Benzothiazole-based compounds as potent endothelial lipase inhibitors.
A series of benzothiazoles with a cyano group was synthesized and evaluated as endothelial lipase (EL) inhibitors for the potential treatment of cardiovascular diseases. Efforts to reduce molecular weight and polarity in the series led to improved physicochemical properties of these compounds, as well as selectivity for EL over hepatic lipase (HL). As a benchmark compound, 8i demonstrated potent EL activity, an acceptable absorption, distribution, metabolism and elimination (ADME) profile and pharmacokinetic (PK) exposure which allowed further evaluation in preclinical animal efficacy studies.
['Meng|Wei|W|', 'Adam|Leonard P|LP|', 'Behnia|Kamelia|K|', 'Zhao|Lei|L|', 'Yang|Richard|R|', 'Kopcho|Lisa M|LM|', 'Locke|Gregory A|GA|', 'Taylor|David S|DS|', 'Yin|Xiaohong|X|', 'Wexler|Ruth R|RR|', 'Finlay|Heather|H|']
D000818:Animals D052160:Benzothiazoles D002318:Cardiovascular Diseases D004353:Drug Evaluation, Preclinical D004791:Enzyme Inhibitors D005786:Gene Expression Regulation D006801:Humans D008049:Lipase D008075:Lipoproteins, HDL D008077:Lipoproteins, LDL D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D008958:Models, Molecular D015394:Molecular Structure D013329:Structure-Activity Relationship
Endothelial lipase Benzothiazole Cardiovascular diseases High density lipoprotein Structure-activity relationship