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ID: ALA1155068

Journal: Bioorg Med Chem Lett

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

Authors: Zimmermann K, Wittman MD, Saulnier MG, Velaparthi U, Langley DR, Sang X, Frennesson D, Carboni J, Li A, Greer A, Gottardis M, Attar RM, Yang Z, Balimane P, Discenza LN, Vyas D.

Abstract: 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(N)Ar reaction and double decarboxylation under mild conditions is demonstrated.

CiteXplore: 18572407

DOI: 10.1016/j.bmcl.2008.05.104