N 4-(3-bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d] pyrimidines as potent multiple receptor tyrosine kinase inhibitors: Design, synthesis, and in vivo evaluation
DOI
10.1016/j.bmc.2012.01.029
Document Type
Journal Article
Publication Date
4-1-2012
Publication Title
Bioorganic and Medicinal Chemistry
Volume
20
Issue
7
First Page
2444
Last Page
2454
ISSN
9680896
Keywords
Antiangiogenic agents, Multiple receptor, Tyrosine kinase inhibitors
Abstract
With the goal of developing multitargeted receptor tyrosine kinase inhibitors that display potent inhibition against PDGFRβ and VEGFR-2 we designed and synthesized eleven N 4-(3-bromophenyl)-7- (substitutedbenzyl) pyrrolo[2,3-d]pyrimidines 9a-19a. These compounds were obtained from the key intermediate N 4-(3-bromophenyl)-7H-pyrrolo[2,3- d]pyrimidine-2,4-diamine 29. Various arylmethyl groups were regiospecifically attached at the N7 of 29 via sodium hydride induced alkylation with substituted arylmethyl halides. Compounds 11a and 19a were potent dual inhibitors of PDGFRβ and VEGFR-2. In a COLO-205, in vivo tumor mouse model 11a demonstrated inhibition of tumor growth, metastasis, and tumor angiogenesis that was better than or comparable to the standard compound TSU-68 (SU6668, 8). © 2012 Elsevier Ltd. All rights reserved.
Open Access
Green Accepted
Preprint
Repository Citation
Gangjee, A., Zaware, N., Raghavan, S., Yang, J., Thorpe, J., & Ihnat, M. (2012). N 4-(3-bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d] pyrimidines as potent multiple receptor tyrosine kinase inhibitors: Design, synthesis, and in vivo evaluation. Bioorganic and Medicinal Chemistry, 20 (7), 2444-2454. https://doi.org/10.1016/j.bmc.2012.01.029