Preparation of oxygenated esters of 4-iodophenylamino benzhydroxamic acids as MEK inhibitors.

Abstract

The title compds. [I; R1 = H, halo, NO2; R2 = H, F; R3 = H, F; R4 = H, I, Br, Cl, F; R5 = H, halo, OH, etc.; n = 1-5; R6-R10 = H, alkyl, cycloalkyl, etc.; W = O, NRa; Ra = H, alkyl; R11 = H, alkyl, Ph, etc.] and their salts, useful in treating cancer, restenosis, psoriasis, atherosclerosis, osteoarthritis, rheumatoid arthritis, heart failure, and chronic pain, were prepd. Thus, reacting 2-(4-iodo-2-methylphenylamino)-3,4,5-trifluorobenzoic acid with O-(2-vinyloxyethyl)hydroxylamine (73%) followed by treatment of the resulting amide with 1M HCl (75%) afforded I [R1-R3 = F; R4 = I; R5 = Me; R6-R11 = H; W = O; n = 1] which showed IC50 of 0.008 μM against phosphorylation of MAP kinase (ERK) in murine colon 26 (C26) carcinoma cells. The present invention also relates to cryst. forms of oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivs. [on SciFinder(R)]