Cofrogliptin (C09-1120-862)

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)In VitroCofrogliptin (HSK7653) (compound 2) has the DPP-4 inhibitory activity with an IC 50 value of 4.18 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoCofrogliptin (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/nat 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. Pharmacokinetic Parameters in ICR miceIV(dose: 0.5 mg/kg) PO(dose: 2 mg/kg) CI(mL/min/kg) V dss (L/kg) t 1/2 (h) C max (ng/mL) t 1/2 (h) AUC 0-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 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: ob/ob miceDosage: 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 monkeysDosage: 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.Form:SolidIC50& Target:DPP-4. Specification: 0.99 Molecular Formula: C18H19F5N4O3S Molecular Weight: 466.43 PubChem CID: 118613788 Isomeric SMILES: CS(=O)(=O)N1C=C2CN(CC2=N1)[C@@H]3C[C@@H]([C@H](O[C@@H]3C(F)(F)F)C4=C(C=CC(=C4)F)F)N