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Synthesis and biological evaluation of cyclopentyl-triazolol-pyrimidine (CPTP) based P2Y12 antagonists
Institution:1. Bio-Organic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, J&K, India;2. Natural Product Microbes, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, J&K, India;1. Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan;2. Core Research for Evolutional Science and Technology (CREST), Science and Technology (JST) Agency, K’s Gobancho, 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan;3. College of Optical Sciences, The University of Arizona, 1630 East University Boulevard, Tucson, Arizona 85721, USA;1. Department of Small Molecule Pharmaceutics, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA;2. Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA;3. Department of Discovery Chemistry, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA;4. Department of Chemistry, Array BioPharma, Boulder, CO 80301, USA
Abstract:In this Letter we describe SAR investigation on the cyclopentyl-triazolol-pyrimidine scaffold in pursuit of new oral P2Y12 inhibitors. Different synthetic routes were developed for variations at the cyclopentyl core. Optimization finally led to compound 2d which was advanced into preclinical development based on better potency and safety profile in comparison to ticagrelor.
Keywords:Anti-platelet  Ticagrelor  Excessive bleeding
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