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).

Keywords

Homopiperazines
Neuronal nicotinic acetylcholine receptors
Piperazines
α4β* receptors

ASJC Scopus subject areas

Pharmacology
Drug Discovery

Access to Document

10.1080/14756360600900513

Cite this

@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",

}

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 - http://www.scopus.com/inward/record.url?scp=33845806475&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845806475&partnerID=8YFLogxK

U2 - 10.1080/14756360600900513

DO - 10.1080/14756360600900513

M3 - Article

C2 - 17252939

AN - SCOPUS:33845806475

VL - 21

SP - 667

EP - 680

IS - 6

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this