Evaluation of the cyclopentane-1,2-dione as a potential bio-isostere of the carboxylic acid functional group |
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| Affiliation: | 1. Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, 231 South 34th St., Philadelphia, PA 19104-6323, United States;2. Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104-6323, United States;1. Institute of Problems of Chemical Physics RAS, Chernogolovka, Russia;2. Institute of Solid State Physics RAS, Chernogolovka, Moscow Region, 142432, Russia;1. Unilever R & D, Olivier Van Noortlaan 120, P.O. Box 114, 3130 AC Vlaardingen, The Netherlands;2. Laboratory of Food Technology and Leuven Food Science and Nutrition Research British Centre (LFoRCe), Department of Microbial and Molecular Systems (M2S), Katholieke Universiteit Leuven, Kasteelpark Arenberg 22, PB 2457, 3001 Leuven, Belgium;1. School of Chemistry, Madurai Kamaraj University, Madurai 625021, India;2. Centre for Green Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, India |
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| Abstract: | Cycloalkylpolyones hold promise in drug design as carboxylic acid bio-isosteres. To investigate cyclopentane-1,2-diones as potential surrogates of the carboxylic acid functional group, the acidity, tautomerism, and geometry of hydrogen bonding of representative compounds were evaluated. Prototypic derivatives of the known thromboxane A2 prostanoid (TP) receptor antagonist, 3-(3-(2-((4-chlorophenyl)sulfonamido)-ethyl)phenyl)propanoic acid, in which the carboxylic acid moiety is replaced by the cyclopentane-1,2-dione unit, were synthesized and evaluated as TP receptor antagonists. Cyclopentane-1,2-dione derivative 9 was found to be a potent TP receptor antagonist with an IC50 value comparable to that of the parent carboxylic acid. These results indicate that the cyclopentane-1,2-dione may be a potentially useful carboxylic acid bio-isostere. |
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| Keywords: | Carboxylic acid bio-isosteres Cyclopentane-1,2-dione |
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