Development of a highly selective, orally bioavailable and CNS penetrant M1 agonist derived from the MLPCN probe ML071

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Abstract

Herein we report the discovery and SAR of a novel series of M1 agonists based on the MLPCN probe, ML071. From this, VU0364572 emerged as a potent, orally bioavailable and CNS penetrant M1 agonist with high selectivity, clean ancillary pharmacology and enantiospecific activity.

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Acknowledgments

The authors thank the NIH and NIMH for support of our M1 muscarinic program (1RO1MH082867-01). Vanderbilt is a Specialized Chemistry Center within the MLPCN (U54MH084659), and ML071 is an MLPCN probe, freely avaialble upon request.

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    Present address: NIH Chemical Genomics Center, National Institute of Health, Bethesda, MD, USA.

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