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1y6a
From Proteopedia
Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor
A series of derivatives of 2-anilino-5-phenyloxazole (5) has been identified as inhibitors of VEGFR2 kinase. Herein we describe the structure-activity relationship (SAR) of this novel template. Optimization of both aryl rings led to very potent inhibitors at both the enzymatic and cellular levels. Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts. X-ray crystallography confirmed the proposed binding mode, and comparison of oxazoles 39 and 46 revealed interesting differences in orientation of 2-pyridyl and 3-pyridyl rings, respectively, attached at the meta position of the 5-phenyl ring.
Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors., Harris PA, Cheung M, Hunter RN 3rd, Brown ML, Veal JM, Nolte RT, Wang L, Liu W, Crosby RM, Johnson JH, Epperly AH, Kumar R, Luttrell DK, Stafford JA, J Med Chem. 2005 Mar 10;48(5):1610-9. PMID:15743202
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1Y6A is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
See VEGFR for additional structural information.
Reference
- Harris PA, Cheung M, Hunter RN 3rd, Brown ML, Veal JM, Nolte RT, Wang L, Liu W, Crosby RM, Johnson JH, Epperly AH, Kumar R, Luttrell DK, Stafford JA. Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9. PMID:15743202 doi:10.1021/jm049538w
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