N1H- and N1-Substituted Phenylguanidines as α7 Nicotinic Acetylcholine (nACh) Receptor Antagonists: Structure-Activity Relationship Studies.
ACS Chem Neurosci
; 12(12): 2194-2201, 2021 06 16.
Article
em En
| MEDLINE
| ID: mdl-34043311
ABSTRACT
We previously reported that N-(3-chlorophenyl)guanidine (1) represents a novel α7 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 α7 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., <10-fold) effect on potency, and the presence of an N1-isopropyl substituent was tolerated. Here, we report the first SAR investigation of this novel α7 nAChR antagonist chemotype.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Nicotínicos
/
Receptor Nicotínico de Acetilcolina alfa7
Limite:
Animals
/
Humans
Idioma:
En
Revista:
ACS Chem Neurosci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos