N, N-disubstituted piperazines and homopiperazines: Synthesis and affinities at α4β2* and α7* neuronal nicotinic acetylcholine receptors

Jianhong Chen; Agripina G. Deaciuc; Linda P. Dwoskin; Peter A. Crooks; Donglu Bai

doi:10.1080/14756360600900513

N, N-disubstituted piperazines and homopiperazines: Synthesis and affinities at α4β2* and α7* neuronal nicotinic acetylcholine receptors

Jianhong Chen
, Agripina G. Deaciuc
, Linda P. Dwoskin
, Peter A. Crooks
, Donglu Bai

Producción científica: Article › revisión exhaustiva

Resumen

A series of N, N-disubstituted piperazines and homopiperazines were prepared and evaluated for binding to natural α4β2* and α7* neuronal nicotinic acetylcholine receptors (nAChRs) using whole brain membrane. Some compounds exhibited good selectivity for α4β2* nAChRs and did not interact with the α7* nAChRs subtype. The most potent analogs were compounds 8-19 (K_i = 10.4 μM), 8-13 (K_i = 12.0 μM), and 8-24 (K_i = 12.8 μM). Thus, linking together a pyridine π-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for α4β2* nAChRs.

Idioma original	English
Páginas (desde-hasta)	667-680
Número de páginas	14
Publicación	Journal of Enzyme Inhibition and Medicinal Chemistry
Volumen	21
N.º	6
DOI	https://doi.org/10.1080/14756360600900513
Estado	Published - dic 2006

Nota bibliográfica

Funding Information:
This work was supported by grants from the National Natural Science Foundation of China and the National Institute on Drug Abuse (DA017548).

Financiación

This work was supported by grants from the National Natural Science Foundation of China and the National Institute on Drug Abuse (DA017548).

Financiadores

Número del financiador

Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse

U19DA017548

National Natural Science Foundation of China (NSFC)

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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10.1080/14756360600900513

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@article{ec8aa09634954e1a9ee804417aa4286d,

title = "N, N-disubstituted piperazines and homopiperazines: Synthesis and affinities at α4β2* and α7* neuronal nicotinic acetylcholine receptors",

abstract = "A series of N, N-disubstituted piperazines and homopiperazines were prepared and evaluated for binding to natural α4β2* and α7* neuronal nicotinic acetylcholine receptors (nAChRs) using whole brain membrane. Some compounds exhibited good selectivity for α4β2* nAChRs and did not interact with the α7* nAChRs subtype. The most potent analogs were compounds 8-19 (Ki = 10.4 μM), 8-13 (Ki = 12.0 μM), and 8-24 (Ki = 12.8 μM). Thus, linking together a pyridine π-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for α4β2* nAChRs.",

keywords = "Homopiperazines, Neuronal nicotinic acetylcholine receptors, Piperazines, α4β* receptors",

author = "Jianhong Chen and Deaciuc, \{Agripina G.\} and Dwoskin, \{Linda P.\} and Crooks, \{Peter A.\} and Donglu Bai",

note = "Funding Information: This work was supported by grants from the National Natural Science Foundation of China and the National Institute on Drug Abuse (DA017548).",

year = "2006",

month = dec,

doi = "10.1080/14756360600900513",

language = "English",

volume = "21",

pages = "667--680",

number = "6",

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TY - JOUR

T1 - N, N-disubstituted piperazines and homopiperazines

T2 - Synthesis and affinities at α4β2* and α7* neuronal nicotinic acetylcholine receptors

AU - Chen, Jianhong

AU - Deaciuc, Agripina G.

AU - Dwoskin, Linda P.

AU - Crooks, Peter A.

AU - Bai, Donglu

N1 - Funding Information: This work was supported by grants from the National Natural Science Foundation of China and the National Institute on Drug Abuse (DA017548).

PY - 2006/12

Y1 - 2006/12

N2 - A series of N, N-disubstituted piperazines and homopiperazines were prepared and evaluated for binding to natural α4β2* and α7* neuronal nicotinic acetylcholine receptors (nAChRs) using whole brain membrane. Some compounds exhibited good selectivity for α4β2* nAChRs and did not interact with the α7* nAChRs subtype. The most potent analogs were compounds 8-19 (Ki = 10.4 μM), 8-13 (Ki = 12.0 μM), and 8-24 (Ki = 12.8 μM). Thus, linking together a pyridine π-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for α4β2* nAChRs.

AB - A series of N, N-disubstituted piperazines and homopiperazines were prepared and evaluated for binding to natural α4β2* and α7* neuronal nicotinic acetylcholine receptors (nAChRs) using whole brain membrane. Some compounds exhibited good selectivity for α4β2* nAChRs and did not interact with the α7* nAChRs subtype. The most potent analogs were compounds 8-19 (Ki = 10.4 μM), 8-13 (Ki = 12.0 μM), and 8-24 (Ki = 12.8 μM). Thus, linking together a pyridine π-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for α4β2* nAChRs.

KW - Homopiperazines

KW - Neuronal nicotinic acetylcholine receptors

KW - Piperazines

KW - α4β receptors

UR - https://www.scopus.com/pages/publications/33845806475

UR - https://www.scopus.com/pages/publications/33845806475#tab=citedBy

U2 - 10.1080/14756360600900513

DO - 10.1080/14756360600900513

M3 - Article

C2 - 17252939

AN - SCOPUS:33845806475

SN - 1475-6366

VL - 21

SP - 667

EP - 680

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

IS - 6

ER -

N, N-disubstituted piperazines and homopiperazines: Synthesis and affinities at α4β2* and α7* neuronal nicotinic acetylcholine receptors

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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