Discovery of a novel class of aldol-derived 1,2,3-triazoles: potent and selective inhibitors of human cytochrome P450 19A1 (aromatase)

James McNulty; Jerald J Nair; Nesrin Vurgun; Benjamin R Difrancesco; Carla E Brown; Bernice Tsoi; Denis J Crankshaw; Alison C Holloway

doi:10.1016/j.bmcl.2011.10.039

Discovery of a novel class of aldol-derived 1,2,3-triazoles: potent and selective inhibitors of human cytochrome P450 19A1 (aromatase)

Bioorg Med Chem Lett. 2012 Jan 1;22(1):718-22. doi: 10.1016/j.bmcl.2011.10.039. Epub 2011 Oct 20.

Authors

James McNulty¹, Jerald J Nair, Nesrin Vurgun, Benjamin R Difrancesco, Carla E Brown, Bernice Tsoi, Denis J Crankshaw, Alison C Holloway

Affiliation

¹ Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ont., Canada L8S 4M1. jmcnult@mcmaster.ca

PMID: 22079757
DOI: 10.1016/j.bmcl.2011.10.039

Abstract

The discovery of a novel five-component 1,2,3-triazole-containing pharmacophore that exhibits potent and selective inhibition of aromatase (CYP 450 19A1) is described. All compounds are derived from an initial aldol reaction of a phenylacetate derivative with an aromatic aldehyde. Structure-activity data generated from both syn- and anti-aldol adducts provides initial insights into the requirements for both potency and selectivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldehydes / chemistry
Antineoplastic Agents / pharmacology*
Aromatase / chemistry*
Aromatase / metabolism
Aromatase Inhibitors / pharmacology*
Chemistry, Pharmaceutical / methods
Drug Design
Humans
Kinetics
Models, Chemical
Models, Molecular
Molecular Conformation
Phenylacetates / chemistry
Recombinant Proteins / chemistry
Structure-Activity Relationship
Triazoles / chemistry
Triazoles / pharmacology*

Substances

Aldehydes
Antineoplastic Agents
Aromatase Inhibitors
Phenylacetates
Recombinant Proteins
Triazoles
Aromatase
CYP19A1 protein, human
phenylacetic acid