title: Design, synthesis and preliminary evaluation of new cinnamoyl pyrrolidine derivatives as potent gelatinase inhibitors.
abstract: A series of new cinnamoyl pyrrolidine derivatives have been synthesized based on the l-hydroxyproline scaffold and inhibiting activities on gelatinase (MMP-2 and -9) and APN were tested. Structure-activity relationship studies showed that the side chain with aromatic ring at C4 in pyrrolidine ring showed better inhibitory activities on gelatinase than aliphatic side chain. Most compounds exhibited poor activities on APN compared with MMP-2. Within this series, three compounds, A8, B9 and C10, have the good potency (IC(50)=5.2-9.7nM) and could be used as lead compounds in the future.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44, West Culture Road, Ji'nan, Shandong 250012, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D002109:Caffeic Acids / Q000737:chemistry; D002934:Cinnamates / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014302:Trinitrobenzenesulfonic Acid / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D002934:Cinnamates; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D011759:Pyrrolidines; C029010:cinnamic acid; D014302:Trinitrobenzenesulfonic Acid; C032519:pyrrolidine; C040048:caffeic acid