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N⁴-(3-Bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d]pyrimidines as potent multiple receptor tyrosine kinase inhibitors: design, synthesis, and in vivo evaluation.

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).

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Gangjee A,Zaware N,Raghavan S,Yang J,Thorpe JE,Ihnat MA

doi

10.1016/j.bmc.2012.01.029

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

2444-54

issue

7

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(12)00059-4

journal_volume

20

pub_type

杂志文章

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