Design,synthesis and biological evaluation of indane derived GPR40 agoPAMs |
| |
| Institution: | 1. Discovery Chemistry, Merck & Co., Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;2. In Vivo Pharmacology, Merck & Co., Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;3. Process Chemistry, Merck & Co., Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;4. In Vitro Pharmacology, Merck & Co., Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;5. Drug Metabolism and Pharmacokinetics, Merck & Co., Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;6. SALAR Discovery, Merck & Co., Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;1. Anticancer Agent Research Center, KRIBB, Cheongju 28116, Republic of Korea;2. Department of Bioengineering, Hanyang University, Seoul 04763, Republic of Korea;3. Department of Chemistry, Chonnam National University, Gwangju 61186, Republic of Korea;4. Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea;1. Merck & Co., Inc., Rahway, NJ 07065, United States;2. University of California at Los Angeles, Department of Chemistry and Biochemistry, Los Angeles, CA 90095, United States;1. Discovery Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States;2. Structural Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States;3. Cardiovascular Pharmacology, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States;4. Pharmacokinetics Pharmacodynamics and Metabolism, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States;5. Biochemistry and Biophysics, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States;6. Medicinal Chemistry Department, Albany Molecular Research, Inc., 26 Corporate Circle, Albany, NY 12203, United States;1. Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul 02792, Republic of Korea;2. Division of Bio-Medical Sciences & Technology, KIST School, Korea University of Science and Technology (UST), Gajungro 217, Youseong-gu, Daejeon 305-350, Republic of Korea;1. Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA;2. Department of Pharmacology, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA;3. Department of Structural Biology, Merck & Co. Inc, PO Box 4, West Point, PA 19486, USA;4. Department of Neuroscience, Merck & Co. Inc., PO Box 4, West Point, PA 19486, USA |
| |
| Abstract: | GPR40 (FFAR1 or FFA1) is a G protein-coupled receptor, primarily expressed in pancreatic islet β-cells and intestinal enteroendocrine cells. When activated by fatty acids, GPR40 elicits increased insulin secretion from islet β-cells only in the presence of elevated glucose levels. Towards this end, studies were undertaken towards discovering a novel GPR40 Agonist whose mode of action is via Positive Allosteric Modulation of the GPR40 receptor (AgoPAM). Efforts were made to identify a suitable GPR40 AgoPAM tool molecule to investigate mechanism of action and de-risk liver toxicity of GPR40 AgoPAMs due to reactive acyl-glucuronide (AG) metabolites. |
| |
| Keywords: | GPR40 AgoPAM FFA1 GPCR Diabetes Indane |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
