91641-02-0Relevant articles and documents
The optimization of a novel selective antagonist for human M2 muscarinic acetylcholine receptor
Li, Miaomiao,Huang, Chen,Wu, Xingyu,Ding, Fan,Hu, Zhoumi,Zhu, Yan,Zhao, Lanxue,Hou, Lina,Chen, Hongzhuan,Wang, Hao,Xu, Jianrong,Tang, Dewei
, (2020/11/02)
Muscarinic acetylcholine receptors (mAChRs) comprise five distinct subtypes denoted M1 to M5. The antagonism of M2 subtype could increase the release of acetylcholine from vesicles into the synaptic cleft and improve postsynaptic functions in the hippocampus via M1 receptor activation, displaying therapeutic potentials for Alzheimer's disease. However, drug development for M2 antagonists is still challenged among different receptor subtypes. In this study, by optimizing a scaffold from virtual screening, we synthesized two focused libraries and generated up to 50 derivatives. By measuring potency and binding selectivity, we discovered a novel M2 antagonist, ligand 47, featuring submicromolar IC50, high M2/M4 selectivity (~30-fold) and suitable lipophilicity (cLogP = 4.55). Further study with these compounds also illustrates the structure–activity relationship of this novel scaffold. Our study could not only provide novel lead structure, which was easy to synthesize, but also offer valuable information for further development of selective M2 ligands.
Microbiological Transformations, Part 9. Microbiological Transformations of 1,2,5,6-Tetrahydropyrroloquinolin-4-one and of Derivatives of 1,2,3,5,6,7-Hexahydropyridoquinoline with the Fungus Cunninghamella elegans
Crabb, Trevor A.,Soilleux, Stephanie L.
, p. 5407 - 5414 (2007/10/02)
Incubation of 1,2,6,7-tetrahydropyridoquinolin-3(5H)-one with C. elegans resulted in oxidation at the C-7 benzylic position, whereas 1-methyl-1,2,6,7-tetrahydropyridoquinolin-5(3H)-one gave products resulting from oxidation at both benzylic positions. cis- and trans-1-Hydroxy-3-methyl-1,2,6,7-tetrahydropyridoquinolin-5(3H)-ones were produced on incubation of 5-methyl-1,2,6,7-tetrahydropyridoquinolin-3(5H)-one with C. elegans, in addition to trans-1-hydroxy-5-methyl-1,2,6,7-tetrahydropyridoquinolin-3(5H)-one.Incubation of 1,2,5,6-tetrahydropyrroloquinolin-4-one with C. elegans resulted in dehydrogenation to 1,2-dihydropyrroloquinolin-4-one.Incubation of 2,3,6,7-tetrahydropyridoquinolin-1(5H)-one with C. elegans resulted in benzylic attack at C-7.