7215-06-7Relevant academic research and scientific papers
6-HYDROXY-4-OXO-1,4-DIHYDROPYRIMIDINE-5-CARBOXAMIDES AS APJ AGONISTS
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Paragraph 0908; 0911, (2017/10/10)
The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.
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.
