Substituted phenylacetic acids

A composition comprising a pharmaceutically acceptable excipient and a compound having the formula:

• wherein
• X is a member selected from the group consisting of O, S, SO, SO2 and NR, wherein R is H, (C1–C8)alkyl, CORa, COORa and CONRaRb wherein Raand Rb are each independently selected from the group consisting of H and (C1–C8)alkyl;
• Y is a member selected from the group consisting of CH2ORc, CO2Rc, CHO, CONRcRm, CH(═NRc), CH(═NORc), C(O)NHSO2Rn), sulfonic acids, sulfinic acids, phosphonic acids, phosphinic acids, activated carboxamides, hydroxamic acids, tetrazole, triazole, hydroxypyrazole, hydroxyoxazole, acidic alcohols and SO2NHX1, wherein X1 is an electron withdrawing group relative to an alkyl group, Rc is a member selected from the group consisting of H, (C1–C8)alkyl, (C3–C8)alkenyl, (C3–C8)alkynyl, (C3–C7)cycloalkyl, (C4–C8)cycloalkyl-alkyl, aryl, aryl(C1–C8)alkyl and (C1–C8)alkylene-Z, wherein Z is selected from the group consisting of CORd, COORd, NRdRe, NRdCONReRf, NRdCORe, NRdCOORe and CONRdRe wherein Rd, Re and Rf are each independently selected from the group consisting of H, (C1–C8)alkyl and phenyl, or optionally two of Rd, Re and Rf when attached to the same nitrogen atom are combined to form a five- or six-membered ring;
• and wherein Rm is selected from the group consisting of H, (C1–C8)alkyl, aryl, OH and SO2Rn, wherein Rn is selected from the group consisting of (C1–C8)alkyl (C1–C8)haloalkyl, (C1–C8)aralkyl, (C1–C8)heteroalkyl, aryl, heteroaryl, (C1–C8)alkoxyl, aryloxyl, alkylamino, dialkylamino, arylamino, diarylamino, haloalkylamino and di(haloalkyl)amino;
• and Rm and Rc are optionally combined with the nitrogen atom to which each is attached to form a five- or six-membered ring;
• HAr is benzo-1,2,3-triazole, optionally substituted with from one to three substituents independently selected from the group consisting of halogen, hydroxy, (C1–C8)alkyl, aryl(C1–C8)alkyl, (C1–C8)alkoxy, (C2–C8)alkenyl, (C2–C8)alkynyl, (C3–C7)cycloalkyl, (C4–C8)cycloalkyl-alkyl, (C1–C8)heteroalkyl, (C2–C5)heterocyclyl, aryl, aryloxy, heterosubstituted(C3–C7)cycloalkyl, heteroalkyl substituted (C3–C7)cycloalkyl, (C1–C8)haloalkyl, O(C1–C8)haloalkyl, nitro, cyano, CO2Rg, CORg, NRgRh, S(O)qRg, SO2NRgRh, NRgCONRhRi, NRgCORh, NRgCOORh and CONRgRh, wherein Rg, Rh and Ri are each independently selected from the group consisting of H and (C1–C8)alkyl, or optionally two of Rg, Rh and Ri when attached to the same nitrogen atom are combined to form a five- or six-membered ring, and the subscript q is an integer of from 0 to 2;
• each R1 and R3 is a member independently selected from the group consisting of halogen, hydroxy, (C1–C8)alkyl, (C2–C8)alkenyl, (C2–C8)alkynyl, (C1–C8)alkoxy, (C3–C7)cycloalkyl, (C4–C8)cycloalkyl-alkyl, (C1–C8)haloalkyl, (C1–C8)heteroalkyl, (C2–C5)heterocyclyl, heterosubstituted(C3–C7)cycloalkyl, heteroalkyl substituted (C3–C7)cycloalkyl, O(C1–C8)haloalkyl, nitro, cyano, phenyl, O-phenyl, NRj-phenyl, S(O)r-phenyl, CORj, COORj, NRjRk, S(O)rRj,SO2NRjRk, NRjCONRkRl, NRjCORk, NRjCOORk and CONRjRk wherein the phenyl ring is optionally substituted and Rj, Rk and Rl are each independently selected from the group consisting of H, (C1–C8)alkyl and (C1–C8)haloalkyl, or optionally two of Rj, Rk and Rl when attached to the same nitrogen atom are combined to form a five- or six-membered ring, and the subscript r is an integer of from 0 to 2;
• R2 is a member selected from the group consisting of H, (C1–C8)alkyl, (C1–C8)haloalkyl, aryl(C1–C8)alkyl and (C1–C4)alkylene-Z, wherein Z is as defined above;
• the subscript m is an integer of from 0 to 4;
• the subscript p is an integer of from 0 to 3;
• and
• pharmaceutically acceptable salts thereof.

A prodrug agent having a formula selected from the group consisting of:

• wherein
• X is a member selected from the group consisting of O, S, SO, SO2 and NR, wherein R is H, (C1–C8)alkyl, CORa, COORa and CONRaRb wherein Ra and Rb are each independently selected from the group consisting of H and (C1–C8)alkyl;
• Y is CO2R″, wherein R″ is selected from the group consisting of alkyl, heteroalkyl, aryl, heteroaryl, phenyl-lower alkyl, benzamido-lower alkyl, di-lower alkylamino-lower alkyl, ureido-lower alkyl, N′-lower alkyl-ureido-lower alkyl, carbamoyl-lower alkyl, halophenoxy substituted lower alkyl and carbamoyl substituted phenyl;
• HAr is benzo-1,2,3-trizole, optionally substituted with from one to three substituents independently selected from the group consisting of halogen, hydroxy, (C1–C8)alkyl, aryl(C1–C8)alkyl, (C1–C8)alkoxy, (C2–C8)alkenyl, (C2–C8)alkynyl, (C3–C7)cycloalkyl, (C4–C8)cycloalkyl-alkyl, (C1–C8)heteroalkyl, (C2–C5)heterocyclyl, aryl, aryloxy, heterosubstituted(C3–C7)cycloalkyl, heteroalkyl substituted (C3–C7)cycloalkyl, (C1–C8)haloalkyl, O(C1–C8)haloalkyl, nitro, cyano, CO2Rg, CORg, NRgRh, S(O)qRg, SO2NRgRh, NRgCONRhRi, NRgCORh, NRgCOORh and CONRgRh, wherein Rg, Rh and Ri are each independently selected from the group consisting of H and (C1–C8)alkyl, or optionally two of Rg, Rh and Ri when attached to the same nitrogen atom are combined to form a five- or six-membered ring, and the subscript q is an integer of from 0 to 2;
• each R1 and R3 is a member independently selected from the group consisting of halogen, hydroxy, (C1–C8)alkyl, (C2–C8)alkenyl, (C2–C8)alkynyl, (C1–C8)alkoxy, (C3–C7)cycloalkyl, (C4–C8)cycloalkyl-alkyl, (C1–C8)haloalkyl, (C1–C8)heteroalkyl, (C2–C5)heterocyclyl, heterosubstituted(C3–C7)cycloalkyl, heteroalkyl substituted (C3–C7)cycloalkyl, O(C1–C8)haloalkyl, nitro, cyano, phenyl, O-phenyl, NRj-phenyl, S(O)r-phenyl, CORj, COORj, NRjRk, S(O)rRj, SO2NRjRk, NRjCONRkRl, NRjCORk, NRjCOORk and CONRjRk wherein the phenyl ring is optionally substituted and Rj, Rk and Rl are each independently selected from the group consisting of H, (C1–C8)alkyl and (C1–C8)haloalkyl, or optionally two of Rj, Rk and Rl when attached to the same nitrogen atom are combined to form a five- or six-membered ring, and the subscript r is an integer of from 0 to 2;
• R2 is a member selected from the group consisting of H, (C1–C8)alkyl, (C1–C8)haloalkyl, aryl(C1–C8)alkyl and (C1–C4)alkylene-Z, wherein Z is as defined above;
• the subscript m is an integer of from 0 to 4;
• the subscript p is an integer of from 0 to 3;
• and
• pharmaceutically acceptable salts thereof.