Discovery and optimization of oxadiazole-based FLAP inhibitors. Issue 20 (15th October 2017)

• Record Type: Journal Article
• Authors: Bartolozzi, Alessandra; Abeywardane, Asitha; Bosanac, Todd; Broadwater, John A.; Chen, Zhidong; Hutzler, J. Matthew; Huber, John D.; Nemoto, Peter; Olague, Alan; Riether, Doris; Simpson, Tom; Takahashi, Hidenori; Wu, Lifen; Zhang, Yunlong; Zindell, Renee M.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 20(2017)
• Page Start: 4652
• Page End: 4659
• Publication Date: 2017-10-15
• Subjects: FLAP -- 5-Lipoxygenase activating protein -- Leukotrienes -- Cardiovascular diseases -- Oxadiazole -- Solubility -- hERG; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.09.007
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.