Novel anti-inflammatory agents

A method for reducing IL-6 and/or VCAM-1 in a subject, comprising administering a therapeutically effective amount of at least one compound of Formula II:

• or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein:
• P is selected from N and CRa1;
• V is selected from N and CRa4;
• W is selected from N and CH;
• U is selected from C═O, C═S, SO2, S═O, and SR1;
• X is selected from O, S, CH2, and NH;
• Ra1, Ra3, and Ra4 are independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, and halogen;
• Ra2 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, heterocycle, amino, amide, fluoro, and bromo;
• Rb2 and Rb6 are independently selected from hydrogen, methyl, and fluoride;
• Rb3 and Rb5 are independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, halogen;
• and amino;
• Rb2 and Rb3 and/or Rb5 and Rb6 may be connected to form a cycloalkyl, phenyl or heterocycle;
• and
• Rd is selected from C1-C6 alkyl, C1-C6 alkoxy, and C3-C6 cycloalkyl, wherein Rd may be connected to Rb3 or Rb5 to form a heterocycle,
• provided that
• at least one of Ra1, Ra2, Ra3, and Ra4 is not hydrogen;
• if —XRd is —OCH2CH2OH, then Rb3 is not pyrrolidine;
• and
• if —XRd is —OMe, then Ra2 is not —CH2-morpholino.

A compound selected from:

• 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-6-morpholinoquinazolin-4(3H)-one;
• 2-(4-(2-(benzyloxy)ethoxy)-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one;
• 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylpyrido[2,3-d]pyrimidin-4(3H)-one;
• 5,7-difluoro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;
• 2-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-5,7-diisopropoxy-3H-quinazolin-4-one;
• 2-[4-(2-hydroxyethoxy)-3,5-dimethyl-phenyl]-6-morpholin-4-ylmethyl-3H-quinazolin-4-one;
• 2-[4-(2,3-Dihydroxy-propoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one;
• 2-[4-(2-hydroxy-ethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-6-morpholin-4-ylmethyl-3H-quinazolin-4-one;
• 2-[4-(2-hydroxy-ethoxy)-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one;
• 2-[4-(2-hydroxy-ethoxy)-naphthalen-1-yl]-5,7-dimethoxy-3H-quinazolin-4-one;
• 2-(2-hydroxymethyl-benzofuran-5-yl)-5,7-dimethoxy-3H-quinazolin-4-one;
• 7-(2-benzyloxy-ethoxy)-2-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-5-methoxy-3H-quinazolin-4-one;
• 7-(2-benzyloxy-ethoxy)-2-(2-hydroxymethyl-benzofuran-5-yl)-5-methoxy-3H-quinazolin-4-one;
• 2-[4-(5,7-dimethoxy-4-oxo-3,4-dihydro-quinazolin-2-yl)-2,6-dimethylphenoxy]-N-methyl-acetamide;
• 2-[4-(5,7-Dimethoxy-4-oxo-3,4-dihydro-quinazolin-2-yl)-2,6-dimethylphenoxy]-N-(4-methoxy-phenyl)-acetamide;
• N-benzyl-2-[4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy]acetamide;
• 2-[4-(4-hydroxy-butoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one;
• 7-chloro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;
• 8-chloro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;
• 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-8-methoxyquinazolin-4(3H)-one;
• 5-chloro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;
• 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-7-methoxyquinazolin-4(3H)-one;
• 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-6-((4-methylpiperazin-1-yl)methyl)quinazolin-4(3H)-one;
• 5,7-Dimethoxy-2-{3-methyl-4-[2-(5-phenyl-4H-[1,2,4]triazol-3-ylamino)-ethoxy]-phenyl}-3H-quinazolin-4-one;
• 2-{3,5-Dimethyl-4-[2-(3-methyl-[1,2,4]oxadiazol-5-ylamino)-ethoxy]-phenyl}-5,7-dimethoxy-3H-quinazolin-4-one;
• N-{2-[4-(5,7-dimethoxy-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl)-2,6-dimethyl-phenoxy]-ethyl}-acetamide;
• N-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylbenzyl)acetamide;
• N-[4-(5,7-dimethoxy-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl)-2,6-dimethyl-benzyl]-acetamide;
• 2-{3,5-Dimethyl-4-[2-(2,2,2-trifluoro-ethylamino)-ethoxy]-phenyl}-5,7-dimethoxy-3H-quinazolin-4-one;
• N-{2-[4-(6,8-Dimethoxy-1-oxo-1,2-dihydro-isoquinolin-3-yl)-2,6-dimethylphenoxy]-ethyl}-formamide;
• 2-(3,5-dimethyl-4-(2-(methylamino)ethoxy)phenyl)-5, dimethoxyquinazolin-4(3H)-one;
• N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)propane-2-sulfonamide;
• 2-(4-(2-(isopropylamino)ethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;
• N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylphenoxy)ethyl)acetamide;
• 2-(4-(2-(dimethylamino)ethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;
• N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-N-methylacetamide;
• N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)formamide;
• N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl), 2,6-dimethylphenoxy)ethyl)-N-methylformamide;
• N-(2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)dimethylamino-N-sulfonamide;
• N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)cyanamide;
• 2-(3,5-dimethyl-4-(2-(5-methylisoxazol-3-ylamino)ethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one:
• 2-(3,5-dimethyl-4-(2-(pyrimidin-2-ylamino)ethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;
• 2-(4-(2-(isoxazol-3-ylamino)ethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;
• 2-(4-(2-(4,6-dimethoxypyrimidin-2-ylamino)ethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;
• 2-[4-(3-hydroxy-propyl)-3,5-dimethoxyphenyl]-5,7-dimethoxy-3H-quinazolin-4-one;
• 2-[4-(3-hydroxy-propyl)-3-methoxy-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one;
• and
• 2-[2-(2-hydroxyethyl)-1H-indol-6-yl]-5,7-dimethoxy-3H-quinazolin-4-one, and
• tautomers, stereoisomers, pharmaceutically acceptable salts, and hydrates thereof.