Tranylcypromine substituted cis -hydroxycyclobutylnaphthamides as potent and selective dopamine D3 receptor antagonists

Jianyong Chen, Beth Levant, Cheng Jiang, Thomas M. Keck, Amy Hauck Newman, Shaomeng Wang

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over the rat and human D2 receptors. Evaluation in a β-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor.

Original languageEnglish (US)
Pages (from-to)4962-4968
Number of pages7
JournalJournal of Medicinal Chemistry
Volume57
Issue number11
DOIs
StatePublished - Jun 12 2014

Fingerprint

Tranylcypromine
Dopamine D3 Receptors
Dopamine Antagonists
Arrestin

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Chen, Jianyong ; Levant, Beth ; Jiang, Cheng ; Keck, Thomas M. ; Newman, Amy Hauck ; Wang, Shaomeng. / Tranylcypromine substituted cis -hydroxycyclobutylnaphthamides as potent and selective dopamine D3 receptor antagonists. In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 11. pp. 4962-4968.
@article{7c63077e332249e28275e01feed65513,
title = "Tranylcypromine substituted cis -hydroxycyclobutylnaphthamides as potent and selective dopamine D3 receptor antagonists",
abstract = "We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over the rat and human D2 receptors. Evaluation in a β-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor.",
author = "Jianyong Chen and Beth Levant and Cheng Jiang and Keck, {Thomas M.} and Newman, {Amy Hauck} and Shaomeng Wang",
year = "2014",
month = "6",
day = "12",
doi = "10.1021/jm401798r",
language = "English (US)",
volume = "57",
pages = "4962--4968",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "11",

}

Tranylcypromine substituted cis -hydroxycyclobutylnaphthamides as potent and selective dopamine D3 receptor antagonists. / Chen, Jianyong; Levant, Beth; Jiang, Cheng; Keck, Thomas M.; Newman, Amy Hauck; Wang, Shaomeng.

In: Journal of Medicinal Chemistry, Vol. 57, No. 11, 12.06.2014, p. 4962-4968.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tranylcypromine substituted cis -hydroxycyclobutylnaphthamides as potent and selective dopamine D3 receptor antagonists

AU - Chen, Jianyong

AU - Levant, Beth

AU - Jiang, Cheng

AU - Keck, Thomas M.

AU - Newman, Amy Hauck

AU - Wang, Shaomeng

PY - 2014/6/12

Y1 - 2014/6/12

N2 - We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over the rat and human D2 receptors. Evaluation in a β-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor.

AB - We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over the rat and human D2 receptors. Evaluation in a β-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor.

UR - http://www.scopus.com/inward/record.url?scp=84902462712&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902462712&partnerID=8YFLogxK

U2 - 10.1021/jm401798r

DO - 10.1021/jm401798r

M3 - Article

C2 - 24848155

AN - SCOPUS:84902462712

VL - 57

SP - 4962

EP - 4968

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 11

ER -