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Dipeptidyl Peptidase IV Inhibitors (dipeptidyl + peptidase_iv_inhibitor)
Selected AbstractsChemInform Abstract: The Asymmetric Synthesis of Sitagliptin, a Selective Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes.CHEMINFORM, Issue 41 2010Feng Liu Abstract Key step in the improved synthetic pathway to sitagliptin (VII), a new DPP-IV inhibitor for the treatment of type 2 diabetes mellitus, is an asymmetric Michael addition to give intermediate (IV). [source] Simultaneous 19F NMR Screening of Prolyl Oligopeptidase and Dipeptidyl Peptidase IV InhibitorsCHEMBIOCHEM, Issue 8 2010Nessim Kichik Abstract Prolyl oligopeptidase (POP) and dipeptidyl peptidase IV (DPP IV) are serine proteases that belong to the same family of enzymes. These peptidases are relevant because of their association with the pathophysiology of serious illnesses, such as type 2 diabetes (DPP IV), and those related to cognitive disorders (POP). Several NMR-based screening methods are being used to find and validate new hit scaffolds. In particular, 19F NMR-based screening methods have proven to be powerful tools for the discovery and development of new inhibitors. Here we present an accurate and reliable 19F NMR-based simultaneous assay that is used to screen for new selective POP and DPP IV inhibitors in compound mixtures. This activity assay consists of the simultaneous performance of POP and DPP-IV 19F NMR activity assays in the presence of their fluorine-containing substrates. Furthermore, the assays were conducted in the presence of 0.01,% v/v of Triton X-100, which is a detergent that disrupts micelle formation, thereby preventing unspecific aggregate-based inhibition. Finally, this 19F NMR methodology was applied to screen for ligands in plant extracts. Our results indicate that this method allows the simultaneous and accurate identification of selective POP and DPP IV inhibitors in these compound mixtures. [source] ChemInform Abstract: Synthesis and Evaluation of Structurally Constrained Imidazolidin Derivatives as Potent Dipeptidyl Peptidase IV Inhibitors.CHEMINFORM, Issue 40 2009Liutang Wang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Substituted Pyrrolidine-2,4-dicarboxylic Acid Amides as Potent Dipeptidyl Peptidase IV Inhibitors.CHEMINFORM, Issue 38 2006Weir-Torn Jiaang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] New Fluorinated Pyrrolidine and Azetidine Amides as Dipeptidyl Peptidase IV Inhibitors.CHEMINFORM, Issue 5 2006Bernard Hulin Abstract For Abstract see ChemInform Abstract in Full Text. [source] Potent and Selective Proline Derived Dipeptidyl Peptidase IV Inhibitors.CHEMINFORM, Issue 5 2005Scott D. Edmondson No abstract is available for this article. [source] Pharmacokinetics and pharmacodynamics of LC15-0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2009Kyoung Soo Lim WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , The importance of efficient drug development using biomarkers has been increasingly emphasized, from preclinical studies to clinical trials. , However, as yet few ,validated' or ,qualified' biomarkers are used in early-stage drug development in terms of clinical pharmacology and disease pathophysiology. WHAT THIS STUDY ADDS , This first-time-in-human study provides evidence of the pharmacological activity of LC15-0444 in humans, by using dipeptidyl peptidase IV activity and active glucagon-like peptide-1 concentrations. , LC15-0444 possesses pharmacokinetic and pharmacodynamic characteristics that support a once-daily dosing regimen. AIMS LC15-0444 is a selective and competitive inhibitor of dipeptidyl peptidase (DPP) IV with potential for the treatment of Type 2 diabetes. The aim was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles after multiple oral ascending doses of LC15-0444 in healthy male subjects. METHODS A dose block-randomized, double-blind, placebo-controlled, parallel group study was performed in three groups with 10 subjects (eight for active drug; two for placebo) per group; each group received 200, 400 or 600 mg of LC15-0444 once daily for 10 days. Blood and urine samples were collected up to 24 h after the first dosing and up to 72 h after the last dosing. RESULTS The LC15-0444 concentration,time profiles exhibited characteristics of multicompartment disposition. No dose- or time-dependent change in PK parameters was observed. Mean elimination half-life was in a range 16.6,20.1 h in the dose groups. Mean renal clearance and fraction of unchanged drug excreted in urine was 18.6,21.9 and 0.40,0.48 l h,1, respectively. In the steady state, mean accumulation ratios by dose groups were between 1.22 and 1.31. More than 80% inhibition of DPP IV activity from baseline was sustained for >24 h in all dose groups. CONCLUSIONS This study provides evidence of the pharmacological activity of LC15-0444 in humans. LC15-0444 possesses PK and PD characteristics that support a once-daily dosing regimen. [source] | ||||||||||