Joerg, Manuela; Khajehali, Elham; van der Westhuizen, Emma T.; C. Choy, K. H.; Shackleford, David M.; Tobin, Andrew B.; Sexton, Patrick M.; Valant, Celine; Capuano, Ben; Christopoulos, Arthur; Scammells, Peter J. published their research in ChemMedChem in 2021. The article was titled ãDevelopment of Novel 4-Arylpyridin-2-one and 6-Arylpyrimidin-4-one Positive Allosteric Modulators of the M1 Muscarinic Acetylcholine Receptorã?Application In Synthesis of 2-Hydroxyphenylboronic acid The article contains the following contents:
This study investigated the structure-activity relationships of 4-phenylpyridin-2-one and 6-phenylpyrimidin-4-one M1 muscarinic acetylcholine receptor (M1 mAChRs) pos. allosteric modulators (PAMs). The presented series focuses on modifications to the core and top motif of the reported leads, MIPS1650 and MIPS1780. Profiling of our novel analogs showed that these modifications result in more nuanced effects on the allosteric properties compared to our previous compounds with alterations to the biaryl pendant. Further pharmacol. characterization of the selected compounds in radioligand binding, IP1 accumulation and β-arrestin 2 recruitment assays demonstrated that, despite primarily acting as affinity modulators, the PAMs displayed different pharmacol. properties across the two cellular assays. The novel PAM I is a potential lead candidate for further development of peripherally restricted M1 PAMs, due to its lower blood-brain-barrier (BBB) permeability and improved exposure in the periphery compared to lead MIPS1780.. The experimental process involved the reaction of 2-Hydroxyphenylboronic acid(cas: 89466-08-0Application In Synthesis of 2-Hydroxyphenylboronic acid)
2-Hydroxyphenylboronic acid(cas: 89466-08-0) belongs to acyl phenylboronic acid. Phenylboronic acid (PBA) has been used to extract β-blockers (a class of aminoalcohol-containing drugs) from aqueous solution, rat, and human plasma. Application In Synthesis of 2-Hydroxyphenylboronic acid
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