Challenges in the development of an M4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 23; pp. 5179 - 5184
• Main Authors: Tarr, James C., Wood, Michael R., Noetzel, Meredith J., Melancon, Bruce J., Lamsal, Atin, Luscombe, Vincent B., Rodriguez, Alice L., Byers, Frank W., Chang, Sichen, Cho, Hyekyung P., Engers, Darren W., Jones, Carrie K., Niswender, Colleen M., Wood, Michael W., Brandon, Nicholas J., Duggan, Mark E., Conn, P. Jeffrey, Bridges, Thomas M., Lindsley, Craig W.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.12.2017
• Subjects: Azetidine; Muscarinic acetylcholine receptor; Positive allosteric modulator (PAM); Schizophrenia; Azetidine; Schizophrenia; Positive allosteric modulator (PAM); M4; Muscarinic acetylcholine receptor

[Display omitted] Herein we describe the continued optimization of M4 positive allosteric modulators (PAMs) within the 5-amino-thieno[2,3-c]pyridazine series of compounds. In this letter, we disclose our studies on tertiary amides derived from substituted azetidines. This series provided excellent C...