Cofrogliptin

• CAT Number: I043414
• CAS Number: 1844874-26-5
• Molecular Formula: C18H19F5N4O3S
• Molecular Weight: 466.43
• Purity: ≥95%
• Synonyms: (2R,3S,5R,6S)-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)-6-(trifluoromethyl)oxan-3-amine
• InChI: InChI=1S/C18H19F5N4O3S/c1-31(28,29)27-7-9-6-26(8-14(9)25-27)15-5-13(24)16(30-17(15)18(21,22)23)11-4-10(19)2-3-12(11)20/h2-4,7,13,15-17H,5-6,8,24H2,1H3/t13-,15+,16+,17-/m0/s1
• InChIKey: GUBOXFWNNXSQNH-SVGFKBNWSA-N
• SMILES: CS(=O)(=O)N1C=C2CN(CC2=N1)C3CC(C(OC3C(F)(F)F)C4=C(C=CC(=C4)F)F)N

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].
Cofrogliptin (HSK7653) (compound 2) has the DPP-4 inhibitory activity with an IC50 value of 4.18 nM[2].
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

Reference

[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.
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