3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 5, 2007, Pages 1274-1279

  Coumar, Mohane Selvaraj ^a   Chang, Chung Nien ^a   Chen, Chiung Tong ^a   Chen, Xin ^a   Chien, Chia Hui ^a   Tsai, Ting Yueh ^a   Cheng, Jai Hong ^a   Wu, Hsin Yi ^a   Han, Chia Hung ^a   Wu, Ssu Hui ^a   Huang, Yu Wen ^a   Hsu, Tsu ^a   Hsu, Li Jen ^a   Chao, Yu Sheng ^a   Hsieh, Hsing Pang ^a   Jiaang, Weir Torn ^a  

^a NATIONAL HEALTH RESEARCH INSTITUTES   (Taiwan)

Author keywords

DPP IV; Type II diabetes

Indexed keywords

3 [2 (2 CYANOPYRROLIDIN 1 YL) 2 OXOETHYLAMINO] 3 METHYLBUTYRAMIDE DERIVATIVE; 6 [[2 [[2 (2 CYANO 1 PYRROLIDINYL) 2 OXOETHYL]AMINO]ETHYL]AMINO]NICOTINONITRILE; ANILINE DERIVATIVE; BENZYLAMINE DERIVATIVE; DIPEPTIDYL PEPTIDASE; DIPEPTIDYL PEPTIDASE 8; DIPEPTIDYL PEPTIDASE II; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCOSE; PHENETHYLAMINE DERIVATIVE; SEPRASE; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ANIMAL MODEL; ARTICLE; DRUG EFFICACY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; IN VITRO STUDY; IN VIVO STUDY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; RAT; SUBSTITUTION REACTION; WISTAR RAT;

ADAMANTANE; ADENOSINE DEAMINASE; AMIDES; ANILINE COMPOUNDS; ANIMALS; ANTIGENS, CD26; BENZYLAMINES; DIABETES MELLITUS, TYPE 2; GLYCOPROTEINS; INHIBITORY CONCENTRATION 50; NITRILES; PHENETHYLAMINES; PYRROLIDINES; RATS; RATS, WISTAR; STRUCTURE-ACTIVITY RELATIONSHIP;

RATTUS NORVEGICUS;

EID: 33846986803     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.12.019     Document Type: Article

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24. OGTT was performed on overnight fasted adult male Wistar rats and the blood glucose was measured with the Accu-Chek Compact System from Roche (Basel, Switzerland). The animals were orally gavaged with the test compounds dissolved in distilled water at a 10 mpk dose. Thirty minutes after the oral dosing of test compounds, the animals were orally gavaged with freshly prepared glucose solution of 400 mg/ml in distilled water at 1.5 g glucose/kg. Blood glucose levels of these dosed animals were monitored at 0, 15, 30, 60, and 120 min after the oral glucose challenge.
25. The in vivo DPP-IV inhibition assay was performed as discussed in ref. 16. Adult male rats were orally gavaged with the test compounds at a single dose of 10 mg/kg. The plasma DPP-IV activity was determined by cleavage rate of Gly-Pro-AMC (H-glycyl-prolyl-7-amino-4-methylcoumarin; BACHEM).