Discovery of 1,3-disubstituted-1H-pyrrole derivatives as potent melanin-concentrating hormone receptor 1 (MCH-R1) antagonists |
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| Authors: | Berglund Susanne Egner Bryan J Gradén Henrik Gradén Joakim Morgan David G A Inghardt Tord Giordanetto Fabrizio |
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| Affiliation: | aMedicinal Chemistry, AstraZeneca R&D Mölndal, Pepparedsleden 1, SE-431 83, Mölndal, Sweden;bCVGI Bioscience, AstraZeneca R&D Alderley Park, Macclesfield, Cheshire SK 104TG, UK;cLead Generation, AstraZeneca R&D Mölndal, Pepparedsleden 1, SE-431 83, Mölndal, Sweden |
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| Abstract: | A series of 1,3-disubstituted-1H-pyrrole-based antagonists of the human Melanin-Concentrating Hormone Receptor 1 (h-MCH-R1) are reported. High-throughput screening of the AstraZeneca compound collection yielded 1, a hit with moderate affinity towards MCH-R1. Subsequent structural manipulations and SAR analysis served to rationalize potency requirements, and 12 was identified as a novel, functional MCH-R1 antagonist with favorable pharmacokinetic properties. |
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| Keywords: | Melanin-Concentrating Hormone MCH MCH-R1 antagonists Obesity |
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