title: Discovery of a novel class of aldol-derived 1,2,3-triazoles: potent and selective inhibitors of human cytochrome P450 19A1 (aromatase).
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.
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ont., Canada L8S 4M1. jmcnult@mcmaster.ca
authors.forename: James
authors.initials: J
authors.lastname: McNulty
authors.forename: Jerald J
authors.initials: JJ
authors.lastname: Nair
authors.forename: Nesrin
authors.initials: N
authors.lastname: Vurgun
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Difrancesco
authors.forename: Carla E
authors.initials: CE
authors.lastname: Brown
authors.forename: Bernice
authors.initials: B
authors.lastname: Tsoi
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Crankshaw
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001141:Aromatase / Q000737:chemistry* / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010648:Phenylacetates / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000447:Aldehydes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D010648:Phenylacetates; D011994:Recombinant Proteins; D014230:Triazoles; D001141:Aromatase; C561410:CYP19A1 protein, human; C025136:phenylacetic acid