Synthesis and antihyperlipidemic activity of some novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-disubstituted pyrimidines.
Synthesis and antihyperlipidemic activity of a series of novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-di-substituted pyrimidines are described. The design of these compounds is based on the earlier QSAR study on the antihyperlipidemic 2-substituted methylthienopyrimidin-4-ones. The newly synthesized condensed 4-chloro-2-chloroalkylpyrimidines (IIIa-n) have exhibited much superior antihyperlipidemic activity, compared to their earlier reported 4-hydroxy analogs. Notably, in this series, five compounds, IIIa, IIIb, IIIc, IIIi and IIIm showed good ability to reduce total cholesterol and two compounds, IIIa and IIIk exhibited better reduction in serum triglycerides. All the newly synthesized compounds have been evaluated by the Triton WR 1339 induced hyperlipidemia in albino Wistar rats model for antihyperlipidemic activity, and their activity is superior to that exhibited by the standard gemfibrozil used in the study. A 3D QSAR study has also been performed to delineate the effect of the substituents at 5 and 6 positions on the antihyperlipidemic activity of 2-chloromethyl-5,6-substituted thieno(2,3-d) pyrimidin-4(3H)-ones (IIa-e).
Kathiravan
Matthu K
MK
Poona College of Pharmacy, Pune 411 038, India.
Shishoo
Chamanlal J
CJ
Kumar
Krishnan Girish
KG
Roy
Saroj Kumar
SK
Mahadik
Kakasheb R
KR
Kadam
Shivajirao S
SS
Jain
Kishor S
KS
D000473:Alkanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000097:blood; D015248:Gemfibrozil / Q000494:pharmacology; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011092:Polyethylene Glycols; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D000473:Alkanes; D000960:Hypolipidemic Agents; D007202:Indicators and Reagents; D011743:Pyrimidines; D014280:Triglycerides; D011092:Polyethylene Glycols; D002784:Cholesterol; D015248:Gemfibrozil; C016811:tyloxapol