Abstract
To address the hERG liability of MCHR1 antagonists such as 1 and 2, new analogs such as 4 and 5 that incorporated a polar heteroaryl group were designed and synthesized. Biological evaluation confirmed that these new analogs retained MCH R1 activity with greatly attenuated hERG liabilities as indicated in the Rb efflux assay.
MeSH terms
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Animals
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Drug Evaluation, Preclinical
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Fishes
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Heptanes / chemistry*
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Hexanes / chemistry*
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Humans
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Kinetics
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Mice
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Models, Chemical
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Molecular Structure
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Obesity / drug therapy
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Receptors, Somatostatin / antagonists & inhibitors*
Substances
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Heptanes
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Hexanes
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MCHR1 protein, human
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Receptors, Somatostatin