Wang, Shan; Zhang, Rong-Hong; Zhang, Hong; Wang, Yu-Chan; Yang, Dan; Zhao, Yong-Long; Yan, Guo-Yi; Xu, Guo-Bo; Guan, Huan-Yu; Zhou, Yan-Hua; Cui, Dong-Bing; Liu, Ting; Li, Yong-Jun; Liao, Shang-Gao; Zhou, Meng published the artcile< Design, synthesis, and biological evaluation of 2,4-diamino pyrimidine derivatives as potent FAK inhibitors with anti-cancer and anti-angiogenesis activities>, Formula: C7H8BrN, the main research area is diamino pyrimidine preparation SAR antitumor antiangiogenesis FAK inhibitor human; Anti-angiogenesis; Antitumor; DAPY; FAK inhibitor; Structure-activity relationship.
A series of 2,4-diamino pyrimidine (DAPY) derivatives I (R1 = 2-ClC6H4, 4-MeOC6H4, 4-BrC6H4, etc.), II (R2 = 4-H2NC6H4, 4-MeOC6H4, 2-O2NC6H4, etc.) were designed, synthesized, and evaluated as inhibitors of focal adhesion kinase (FAK) with antitumor and anti-angiogenesis activities. Most compounds effectively suppressed the enzymic activities of FAK, and the IC50s of I (R1 = 2-ClC6H4) and II (R2 = 2-MeOC6H4) were 2.75 and 1.87 nM, resp. They exhibited strong antiproliferative effects against seven human cancer cells, with IC50 values against two FAK-overexpressing pancreatic cancer cells (PANC-1 and BxPC-3) of 0.98μM, 0.55μM, and 0.11μM, 0.15μM, resp. Moreover, the above two compounds obviously suppressed the colony formation, migration, and invasion of PANC-1 cells in a dose-dependent manner. Meanwhile, these two compounds could induce the apoptosis of PANC-1 cells and arrest the cell cycle in G2/M phase according to the flow cytometry assay. Western blot revealed that these compounds effectively inhibited the FAK/PI3K/Akt signal pathway and significantly decreased the expression of cyclin D1 and Bcl-2. In addition, the above compounds potently inhibited the antiproliferative of HUVECs and obviously altered the cell morphol and also significantly inhibited the migration, tube formation of HUVECs and severely impaired the angiogenesis in the zebrafish model. Overall, these results revealed the potential of these compounds as promising candidates for further preclin. studies.
European Journal of Medicinal Chemistry published new progress about Angiogenesis. 3959-07-7 belongs to class bromides-buliding-blocks, and the molecular formula is C7H8BrN, Formula: C7H8BrN.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary