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

Article Details

Citation

Copy to clipboard

Hodous BL, Geuns-Meyer SD, Hughes PE, Albrecht BK, Bellon S, Caenepeel S, Cee VJ, Chaffee SC, Emery M, Fretland J, Gallant P, Gu Y, Johnson RE, Kim JL, Long AM, Morrison M, Olivieri PR, Patel VF, Polverino A, Rose P, Wang L, Zhao H

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

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

PubMed ID

17350837 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
Angiopoietin-1 receptor	Q02763	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE	Angiopoietin-1 receptor	IC 50 (nM)	17	N/A	N/A	Details