Design and chemical synthesis of [1,2,4]triazol[1,5-c]pyrimidin-5-yl amines, a novel class of VEGFR-2 kinase inhibitors

Design and chemical synthesis of [1,2,4]triazol[1,5-c]pyrimidin-5-yl amines, a novel class of VEGFR-2 kinase inhibitors Full article

Journal

Tetrahedron Letters
ISSN: 0040-4039 , E-ISSN: 1873-3581

Output data

Year: 2009, Volume: 50, Number: 27, Pages: 3809-3812 Pages count : 4 DOI: 10.1016/j.tetlet.2009.04.062

Authors

Kiselyov Alexander S. ¹ , Piatnitski Chekler Eugene L. ² , Chernisheva Natalia B. ³ , Salamandra Lev K. ³ , Semenov Victor V. ³

Affiliations

1	deCODE Chemistry, 2501 Davey Road, Woodridge, IL 60517, USA
2	Department of Chemistry, ImClone Systems Inc., 180 Varick Street, New York, NY 10014, USA
3	N. D. Zelinsky Institute of Organic Chemistry, RAN, 47 Leninsky Prospekt, 117918, Russia

The Letter describes a facile approach to 7,8-dihydro[1,2,4]triazol[1,5-c]pyrimidin-5-yl amines, a novel class of potent inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). The synthetic sequence is centered around preparation of the key 3(5)-cyanomethyl-1,2,4-triazole intermediates and their Knoevenagel condensation with aromatic aldehydes. A subsequent three-step conversion of Knoevenagel adducts involving a reduction of vinyl nitriles followed by the reaction of the resulting amines with aryl isothiocyanates and cyclization of the respective thioureas yielded targeted heterocycles as a 1:1 mixture of tautomers. A representative molecule featured sound activity against VEGFR-2 in both enzymatic and cellular assays.

Kiselyov A.S. , Piatnitski Chekler E.L. , Chernisheva N.B. , Salamandra L.K. , Semenov V.V.
Design and chemical synthesis of [1,2,4]triazol[1,5-c]pyrimidin-5-yl amines, a novel class of VEGFR-2 kinase inhibitors
Tetrahedron Letters. 2009. V.50. N27. P.3809-3812. DOI: 10.1016/j.tetlet.2009.04.062 WOS Scopus OpenAlex

Web of science:	WOS:000266890000019
Scopus:	2-s2.0-65549125376
OpenAlex:	W1994517041

DB	Citing
OpenAlex	10
Scopus	9
Web of science	10