Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]-1H-indoles: Potent and selective aromatase inhibitors

Lead optimization of 4-imidazolylflavans: New promising aromatase inhibitors

“…The (þ) enantiomer was found to be a highly potent inhibitor, being 1.5 and 10 times more active than its racemate and the (À) enantiomer, respectively. This result confirms the importance of the chiral center configuration towards aromatase inhibition, as previously observed for vorozole [23] and for indole derivatives [21].…”

“…In the present work, the synthesis of the non-substituted 7,8-benzo-4-imidazolylflavan was performed and cyano and hydroxyl groups were also introduced at the 4 0 position of the B ring. First, the cyano group is common in several aromatase inhibitors such as anastrozole, letrozole or pyrazole based heterocycles [20]; in the azole family of aromatase inhibitors (letrozole, indole derivatives [21]), the presence of a para-cyano phenyl group is known to be important for activity. Secondly, we have previously demonstrated, that a 4 0 -hydroxy substitution was responsible for an increase in aromatase inhibition in the case of a 4-imidazolyl-7-methoxyflavan [13].…”

Biophysical Screening of a Focused Library for the Discovery of CYP121 Inhibitors as Novel Antimycobacterials

“…The essential role of CYP121 for Mtb survival and our expertise in developing potent and selective human steroidogenic CYP enzyme inhibitors motivated us to identify novel CYP121 inhibitors with increased efficiency and improved properties relative to the azole antifungals …”

A protocol to remove colored metabolites and other inhibitors from plant tissues to facilitate RNA isolation suitable for downstream applications

“…The other ring systems used in the design of the series of DASIs discussed herein have been previously incorporated in either AIs (benzofuran), STS inhibitors (benzoxazoles), or both (indoles). For the latter series, this is exemplified by a range of novel aromatase inhibitors based on 2‐, 3‐, 4‐, 5‐, 6‐, or 7‐[(aryl)(azolyl)methyl]‐1 H ‐indole systems,40–43 from which the most potent compound is 4‐[(1 H ‐imidazol‐1‐yl)(1 H ‐indol‐4‐yl)methyl]benzonitrile, with an IC 50 value of 11.5 n M when evaluated in a microsomal preparation of human placental tissue 43. The potency of the two indole‐containing derivatives described herein ( 45 and 52 ) against aromatase is similar, with IC 50 values in the low nanomolar range (IC 50 AROM =2.7 and 2.3 n M , respectively).…”