BENZOIC ACID COMPOUNDS FOR REDUCING URIC ACID

摘要

Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I. The uric acid-lowering effects of the compounds of this invention 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, cognitive impairment, early-onset essential hypertension, and Plasmodium falciparum-induced inflammation.;;In Formula I, t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. R7 is hydrogen or alkyl having from 1 to 3 carbon atoms. R6 is hydrogen, hydroxy, halo, alkyl having from 1 to 3 carbon atoms, alkoxy having from 1 to 3 carbon atoms, nitro, thio, alkylthio, or cyano. X is C(O) or NH(R8) wherein R8 is hydrogen or alkyl having from 1 to 3 carbon atoms; provided that when X is C(O), r is 0 and t is 0. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, perfluoromethoxy, nitro, and amino; 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.

主权项

1. A method of reducing the uric acid concentration in blood of, or increasing uric acid excretion from, a mammalian subject, comprising administering to the subject a compound represented by Formula I or a pharmaceutically acceptable salt thereof, in an amount effective to reduce the uric acid concentration in blood of, or increase uric acid excretion from, the subject wherein t is 0 or 1; q is 0 or 1; r is 0, 1 or 2; R7 is hydrogen or alkyl having from 1 to 3 carbon atoms; R6 is hydrogen, hydroxy, halo, alkyl having from 1 to 3 carbon atoms, alkoxy having from 1 to 3 carbon atoms, nitro, thio, alkylthio, or cyano; X is C(O) or NH(R8) wherein R8 is hydrogen or alkyl having from 1 to 3 carbon atoms; provided that when X is C(O), r is 0 and t is 0; A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, perfluoromethoxy, nitro, and amino; 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; orcycloalkyl 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.