Novel compounds and compositions and methods of use

A compound of formula (II), wherein the compound of formula (II) is a 3-substituted-5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole wherein the substituent at the 3-position is —RB, or pharmaceutically acceptable salt, solvate, or tautomer thereof:

• wherein,
• RB is —SCH2C(═O)R1a, —SCH2-tetrazolyl, —SCH2C(═O)NHOH, —SCH2C(═O)O-alkyl-OC(═O)R3a, —SCH2C(═O)O-alkyl-OC(═O)OR3a, —SCH2C(═O)O-alkyl-OC(═O)NR4aR4b, or —SCH2C(Oalkyl)3;
• R1a is OR2a, SR3a, NR4aR4b, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, or a combination thereof, wherein
• R2a is substituted C1-C4 alkyl, optionally substituted C5-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl;
• or
• R2a is a pharmaceutically acceptable cation;
• or
• R2a is —[C(R5a)(R5b)]mR5c;
• R3a is hydrogen, optionally substituted C1-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl;
• or
• R3a is —[C(R5a)(R5b)]nR5c;
• R4a is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• and
• R4b is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• or
• R4b is —[C(R5a)(R5b)]nR5c, wherein
• each R5a is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• each R5b is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• R5c is hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4alkylamine, optionally substituted -L-di(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• wherein L is a bond, —C(O)—, —S(O), or —S(O)2;
• y1 is 0, 1, 2 or 3;
• Y is OH, OMe, COOH, SO3H, OSO3H, OS(O)2NH2, P(O)(OH)2, OP(O)(OH)2, OP(O)(OH)(O—C1-4 alkyl) or NY2Y3Y4;
• wherein
• Y2 and Y3 are each independently hydrogen or methyl;
• or
• Y2 and Y3 are taken together with the nitrogen to which they are attached to form a five or six membered ring that optionally contains an oxygen atom or a second nitrogen atom;
• and
• Y4 is an electron pair or an oxygen atom;
• m is 1, 2, 3, 4;
• n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• and wherein if R2a is —[C(R5a)(R5b)]mR5c then at least one of R5a, R5b and R5c is not hydrogen.

A method for decreasing uric acid levels in one or more tissues or organs, blood, serum, urine, or combinations thereof of an individual in need of decreased uric acid levels, comprising administering to the individual a uric acid level decreasing amount of:

• (i) a compound of formula (I);
• or
• (ii) a compound of formula (II), wherein the compound of formula (II) is a 3-substituted-5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole wherein the substituent at the 3-position is —RB;
• (iii) a compound of formula (III);
• or
• (iv) a combination thereof;
• wherein
• X is CH or N;
• W is O, S, S(O), S(O)2, NH, N (optionally substituted alkyl), NC(O)(optionally substituted alkyl) or CH2;
• R1 is H, Cl, Br, I, NH2, methyl, ethyl, n-propyl, i-propyl, optionally substituted methyl, optionally substituted ethyl, optionally substituted n-propyl, optionally substituted i-propyl, CF3, CHF2 or CH2F;
• R3 and R3′ are independently selected from H and lower alkyl, or R3 and R3′ together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O;
• R2 is selected from the group consisting of (a), (b), (c) and (d):
• wherein
• represents a carbon-carbon single bond or a carbon-carbon double bond;
• Q and Q′ are independently selected from N and CH;
• RP is methyl, ethyl, propyl, i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclopropylmethyl;
• R8, R9 and R10 are independently selected from H, F, Cl, Br, CH3, CF3, CFH2, CF2H, ethyl, i-propyl, cyclopropyl, methoxy, OH, OCF3, NH2 and NHCH3;
• R11 is Cl, Br, I, CH3, CF3, methoxy, i-propyl, cyclopropyl, tert-butyl, cyclobutyl or methyl;
• and
• R12, R13, R14 and R15 are independently H or methyl;
• RB is —SCH2C(═O)R1a, —SCH2-tetrazolyl, —SCH2C(═O)NHOH, —SCH2C(═O)O-alkyl-OC(═O)R3a, —SCH2C(═O)O-alkyl-OC(═O)OR3a, —SCH2C(═O)O-alkyl-OC(═O)NR4aR4b, or —SCH2C(Oalkyl)3;
• R1a is OR2a, SR3a, NR4aR4b at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, or a combination thereof, wherein
• R2a is substituted C1-C4 alkyl, optionally substituted C5-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl;
• or
• R2a is a pharmaceutically acceptable cation;
• or
• R2a is —[C(R5a)(R5b)]mR5c;
• R3a is hydrogen, optionally substituted C1-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl;
• or
• R3a is —[C(R5a)(R5b)]nR5c;
• R4a is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• and
• R4b is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• or
• R4b is —[C(R5a)(R5b)]nR5c, wherein
• each R5a is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• each R5b is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• R5c is hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4alkylamine, optionally substituted -L-di(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• wherein L is a bond, —C(O)—, —S(O), or —S(O)2;
• y1 is 0, 1, 2 or 3;
• Y is OH, OMe, COOH, SO3H, OSO3H, OS(O)2NH2, P(O)(OH)2, OP(O)(OH)2, OP(O)(OH)(O—C1-4 alkyl) or NY2Y3Y4;
• wherein
• Y2 and Y3 are each independently hydrogen or methyl;
• or
• Y2 and Y3 are taken together with the nitrogen to which they are attached to form a five or six membered ring that optionally contains an oxygen atom or a second nitrogen atom;
• and
• Y4 is an electron pair or an oxygen atom;
• m is 1, 2, 3, 4;
• n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• and wherein if R2a is —[C(R5a)(R5b)]mR5c then at least one of R5a, R5b and R5c is not hydrogen;
• R4 is H, lower alkyl, lower alkenyl or lower alkynyl;
• R5, R5′, R6, R6′ and R7 are independently selected from H, F, Cl, Br, I, methyl, ethyl, n-propyl, i-propyl, substituted methyl, substituted ethyl, substituted n-propyl, substituted i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, CF3, CHF2, CH2F, NH2, NHR′, NR′R″, OR′, SR′, C(O)R′, CO2H, a salt of CO2H, COOR′, CONH2, CONHR′, CONR′R″, SO3H, a salt of SO3H, S(O)2R′, S(O)2NH2, S(O)2NHR′, S(O)2NR′R″, aryl or a heterocycle, wherein
• R′ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)(C1-3 alkyl), CONHC1-3 alkyl, aryl or a heterocycle;
• R″ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)2, CONHC1-3 alkyl, aryl or a heterocycle;
• or
• R′ and R″ together with the nitrogen atom to which they are attached form a 4-, 5-, or 6-membered heterocyclic ring;
• or a metabolite, pharmaceutically acceptable salt, solvate, ester, tautomer or prodrug thereof.

A method of treating or preventing a condition characterized by abnormal tissue or organ levels of uric acid in an individual comprising administering to the individual an effective amount of:

• (i) a compound of formula (I);
• or
• (ii) a compound of formula (II), wherein the compound of formula (II) is a 3-substituted-5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole wherein the substituent at the 3-position is —RB;
• or
• (iii) a compound of formula (III);
• or
• (iv) a combination thereof;
• wherein
• X is CH or N;
• W is O, S, S(O), S(O)2, NH, N (optionally substituted alkyl), NC(O)(optionally substituted alkyl) or CH2;
• R1 is H, Cl, Br, I, NH2, methyl, ethyl, n-propyl, i-propyl, optionally substituted methyl, optionally substituted ethyl, optionally substituted n-propyl, optionally substituted i-propyl, CF3, CHF2 or CH2F;
• R3 and R3′ are independently selected from H and lower alkyl, or R3 and R3′ together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O;
• R2 is selected from the group consisting of (a), (b), (c) and (d):
• wherein
• represents a carbon-carbon single bond or a carbon-carbon double bond;
• Q and Q′ are independently selected from N and CH;
• RP is methyl, ethyl, propyl, i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclopropylmethyl;
• R8, R9 and R19 are independently selected from H, F, Cl, Br, CH3, CF3, CFH2, CF2H, ethyl, i-propyl, cyclopropyl, methoxy, OH, OCF3, NH2 and NHCH3;
• R11 is Cl, Br, I, CH3, CF3, methoxy, i-propyl, cyclopropyl, tert-butyl, cyclobutyl or methyl;
• and
• R11, R13, R14 and R15 are independently H or methyl;
• RB is —SCH2C(═O)R1a, —SCH2-tetrazolyl, —SCH2C(═O)NHOH, —SCH2C(═O)O-alkyl-OC(═O)R3a, —SCH2C(═O)O-alkyl-OC(═O)OR3a, —SCH2C(═O)O-alkyl-OC(═O)NR4aR4b, or —SCH2C(Oalkyl)3;
• R1a is OR2a, SR3a, NR4aR4b at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, or a combination thereof, wherein
• R2a is substituted C1-C4 alkyl, optionally substituted C5-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl;
• or
• R2a is a pharmaceutically acceptable cation;
• or
• R2a is —[C(R5a)(R5b)]mR5c;
• R3a is hydrogen, optionally substituted C1-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl;
• or
• R3a is —[C(R5a)(R5)]nR5c;
• R4a is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• and
• R4b is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• or
• R4b is —[C(R5a)(R5b)]nR5c, wherein
• each R5a is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• each R5b is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• R5c is hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4alkylamine, optionally substituted -L-di(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• wherein L is a bond, —C(O)—, —S(O), or —S(O)2;
• y1 is 0, 1, 2 or 3;
• Y is OH, OMe, COOH, SO3H, OSO3H, OS(O)2NH2, P(O)(OH)2, OP(O)(OH)2, OP(O)(OH)(O—C1-4 alkyl) or NY2Y3Y4;
• wherein
• Y2 and Y3 are each independently hydrogen or methyl;
• or
• Y2 and Y3 are taken together with the nitrogen to which they are attached to form a five or six membered ring that optionally contains an oxygen atom or a second nitrogen atom;
• and
• Y4 is an electron pair or an oxygen atom;
• m is 1, 2, 3, 4;
• n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• and wherein if Rea is —[C(R5a)(R5b)]mR5c then at least one of R5a, R5b and R5c is not hydrogen;
• R4 is H, lower alkyl, lower alkenyl or lower alkynyl;
• R5, R5′, R6, R6′ and R7 are independently selected from H, F, Cl, Br, I, methyl, ethyl, n-propyl, i-propyl, substituted methyl, substituted ethyl, substituted n-propyl, substituted i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, CF3, CHF2, CH2F, NH2, NHR′, NR′R″, OR′, SR′, C(O)R′, CO2H, a salt of CO2H, COOR′, CONH2, CONHR′, CONR′R″, SO3H, a salt of SO3H, S(O)2R′, S(O)2NH2, S(O)2NHR′, S(O)2NR′R″, aryl or a heterocycle, wherein
• R′ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)(C1-3 alkyl), CONHC1-3 alkyl, aryl or a heterocycle;
• R″ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)2, CONHC1-3 alkyl, aryl or a heterocycle;
• or
• R′ and R″ together with the nitrogen atom to which they are attached form a 4-, 5-, or 6-membered heterocyclic ring;
• or a metabolite, pharmaceutically acceptable salt, solvate, ester, tautomer or prodrug thereof.

A method of treating or preventing cancer which also maintains uric acid levels at pretreatment levels or causes a decrease in uric acid levels, comprising administering:

• a) an effective amount of an anticancer agent;
• b) a uric acid level maintaining or lowering amount of:
• (i) a compound of formula (I);
• or
• (ii) a compound of formula (II), wherein the compound of formula (II) is a 3-substituted-5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole wherein the substituent at the 3-position is —RB;
• or
• (iii) a compound of formula (III);
• or
• (iv) a combination thereof;
• wherein
• X is CH or N;
• W is O, S, S(O), S(O)2, NH, N (optionally substituted alkyl), NC(O)(optionally substituted alkyl) or CH2;
• R1 is H, Cl, Br, I, NH2, methyl, ethyl, n-propyl, i-propyl, optionally substituted methyl, optionally substituted ethyl, optionally substituted n-propyl, optionally substituted i-propyl, CF3, CHF2 or CH2F;
• R3 and R3′ are independently selected from H and lower alkyl, or R3 and R3′ together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O;
• R2 is selected from the group consisting of (a), (b), (c) and (d):
• wherein
• represents a carbon-carbon single bond or a carbon-carbon double bond;
• Q and Q′ are independently selected from N and CH;
• RP is methyl, ethyl, propyl, i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclopropylmethyl;
• R8, R9 and R10 are independently selected from H, F, Cl, Br, CH3, CF3, CFH2, CF2H, ethyl, i-propyl, cyclopropyl, methoxy, OH, OCF3, NH2 and NHCH3;
• R11 is Cl, Br, I, CH3, CF3, methoxy, i-propyl, cyclopropyl, tert-butyl, cyclobutyl or methyl;
• and
• R12, R13, R14 and R15 are independently H or methyl;
• RB is —SCH2C(═O)R1a, —SCH2-tetrazolyl, —SCH2C(═O)NHOH, —SCH2C(═O)O-alkyl-OC(═O)R3a, —SCH2C(═O)O-alkyl-OC(═O)OR3a, —SCH2C(═O)O-alkyl-OC(═O)NR4aR4b, or —SCH2C(Oalkyl)3;
• R1a is OR2a, SR3a, NR4aR4b at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, or a combination thereof, wherein
• R2a is substituted C1-C4 alkyl, optionally substituted C5-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl;
• or
• R2a is a pharmaceutically acceptable cation;
• or
• R2a is —[C(R5a)(R5b)]mR5c;
• R3a is hydrogen, optionally substituted C1-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl;
• or
• R3a is —[C(R5a)(R5b)]nR5c;
• R4a is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• and
• R4b is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• or
• R4b is —[C(R5a)(R5b)]nR5c, wherein
• each R5a is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• each R5b is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• R5c is hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4alkylamine, optionally substituted -L-di(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• wherein L is a bond, —C(O)—, —S(O), or —S(O)2;
• y1 is 0, 1, 2 or 3;
• Y is OH, OMe, COOH, SO3H, OSO3H, OS(O)2NH2, P(O)(OH)2, OP(O)(OH)2, OP(O)(OH)(O—C1-4 alkyl) or NY2Y3Y4;
• wherein
• Y2 and Y3 are each independently hydrogen or methyl;
• or
• Y2 and Y3 are taken together with the nitrogen to which they are attached to form a five or six membered ring that optionally contains an oxygen atom or a second nitrogen atom;
• and
• Y4 is an electron pair or an oxygen atom;
• m is 1, 2, 3, 4;
• n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• and wherein if R2a is —[C(R5a)(R5b)]mR5c then at least one of R5a, R5b and R5c is not hydrogen;
• R4 is H, lower alkyl, lower alkenyl or lower alkynyl;
• R5, R5′, R6, R6′ and R7 are independently selected from H, F, Cl, Br, I, methyl, ethyl, n-propyl, i-propyl, substituted methyl, substituted ethyl, substituted n-propyl, substituted i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, CF3, CHF2, CH2F, NH2, NHR′, NR′R″, OR′, SR′, C(O)R′, CO2H, a salt of CO2H, COOR′, CONH2, CONHR′, CONR′R″, SO3H, a salt of SO3H, S(O)2R′, S(O)2NH2, S(O)2NHR′, S(O)2NR′R″, aryl or a heterocycle, wherein
• R′ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)(C1-3 alkyl), CONHC1-3 alkyl, aryl or a heterocycle;
• R″ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)2, CONHC1-3 alkyl, aryl or a heterocycle;
• or
• R′ and R″ together with the nitrogen atom to which they are attached form a 4-, 5-, or 6-membered heterocyclic ring;
• or a metabolite, pharmaceutically acceptable salt, solvate, ester, tautomer or prodrug thereof.

A pharmaceutical composition comprising:

• (i) a compound of formula (I);
• or
• (ii) a compound of formula (II), wherein the compound of formula (II) is a 3-substituted-5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole wherein the substituent at the 3-position is —RB;
• or
• (iii) a compound of formula (III);
• or
• (iv) a combination thereof;
• wherein
• X is CH or N;
• W is O, S, S(O), S(O)2, NH, N (optionally substituted alkyl), NC(O)(optionally substituted alkyl) or CH2;
• R1 is H, Cl, Br, I, NH2, methyl, ethyl, n-propyl, i-propyl, optionally substituted methyl, optionally substituted ethyl, optionally substituted n-propyl, optionally substituted i-propyl, CF3, CHF2 or CH2F;
• R3 and R3′ are independently selected from H and lower alkyl, or R3 and R3′ together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O;
• R2 is selected from the group consisting of (a), (b), (c) and (d):
• wherein
• represents a carbon-carbon single bond or a carbon-carbon double bond;
• Q and Q′ are independently selected from N and CH;
• RP is methyl, ethyl, propyl, i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclopropylmethyl;
• R8, R9 and R10 are independently selected from H, F, Cl, Br, CH3, CF3, CFH2, CF2H, ethyl, i-propyl, cyclopropyl, methoxy, OH, OCF3, NH2 and NHCH3;
• R11 is Cl, Br, I, CH3, CF3, methoxy, i-propyl, cyclopropyl, tert-butyl, cyclobutyl or methyl;
• and
• R12, R13, R14 and R15 are independently H or methyl;
• RB is —SCH2C(═O)R1a, —SCH2-tetrazolyl, —SCH2C(═O)NHOH, —SCH2C(═O)O-alkyl-OC(═O)R3a, —SCH2C(═O)O-alkyl-OC(═O)OR3a, —SCH2C(═O)O-alkyl-OC(═O)NR4aR4b, or —SCH2C(Oalkyl)3;
• R1a is OR2a, SR3a, NR4aR4b at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, or a combination thereof, wherein
• R2a is substituted C1-C4 alkyl, optionally substituted C5-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl;
• or
• R2a is a pharmaceutically acceptable cation;
• or
• R2a is —[C(R5a)(R5b)]mR5c;
• R3a is hydrogen, optionally substituted C1-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl;
• or
• R3a is —[C(R5a)(R5b)]nR5c;
• R4a is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• and
• R4b is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• or
• R4b is —[C(R5a)(R5b)]nR5c, wherein
• each R5a is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• each R5b is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• R5c is hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4alkylamine, optionally substituted -L-di(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• wherein L is a bond, —C(O)—, —S(O), or —S(O)2;
• y1 is 0, 1, 2 or 3;
• Y is OH, OMe, COOH, SO3H, OSO3H, OS(O)2NH2, P(O)(OH)2, OP(O)(OH)2, OP(O)(OH)(O—C1-4 alkyl) or NY2Y3Y4;
• wherein
• Y2 and Y3 are each independently hydrogen or methyl;
• or
• Y2 and Y3 are taken together with the nitrogen to which they are attached to form a five or six membered ring that optionally contains an oxygen atom or a second nitrogen atom;
• and
• Y4 is an electron pair or an oxygen atom;
• m is 1, 2, 3, 4;
• n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• and wherein if R2a is —[C(R5a)(R5b)]mR5c then at least one of R5a, R5b and R5c is not hydrogen;
• R4 is H, lower alkyl, lower alkenyl or lower alkynyl;
• R5, R5′, R6, R6′ and R7 are independently selected from H, F, Cl, Br, I, methyl, ethyl, n-propyl, i-propyl, substituted methyl, substituted ethyl, substituted n-propyl, substituted i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, CF3, CHF2, CH2F, NH2, NHR′, NR′R″, OR′, SR′, C(O)R′, CO2H, a salt of CO2H, COOR′, CONH2, CONHR′, CONR′R″, SO3H, a salt of SO3H, S(O)2R′, S(O)2NH2, S(O)2NHR′, S(O)2NR′R″, aryl or a heterocycle, wherein
• R′ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)(C1-3 alkyl), CONHC1-3 alkyl, aryl or a heterocycle;
• R″ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)2, CONHC1-3 alkyl, aryl or a heterocycle;
• or
• R′ and R″ together with the nitrogen atom to which they are attached form a 4-, 5-, or 6-membered heterocyclic ring;
• or a metabolite, pharmaceutically acceptable salt, solvate, ester, tautomer or prodrug thereof;
• and
• (v) optionally one or more pharmaceutically acceptable carriers.

A method of reducing serum uric acid levels in an individual, comprising administering:

• (i) a compound of formula (I);
• or
• (ii) a compound of formula (II), wherein the compound of formula (II) is a 3-substituted-5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazole wherein the substituent at the 3-position is —RB;
• or
• (iii) a compound of formula (III);
• or
• (iv) a combination thereof;
• wherein
• X is CH or N;
• W is O, S, S(O), S(O)2, NH, N (optionally substituted alkyl), NC(O)(optionally substituted alkyl) or CH2;
• R1 is H, Cl, Br, I, NH2, methyl, ethyl, n-propyl, i-propyl, optionally substituted methyl, optionally substituted ethyl, optionally substituted n-propyl, optionally substituted i-propyl, CF3, CHF2 or CH2F;
• R3 and R3′ are independently selected from H and lower alkyl, or R3 and R3′ together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O;
• R2 is selected from the group consisting of (a), (b), (c) and (d):
• wherein
• represents a carbon-carbon single bond or a carbon-carbon double bond;
• Q and Q′ are independently selected from N and CH;
• RP is methyl, ethyl, propyl, i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclopropylmethyl;
• R8, R9 and R10 are independently selected from H, F, Cl, Br, CH3, CF3, CFH2, CF2H, ethyl, i-propyl, cyclopropyl, methoxy, OH, OCF3, NH2 and NHCH3;
• R11 is Cl, Br, I, CH3, CF3, methoxy, i-propyl, cyclopropyl, tert-butyl, cyclobutyl or methyl;
• and
• R12, R13, R14 and R15 are independently H or methyl;
• RB is —SCH2C(═O)R1a, —SCH2-tetrazolyl, —SCH2C(═O)NHOH, —SCH2C(═O)O-alkyl-OC(═O)R3a, —SCH2C(═O)O-alkyl-OC(═O)OR3a, —SCH2C(═O)O-alkyl-OC(═O)NR4aR4b, or —SCH2C(Oalkyl)3;
• R1a is OR2a, SR3a, NR4aR4b at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, or a combination thereof, wherein
• R2a is substituted C1-C4 alkyl, optionally substituted C5-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl;
• or
• R2a is a pharmaceutically acceptable cation;
• or
• R2a is —[C(R5a)(R5b)]mR5c;
• R3a is hydrogen, optionally substituted C1-C10 alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl;
• or
• R3a is —[C(R5a)(R5b)]nR5c;
• R4a is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• and
• R4b is hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl;
• or
• R4b is —[C(R5a)(R5b)]nR5c, wherein
• each R5a is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• each R5b is independently hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4 alkylamine, optionally substituted -L-di-(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• R5c is hydrogen, halogen, cyano, nitro, at least one amino acid, a peptide, a lipid, a phospholipid, a glycoside, a nucleoside, a nucleotide, oligonucleotide, polyethylene glycol, -L-OH, -L-SH, -L-NH2, substituted -L-C1-C3 alkyl, optionally substituted -L-C4-C9 alkyl, optionally substituted L-C2-C5 alkenyl, optionally substituted L-C2-C5 alkynyl, optionally substituted L-C2-C5 heteroalkyl, optionally substituted -L-C3-C7 cycloalkyl, optionally substituted L-C3-C7 cycloalkenyl, optionally substituted -L-C3-C7 heterocycloalkyl, optionally substituted -L-C1-C4 haloalkyl, optionally substituted -L-C1-C4 alkoxy, optionally substituted -L-C1-C4alkylamine, optionally substituted -L-di(C1-C4)alkylamine, optionally substituted -L-C5-C7 aryl, optionally substituted -L-C5-C7 heteroaryl,
• wherein L is a bond, —C(O)—, —S(O), or —S(O)2;
• y1 is 0, 1, 2 or 3;
• Y is OH, OMe, COOH, SO3H, OSO3H, OS(O)2NH2, P(O)(OH)2, OP(O)(OH)2, OP(O)(OH)(O—C1-4 alkyl) or NY2Y3Y4;
• wherein
• Y2 and Y3 are each independently hydrogen or methyl;
• or
• Y2 and Y3 are taken together with the nitrogen to which they are attached to form a five or six membered ring that optionally contains an oxygen atom or a second nitrogen atom;
• and
• Y4 is an electron pair or an oxygen atom;
• m is 1, 2, 3, 4;
• n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• and wherein if R2a is —[C(R5a)(R5b)]mR5c then at least one of R5a, R5b and R5c is not hydrogen;
• R4 is H, lower alkyl, lower alkenyl or lower alkynyl;
• R5, R5′, R6, R6′ and R7 are independently selected from H, F, Cl, Br, I, methyl, ethyl, n-propyl, i-propyl, substituted methyl, substituted ethyl, substituted n-propyl, substituted i-propyl, cyclopropyl, cyclobutyl, cyclopentyl, CF3, CHF2, CH2F, NH2, NHR′, NR′R″, OR′, SR′, C(O)R′, CO2H, a salt of CO2H, COOR′, CONH2, CONHR′, CONR′R″, SO3H, a salt of SO3H, S(O)2R′, S(O)2NH2, S(O)2NHR′, S(O)2NR′R″, aryl or a heterocycle, wherein
• R′ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)(C1-3 alkyl), CONHC1-3 alkyl, aryl or a heterocycle;
• R″ is H, C1-3 alkyl, substituted C1-3 alkyl wherein said substituents are selected from CF3, OH, OC1-3 alkyl, COC1-3 alkyl, COOH, COOC1-3 alkyl, NH2, NHC1-3 alkyl, N(C1-3 alkyl)2, CONHC1-3 alkyl, aryl or a heterocycle;
• or
• R′ and R″ together with the nitrogen atom to which they are attached form a 4-, 5-, or 6-membered heterocyclic ring;
• or a metabolite, pharmaceutically acceptable salt, solvate, ester, tautomer or prodrug thereof.