Balancing Oral Exposure with Cyp3A4 Inhibition in Benzimidazole-based IGF-IR Inhibitors
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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.
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PMID: 38106612 PMC: 10724362. DOI: 10.1016/j.patter.2023.100865.
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