Use of (1R, 2R)-3-(3-dimenthyl amino-1-ethyl-2-methyl-propyl) phenol for treating inflammatory pain

摘要

Mixture (X) of at least one analgesic (A) and an inhibitor (B) of cyclo-oxygenase II (COXII). Mixture (X) of at least one analgesic (A) and an inhibitor (B) of cyclo-oxygenase II (COXII), where (A) is a phenyl-substituted tertiary amine of formulae (I)-(III), as racemates, pure or mixed stereoisomers (particularly enantiomers or diastereoisomers), optionally in the form of acids, bases, salts or solvates, preferably hydrates. [Image] X : hydroxy, fluoro, chloro, hydrogen or OCOR 7; R 11-4C linear, branched, saturated or unsaturated alkyl, optionally substituted one or more times, in (I), or 1-4C alkyl, benzyl, trifluoromethyl, hydroxy, benzyloxy. 1-3C alkoxy, chloro or fluoro in (II); R 2 and R 3hydrogen or 1-4C alkyl (as for R 1) or together form an optionally substituted 4-7C cycloalkyl; R 9-R 1 3hydrogen, fluoro, chloro, bromo, iodo, (di)fluoromethyl, trifluoromethyl, hydroxy, thiol, OR 1 4, trifluoromethoxy, SR 1 4, NR 1 7R 1 8, (trifluoro)methyl- sulfinyl or -sulfonyl, cyano, COOR 1 4, nitro, CONR 1 7R 1 8, 1-6C alkyl (as above) or phenyl, optionally substituted one or more times; R 1 41-6C alkyl, pyridyl, thienyl, thiazolyl, phenyl, benzyl, phenethyl (all optionally substituted one or more times), PO(O-1-4C alkyl)-2, COO1-5C alkyl, CONH(1-3C alkylphenyl), CO(1-5C)alkyl, COCHR 1 7-NHR 1 8, or CO-phenylene-R 1 5; R 1 5ortho-OCO(1-3C)alkyl, or meta- or para-CH 2N(R 1 6) 2; R 1 61-4C alkyl or morpholino, and all alkyl in R 1 4-R 1 6 are optionally substituted one or more times; R 1 7 and R 1 8hydrogen, 1-6C alkyl (as above), phenyl, benzyl or phenethyl, all optionally substituted one or more times; R 1 0 with either of R 9 or R 1 together : a OCH 2O, OCH 2CH 2O, OCH=CH, CH=CHO, CH=CMeO, OCMe=CH, (CH 2) 4 or OCH=CHO ring; proviso: in (III), when R 9, R 1 1 and R 1 3 are all hydrogen, one of R 1 0 and R 1 2 is hydrogen and the other methoxy, then X is nor hydroxy. ACTIVITY : Analgesic. In the mouse writhing test ( J. Pharmacol. Exp. Ther., 228 (1984) 1) animals were treated with (a) (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol (X); (b) rofecoxib (Y) or (c) a mixture of both at ratio 1:2, then after 30 minutes injected with acetic acid. The ED50 for reduction of writhing was 33 mg/kg for (X) alone and 60.1 mg/kg for (Y) alone, but only 23.3 mg/kg (compare 47 mg/kg for an additive effect) for the mixture. MECHANISM OF ACTION : None given.