So far, in addition to halogen atoms, other non-metallic atoms can become part of the aromatic heterocycle, and the target ring system is still aromatic.Temple, Kayla J.; Engers, Julie L.; Long, Madeline F.; Gregro, Alison R.; Watson, Katherine J.; Chang, Sichen; Jenkins, Matthew T.; Luscombe, Vincent B.; Rodriguez, Alice L.; Niswender, Colleen M.; Bridges, Thomas M.; Conn, P. Jeffrey; Engers, Darren W.; Lindsley, Craig W. researched the compound: 4-Bromo-2,5-dichloropyridine( cas:1184917-16-5 ).Quality Control of 4-Bromo-2,5-dichloropyridine.They published the article 《Discovery of a novel 3,4-dimethylcinnoline carboxamide M4 positive allosteric modulator (PAM) chemotype via scaffold hopping》 about this compound( cas:1184917-16-5 ) in Bioorganic & Medicinal Chemistry Letters. Keywords: muscarinic acetylcholine receptor M4 pos allosteric modulator SAR; M(4); Muscarinic acetylcholine receptor; Positive allosteric modulator (PAM); Structure activity relationship (SAR). We’ll tell you more about this compound (cas:1184917-16-5).
This Letter details our efforts to replace the 2,4-dimethylquinoline carboxamide core of our previous M4 PAM series, which suffered from high predicted hepatic clearance and protein binding. A scaffold hopping exercise identified a novel 3,4-dimethylcinnoline carboxamide core that provided good M4 PAM activity and improved clearance and protein binding profiles.
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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI