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...
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Published in | Bioorganic & medicinal chemistry Vol. 18; no. 14; pp. 4075 - 4080 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
15.07.2008
Elsevier |
Subjects | |
Online Access | Get full text |
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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. |
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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 |