Balancing oral exposure with Cyp3A4 inhibition in benzimidazole-based IGF-IR inhibitors

3-(Benzimidazol-2-yl)-pyridine-2-one-based ATP competitive inhibitors of Insulin-like Growth Factor 1 Kinase (IGF-IR) were optimized for reduced Cyp3A4 inhibition and improved oral exposure. The use of malonate as methyl anion synthon via S NAr reaction and double decarboxylation under mild conditio...

Full description

Saved in:
Bibliographic Details
Published inBioorganic & medicinal chemistry Vol. 18; no. 14; pp. 4075 - 4080
Main Authors Zimmermann, Kurt, Wittman, Mark D., Saulnier, Mark G., Velaparthi, Upender, Langley, David R., Sang, Xiaopeng, Frennesson, David, Carboni, Joan, Li, Aixin, Greer, Ann, Gottardis, Marco, Attar, Ricardo M., Yang, Zheng, Balimane, Praveen, Discenza, Lorell N., Vyas, Dolatrai
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 15.07.2008
Elsevier
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:3-(Benzimidazol-2-yl)-pyridine-2-one-based ATP competitive inhibitors of Insulin-like Growth Factor 1 Kinase (IGF-IR) were optimized for reduced Cyp3A4 inhibition and improved oral exposure. The use of malonate as methyl anion synthon via S NAr reaction and double decarboxylation under mild conditions is demonstrated. 3-(Benzimidazol-2-yl)-pyridine-2-one-based ATP competitive inhibitors of Insulin-like Growth Factor 1 Kinase (IGF-IR) were optimized for reduced Cyp3A4 inhibition and improved oral exposure. The use of malonate as methyl anion synthon via S NAr reaction and double decarboxylation under mild conditions is demonstrated.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0960-894X
0968-0896
1464-3405
1464-3391
DOI:10.1016/j.bmcl.2008.05.104