Anti-inflammatory agents
Disclosed are novel compounds that are useful in regulating the expression of interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1), and their use in the treatment and/or prevention of cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s). Also, disclosed are compositions comprising the novel compounds, as well as methods for their preparation.
1. A compound of Formula V:
or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein:
Q is CH;
U is C═O;
Y is oxygen;
A is C 1 -C 2 alkyl;
D may be absent or present, and if present is selected from hydroxy, pyrrolinin-1-yl, and NR 1 R 2 ;
R 1 and R 2 are independently selected from hydrogen and acetyl;
Ra 2 is hydrogen;
Ra 1 and Ra 3 are both methoxy;
Rb 2 and Rb 6 are both hydrogen; and
Rb 3 is selected from hydrogen, methyl and ethyl.
2. A compound selected from:
2-(3,5-dimethoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;
2-(3-(2-hydroxyethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;
2-(3-(2-hydroxyethoxy)-5-methylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;
5,7-dimethoxy-2-(3-methoxy-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)quinazolin-4(3H)-one;
N-(2-(3-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-5-methoxyphenoxy)ethyl)acetamide; and
5,7-dimethoxy-2-(3-methoxyphenyl)quinazolin-4(3H)-one;
or a pharmaceutically acceptable salt or hydrate thereof.
3. A compound that is 5,7-dimethoxy-2-(3-methoxy-5-(2-(pyrrolidin-1-yl)ethoxy)phenyl)quinazolin-4(3H)-one or a pharmaceutically acceptable salt or hydrate thereof.
4. A pharmaceutical composition comprising a compound or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate according to claim 1 .
5. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or hydrate according to claim 2 .
6. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or hydrate according to claim 3 .