Chemistry is the experimental and theoretical study of materials on their properties at both the macroscopic and microscopic levels. 379270-35-6, Name is Phenyl hydrogen ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate, molecular formula is C15H18N5O4P. In an article, author is Yang, Xicheng,once mentioned of 379270-35-6, Category: piperidines.
Discovery, cocrystallization and biological evaluation of novel piperidine derivatives as high affinity Ls-AChBP ligands possessing alpha 7 nAChR activities
A series of novel pyridine-substituted piperidine derivatives were discovered as low nanomolar Is-AChBP ligands with alpha 7 nAChR partial agonism or antagonism activities. A high-resolution antagonist bound Ls-AChBP complex was successfully resolved with a classic Loop C opening phenomenon and unique sulfur-it interactions which deviated from our previous docking mode to a large extent. With the knowledge of the co-complex, 27 novel piperidine derivatives were designed and synthesized. The structure-activity relationships (SARs) of the aromatic and pyridine regions were well established and binding modes were illustrated with the help of molecular docking which indicated that interactions with Trp 143 and the water bridge are essential for the high binding affinities. Halogen bonding as well as the space around 5′- or 6′- position of the pyridine ring was also proposed to influence the binding conformation of the compounds. Notably, two enantiomers of compound 2 showed opposite functions toward alpha 7 nAChR and compound (S)-2 showed sub-nanomolar affinity (K-i = 0.86 nM) on Ls-AChBP and partial agonism (pEC(50) = 4.69 +/- 0.11,Emax = 36.1%) on alpha 7 nAChR with reasonable pharmacokinetics (PK) properties and fine ability of blood-brain-barrier (BBB) penetration. This study provided promising hits to develop candidates targeting nAChR-related CNS diseases. (C) 2018 Elsevier Masson SAS. All rights reserved.
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Reference:
Piperidine – Wikipedia,
,Piperidine | C5H11N – PubChem