91055-64-0Relevant academic research and scientific papers
CYCLIC AMINOMETHYL PYRIMIDINE DERIVATIVE
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Paragraph 0283, (2016/06/01)
The present invention provides a cyclic aminomethyl pyrimidine derivative and a pharmaceutically acceptable salt thereof with high selectivity for dopamine D4 receptors, which are useful for treating a disease such as attention deficit hyperactivity disorder. Specifically, a compound of formula (1) or a pharmaceutically acceptable salt thereof is provided, wherein n and m are independently 1 or 2; Ra is C1-6 alkyl group, C3-6 cycloalkyl group, or amino group; Rb is hydrogen atom, C1-6 alkyl group or the like, provided that when Ra is amino group, then Rb is hydrogen atom; Rc1 and Rc2 are independently hydrogen atom, or C1-6 alkyl group; Rd1 and Rd2 are independently hydrogen atom, fluorine atom or the like; ring Q is an optionally-substituted pyridyl group or an optionally-substituted isoquinolyl group; and the bond having a dashed line is a single or double bond.
Negishi cross-coupling enabled synthesis of novel NAD+-dependent DNA ligase inhibitors and SAR development
Murphy-Benenato, Kerry E.,Gingipalli, Lakshmaiah,Boriack-Sjodin, P. Ann,Martinez-Botella, Gabriel,Carcanague, Dan,Eyermann, Charles J.,Gowravaram, Madhu,Harang, Jenna,Hale, Michael R.,Ioannidis, Georgine,Jahic, Harris,Johnstone, Michele,Kutschke, Amy,Laganas, Valerie A.,Loch, James T.,Miller, Matthew D.,Oguto, Herbert,Patel, Sahil Joe
, p. 5172 - 5177 (2015/11/09)
Two novel compounds, pyridopyrimidines (1) and naphthyridines (2) were identified as potent inhibitors of bacterial NAD+-dependent DNA ligase (Lig) A in a fragment screening. SAR was guided by molecular modeling and X-ray crystallography. It was observed that the diaminonitrile pharmacophore made a key interaction with the ligase enzyme, specifically residues Glu114, Lys291, and Leu117. Synthetic challenges limited opportunities for diversification of the naphthyridine core, therefore most of the SAR was focused on a pyridopyrimidine scaffold. The initial diversification at R1 improved both enzyme and cell potency. Further SAR developed at the R2 position using the Negishi cross-coupling reaction provided several compounds, among these compounds 22g showed good enzyme potency and cellular potency.
