2′ Biaryl amides as novel and subtype selective M1 agonists. Part II: Further optimization and profiling

Brian Budzik; Vincenzo Garzya; Dongchuan Shi; Graham Walker; Yann Lauchart; Adam J. Lucas; Ralph A. Rivero; Christopher J. Langmead; Jeannette Watson; Zining Wu; Ian T. Forbes; Jian Jin

doi:10.1016/j.bmcl.2010.04.127

2′ Biaryl amides as novel and subtype selective M₁ agonists. Part II: Further optimization and profiling

Brian Budzik, Vincenzo Garzya, Dongchuan Shi, Graham Walker, Yann Lauchart, Adam J. Lucas, Ralph A. Rivero, Christopher J. Langmead, Jeannette Watson, Zining Wu, Ian T. Forbes, Jian Jin

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Further optimization of the biaryl amide series via extensively exploring structure-activity relationships resulted in potent and subtype selective M ₁ agonists exemplified by compounds 9a and 9j with good rat PK properties including CNS penetration. Synthesis, structure-activity relationships, subtype selectivity for M₁ over M_2-5, and DMPK properties of these novel compounds are described.

Original language	English
Pages (from-to)	3545-3549
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2010.04.127
State	Published - 2010
Externally published	Yes

Keywords

2′ biaryl amides
CNS-penetrant and orally bioavailable M1 agonist
Subtype selective M1 agonist
Subtype selective M1 muscarinic acetylcholine receptor agonist

Access to Document

10.1016/j.bmcl.2010.04.127

Cite this

Budzik, B., Garzya, V., Shi, D., Walker, G., Lauchart, Y., Lucas, A. J., Rivero, R. A., Langmead, C. J., Watson, J., Wu, Z., Forbes, I. T., & Jin, J. (2010). 2′ Biaryl amides as novel and subtype selective M₁ agonists. Part II: Further optimization and profiling. Bioorganic and Medicinal Chemistry Letters, 20(12), 3545-3549. https://doi.org/10.1016/j.bmcl.2010.04.127

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AU - Walker, Graham

AU - Lauchart, Yann

AU - Lucas, Adam J.

AU - Rivero, Ralph A.

AU - Langmead, Christopher J.

AU - Watson, Jeannette

AU - Wu, Zining

AU - Forbes, Ian T.

AU - Jin, Jian

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KW - Subtype selective M1 agonist

KW - Subtype selective M1 muscarinic acetylcholine receptor agonist

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