title: Optimization of gefitinib analogues with potent anticancer activity.
abstract: The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues.
authors.affiliation: Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 974, Taiwan.
authors.forename: Kai-Hao
authors.initials: KH
authors.lastname: Yin
authors.affiliation: Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 974, Taiwan.
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 974, Taiwan.
authors.forename: Rohidas S
authors.initials: RS
authors.lastname: Sulake
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan.
authors.forename: Su-Pei
authors.initials: SP
authors.lastname: Wang
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan. Electronic address: jichao@faculty.nctu.edu.tw.
authors.forename: Jui-I
authors.initials: JI
authors.lastname: Chao
authors.affiliation: Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 974, Taiwan. Electronic address: chinpiao@mail.ndhu.edu.tw.
authors.forename: Chinpiao
authors.initials: C
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D010879:Piperazines / Q000737:chemistry; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: A549; Anti-cancer; EGFR; Gefitinib; Iressa