abstract |
Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof. In Formula (I) m is 0, 1, 2, 3 or 4; n is 0 or 1; m + n is not more than 4; t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. R 6 is hydrogen, methyl or ethyl and R 12 is hydrogen or methyl, or R 6 is hydroxy and R 12 is hydrogen, or R 6 is O and R 12 is absent, or R 6 and R 12 together are -CH 2 CH 2 -. R 7 is hydrogen or alkyl having from 1 to 3 carbon atoms. One of R 8 and R 9 is alkyl having from 1 to 3 carbon atoms, and the other is hydrogen or alkyl having from 1 to 3 carbon atoms. R 10 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms or alkoxy having from 1 to 3 carbon atoms. X is C(O) and r is 0 and t is 0; or X is NH(R 11 ) wherein R 11 is hydrogen or alkyl having from 1 to 3 carbon atoms. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of Formula (I) by a ring carbon; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently monosubstituted by methyl or ethyl. The uric acid-lowering effects of the Compounds of Formula (I) are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, and cognitive impairment. |