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

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• 作者：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
• 关键词：Subtype selective M1 muscarinic acetylcholine receptor agonist ; Subtype selective M1 agonist ; CNS-penetrant and orally bioavailable M1 agonist ; 2′ ; biaryl amides
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 June 2010
• 年：2010
• 卷：20
• 期：12
• 页码：3545-3549
• 全文大小：2671 K

文摘

Further optimization of the biaryl amide series via extensively exploring structure–activity relationships resulted in potent and subtype selective M₁ 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.