Bioorg Med Chem Lett. 2007 May 15;17(10):2886-9. Epub 2007 Feb 25.

Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors.

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Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. bhodous@amgen.com

Abstract

A novel class of selective Tie-2 inhibitors was derived from a multi-kinase inhibitor 1. By reversing the amide connectivity and incorporating aminotriazine or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR selectivity could be achieved with 3-substituted terminal aryl rings. X-ray co-crystal structure analysis aided inhibitor design. This series was evaluated on the basis of potency, selectivity, and rat pharmacokinetic parameters.

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Structures reported by this article

Synthesis, Structural Analysis, And Sar Studies Of Triazine Derivatives As Potent, Selective Tie-2 Inhibitors

PDB: 2OSC

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 2.8 Å

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