Discovery of novel dual inhibitors of VEGFR and PI3K kinases containing 2-ureidothiazole scaffold

注册 English

Discovery of novel dual inhibitors of VEGFR and PI3K kinases containing 2-ureidothiazole scaffold

Lin Li , Cun-Long Zhang , Hong-Rui Song , Chun-Yan Tan , Huai-Wei Ding , Yu-Yang Jiang

Citation: Lin Li, Cun-Long Zhang, Hong-Rui Song, Chun-Yan Tan, Huai-Wei Ding, Yu-Yang Jiang. Discovery of novel dual inhibitors of VEGFR and PI3K kinases containing 2-ureidothiazole scaffold[J]. Chinese Chemical Letters, 2016, 27(01): 1-6. doi: 10.1016/j.cclet.2015.09.008 shu

shu

Discovery of novel dual inhibitors of VEGFR and PI3K kinases containing 2-ureidothiazole scaffold

1.
a Department of Chemistry, Tsinghua University, Beijing 100084, China;
2.
b School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110000, China;
3.
c The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518000, China

通讯作者: Huai-Wei Ding,
Yu-Yang Jiang,

基金项目:
The authors would like to thank the financial supports from the NSFC(No. 21272134) (No. 21272134)

Shenzhen Municipal government SZSITIC(Nos. JCYJ20130402145002384, ZDSY20120619141412872). (Nos. JCYJ20130402145002384, ZDSY20120619141412872)

摘要: A series of compounds possessing 2-(3-phenyl)ureidothiazol-4-formamide derivatives with a 2-ureidothiazole scaffold were designed and synthesized. Some compounds demonstrated inhibition of cell proliferation against both MDA-MB-231 and HepG2 cell lines using Sorafenib as the positive control. Compounds 6i showed a good to moderate inhibition on VEGFR-2 and PI3Kα which was proved by further molecular docking study. This study suggests that compound 6i is a potential dual inhibitor of VEGFR-2 and PI3Kα and is applicable for further investigation.

关键词:

2-Aminothiazole
/ VEGFR
/ PI3K
/ Anticancer

English

Discovery of novel dual inhibitors of VEGFR and PI3K kinases containing 2-ureidothiazole scaffold

1.
a Department of Chemistry, Tsinghua University, Beijing 100084, China;
2.
b School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110000, China;
3.
c The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518000, China

Corresponding author: Huai-Wei Ding, Yu-Yang Jiang,

Received Date: 22 April 2015
Available Online: 21 September 2015
Fund Project:

Abstract: A series of compounds possessing 2-(3-phenyl)ureidothiazol-4-formamide derivatives with a 2-ureidothiazole scaffold were designed and synthesized. Some compounds demonstrated inhibition of cell proliferation against both MDA-MB-231 and HepG2 cell lines using Sorafenib as the positive control. Compounds 6i showed a good to moderate inhibition on VEGFR-2 and PI3Kα which was proved by further molecular docking study. This study suggests that compound 6i is a potential dual inhibitor of VEGFR-2 and PI3Kα and is applicable for further investigation.

Key words:

2-Aminothiazole
/ VEGFR
/ PI3K
/ Anticancer

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