Unknown

Dataset Information

0

Tranylcypromine substituted cis-hydroxycyclobutylnaphthamides as potent and selective dopamine D? 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 (K(i) = 12.8 ?M), 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 ?-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor.

SUBMITTER: Chen J 

PROVIDER: S-EPMC4216217 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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

Chen Jianyong J   Levant Beth B   Jiang Cheng C   Keck Thomas M TM   Newman Amy Hauck AH   Wang Shaomeng S  

Journal of medicinal chemistry 20140603 11

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)  ...[more]

Similar Datasets

Unknown "Reversine" and its 2-substituted adenine derivatives as potent and selective A3 adenosine receptor antagonists.
| S-EPMC3474371 | biostudies-other
Unknown Substituted tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor.
| S-EPMC3849818 | biostudies-literature
Unknown N-substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines are opioid receptor pure antagonists.
| S-EPMC2585695 | biostudies-literature
Unknown Simple Tetrahydroisoquinolines Are Potent and Selective Kappa Opioid Receptor Antagonists.
| S-EPMC5512122 | biostudies-literature
Unknown Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores.
| S-EPMC5767125 | biostudies-literature
Unknown Discovery, optimization, and characterization of novel D2 dopamine receptor selective antagonists.
| S-EPMC4315423 | biostudies-literature
Unknown Discovery of 3-substituted aminocyclopentanes as potent and orally bioavailable NR2B subtype-selective NMDA antagonists.
| S-EPMC3369735 | biostudies-literature
Unknown Synthesis and biological evaluation of substituted desloratadines as potent arginine vasopressin V2 receptor antagonists.
| S-EPMC6271649 | biostudies-other
Unknown 8-alkylthio-6-thio-substituted theophylline analogues as selective noncompetitive progesterone receptor antagonists.
| S-EPMC3384716 | biostudies-other
Unknown Analgesic and anti-inflammatory properties of novel, selective, and potent EP4 receptor antagonists.
| S-EPMC5464344 | biostudies-literature