevention or treatment of various PAF-induced diseases.