Biological evaluation of 1-alkyl-3-phenylthioureas as orally active HDL-elevating agents.
A series of 1-alkyl-3-phenylthiourea analogues were prepared and evaluated as HDL- and Apo A-I-elevating and triglyceride-lowering agents. Several derivatives were superior to gemfibrozil. The optimal analogue (HDL376) was shown to raise HDL cholesterol in the rat, hamster, dog, and monkey models.
Coppola
Gary M
GM
Department of Diabetes and Metabolism, Novartis Institutes for Biomedical Research, 100 Technology Square, Cambridge, MA 02139, USA. gary.coppola@novartis.com
Damon
Robert E
RE
Eskesen
J Bruce
JB
France
Dennis S
DS
Paterniti
James R
JR
D000284:Administration, Oral; D000818:Animals; D002499:Centrifugation, Density Gradient; D008076:Cholesterol, HDL / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D015248:Gemfibrozil / Q000494:pharmacology*; D000882:Haplorhini; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008956:Models, Chemical; D010670:Phenylthiourea / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D008076:Cholesterol, HDL; D008055:Lipids; D008075:Lipoproteins, HDL; D014280:Triglycerides; D010670:Phenylthiourea; D015248:Gemfibrozil