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Bioorg Med Chem Lett. 2009 Jan 15;19(2):373-7. doi: 10.1016/j.bmcl.2008.11.065. Epub 2008 Nov 24.

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.

Author information

1
GlaxoSmithKline, Oncology R&D, 5 Moore Drive, PO Box 13398, Research Triangle Park, NC 27709-3398, USA.

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.

PMID:
19081716
DOI:
10.1016/j.bmcl.2008.11.065
[Indexed for MEDLINE]

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