Synthesis and Hypolipidemic Activities of Novel 2-[4-[(Diethoxyphosphoryl)methyl]phenyl]quinazolines and 4(3H)-Quinazolinones
- 1 January 1996
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 39 (7) , 1433-1437
- https://doi.org/10.1021/jm9506938
Abstract
The novel compound NO-1886, 4-[(diethoxyphosphoryl)methyl]-N-(4-bromo-2-cyanophenyl)benzamide, is a hypolipidemic agent, which appears to increase lipoprotein lipase activity in rats. Various analogs of NO-1886 were synthesized to study the structure−activity relationship of this hypolipidemic drug. A novel series of quinazolines and 4(3H)-quinazolinones were prepared by cyclization of NO-1886 derivatives. Derivatives bearing a 4-[(diethoxyphosphoryl)methyl]phenyl group at the 2-position were found to lower triglyceride and total cholesterol levels. In accord with the decrease in log P*, quinazolines and 4(3H)-quinazolinones showed good absorption and hypolipidemic activity. When the quinazolinone ring system is substituted at positions 6 and 7 with methoxy groups, increased hypolipidemic activity was observed. The highest hypolipidemic activity was observed when the 3-position was substituted by a methyl or benzyl group.Keywords
This publication has 7 references indexed in Scilit:
- The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis.Journal of Clinical Investigation, 1993
- Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerizationJournal of Medicinal Chemistry, 1990
- Synthesis and anticonvulsant activity of some new 2-substituted 3-aryl-4(3H)-quinazolinonesJournal of Medicinal Chemistry, 1990
- Hypolipidemic 2-[4-(1,1-dimethylethyl)phenyl]-4H-3,1-benzoxazin-4-ones. Structure-activity relationships of a novel series of high-density lipoprotein elevatorsJournal of Medicinal Chemistry, 1989
- Negative inotropic activity of para-substituted diethyl benzylphosphonates related to fostedilEuropean Journal of Medicinal Chemistry, 1987
- Synthesis of substituted 2‐methyl‐3‐(3,4‐dimethoxy/dihydroxyphenylethyl)4‐quinazolones as possible antiparkinson drugsJournal of Heterocyclic Chemistry, 1979
- Preparation of quinazoline derivatives through ring‐closure of aromatic ortho‐cyano‐acylamino compounds in alkaline alcoholic or phenolic medium. I. 4‐RO‐substituted quinazolinesRecueil des Travaux Chimiques des Pays-Bas, 1957