- Metabolism investigation leading to novel drug design 2: Orally active prostacyclin mimetics. Part 5
-
A metabolism study of FK788 (2) led to the discovery of new diphenylcarbamoyl derivatives as prostacyclin mimetics without the PG skeleton. We designed and evaluated PGI2 mimetics based on blocking the main metabolic pathway of FK788. The new compound 7c was found to be equipotent to FK788 towards PGI2 agonist activity and metabolically more stable than FK788.
- Takamura, Fujiko,Tanaka, Akira,Takasugi, Hisashi,Taniguchi, Kiyoshi,Nishio, Mie,Seki, Jiro,Hattori, Kouji
-
p. 4475 - 4478
(2007/10/03)
-
- 3-piperidyl-4-oxoquinazoline derivatives and pharmaceutical compositions comprising the same
-
3-piperidyl-4-oxoquinazoline derivatives are provided, which is represented by the formula (I): wherein R represents an amino group or a cyclic amino group such as dibenzoazepine, each of which is substituted with a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, or the like, n is an integer of 1 to 3, R3and R4independently represents a hydrogen atom, a lower alkyl group, or the like, or a pharmaceutically acceptable salt thereof. Compounds (I) of the present invention have excellent MTP-inhibitory activity. Thus, these compounds not only inhibit formation of LDL that is a cause of arteriosclerotic diseases but also regulate TG, cholesterol, and lipoproteins such as LDL in the blood and regulate cellular lipids through regulation of MTP activity. They can also be used as a new type of preventive or therapeutic agents for hyperlipemia or arteriosclerotic diseases. Furthermore, they can be used as therapeutic or preventive agents for pancreatitis, obesity, hypercholesterolemia, and hypertriglyceridemia.
- -
-
-