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SAR of PXR transactivation in benzimidazole-based IGF-1R kinase inhibitors

Authors :
Charles Struzynski
Sean Kim
Steven P. Seitz
David B. Frennesson
Ricardo M. Attar
Ann Greer
Dolatrai M. Vyas
Joan M. Carboni
Xiaopeng Sang
Mark D. Wittman
Marco M. Gottardis
Saulnier Mark G
Lorell Discenza
Aixin Li
Kurt Zimmermann
Michael Sinz
Francis Y. Lee
Liqi He
Praveen Balimane
Zheng Yang
Upender Velaparthi
Source :
Bioorganicmedicinal chemistry letters. 20(5)
Publication Year :
2009

Abstract

The SAR of PXR transactivation by 3-(benzimidazol-2-yl)-pyridine-2-one based ATP competitive inhibitors of Insulin-like Growth Factor 1 Receptor kinase (IGF-1R) is discussed. Compounds without PXR transactivation, with in vivo antitumor activity, reduced protein binding and improved oral exposure are presented.

Details

ISSN :
14643405
Volume :
20
Issue :
5
Database :
OpenAIRE
Journal :
Bioorganicmedicinal chemistry letters
Accession number :
edsair.doi.dedup.....13894aac7ddfa8d58651e185aff97076