Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase

Stanley D Chamberlain; Joseph W Wilson; Felix Deanda; Samarjit Patnaik; Anikó M Redman; Bin Yang; Lisa Shewchuk; Peter Sabbatini; M Anthony Leesnitzer; Arthur Groy; Charity Atkins; Roseanne Gerding; Anne M Hassell; Huangshu Lei; Robert A Mook Jr; Ganesh Moorthy; Jason L Rowand; Kirk L Stevens; Rakesh Kumar; J Brad Shotwell

doi:10.1016/j.bmcl.2008.11.046

Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase

Bioorg Med Chem Lett. 2009 Jan 15;19(2):469-73. doi: 10.1016/j.bmcl.2008.11.046. Epub 2008 Nov 18.

Affiliation

¹ GlaxoSmithKline, Oncology R&D, 5 Moore Drive, 3.4184.4B, PO Box 13398, Research Triangle Park, NC 27709-3398, USA.

PMID: 19056263
DOI: 10.1016/j.bmcl.2008.11.046

Abstract

The evaluation of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines as inhibitors of the IGF-1R (IGF-IR) receptor tyrosine kinase is reported. Examples demonstrate nanomolar potencies in in vitro enzyme and mechanistic cellular assays as well as promising in vivo pharmacokinetics in rat.

MeSH terms

Animals
Drug Discovery
Models, Molecular
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacokinetics
Protein Kinase Inhibitors / pharmacology*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Rats
Receptor, IGF Type 1 / antagonists & inhibitors*

Substances

Protein Kinase Inhibitors
Pyrimidines
Receptor, IGF Type 1