| Identification | Back Directory | [Name]
D-arabino-Hexitol, 5-amino-2,6-anhydro-1,3,4,5-tetradeoxy-6-C-(2,5-difluorophenyl)-3-[2,6-dihydro-2-(methylsulfonyl)pyrrolo[3,4-c]pyrazol-5(4H)-yl]-1,1,1-trifluoro-, (6R)- | [CAS]
1844874-26-5 | [Synonyms]
cofrogliptin
Compound COFROGLIPTIN
D-arabino-Hexitol, 5-amino-2,6-anhydro-1,3,4,5-tetradeoxy-6-C-(2,5-difluorophenyl)-3-[2,6-dihydro-2-(methylsulfonyl)pyrrolo[3,4-c]pyrazol-5(4H)-yl]-1,1,1-trifluoro-, (6R)- | [Molecular Formula]
C18H19F5N4O3S | [MOL File]
1844874-26-5.mol | [Molecular Weight]
466.43 |
| Chemical Properties | Back Directory | [Boiling point ]
524.0±60.0 °C(Predicted) | [density ]
1.68±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
8.66±0.70(Predicted) | [color ]
White to off-white | [InChIKey]
GUBOXFWNNXSQNH-GYDUIUCANA-N | [SMILES]
C([C@H]1O[C@H](C2C=C(F)C=CC=2F)[C@@H](N)C[C@H]1N1CC2=NN(S(=O)(=O)C)C=C2C1)(F)(F)F |&1:1,3,12,15,r| |
| Hazard Information | Back Directory | [Uses]
Cofrogliptin (HSK7653) (compound 2), a tetrahydropyran derivative, is a potent oral dipeptidyl aminopeptidase 4 (DPP-4) inhibitor with Long-acting antidiabetic efficacy. Cofrogliptin (compound 2) has a great potential for type 2 diabetes mellitus (T2DM) [1]. | [in vivo]
Cofrogliptin (HSK7653) (compound 2) (IV: 0.5 mg/kg; PO: 2 mg/kg) exhibits extremely long half-lives and low rate of reduction of drug concentration after orally administration.
Cofrogliptin (compound 2) (Single, orally, 3 mg/kg, 10 mg/kg, 30 mg/kg) increases of half-lives, has high oral exposure, low i.v. clearance and hepatic microsomal clearance after intravenous dosing.
Cofrogliptin (compound 2) (Single, orally, 10 mg/kg) exhibits longe inhibition time of DPP-4 and decreases HbA1c level
at the doses of 3 and 10 mg/kg in ob/ob mice. Cofrogliptin (compound 2) (Single, orally, 10 mg/kg) also has a great potential of biweekly regimen for T2DM as indicated in rhesus monkeys[2].
Pharmacokinetic Parameters in ICR mice[2]
| IV(dose: 0.5 mg/kg) | | | | PO(dose: 2 mg/kg) | | | | | CI(mL/min/kg) | Vdss(L/kg) | t1/2(h) | | Cmax(ng/mL) | t1/2(h) | AUC0-t(ng h/mL) | F% | | Omarigliptin | 7.39±2.1 | 1.65±0.27 | 3.05±0.6 | | 798±122 | 4.65±1.4 | 4095±552 | 95.0±29 | | Cofrogliptin (compound 2) | 2.57±0.09 | 3.30±0.33 | 25.6±9.6 | | 352±20 | 29.9±3.2 | 7898±873 | 62.2±6.9 |
| Animal Model: | ob/ob mice[2] | | Dosage: | 3 mg/kg, 10 mg/kg, 30 mg/kg | | Administration: | Single, orally, 3 mg/kg, 10 mg/kg, 30 mg/kg | | Result: | Exhibited strong inhibition capability of plasma DPP-4 in a dose dependent manner. |
| Animal Model: | rhesus monkeys[2] | | Dosage: | 10 mg/kg | | Administration: |
Single, orally, 10 mg/kg | | Result: | Possessed the capability of plasma DPP-4 inhibition over 80% for at least 12 days.
Remained the plasma DPP-4 inhibition rates of 76.16% and 43.41%, respectively at the end of second week and third week after administration.
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| [IC 50]
DPP-4 | [References]
[1] International Nonproprietary Names for Pharmaceutical Substances (INN)
[2] Chen Zhang, et al. Design, Synthesis, and Evaluation of a Series of Novel Super Long-Acting DPP-4 Inhibitors for the Treatment of Type 2 Diabetes. J Med Chem. 2020 Jul 9;63(13):7108-7126. DOI:10.1021/acs.jmedchem.0c00374 |
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