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ID: ALA1154545
Journal: Bioorg Med Chem Lett
Title: Optimization of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine inhibitors of IGF-1R: elimination of an acid-mediated decomposition pathway.
Authors: Chamberlain SD, Redman AM, Patnaik S, Brickhouse K, Chew YC, Deanda F, Gerding R, Lei H, Moorthy G, Patrick M, Stevens KL, Wilson JW, Brad Shotwell J.
Abstract: Initial evaluation of a series 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines revealed a C(1') carboxamide was preferred for sub-micromolar in vitro potency against IGF-1R. Subsequent solution stability studies with 1 revealed a susceptibility toward acid-induced intramolecular cyclization with the C(1') carboxamide. Herein, we describe several successful approaches toward generating both potent and acid-stable inhibitors of IGF-1R within the 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine template.
CiteXplore: 19081716