Bioorg Med Chem Lett. 2010 Sep 1;20(17):5027-30. Epub 2010 Jul 15.

Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase.

Sampognaro AJ, Wittman MD, Carboni JM, Chang C, Greer AF, Hurlburt WW, Sack JS, Vyas DM.

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Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, USA. anthony.sampognaro@bms.com

Abstract

Pyrrolidine, pyrrolidinone, carbocyclic, and acyclic groups were used as isosteric proline replacements in a series of insulin-like growth factor I receptor kinase/insulin receptor kinase inhibitors. Examples that were similar in potency to proline-containing reference compounds were shown to project a key fluoropyridine amide into a common space, while less potent compounds were not able to do so for reasons of stereochemistry or structural rigidity.

PMID:: 20675137; [PubMed - indexed for MEDLINE]

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Structures reported by this article

Crystal Structure Of Insulin-Like Growth Factor 1 Receptor (Igf-1r-Wt) Complex With A Carbon-Linked Proline Isostere Inhibitor (34)

PDB: 3NW7

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 2.11 Å

See all 3 structures...

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Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase.

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