
Journal of Medicinal Chemistry p. 3482 - 3487 (1995)
Update date:2022-08-02
Topics:
Rewcastle
Denny
Bridges
Zhou
Cody
McMichael
Fry
A series of 4-substituted quinazolines and related compounds have been prepared and evaluated for their ability to inhibit the tyrosine kinase activity of the epidermal growth factor receptor on a phospholipase C-γ1- derived substrate. The results show a narrow structure-activity relationship (SAR) for the basic ring system, with quinazoline being the preferred chromophore and benzylamino and anilino the preferred side chains. In the 4- anilino series, substitution on the 3-position of the phenyl ring with small lipophilic electron-withdrawing groups provided analogues with enhanced potency. Two series of compounds [4-(phenylmethyl)amino and 4-(3- bromophenyl)amino] were studied to determine SARs for quinazoline substituents. In the more active 4-(3-bromophenyl)amino series, electron- donating groups (NH2, OMe) at the 6- or 7-position increased activity, in a pattern consistent with a requirement for high electron density in the vicinity of the 8-position of the quinazoline ring. The 6,7-dimethoxy derivatives were the most effective in both series, with the 4-(3- bromophenyl)amino derivative (3) having an IC50 of 0.029 nM, making it by far the most potent reported inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor enzyme.
View MoreLiao Cheng All Win Chemicals Co.,LTD
Contact:86+0635-2991582
Address:Room 402,Unit 1,No.27 building.Zhong tong shi dai haoyuan,liaocheng city,Shan dong Province.China
Contact:+86+21-58956006 15800617331
Address:402 Room, 150# Cailun Road, Zhangjiang high tech park, Shanghai
Jinan Kaypharm Chemical Co.,Ltd
Contact:86-0531-86986780
Address:Room101,No189-2,Huayuan Road,Jinan City,Shandong Province
Contact:+86-13914766747
Address:Floors 21&22, Jin Cheng Tower, No. 216 Middle Longpan Road, Nanjing
Neworld Chemical Co., Ltd Shanghai(expird)
Contact:+86-21-62202658
Address:11F, Blvd 2, No. 1969 PuXing Rd, Shanghai
Doi:10.1039/j39690001424
(1969)Doi:10.1002/cctc.201900047
(2019)Doi:10.1039/j39690001367
(1969)Doi:10.1021/om800874d
(2009)Doi:10.1055/s-1999-3463
(1999)Doi:10.1002/ejoc.200801269
(2009)