Long, Madeline F. published the artcileDiscovery of a novel 2,4-dimethylquinoline-6-carboxamide M4 positive allosteric modulator (PAM) chemotype via scaffold hopping, Safety of 2-Chloro-5-(trifluoromethyl)pyrazine, the main research area is dimethylquinoline carboxamide derivative preparation muscarinic M4 receptor CNS; M(4); Muscarinic acetylcholine receptor; Positive allosteric modulator (PAM); Structure-Activity Relationship (SAR).
This Letter details our efforts to replace the 3-amino moiety, an essential pharmacophore for M4 PAM activity in most M4 PAMs to date, within the thieno[2,3-b]pyridine core, as the β-amino carboxamide motif has been shown to engender poor solubility, varying degrees of P-gp efflux and represents a structural alert. A scaffold hopping exercise identified a novel 2,4-dimethylquinoline carboxamide core that provided M4 PAM activity and good CNS penetration without an amino moiety. In addition, MacMillan photoredox catalysis chem. was essential for construction of the 2,4-dimethylquinoline core.
Bioorganic & Medicinal Chemistry Letters published new progress about Central nervous system agents. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Safety of 2-Chloro-5-(trifluoromethyl)pyrazine.