Synthesis and biological characterization of 3-(imidazol-1-ylmethyl)piperidine sulfonamides as aromatase inhibitors

Mauro Di Matteo; Alessandra Ammazzalorso; Federico Andreoli; Irene Caffa; Barbara De Filippis; Marialuigia Fantacuzzi; Letizia Giampietro; Cristina Maccallini; Alessio Nencioni; Marco Daniele Parenti; Debora Soncini; Alberto Del Rio; Rosa Amoroso

doi:10.1016/j.bmcl.2016.04.078

Synthesis and biological characterization of 3-(imidazol-1-ylmethyl)piperidine sulfonamides as aromatase inhibitors

Bioorg Med Chem Lett. 2016 Jul 1;26(13):3192-3194. doi: 10.1016/j.bmcl.2016.04.078. Epub 2016 Apr 28.

Affiliations

¹ Department of Pharmacy, University of Chieti 'G. d'Annunzio', via dei Vestini 31, 66100 Chieti, Italy.
² Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy.
³ Department of Internal Medicine, University of Genoa, V.le Benedetto XV 6, 16132 Genoa, Italy; IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
⁴ Institute of Organic Synthesis and Photoreactivity (ISOF), National Research Council (CNR), Via P. Gobetti 101, 40129 Bologna, Italy.
⁵ Institute of Organic Synthesis and Photoreactivity (ISOF), National Research Council (CNR), Via P. Gobetti 101, 40129 Bologna, Italy; Innovamol Srls, Viale Alfeo Corrassori 24, Modena 41124, Italy.

PMID: 27161804
DOI: 10.1016/j.bmcl.2016.04.078

Abstract

The most frequently used treatment for hormone receptor positive breast cancer in post-menopausal women are aromatase inhibitors. In order to develop new aromatase inhibitors, we designed and synthesized new imidazolylmethylpiperidine sulfonamides using the structure of the previously identified aromatase inhibitor SYN 20028567 as starting lead. By this approach, three new aromatase inhibitors with IC50 values that are similar to that of letrozole and SYN 20028567 were identified.

Keywords: Anticancer agents; Aromatase inhibitor; Imidazole; Sulfonamide; Synthesis.

Publication types

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

MeSH terms

Aromatase / metabolism*
Aromatase Inhibitors / chemical synthesis
Aromatase Inhibitors / chemistry
Aromatase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Humans
Molecular Structure
Piperidines / chemical synthesis
Piperidines / chemistry
Piperidines / pharmacology*
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Aromatase Inhibitors
Piperidines
Sulfonamides
Aromatase