메뉴 건너뛰기
Bioorganic and Medicinal Chemistry Letters
Volumn 18, Issue 20, 2008, Pages 5435-5438
(3R)-3-Amino-4-(2,4,5-trifluorophenyl)-N-{4-[6-(2-methoxyethoxy)benzothiazol-2-yl]tetrahydropyran-4-yl}butanamide as a potent dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Author keywords

[No Author keywords available]
Indexed keywords

3 AMINO 4 (2,4,5 TRIFLUOROPHENYL) N [4 [6 (2 METHOXYETHOXY)BENZOTHIAZOL 2 YL]TETRAHYDROPYRAN 4 YL]BUTANAMIDE; 6 (3 AMINO 1 PIPERIDINYL) 1 (2 CYANOBENZYL) 3 METHYLURACIL; BENZOTHIAZOLE DERIVATIVE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; SAXAGLIPTIN; SITAGLIPTIN; UNCLASSIFIED DRUG; VILDAGLIPTIN;
EID: 53349165532     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.09.042     Document Type: Article
Times cited : (43)
References (42)
  • 32
    • 33750035214 scopus 로고    scopus 로고
    • Recently, the preparation of 4-benzyl-4-aminopiperidines by the Ellman reaction was reported with the use of excess Grignard reagent in moderate yield
    • Recently, the preparation of 4-benzyl-4-aminopiperidines by the Ellman reaction was reported with the use of excess Grignard reagent in moderate yield. Caldwell J.J., and Collins I. Synlett (2006) 2565
    • (2006) Synlett , pp. 2565
    • Caldwell, J.J.1    Collins, I.2
  • 38
    • 53349167058 scopus 로고    scopus 로고
    • An extract from Caco-2 was used as the source of DPP-IV in the assay. The cell extract was prepared from cells solubilized in lysis buffer (10 mM, Tris-HCl (pH 8.0), 0.15 M NaCl, 0.04 U aprotinin, 0.50% nonidet-P40) that were then centrifuged at 18,500g for 1 h at 4 °C to remove the cell debris. The assay was conducted by adding 5 μg of solubilized Caco-2 protein, diluted to a final volume of 135 μL in an assay buffer (25 mM Tris-HCl (pH 7.4), 0.14 M NaCl, 10 mM KCl, 1% (w/v) BSA) to 96-well flat-bottom plates. The reaction was initiated by adding 15 μL of 0.4 mM substrate (Ala-Pro-AFC). The reaction was run for 20 min at 37 °C, and then 10 μL of 25% acetic acid was added to stop the reaction. Fluorescence was measured using Fusionα (excitation 380 nm; emission 485 nm). The test compounds and solvent controls were added to the assay buffer.
    • An extract from Caco-2 was used as the source of DPP-IV in the assay. The cell extract was prepared from cells solubilized in lysis buffer (10 mM, Tris-HCl (pH 8.0), 0.15 M NaCl, 0.04 U aprotinin, 0.50% nonidet-P40) that were then centrifuged at 18,500g for 1 h at 4 °C to remove the cell debris. The assay was conducted by adding 5 μg of solubilized Caco-2 protein, diluted to a final volume of 135 μL in an assay buffer (25 mM Tris-HCl (pH 7.4), 0.14 M NaCl, 10 mM KCl, 1% (w/v) BSA) to 96-well flat-bottom plates. The reaction was initiated by adding 15 μL of 0.4 mM substrate (Ala-Pro-AFC). The reaction was run for 20 min at 37 °C, and then 10 μL of 25% acetic acid was added to stop the reaction. Fluorescence was measured using Fusionα (excitation 380 nm; emission 485 nm). The test compounds and solvent controls were added to the assay buffer.
  • 41
    • 53349161733 scopus 로고    scopus 로고
    • Male SD rats (7-8 weeks of age) were starved overnight. The rats were orally administered a vehicle (distilled water, 5 mL/kg) or 12u (1, 3, 10 mg/kg; 5 mL/kg); then, blood samples were taken from the jugular vein at intervals of 30 min, 2 h, and 4 h after treatment. Plasma samples were centrifuged at 1400g for 10 min at 4 C. The assay was conducted by adding 20 μL of rat plasma to 96-well flat-bottom plates. The reaction was initiated by adding 20 μL of 0.4 mM substrate (Ala-Pro-AFC, diluted in 200 mM Hepes, 0.2 mg/mL BSA, pH 7.5). The reaction was run for 15 min at room temperature and then 6 μL of 25% acetic acid was added to stop the reaction. Fluorescence was measured using Fusionα (excitation 380 nm; emission 485 nm). Male ICR mice (6 weeks of age) were starved overnight.
    • Male SD rats (7-8 weeks of age) were starved overnight. The rats were orally administered a vehicle (distilled water, 5 mL/kg) or 12u (1, 3, 10 mg/kg; 5 mL/kg); then, blood samples were taken from the jugular vein at intervals of 30 min, 2 h, and 4 h after treatment. Plasma samples were centrifuged at 1400g for 10 min at 4 C. The assay was conducted by adding 20 μL of rat plasma to 96-well flat-bottom plates. The reaction was initiated by adding 20 μL of 0.4 mM substrate (Ala-Pro-AFC, diluted in 200 mM Hepes, 0.2 mg/mL BSA, pH 7.5). The reaction was run for 15 min at room temperature and then 6 μL of 25% acetic acid was added to stop the reaction. Fluorescence was measured using Fusionα (excitation 380 nm; emission 485 nm). Male ICR mice (6 weeks of age) were starved overnight.
  • 42
    • 53349145103 scopus 로고    scopus 로고
    • The mice were orally administered a vehicle (distilled water, 10 mL/kg) or 12u (30 mg/kg; 10 mL/kg). The blood glucose concentration was determined by a glucometer from blood taken from a nick in the tail, 30 min after the treatment. The mice were then orally challenged with glucose (2 g/kg; 10 mL/kg). The blood glucose levels were determined from tail bleeds taken at intervals of 20, 40, 60, and 120 min after the glucose challenge.
    • The mice were orally administered a vehicle (distilled water, 10 mL/kg) or 12u (30 mg/kg; 10 mL/kg). The blood glucose concentration was determined by a glucometer from blood taken from a nick in the tail, 30 min after the treatment. The mice were then orally challenged with glucose (2 g/kg; 10 mL/kg). The blood glucose levels were determined from tail bleeds taken at intervals of 20, 40, 60, and 120 min after the glucose challenge.

* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.