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Discovery and optimization of oxadiazole-based FLAP inhibitors |
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| Authors: | Alessandra Bartolozzi Asitha Abeywardane Todd Bosanac John A Broadwater Zhidong Chen J Matthew Hutzler John D Huber Peter Nemoto Alan Olague Doris Riether Tom Simpson Hidenori Takahashi Lifen Wu Yunlong Zhang Renee M Zindell |
| Institution: | 1. Small Molecule Discovery Research, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT 06877-0368, USA;2. CardioMetabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT 06877-0368, USA |
| Abstract: | Structure activity relationship (SAR) investigation of an oxadiazole based series led to the discovery of several potent FLAP inhibitors. Lead optimization focused on achieving functional activity while improving physiochemical properties and reducing hERG inhibition. Several compounds with favorable in vitro and in vivo properties were identified that were suitable for advanced profiling. |
| Keywords: | FLAP 5-Lipoxygenase activating protein Leukotrienes Cardiovascular diseases Oxadiazole Solubility hERG |
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