Preparation of heterocyclyl sulfonylbenzene compounds as anti-inflammatory/analgesic agents.

Abstract

This invention provides a compd. of formula (I) or its pharmaceutically acceptable salt thereof [wherein A is partially unsatd. or unsatd. five membered heterocyclic, or partially unsatd. or unsatd. five membered carbocyclic, wherein the 4-(sulfonyl)phenyl and the 4-substituted Ph in formula I are attached to ring atoms of Ring A, which are adjacent to each other; R1 is optionally substituted aryl or heteroaryl, with the proviso that when A is pyrazole, R1 is heteroaryl; R2 is C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkylamino, C1-4 dialkylamino or amino; R3, R4 and R5 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl or the like; or two of R3, R4 and R5 are taken together with atoms to which they are attached and form a 4-7 membered ring; R6 and R7 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino or N,N-di C1-4 alkylamino; and m and n are independently 1, 2, 3 or 4]. This invention also provides a pharmaceutical compn. useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens. This invention relates to compd. and pharmaceutical compns. for the treatment of cyclooxygenase mediated diseases. These compds. inhibit the biosynthesis of prostaglandins by intervention of the action of the enzyme cyclooxygenase on arachidonic acid, and are therefore useful in the treatment or alleviation of inflammation and other inflammation assocd. disorders, such as arthritis, in mammals (no data). Thus, To a stirred soln. of 1-[4-(Methylsulfonyl)phenyl]-5-(4-bromophenyl)-3-trifluoromethyl-1H-pyrazole (0.27 g) in DME (8 mL) was added 3-thiophenboronic acid (0.09 g), bis(triphenylphosphine)palladium(II)chloride (0.05 g) and satd. NaHCO3 soln. (2 mL) at room temp. under nitrogen. The mixt. was heated at reflux temp. for 16 h, and cooled down to room temp. to give, after purifn. by flash chromatog. eluting with Et acetate/hexane (1/1), 1-[4-(Methylsulfonyl)phenyl]-5-[4-(2-thienyl)phenyl]-3-trifluoromethyl-1H-pyrazole (II) in 64 % yield. [on SciFinder(R)]