Compounds, compositions and methods of using same for modulating uric acid levels

Abstract

A compound having the following structure: Or a metabolite, solvate, polymorph, ester, tautomer or prodrug thereof, Wherein W is O or S; R1 is H, F, Cl, BrJ.-CKzF^H, -CF3, CN, OH, -NO2, -NH2, -NH(Ci-4alkyl), -N(Ci-4 alkyl)(Ci-4alkyl), -SO2CH3, -SO2NH2, -SO2 NHCH3, -CO2-Ci-4alkyl, Ci-4alky1, Ci-ί alkenyl, Ci-4alkoxy, Ci-4S-alkyl, Ca-ecycloalkyl, optionally substituted Ci-eheterocycloalkyl, optionally substituted phenyl, or optionally substituted 5 or 6 membered heteroaryl; Rd is F, Ci, Br, I, CF3, aryl, heteroaryl, CN, NO2, NH2, NHR’, OH, OR’, SH, SR',C(O)R*, CO2H, COOR', CONH2, CONHR', CONR'R", SO3H, SO3R', S(O)2R’, S(O)2NH2,S(O)2NHR’, or S(O)2NR'R"; Rtn is zero to four substituents· independently selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heteroalkenyl, optionally substituted hetergalkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, halo, CN, NH2, NHR’, NR'R", OH, OR', SH, SR', C(O)R‘, CO2H, COOR', CONH2,CONHR', CONR’R", SO3H, S(O)2R', S(O)2NH2, S(O)2NHR, or S(0).2NR'R”· each R' is independently methyl, ethyl, npropyI, i-propyl, n-butyl, i-butyl, s-butyl, tbutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyl methyl or phenyl; each R" is independently methyl, ethyl, npropyl, i-propyl, ή-butyl, i-butyl, s-butyl, tbutyl, cydopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl or phenyl; or R' and R" are together with the atom to which they are attached form an optionally substituted, Saturated or unsaturated.4-, 5- or 6membered ring; Rx ahd Rx‘ arb each independently H, optionally substituted jalkyl, optionally substituted alkenyl, optiohaljy substituted alkynyl, optionally substituted heteroalkyl, optionally substituted heteroalkenyl, optionally substituted heterqalkyriyl, optionally substituted cycloalkyi, optionally substituted cycloalkenyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, halo, CN, NH2, NHR’, NR'R", OH, OR', SH, SR’, C(O)R’, CO2H, COOR', CONH2, CONHR', CONR’R’ SOsH, S(O)2R', S(O)2NH2, S(O)2NHR', or S(O)2NR’R"; or Rx and Rx‘ together with the carbon atom to whrch they are attached / form an optionally Mibstitufed noh-aromatic 3-7 membered ring, optionally, comprising 1 or 2 heteroatoms selected from 0, N and S; B3 is OB1, NB22, or an amino acid residue or an alkyfester thereof; B1 is optionally substituted Ci-β alkyl or a phprmaceuticaWy acceptable cation; and each is independently H Oroptionally substituted alkyl. and pharmaceutical composition comprising a therapeutically effective amount of the compound for use in the treatment of gout and hyperuricemia.