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N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists: Structure-Activity Relationship Studies

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  • Osama Alwassil
  • Shailesh Khatri
  • Marvin K. Schulte
  • Sanjay S. Aripaka
  • Mikkelsen, Jens D.
  • Malgorzata Dukat

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.,

OriginalsprogEngelsk
TidsskriftACS Chemical Neuroscience
Vol/bind12
Udgave nummer12
Sider (fra-til)2194-2201
Antal sider8
ISSN1948-7193
DOI
StatusUdgivet - 2021

ID: 273696892