Details for Patent: 8,242,154

Title:	Compounds, compositions and methods of using same for modulating uric acid levels
Abstract:	Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.
Inventor(s):	Gunic; Esmir (San Diego, CA), Girardet; Jean-Luc (San Diego, CA), Vernier; Jean-Michel (San Diego, CA), Tedder; Martina E. (Capistrano Beach, CA), Paisner; David A. (Encinitas, CA)
Assignee:	Ardea Biosciences, Inc. (San Diego, CA)
Filing Date:	Sep 04, 2009
Application Number:	12/554,719
Claims:	1. A compound of formula (II), or a pharmaceutically acceptable salt, ester or tautomer thereof: ##STR00199## wherein: W is O, S, S(O), S(O).sub.2, NH, N(optionally substituted alkyl), CH.sub.2, CH.sub.2O, CH.sub.2S or CH.sub.2NH; R.sup.1 is F, Cl, Br, I, CH.sub.2F, CF.sub.2H, CF.sub.3, CN, OH, NO.sub.2, NH.sub.2, NH(alkyl) or N(alkyl)(alkyl), SO.sub.2CH.sub.3, SO.sub.2NH.sub.2, SO.sub.2NHCH.sub.3, CO.sub.2-alkyl, optionally substituted alkenyl, optionally substituted alkoxy, optionally substituted S-alkyl, optionally substituted cycloalkyl, optionally substituted heterocycle, or optionally substituted aryl; a is 0, 1 or 2; R.sup.a is H or optionally substituted C.sub.1-3 alkyl; R.sup.a' is H or optionally substituted C.sub.1-3 alkyl; or R.sup.a and R.sup.a' together with the carbon atom to which they are attached form an optionally substituted, 3-, 4-, 5- or 6-membered ring, optionally comprising 1 or 2 heteroatoms selected from O, N and S; R.sup.b, R.sup.c, R.sup.e and R.sup.f are each independently H, F, Cl, Br, I, CF.sub.3, CN, alkyl, cycloalkyl, cyclopropylmethyl, NH.sub.2, NHR', NR'R'', OH, OR', SH, SR', C(O)R', CO.sub.2H, COOR', CONH.sub.2, CONHR', CONR'R'', SO.sub.3H, S(O).sub.2R', S(O).sub.2NH.sub.2, S(O).sub.2NHR', S(O).sub.2NR'R'', aryl, heterocyclyl or heteroaryl; R.sup.d is F, Cl, Br, I, CF.sub.3, CN, NH.sub.2, NHR', NR'R'', OH, OR', SH, SR', C(O)R', CO.sub.2H, COOR', CONH.sub.2, CONHR', CONR'R'', SO.sub.3H, S(O).sub.2R', S(O).sub.2NH.sub.2, S(O).sub.2NHR', S(O).sub.2NR'R'', aryl, heterocyclyl or heteroaryl; wherein R' is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl or phenyl; R'' is methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl or phenyl; or R' and R'' together with the nitrogen atom to which they are attached form an optionally substituted, saturated or unsaturated 4-, 5- or 6-membered heterocyclic ring; or R.sup.b and R.sup.c, or R.sup.c and R.sup.d, or R.sup.d and R.sup.e, or R.sup.e and R.sup.f together with the two carbon atoms to which they are attached, form an optionally substituted, aromatic or non-aromatic, 5-, 6- or 7-membered ring, optionally comprising 1 or 2 heteroatoms selected from O, N and S, and wherein said ring may be optionally fused to 1 or 2 additional optionally substituted, aromatic or non-aromatic, 5-, 6- or 7-membered rings, optionally comprising 1 or 2 heteroatoms selected from O, N and S; and wherein the optional substituents are each independently F, Cl, Br, I, CF.sub.3, CN, alkyl, cycloalkyl, cyclopropylmethyl, NH.sub.2, NHR', NR'R'', OH, OR', SH, SR', C(O)R', CO.sub.2H, COOR', CONH.sub.2, CONHR', CONR'R'', SO.sub.3H, S(O).sub.2R', S(O).sub.2NH.sub.2, S(O).sub.2NHR', S(O).sub.2NR'R'', aryl, heterocyclyl or heteroaryl; x is 0 or 1; y is 0 or 1; z is 0 or 1; R.sup.x, R.sup.x', R.sup.y, R.sup.y', R.sup.z and R.sup.z' are each independently H, F, Cl, Br, or optionally substituted C.sub.1-3 alkyl; or R.sup.x and R.sup.x', or R.sup.y and R.sup.y', or R.sup.z and R.sup.z', or R.sup.x and R.sup.y, or R.sup.y and R.sup.z, or R.sup.x and R.sup.z together with the carbon atoms to which they are attached, form an optionally substituted, aromatic or non-aromatic, 3-7 membered ring, optionally comprising 1 or 2 heteroatoms selected from O, N and S, and wherein said ring may be optionally fused to 1 or 2 additional optionally substituted, aromatic or non-aromatic, 5-, 6- or 7-membered rings, optionally comprising 1 or 2 heteroatoms selected from O, N and S; A is H, C(O)O--B.sup.1 or C(O)NH--B.sup.2; wherein B' is H, optionally substituted C.sub.1-6 alkyl or a pharmaceutically acceptable cation; B.sup.2 is H or optionally substituted C.sub.1-6 alkyl; and wherein all alkyl, alkylene, cycloalkyl, heterocyclyl, aryl and heteroaryl moieties may be optionally further substituted. 2. The compound of claim 1, wherein W is S. 3. The compound of claim 1, wherein R.sup.1 is F, Cl, Br, CH.sub.2F, CF.sub.2H, CF.sub.3, NH.sub.2, or optionally substituted phenyl. 4. The compound of claim 1, wherein W is S; and R.sup.1 is Br. 5. The compound of claim 1, wherein a is 1; R.sup.a is H; and R.sup.a' is H. 6. The compound of claim 1, wherein A is C(O)O--B.sup.1. 7. The compound of claim 1, wherein A is C(O)O--B.sup.1; x is 1; and R.sup.x and R.sup.x' are not H. 8. The compound of claim 1, wherein R.sup.x and R.sup.x' together with the carbon atoms to which they are attached, form an optionally substituted, non-aromatic 3 membered ring. 9. The compound of claim 1, wherein R.sup.b, R.sup.c, R.sup.e and R.sup.f are all H. 10. The compound of claim 1, wherein R.sup.b and R.sup.c together with the two carbon atoms to which they are attached, form an aromatic, 6-membered ring. 11. A method of treating gout in an individual, the method comprising administering to the individual a therapeutically effective amount of a compound of claim 1. 12. A method of treating hyperuricemia in an individual or reducing serum uric acid in an individual in need thereof, the method comprising administering to the individual a therapeutically effective amount of a compound of claim 1. 13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, and a pharmaceutically acceptable excipient.