Format

Send to

Choose Destination
J Med Chem. 2014 Jun 12;57(11):4962-8. doi: 10.1021/jm401798r. Epub 2014 Jun 3.

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

Author information

1
Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.

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 (K(i) = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has K(i) 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.

PMID:
24848155
PMCID:
PMC4216217
DOI:
10.1021/jm401798r
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center