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

Research output: Contribution to journal › Article › peer-review

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 (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.

Original language	English
Pages (from-to)	667-680
Number of pages	14
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	21
Issue number	6
DOIs	https://doi.org/10.1080/14756360600900513
State	Published - Dec 2006

Bibliographical 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).

Funding

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

Funders	Funder number
National Institute on Drug Abuse	U19DA017548
National Natural Science Foundation of China (NSFC)

Keywords

Homopiperazines
Neuronal nicotinic acetylcholine receptors
Piperazines
α4β* receptors

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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10.1080/14756360600900513

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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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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