title: Synthesis and evaluation of 4-(2-pyrimidinylamino) benzamides inhibitors of hedgehog signaling pathway.
abstract: A novel series of hedgehog signaling pathway inhibitors has been designed based on the 4-(2-pyrimidinylamino) benzamides scaffold. The synthesis and SAR of these compounds are described. Optimization leads to the identification of compound 3c, a potent and orally available agent with improved physicochemical and pharmacokinetic properties.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an 710061, P.R. China; Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China. Electronic address: xmhcpu@163.com.
authors.forename: Minhang
authors.initials: M
authors.lastname: Xin
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wen
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tang
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Chongxing
authors.initials: C
authors.lastname: Tu
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Shen
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Mengyu
authors.initials: M
authors.lastname: Wang
authors.affiliation: Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
authors.forename: Liandi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D053823:Hedgehog Proteins; D011743:Pyrimidines
keywords: Hedgehog signaling pathway; Inhibitors; Pharmacokinetic properties; SAR