Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
7459450
Reference Type
Journal Article
Title
Design, synthesis and receptor affinity of novel conformationally restricted Ï ligands based on the [4.3.3]propellane scaffold
Author(s)
Torres-Gã³Mez, H; Lehmkuhl, K; Schepmann, D; Wã¼Nsch, B
Year
2013
Is Peer Reviewed?
Yes
Journal
European Journal of Medicinal Chemistry
ISSN:
0223-5234
EISSN:
1768-3254
Publisher
Elsevier Masson SAS
Volume
70
Page Numbers
78-87
Language
English
DOI
10.1016/j.ejmech.2013.09.021
Abstract
A series of novel diastereoisomeric Ï ligands 3 was designed, synthesized and pharmacologically evaluated. The highly rigid [4.3.3]propellane scaffold was used to fix the three dimensional orientation of the pharmacophoric moieties required for Ï affinity. The syn,syn-configured aminocarbamate syn,syn-3a reveals the most promising Ï1 affinity (K i = 77 nM) and selectivity over the Ï2 subtype (21-fold). The Ï2 affinity of all four diastereomers 3 was in the low micromolar range. Analysis of the distance between the hydrophobic regions (phenyl moieties) of the diastereomers 3 led to the longest range of distances (10.3-15.2 à ) for the most potent Ï1 ligand syn,syn-3a, which is in good agreement with pharmacophore models. © 2013 Elsevier Masson SAS. All rights reserved.
Keywords
Conformational restriction; Pharmacophore models; Stereoselective reduction; [4.3.3]Propellane; Ï Ligands; (anti 11 oxo[4.3.3] propellan 8 yl) n (2 methoxy 5 methylphenyl)carbamate; (syn 11 oxo[4.3.3]propellan 8 yl) n (2 methoxy 5 methylphenyl)carbamate; anti 11 hydroxy[4.3.3]propellan 8 one; hydrocarbon; syn 11 hydroxy[4.3.3]propellan 8 one; tetramethyl 8,11 dioxo[4.3.3]propellane 7,9,10,12 tetracarboxylate; unclassified drug; [(8 anti 11 anti) (11 benzylamino)[4.3.3]propellan 8 yl] n (2 methoxy 5 methylphenyl)carbamate; [(8 anti 11 anti) 11 hydroxy[4.3.3]propellan 8 yl] n (2 methoxy 5 methylphenyl)carbamate; [(8 anti 11 syn) 11 hydroxy[4.3.3]propellan 8 yl] n (2 methoxy 5 methylphenyl)carbamate; [(8 anti 11 syni) (11 benzylamino)[4.3.3]propellan 8 yl] n (2 methoxy 5 methylphenyl)carbamate; [(8 syn 11 anti) (11 benzylamino)[4.3.3]propellan 8 yl] n (2 methoxy 5 methylphenyl)carbamate; [(8 syn 11 anti) 11 hydroxy[4.3.3]propellan 8 yl] n (2 methoxy 5 methylphenyl)carbamate; [(8 syn 11 syn) (11 benzylamino)[4.3.3]propellan 8 yl] n (2 methoxy 5 methylphenyl)carbamate; [(8 syn 11 syn) 11 hydroxy[4.3.3]propellan 8 yl] n (2 methoxy 5 methylphenyl)carbamate; [4.3.3]propellane 8,11 dione; animal tissue; article; binding affinity; binding assay; diastereoisomer; drug design; drug synthesis; molecular model; nonhuman; pharmacophore; protein determination; rat; receptor binding; Conformational restriction; Pharmacophore models; Stereoselective reduction; [4.3.3]Propellane; Ï Ligands; Animals; Brain; Bridged Compounds; Dose-Response Relationship, Drug; Drug Design; Guinea Pigs; Ligands; Liver; Molecular Conformation; Rats; Receptors, sigma; Stereoisomerism; Structure-Activity Relationship
Tags
Other
•
Harmful Algal Blooms- Health Effects
April 2021 Literature Search
Scopus
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity