Bioorg Med Chem Lett. 2009 Jan 15;19(2):360-4. doi: 10.1016/j.bmcl.2008.11.077. Epub 2008 Nov 24.

Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.

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GlaxoSmithKline, Oncology R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA.

Abstract

The SAR of C5' functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays.

PMID:: 19071018; [PubMed - indexed for MEDLINE]

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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. [Bioorg Med Chem Lett. 2009]
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Review [Progress in the studies on small molecule IGF-1R inhibitors]. [Yao Xue Xue Bao. 2008]
Review [Progress in the studies on small molecule IGF-1R inhibitors].
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Cited by 4 PubMed Central articles

Enzyme kinetics and interaction studies for human JNK1β1 and substrates activating transcription factor 2 (ATF2) and c-Jun N-terminal kinase (c-Jun). [J Biol Chem. 2012]
Enzyme kinetics and interaction studies for human JNK1β1 and substrates activating transcription factor 2 (ATF2) and c-Jun N-terminal kinase (c-Jun).
Figuera-Losada M, LoGrasso PV. J Biol Chem. 2012 Apr 13; 287(16):13291-302. Epub 2012 Feb 17.
Analysis of conditions affecting auto-phosphorylation of human kinases during expression in bacteria. [Protein Expr Purif. 2012]
Analysis of conditions affecting auto-phosphorylation of human kinases during expression in bacteria.
Shrestha A, Hamilton G, O'Neill E, Knapp S, Elkins JM. Protein Expr Purif. 2012 Jan; 81(1):136-43. Epub 2011 Oct 1.
Understanding the specificity of a docking interaction between JNK1 and the scaffolding protein JIP1. [J Phys Chem B. 2011]
Understanding the specificity of a docking interaction between JNK1 and the scaffolding protein JIP1.
Yan C, Kaoud T, Lee S, Dalby KN, Ren P. J Phys Chem B. 2011 Feb 17; 115(6):1491-502. Epub 2011 Jan 25.

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Structures reported by this article

Jnk1 Complexed With A Bis-Anilino-Pyrrolopyrimidine Inhibitor

PDB: 3ELJ

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 1.8 Å

See all 2 structures...

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Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kina...
Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.
Bioorg Med Chem Lett. 2009 Jan 15 ;19(2):360-4. doi: 10.1016/j.bmcl.2008.11.077. Epub 2008 Nov 24 .

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