Development of novel M-1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012

作者：Melancon Bruce J^*; Utley Thomas J; Sevel Christian; Mattmann Margrith E; Cheung Yiu Yin; Bridges Thomas M; Morrison Ryan D; Sheffler Douglas J; Niswender Colleen M; Daniels J Scott; Conn P Jeffrey; Lindsley Craig W; Wood Michael R

来源：Bioorganic & Medicinal Chemistry Letters, 2012, 22(15): 5035-5040.

DOI：10.1016/j.bmcl.2012.06.018

• Muscarinic acetylcholine receptor 1
• M-1 antagonist
• ML012
• VU0455691
• VU0452865

This Paper describes the continued optimization of an MLPCN probe molecule M-1 antagonist (ML012) through an iterative parallel synthesis approach. After several rounds of modifications of the parent compound, we arrived at a new azetidine scaffold that displayed improved potency while maintaining a desirable level of selectivity over other muscarinic receptor subtypes. Data for representative molecules 7w (VU0452865) and 12a (VU0455691) are presented.

• 出版日期2012-8-1