title: Design, synthesis, and preliminary evaluation of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives as potential iNOS inhibitors.
abstract: A series of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives were synthesized and evaluated for their abilities to inhibit inducible nitric oxide synthase (iNOS) isoform. All target compounds were prepared in 11 steps from commercially trans-4-hydroxy-L-proline. The preliminary pharmacological test showed that three compounds, 17, 21, and 30, have the good potency (IC(50)=2.36, 2.68, 2.5 microM, respectively) which are compared to the NOS inhibitor N(G)-nitroarginine(L-NNA) (IC(50)=14.74 microM), and could be used as lead compounds for exploring new iNOS inhibitors in the future.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44, Wenhuaxi Road, Ji'nan, Shandong 250012, PR China.
authors.forename: Feng-Zhi
authors.initials: FZ
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
authors.forename: Hua-Wei
authors.initials: HW
authors.lastname: Zhu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Xu
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II