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).
Fused pyrimidine derivatives R 0515Synthesis and Antihyperlipidemic Activity of Some Novel Condensed 2-Chloroalkyl-4-chloro/hydroxy-5,6-disubstituted Pyrimidines. -The new compounds (IV) exhibit much superior antihyperlipidemic activity compared to their known 4-hydroxy analogues. They show good ability to reduce total cholesterol and derivative (IVb) exhibits better reduction of serum triglycerides. A 3D QSAR study is also performed to delineate the effect of the substituents at 5 and 6 position on the antihyperlipidemic activity of intermediates (III). -(KATHIRAVAN, M. K.; SHISHOO, C. J.; KUMAR, K. G.; ROY, S. K.; MAHADIK, K. R.; KADAM, S. S.; JAIN*, K. S.; Arzneim.-Forsch. 57 (2007) 9, 599-606; Sinhgad Coll. Pharm., Pune 411 041, India; Eng.) -H. Haber 04-174
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