Design and synthesis of butynyloxyphenyl β-sulfone piperidine hydroxamates as TACE inhibitors

A series of butynyloxyphenyl β-sulfone piperidine hydroxamate TACE inhibitors was designed and synthesized. The resulting structure–activity relationship and MMP selectivity of the series were examined. Of the compounds investigated, 17s has excellent in vitro potency against isolated TACE enzyme, s...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2006-08, Vol.16 (15), p.3927-3931
Hauptverfasser:	Park, Kaapjoo, Aplasca, Alexis, Du, Mila T., Sun, LinHong, Zhu, Yi, Zhang, Yuhua, Levin, Jeremy I.
Format:	Artikel
Sprache:	eng
Schlagworte:	ADAM Proteins - antagonists & inhibitors ADAM17 Protein Animals Biological and medical sciences Drug Design Medical sciences Mice Miscellaneous MMP selectivity Pharmacology. Drug treatments Piperidines - chemical synthesis Piperidines - chemistry Piperidines - pharmacology Structure-Activity Relationship TACE inhibitors β-Sulfone piperidine hydroxamates
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	A series of butynyloxyphenyl β-sulfone piperidine hydroxamate TACE inhibitors was designed and synthesized. The resulting structure–activity relationship and MMP selectivity of the series were examined. Of the compounds investigated, 17s has excellent in vitro potency against isolated TACE enzyme, shows good selectivity over MMP-1, -2, -7, -8, -9, -13, and -14, and oral activity in an in vivo mouse model of TNF-α production.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2006.05.026