| 摘要 |
FIELD: organic chemistry, medicine, pharmacy. ^ SUBSTANCE: invention relates to derivatives and intermediate compounds of N-adamantylmethyl that possess antagonistic activity with respect to P2X7 receptors and used in preparing a drug for its using in treatment of rheumatic arthritis and respiratory ways obstructive disease. Compounds have formula (I): wherein m means 1, 2 or 3; each R1 represents hydrogen atom; A represents -C(O)NH or -NHC(O); Ar represents group of the formulae (II) (III) or (IV) wherein one radical among R2 and R3 represents halogen atom or (C1-C6)-alkyl and another radical among R2 and R3 represents hydrogen atom; R4 represents group of the formula (V) wherein X represents oxygen or sulfur atom or group: >N-R8; n means 0 or 1; R5 represents (C1-C5)-alkyl group that can be possibly substituted with at least one substitute chosen from hydroxyl; each R6 and R7 represents independently hydrogen atom, (C1-C6)-alkyl (possibly substituted with at least one substitute chosen from hydroxyl and di-(C1-C4)-alkylamino-group that is possibly substituted with at least one hydroxyl group) or (C3-C8)-cycloalkyl (possibly substituted with at least one substitute chosen from hydroxyl); R8 represents hydrogen atom or (C1-C5)-alkyl group that can be possibly substituted with at least one substitute chosen from hydroxyl under condition that: (a) when n means 0 then A represents -NHC(O); (b) when n means 1, X represents oxygen atom and a represents -C(O)NH then R6 and R7 are not hydrogen atom simultaneously or both are not unsubstituted (C1-C6)-alkyl simultaneously, or when one of R6 and R7 represents hydrogen atom then another radical among R6 and R7 is not unsubstituted (C1-C6)-alkyl, and (c) when n means 1, X represents oxygen, sulfur atom or >NH and A represents -NHC(O) then R6 and R7 both are not hydrogen atom simultaneously or both are not unsubstituted (C1-C6)-alkyl simultaneously, or when one among R6 and R7 represents hydrogen atom then another among R and R7 is not unsubstituted (C1-C)-alkyl or -CH2CH2OH; or its pharmaceutically acceptable salt or solvate. Also, invention relates to methods (variants) for synthesis of compounds of the formula (I), pharmaceutical composition, pharmaceutical composition containing compound of the formula (I), method for its preparing, using compound of the formula (I) and methods for treatment of arthritis, osteoarthritis or respiratory ways obstructive disease. ^ EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of synthesis of compounds. ^ 30 cl, 36 ex |
