Journal article
Investigation of aryl halides as ketone bioisosteres: Refinement of potent and selective inhibitors of human cytochrome P450 19A1 (aromatase)
Abstract
Bioisosteric replacement of cyclic ketone functionality with aryl halides was investigated on a centrally-flexible, five-component 1,2,3-triazole-containing pharmacophore, resulting in enhanced inhibition of aromatase (CYP450 19A1). Structure-activity data generated from both syn- and anti-aldol precursors provides significant insights into the requirements for enhanced potency, validating this novel ketone-to-aryl halide bioisostere hypothesis.
Authors
McNulty J; Nielsen AJ; Brown CE; DiFrancesco BR; Vurgun N; Nair JJ; Crankshaw DJ; Holloway AC
Journal
Bioorganic & Medicinal Chemistry Letters, Vol. 23, No. 22, pp. 6060–6063
Publisher
Elsevier
Publication Date
11 2013
DOI
10.1016/j.bmcl.2013.09.030
ISSN
0960-894X