Aromatic liver X-receptor modulators

A compound corresponding to Formula IV and the isomers, tautomers, salts and prodrugs thereof:

• 68
• wherein:
• M17 is hydrogen, hydrocarbyl, substituted hydrocarbyl, hydrocarbyloxy, heterocyclo, amino, or acyl;
• M18 is hydrocarbyl, substituted hydrocarbyl, or heterocyclo;
• M34 and M35 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, amino, alkoxy, halogen, or nitro;
• p and q are independently 0, 1,or 2;
• X25 and X26 are independently hydrogen, optionally substituted alkyl, nitro or halo, and
• X53 is hydrocarbyl, substituted hydrocarbyl or heterocyclo.

A compound corresponding to Formula V and the isomers, tautomers, salts and prodrugs thereof:

• 69
• wherein:
• the X ring, the M ring and the Y ring are independently aromatic;
• A is oxygen, sulfur, sulfoxide, sulfone, —NHC(═A2)— or —C(═A2)NH—;
• A2 is oxygen or sulfur;
• M1, M2, M3, M4, and M5 are independently a bond, carbon, nitrogen, oxygen or sulfur, provided, however, no more than one of M1, M2, M3, M4, and M5 is a bond;
• M19 is a bond, hydrocarbyl or substituted hydrocarbyl;
• M20 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclo;
• M34 and M35 are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl, or M34 and M35 are bonded to adjacent carbon atoms and together with the atoms to which they are bonded form a fused ring system;
• p and q are independently 0, 1,or 2;
• X1, X2, X3, and X4 are independently a bond, carbon, nitrogen, oxygen or sulfur, provided, however, no more than one of X1, X2, X3, and X4 is a bond;
• X11, X22, X33, and X44, are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl;
• provided, however, X11, X22, X33, or X44 is not present when X1, X2, X3 or X4, respectively, is a bond;
• X50 is carbon, sulfur or sulfoxide;
• X51 is oxygen, sulfur, or NX52;
• X52 is hydrogen, hydrocarbyl, or substituted hydrocarbyl;
• X53 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclo, or amino;
• Y1, Y2, Y3, Y4, and Y5 are independently a bond, carbon, nitrogen, oxygen or sulfur, provided, however, no more than one of Y1, Y2, Y3, Y4 and Y5 is a bond;
• and
• Y11, Y22, Y33, Y44, and Y55 are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl, or one of Y11 and Y22, Y22 and Y33 or Y33 and Y44 and Y44 and Y55 and the atoms to which they are attached form a fused ring;
• provided, however, Y11, Y22, Y33, Y44 or Y55 is not present when Y1, Y2, Y3 Y4, or Y5, respectively, is a bond.

A compound corresponding to Formula VI and the isomers, tautomers, salts and prodrugs thereof:

• 70
• wherein:
• M19 is a bond, hydrocarbyl or substituted hydrocarbyl;
• M20 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclo;
• M34 and M35 are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl, or M34 and M35 are bonded to adjacent carbon atoms and together with the atoms to which they are bonded form a fused ring system;
• the sum of p and q is 1;
• X25 and X26 are independently hydrogen, optionally substituted alkyl, nitro or halo;
• X53 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclo, or amino;
• Y1, Y2, Y3, Y4, and Y5 are independently a bond, carbon, nitrogen, oxygen or sulfur, provided, however, no more than one of Y1, Y2, Y3, Y4 and Y5 is a bond;
• and
• Y11, Y22, Y33, Y44, and Y55 are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl, or one of Y11, and Y22, Y22 and Y33 or Y33 and Y44 and Y44 and Y55 and the atoms to which they are attached form a fused ring;
• provided, however, Y11, Y22, Y33, Y44 or Y55 is not present when Y1, Y2, Y3 Y4, or Y5, respectively, is a bond.

A compound corresponding to Formula VII and the isomers, tautomers, salts and prodrugs thereof:

• 71
• wherein:
• the X ring and the M ring are independently aromatic rings;
• A is oxygen, sulfur, sulfoxide, sulfone, —NHC(═A2)— or —C(═A2)NH—;
• A2 is oxygen or sulfur;
• M1, M2, M3, M4, M5, and M6, are independently a bond, carbon, nitrogen, oxygen or sulfur, provided, however, no more than one of M1, M2, M3, M4, M5, and M6, is a bond;
• M21 in combination with the nitrogen atom to which it is bonded form a heterocylcic ring;
• M34 and M35 are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl, or M34 and M35 are bonded to adjacent carbon atoms and together with the atoms to which they are bonded form a fused ring system;
• p and q are independently 0, 1,or 2;
• X1, X2, X3, and X4 are independently a bond, carbon, nitrogen, oxygen or sulfur, provided, however, no more than one of X1, X2, X3, and X4 is a bond;
• X11, X22, X33, and X44, are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl;
• provided, however, X11, X22, X33, or X44 is not present when X1, X2, X3 or X4, respectively, is a bond;
• X50 is carbon, sulfur or sulfoxide;
• X51 is oxygen, sulfur, or NX52;
• X52 is hydrogen, hydrocarbyl, or substituted hydrocarbyl;
• and
• X53 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclo, or amino.

A compound corresponding to Formula VIII and the isomers, tautomers, salts and prodrugs thereof:

• 72
• wherein;
• M21 in combination with the nitrogen atom to which it is bonded form a heterocylcic ring;
• M34 and M35 are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl, or M34 and M35 are bonded to adjacent carbon atoms and together with the atoms to which they are bonded form a fused ring system;
• p and q are independently 0, 1,or 2;
• X25 and X26 are independently hydrogen, optionally substituted alkyl, nitro or halo;
• and
• X53 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclo, or amino.

A compound corresponding to Formula IX and the isomers, tautomers, salts and prodrugs thereof:

• 73
• wherein;
• M34 and M35 are independently an electron pair, hydrogen, hydrocarbyl, substituted hydrocarbyl, hydroxy, hydrocarbyloxy, substituted hydrocarbyloxy, mercapto, halo, heterocyclo, cyano, nitro, amino, acyloxy, or acyl, or M34 and M35 are bonded to adjacent carbon atoms and together with the atoms to which they are bonded form a fused ring system;
• M40 is hydrocarbyl or substituted hydrocarbyl;
• p and q are independently 0, 1,or 2;
• X25 and X26 are independently hydrogen, optionally substituted alkyl, nitro or halo;
• and
• X53 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclo, or amino.

A compound selected from the group consisting of

• methyl 3-[({2-[(3-chloro-2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzoate;
• methyl 3-[({2-[(thien-2-ylcarbonyl)amino]phenyl}thio)methyl]benzoate;
• methyl 3-[({2-[(trichloroacetyl)amino]phenyl}thio)methyl]benzoate;
• methyl 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzoate;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-isopentyl benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(4-methoxy benzyl) benzamide;
• 2,2-dimethyl-N-[2-({3-[(4-methylpiperazin-1-yl)carbonyl]benzyl}thio)phenyl]propanamide;
• 2,2-dimethyl-N-[2-({3-[(4-phenylpiperazin-1-yl)carbonyl]benzyl}thio)phenyl]propanamide;
• 2,2-dimethyl-N-(2-{[3-(piperidin-1-ylcarbonyl)benzyl]thio}phenyl) propanamide;
• N-(1,3-benzodioxol-5-ylmethyl)-3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-phenyl benzamide;
• N-benzyl-3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzamide;
• N-[2-({3-[(4-benzylpiperidin-1-yl)carbonyl]benzyl}thio)phenyl]-2,2-dimethylpropanamide;
• N-butyl-3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzamide;
• N-cyclohexyl-3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(3-fluoro benzyl)benzamide;
• N-(2,6-dimethoxybenzyl)-3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio) methyl]benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(2-furylmethyl) benzamide;
• methyl N-{3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzoyl}glycinate;
• methyl N-{3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzoyl}serinate;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(tetrahydro furan-2-ylmethyl)benzamide;
• N-(2,3-dimethoxybenzyl)-3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(2-ethoxy benzyl)benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(4-fluoro benzyl)benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(2-methoxy benzyl)benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(3-methoxy benzyl)benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-[4-(trifluoro methoxy)benzyl]benzamide;
• 3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]-N-(3,4,5-trimethoxybenzyl)benzamide;
• N-(3,4-dimethoxybenzyl)-3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzamide;
• N-(2,4-dimethoxybenzyl)-3-[({2-[(2,2-dimethylpropanoyl)amino]phenyl}thio)methyl]benzamide;
• N-{2-[(3-{[(2,4-dimethoxybenzyl)amino]carbonyl}benzyl)thio]phenyl}pyridine-2-carboxamide;
• N-{2-[(3-{[(2,6-dimethoxybenzyl)amino]carbonyl}benzyl)thio]phenyl}pyridine-2-carboxamide;
• 2-({2-[(3-{[(2,4-dimethoxybenzyl)amino]carbonyl}benzyl)thio]phenyl}amino)-2-oxoethylacetate;
• 3-[({2-[(3-{[(2,4-dimethoxybenzyl)amino]carbonyl}benzyl)thiophenyl}amino)carbonyl]-2-methylphenyl acetate;
• 2-({2-[(3-{[(2,4dimethoxybenzyl)amino]carbonyl}benzyl)thio]phenyl}amino) -1-methyl-2-oxoethyl acetate;
• 2-({2-[(3-{[(2,4-dimethoxybenzyl)amino]carbonyl}benzyl)thio]phenyl amino)-2-oxo-1-phenylethyl acetate;
• N-{2-[(3-{[(2,4-dimethoxybenzyl)amino]carbonyl}benzyl)thio]phenyl}-2-methoxybenzamide;
• N-{2-[(3-{[(2,4-dimethoxybenzyl)amino]carbonyl}benzyl)thio]phenyl}nicotinamide;
• N-(2,4-dimethoxybenzyl)-3-{[(2-{[N-(2methoxyethyl)glycyl]amino}phenyl)thio]methyl}benzamide;
• N-(2,4-dimethoxybenzyl)-3-[({2-[(piperidin-1-ylacetyl)amino]phenyl}thio) methyl]benzamide;
• N-(2,4-dimethoxybenzyl)-3-{[(2-{[N-(tetrahydrofuran-2-ylmethyl)glycyl]amino}phenyl)thio]methyl}benzamide;
• N-(2,4-dimethoxybenzyl)-3-[({3-[(2,2-dimethylpropanoyl)amino]pyridin-2-yl}thio)methyl]benzamide;
• 3-[({2-[(cyclopentylcarbonyl)amino]phenyl}thio)methyl]-N-(2,4-dimethoxybenzyl)benzamide;
• N-(2,4-dimethoxybenzyl)-3-{[(2-{[(1-phenylcyclopropyl)carbonyl]amino}phenyl)thio]methyl}benzamide;
• 3-({[2-({[1-(4-chlorophenyl)cyclopentyl]carbonyl}amino)phenyl]thio}methyl)-N-(2,4-dimethoxybenzyl)benzamide;
• 6-chloro-N-{2-[(3-{[(2,4-dimethoxybenzyl)amino]carbonyl}benzylthio]phenyl}nicotinamide;
• 6-chloro-N-{2-[(3-{[(2,6-dimethoxybenzyl)amino]carbonyl}benzyl) thio]phenyl}nicotinamide;
• 3-({2-[(3-chloro-2,2-dimethylpropanoyl)amino]benzyl}thio)-N-(2,4-dimethoxybenzyl)benzamide;
• 3-({2-[(cyclopentylcarbonyl)amino]benzyl}thio)-N-(2,4-dimethoxy benzyl)benzamide;
• N-(2,4-dimethoxybenzyl)-3-({2-[(2,2-dimethylpropanoyl)amino]benzyl}thio)benzamide;
• 3-({2-[(3-chloro-2,2-dimethylpropanoyl)amino]benzyl}thio)-N-(2,6-dimethoxybenzyl)benzamide;
• 3-({2-[(cyclopentylcarbonyl)amino]benzyl}thio)-N-(2,6-dimethoxybenzyl) benzamide;
• N-(2,6-dimethoxybenzyl)-3-({2-[(2,2-dimethylpropanoyl)amino]benzyl}thio)benzamide;
• N-(2,6-dimethoxybenzyl)-3-({2-[(trichloroacetyl)amino]benzyl}thio) benzamide;
• N-(2,6-dimethoxybenzyl)-3-({2-[(3,3-dimethylbutanoyl)amino]benzyl}thio) benzamide.