title: Synthesis and potent inhibitory activities of carboxybenzyl-substituted 8-(3-(R)-aminopiperidin-1-yl)-7-(2-chloro/cyanobenzyl)-3-methyl-3,7-dihydro-purine-2,6-diones as dipeptidyl peptidase IV (DPP-IV) inhibitors.
abstract: Fourteen 3-methyl-3,7-dihydro-purine-2,6-dione derivatives 1-14 bearing carboxybenzyl and 2-chloro/cyanobenzyl groups at the N-1 and N-7 positions, respectively, were synthesized as dipeptidyl peptidase IV (DPP-IV) inhibitors. These compounds were characterized on the basis of NMR ((1)H and (13)C) and ESI MS data. In vitro bioassay indicates that most of these compounds showed moderate to good inhibitory activities against DPP-IV. Among them, compound 13 (IC50=36 nM) exhibited comparable activity with a positive control, Sitagliptin (IC50=16 nM). In addition, the structure-activity relationship of these compounds is also briefly discussed.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Di-Wei
authors.initials: DW
authors.lastname: Mo
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Radiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Pang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: xibaomin@sohu.com.
authors.forename: Bao-Min
authors.initials: BM
authors.lastname: Xi
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: whchen@smu.edu.cn.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
mesh_terms: D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001593:Benzyl Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011687:Purines; D018819:Dipeptidyl Peptidase 4
keywords: 3-Methyl-3,7-dihydro-purine-2,6-dione; Diabetes; Dipeptidyl peptidase IV inhibitor; Inhibitory activity; Synthesis