title: The discovery of novel N-(2-pyrimidinylamino) benzamide derivatives as potent hedgehog signaling pathway inhibitors.
abstract: Hedgehog signaling pathway inhibitors are emerging as new therapeutic intervention against cancer. A novel series of N-(2-pyrimidinylamino) benzamide derivatives as hedgehog signaling pathway inhibitors were designed and synthesized. Most compounds presented significant inhibitory effect on hedgehog signaling pathway, among which 21 compounds exhibited more potent than vismodegib. Furthermore, compound 6a showed moderate pharmacokinetic properties in vivo, representing a promising lead compound for further exploration.
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No. 699-18, Xuan Wu District, Nanjing 210042, PR China. Electronic address: xmhcpu@163.com.
authors.forename: Minhang
authors.initials: M
authors.lastname: Xin
authors.forename: Jun
authors.initials: J
authors.lastname: Wen
authors.forename: Feng
authors.initials: F
authors.lastname: Tang
authors.forename: Chongxing
authors.initials: C
authors.lastname: Tu
authors.forename: Han
authors.initials: H
authors.lastname: Shen
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D053823:Hedgehog Proteins; D011743:Pyrimidines; C037689:benzamide; C030986:pyrimidine
keywords: Hedgehog signaling; Hedgehog signaling pathway inhibitors; Lead compound; Synthesize