Design and synthesis of novel potent and selective integrin alphanubeta3 antagonists--novel synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone acetates

Werner Seitz; Hervé Geneste; Gisela Backfisch; Jürgen Delzer; Claudia Graef; Wilfried Hornberger; Andreas Kling; Thomas Subkowski; Norbert Zimmermann

doi:10.1016/j.bmcl.2007.11.089

Design and synthesis of novel potent and selective integrin alphanubeta3 antagonists--novel synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone acetates

Bioorg Med Chem Lett. 2008 Jan 15;18(2):527-31. doi: 10.1016/j.bmcl.2007.11.089. Epub 2007 Nov 28.

Authors

Werner Seitz¹, Hervé Geneste, Gisela Backfisch, Jürgen Delzer, Claudia Graef, Wilfried Hornberger, Andreas Kling, Thomas Subkowski, Norbert Zimmermann

Affiliation

¹ BASF AG, Main Research Laboratory, D-67056 Ludwigshafen, Germany.

PMID: 18068982
DOI: 10.1016/j.bmcl.2007.11.089

Abstract

An unexpected ring contraction of benzazepinone based alpha(nu)beta(3) antagonists led to the design of quinolinone-type derivatives. Novel and efficient synthetic routes to isoquinolinone, benzoxazinone, and quinazolinone acetates were established. Nanomolar alpha(nu)beta(3) antagonists based on these new scaffolds were prepared. Moreover, benzoxazinones 15a and 15b exhibited high microsomal stability and good permeability.

MeSH terms

Benzoxazines / chemical synthesis
Benzoxazines / chemistry*
Benzoxazines / pharmacology
Drug Design
Enzyme-Linked Immunosorbent Assay
Integrin alphaVbeta3 / antagonists & inhibitors*
Isoquinolines / chemical synthesis
Isoquinolines / chemistry*
Isoquinolines / pharmacology
Quinazolines / chemical synthesis
Quinazolines / chemistry*
Quinazolines / pharmacology
Structure-Activity Relationship

Substances

Benzoxazines
Integrin alphaVbeta3
Isoquinolines
Quinazolines