7215-02-3Relevant academic research and scientific papers
Challenges in the development of an M4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides
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.,Jeffrey Conn,Bridges, Thomas M.,Lindsley, Craig W.
, p. 5179 - 5184 (2017/11/03)
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 CNS penetration, which had been challenging to consistently achieve in other amide series. Efforts to mitigate high clearance, aided by metabolic softspot analysis, were unsuccessful and precluded this series from further consideration as a preclinical candidate. In the course of this study, we found that potassium tetrafluoroborate salts could be engaged in a tosyl hydrazone reductive cross coupling reaction, a previously unreported transformation, which expands the synthetic utility of the methodology.
Catalytic Enantioselective Intermolecular Desymmetrization of Azetidines
Wang, Zhaobin,Sheong, Fu Kit,Sung, Herman H. Y.,Williams, Ian D.,Lin, Zhenyang,Sun, Jianwei
supporting information, p. 5895 - 5898 (2015/05/27)
The first catalytic asymmetric desymmetrization of azetidines is disclosed. Despite the low propensity of azetidine ring opening and challenging stereocontrol, smooth intermolecular reactions were realized with excellent efficiency and enantioselectivity.
