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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists : Structure-Activity Relationship Studies. / Alwassil, Osama; Khatri, Shailesh; Schulte, Marvin K.; Aripaka, Sanjay S.; Mikkelsen, Jens D.; Dukat, Malgorzata.

In: ACS Chemical Neuroscience, Vol. 12, No. 12, 2021, p. 2194-2201.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Alwassil, O, Khatri, S, Schulte, MK, Aripaka, SS, Mikkelsen, JD & Dukat, M 2021, 'N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists: Structure-Activity Relationship Studies', ACS Chemical Neuroscience, vol. 12, no. 12, pp. 2194-2201. https://doi.org/10.1021/acschemneuro.1c00212

APA

Alwassil, O., Khatri, S., Schulte, M. K., Aripaka, S. S., Mikkelsen, J. D., & Dukat, M. (2021). N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists: Structure-Activity Relationship Studies. ACS Chemical Neuroscience, 12(12), 2194-2201. https://doi.org/10.1021/acschemneuro.1c00212

Vancouver

Alwassil O, Khatri S, Schulte MK, Aripaka SS, Mikkelsen JD, Dukat M. N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists: Structure-Activity Relationship Studies. ACS Chemical Neuroscience. 2021;12(12):2194-2201. https://doi.org/10.1021/acschemneuro.1c00212

Author

Alwassil, Osama ; Khatri, Shailesh ; Schulte, Marvin K. ; Aripaka, Sanjay S. ; Mikkelsen, Jens D. ; Dukat, Malgorzata. / N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists : Structure-Activity Relationship Studies. In: ACS Chemical Neuroscience. 2021 ; Vol. 12, No. 12. pp. 2194-2201.

Bibtex

@article{73ae715578bf49baa6cfa5a9b7126492,
title = "N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists: Structure-Activity Relationship Studies",
abstract = "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.,",
keywords = "alpha 7 nAChR, SAR, electrophysiology, antagonist, phenylguanidines, ALLOSTERIC MODULATORS, ARYLGUANIDINES, BINDING",
author = "Osama Alwassil and Shailesh Khatri and Schulte, {Marvin K.} and Aripaka, {Sanjay S.} and Mikkelsen, {Jens D.} and Malgorzata Dukat",
year = "2021",
doi = "10.1021/acschemneuro.1c00212",
language = "English",
volume = "12",
pages = "2194--2201",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "12",

}

RIS

TY - JOUR

T1 - N1H- and N1-Substituted Phenylguanidines as alpha 7 Nicotinic Acetylcholine (nACh) Receptor Antagonists

T2 - Structure-Activity Relationship Studies

AU - Alwassil, Osama

AU - Khatri, Shailesh

AU - Schulte, Marvin K.

AU - Aripaka, Sanjay S.

AU - Mikkelsen, Jens D.

AU - Dukat, Malgorzata

PY - 2021

Y1 - 2021

N2 - 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.,

AB - 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.,

KW - alpha 7 nAChR

KW - SAR

KW - electrophysiology

KW - antagonist

KW - phenylguanidines

KW - ALLOSTERIC MODULATORS

KW - ARYLGUANIDINES

KW - BINDING

U2 - 10.1021/acschemneuro.1c00212

DO - 10.1021/acschemneuro.1c00212

M3 - Journal article

C2 - 34043311

VL - 12

SP - 2194

EP - 2201

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 12

ER -

ID: 273696892