N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists: Structure-Activity Relationship Studies
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We previously reported that N-(3-chlorophenyl)guanidine (1) represents a novel alpha 7 nicotinic ACh (nACh) receptor antagonist chemotype. In the present study, a small series of compounds was synthesized with the intent to investigate the structure-activity relationship (SAR). Preliminary data suggested that the N-methyl analog of 1, 2, was several times more potent. Therefore, the chloro group at the aryl 3-position of 1 and its N1-methyl counterpart 2 were replaced with a number of substituents considering the electronic, lipophilic, and steric nature of the substituents. The potencies of the compounds to inhibit acetylcholine (ACh)-induced responses were obtained in Xenopus laevis oocytes expressing human alpha 7 nicotinic ACh receptors (nAChRs) using a two-electrode voltage-clamp assay. We found that the nature of the 3-position substituents had relatively little (i.e.,
Original language | English |
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Journal | ACS Chemical Neuroscience |
Volume | 12 |
Issue number | 12 |
Pages (from-to) | 2194-2201 |
Number of pages | 8 |
ISSN | 1948-7193 |
DOIs | |
Publication status | Published - 2021 |
- alpha 7 nAChR, SAR, electrophysiology, antagonist, phenylguanidines, ALLOSTERIC MODULATORS, ARYLGUANIDINES, BINDING
Research areas
ID: 273696892