Synthesis and SAR of 5-aryl-furan-2-carboxamide derivatives as potent urotensin-II receptor antagonists |
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Authors: | Chae Jo Lim Nam Hui Kim Hye Jin Park Byung Ho Lee Kwang-Seok Oh Kyu Yang Yi |
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Institution: | 1. Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 34114, Republic of Korea;2. Department of Medicinal Chemistry and Pharmacology, KRICT School, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea |
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Abstract: | The synthesis and biological evaluation as potential urotensin-II receptor antagonists of a series of 5-arylfuran-2-carboxamide derivatives 1, bearing a 4-(3-chloro-4-(piperidin-4-yloxy)benzyl)piperazin-1-yl group, are described. The results of a systematic SAR investigation of furan-2-carboxamides with C-5 aryl groups possessing a variety of aryl ring substituents led to identification of the 3,4-difluorophenyl analog 1y as a highly potent UT antagonist with an IC50 value of 6?nM. In addition, this substance was found to display high metabolic stability, and low hERG inhibition and cytotoxicity, and to have an acceptable PK profile. |
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Keywords: | Urotensin-II receptor Antagonists 5-Aryl-furan-2-carboxamide Cardiovascular disease |
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