Design and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists

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Abstract

Biaryl urea lead compound 1 was discovered earlier in our MCH antagonist program. Novel benzimidazole analogues with increased chemical stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model.

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Acknowledgments

The authors thank Dr. Michael P. Graziano, Dr. Margaret Van Heek, and Dr. John W. Clader for their support and helpful discussions. We thank Dr. Briendra Pramanik’s group and Dr. Tse-Ming Chan’s group for analytical support.

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