title: Synthesis and evaluation of 4-(2-hydroxypropyl)piperazin-1-yl) derivatives as Hsp90 inhibitors.
abstract: We previously reported 4-(3-((6-bromonaphthalen-2-yl)oxy)-2-hydroxypropyl)-N,N-dimethylpiperazine-1-sulfonamide (1) as a novel heat shock protein 90 inhibitor with moderate activity. In our ongoing efforts for the discovery of Hsp90 modulators we undertake structural investigations on 1. Series of the titled compound were designed, synthesized and evaluated. We have found that compounds with a hydroxyl group at C-4 of the aryl ring on the piperazine moiety possess Hsp90 inhibition properties. Compound 6f with improved activity could be further developed and optimized as Hsp90 inhibitor.
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Bahidja
authors.initials: B
authors.lastname: Cherfaoui
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Tian-Kun
authors.initials: TK
authors.lastname: Guo
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hao-Peng
authors.initials: HP
authors.lastname: Sun
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Cheng
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xuxiao_li@126.com.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: youqidong@gmail.com.
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
keywords: Hsp90 inhibitors; Structure-based drug design; Structure–activity relationships