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.
|
![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)- Structure](/CAS/20211123/GIF/1844874-26-5.gif)
