European Journal of Medicinal Chemistry p. 50 - 62 (2016)
Update date:2022-08-04
Topics:
Eldehna, Wagdy M.
Abou-Seri, Sahar M.
El Kerdawy, Ahmed M.
Ayyad, Rezk R.
Hamdy, Abdallah M.
Ghabbour, Hazem A.
Ali, Mamdouh M.
Abou El Ella, Dalal A.
A series of anilinophthalazine derivatives 4a-j was initially synthesized and tested for its VEGFR-2 inhibitory activity where it showed promising activity (IC50 = 0.636-5.76 μM). Molecular docking studies guidance was used to improve the binding affinity for series 4a-j towards VEGFR-2 active site. This improvement was achieved by increasing the hydrophobic interaction with the hydrophobic back pocket of the VEGFR-2 active site lined with the hydrophobic side chains of Ile888, Leu889, Ile892, Val898, Val899, Leu1019 and Ile1044. Increasing the hydrophobic interaction was accomplished by extending the anilinophthalazine scaffold with a substituted phenyl moiety through an uriedo linker which should give this extension the flexibility required to accommodate itself deeply into the hydrophobic back pocket. As planned, the designed uriedo-anilinophthalazines 7a-i showed superior binding affinity than their anilinophthalazine parents (IC50 = 0.083-0.473 μM). In particular, compounds 7g-i showed IC50 of 0.086, 0.083 and 0.086 μM, respectively, which are better than that of the reference drug sorafenib (IC50 = 0.09 μM).
View MoreShijiazhuang Yunxuan Im&Export Co.,Ltd.
Contact:+86-311-83037514
Address:No.6 Hongbin Road
Contact:+86-15850770348
Address:51 OF XIANGFANGCUN ROAD, Nanjing 210002, China
ClickChem Technology Co., Limited
Contact:+86-0310-6519966/0531-52893837
Address:No.750 Shunhua Road, High-Tech Zone, Jinan city, Shandong China
Suzhou Sinosun Imp.&Exp. Corporation
website:http://www.szsinosun.com
Contact:+86-512-63488895,63488616
Address:No.758 East Jiangling Road Wujiang Economic & Technological Developmenty Zone Jiangsu China
Contact:86-25-58619180
Address:Nanjing High-Tech Zone 10 Xinghuo Road Pukou District Nanjing, Jiangsu 210061 The People's Republic of China
Doi:10.1055/s-1982-30087
(1982)Doi:10.1002/jps.2600620542
(1973)Doi:10.1021/jo00331a029
(1981)Doi:10.1016/S0040-4020(01)93448-9
(1973)Doi:10.1134/S107036320705009X
(2007)Doi:10.1070/MC2006v016n01ABEH002213
(2006)