Synthesis and pharmacological study of antihyperlipaemic activity of 2-substituted thieno(2,3-d)pyrimidin-4(3H)-ones.
A series of 2-substituted thieno(2,3-d)pyrimidin-4-(3H) ones (1-15) was prepared by the reaction of thiophene ortho-aminoester (IV) with a variety of nitriles (V) under acidic conditions, and screened for antihyperlipaemic activity in various animal models. While most of these compounds were found active, 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d) pyrimidin-4(3H)-one (5) was found to be the most active of all. The serum triglyceride lowering activity exhibited by 5 was found comparable to that of clofibrate and riboflavin tetrabutyrate. Compound 5 was also found to be safe as indicated by acute and chronic toxicity studies in mice and rats.
Shishoo
C J
CJ
Department of Pharmaceutical Chemistry, Lallubhai Motilal College of Pharmacy, Ahmedabad, India.
Devani
M B
MB
Bhadti
V S
VS
Jain
K S
KS
Rathod
I S
IS
Goyal
R K
RK
Gandhi
T P
TP
Patel
R B
RB
Naik
S R
SR
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002791:Cholesterol, Dietary / Q000494:pharmacology; D000431:Ethanol; D005260:Female; D006168:Guinea Pigs; D006937:Hypercholesterolemia / Q000517:prevention & control; D006949:Hyperlipidemias / Q000139:chemically induced / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D007202:Indicators and Reagents; D008055:Lipids; D011744:Pyrimidinones; D000431:Ethanol; C065127:2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidin-4(3H)-one