Synthesis of ethyl 2-(4-chlorophenyl)-5-(2-furyl)-4-oxazoleacetate, a hypolipidemic agent, and related compounds.
A series of 2-aryl and 2-alkyl derivatives of 5-furyl-4-oxazoleacetic acid and their homologues having alkyl groups at the alpha-position of the acids were synthesized and evaluated for their hypolipidemic activities in Sprague-Dawley rats. On the basis of the structure-activity relationships and subacute toxicities, ethyl 2-(4-chlorophenyl)-5-(2-furyl)-4-oxazoleacetate (35) was selected as a candidate compound for development. Compound 35 reduced serum cholesterol and triglyceride levels by 23% and 35%, respectively, at a dose of 0.05% in a diet in normal rats, and it was about 10 times more active in hereditary hyperlipidemic rats (THLR/1) than in normal rats. Compound 35 inhibited platelet aggregation in vitro and also normalized hyperaggregability of hyperlipidemic plasma platelet ex vivo.
Moriya
T
T
Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Seki
M
M
Takabe
S
S
Matsumoto
K
K
Takashima
K
K
Mori
T
T
Odawara
A
A
Takeyama
S
S
D000818:Animals; D002784:Cholesterol / Q000097:blood; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood
D000960:Hypolipidemic Agents; D010080:Oxazoles; D014280:Triglycerides; C052488:ethyl 2-(4-chlorophenyl)-5-(2-furyl)-4-oxzoleacetate; D002784:Cholesterol