title: Design, synthesis and antiproliferative activity of 2-acetamidothiazole-5-carboxamide derivatives.
abstract: In order to develop a new series of dual inhibitors of SRC and ABL, and to investigate whether the pyrimidin- 4-ylamino moiety is critical for dasatinib's activity, acetyl substitution was adopted as alternate scaffold at the 2-amino group. Eighteen novel dasatinib derivatives were developed by a parallel synthesis approach and evaluated for their antiproliferative effects. Preliminary tests showed that some of the target compounds IId, IIe and IIf manifested strong antiproliferative activity against MCF-7, MDA-MB 231 and HT-29 cells. Easpecially IId proved to be the most potent compound. Structure-activity relationship studies indicate that the introduction of acetyl substitution as alternate scaffold of pyrimidin-4-ylamino reduced the activity.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, PR China.
authors.forename: Wukun
authors.initials: W
authors.lastname: Liu
authors.forename: Jinpei
authors.initials: J
authors.lastname: Zhou
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Fan
authors.initials: F
authors.lastname: Qi
authors.forename: Huibin
authors.initials: H
authors.lastname: Zhang
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Cheng
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000069439:Dasatinib; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib