title: Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti-HIV agents.
abstract: Novel polyhalo 2,4-diaminoquinazolines 3a-3d were prepared by reacting polyhaloisophthalonitriles with guanidine carbonate under solvent-free conditions and in the absence of a catalyst with good yields (74-95%). A series of highly functionalized 2,4-diaminoquinazolines 4-5 were then synthesized based on 3a-3c. The anticancer activities of compounds 3-5 were evaluated in vitro against human cell lines such as Skov-3, HL-60, A431, A549, and HepG-2. Some of the compounds showed excellent cytotoxic activity and 5a was found to be the most potent derivative, with an IC(50) value lower than 2.5 microg/mL against the five tumor cell lines, making it more active than cisplatin. Representative compounds were also preliminarily evaluated as HIV-1 inhibitors in vitro, and 3c showed the most potent anti-HIV-1 activity with EC(50) values of 0.6 and 1.6 microg/mL, and TI values of >59.6 and 66.6, respectively.
authors.affiliation: Key Laboratory of Medicinal Chemistry for Natural Resources (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
authors.forename: Sheng-Jiao
authors.initials: SJ
authors.lastname: Yan
authors.forename: Han
authors.initials: H
authors.lastname: Zheng
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D011799:Quinazolines; C013474:2,4-diaminoquinazoline