Physicochemical Properties
| Molecular Formula | C18H19F5N4O3S |
| Molecular Weight | 466.43 |
| Exact Mass | 466.109 |
| CAS # | 1844874-26-5 |
| PubChem CID | 118613788 |
| Appearance | White to off-white solid powder |
| LogP | 1.4 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 31 |
| Complexity | 766 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | C([C@@H]1[C@@H](C[C@@H]([C@H](O1)C1C=C(C=CC=1F)F)N)N1CC2C(C1)=NN(S(=O)(C)=O)C=2)(F)(F)F |
| InChi Key | GUBOXFWNNXSQNH-SVGFKBNWSA-N |
| InChi Code | 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 |
| Chemical Name | (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 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Cofrogliptin (HSK7653) (compound 2) exhibits DPP-4 inhibitory action, with an IC50 of 4.18 nM[2]. |
| ln Vivo | Cofrogliptin (HSK7653) (Compound 2) (IV: 0.5 mg/kg; PO: 2 mg/kg) demonstrates an unusually long half-life and a modest rate of reduction in drug concentration after oral administration. Colagliptin (Compound 2) (single dosage, oral, 3 mg/kg, 10 mg/kg, 30 mg/kg) has prolonged half-life, high oral exposure, venous clearance and hepatic microsomal clearance after intravenous injection Low. Cofrogliptin (Compound 2) (single dose, oral, 10 mg/kg) displayed extended DPP-4 inhibition in ob/ob mice and lowered HbA1c levels at dosages of 3 and 10 mg/kg. Cofrogliptin (compound 2) (single dose, oral, 10 mg/kg) also has significant potential for biweekly treatment of T2DM in rhesus monkeys [2]. ICR mouse pharmacokinetic parameters [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% Ologliptin 7.39±2.1 1.65±0.27 3.05±0.6 798±122 4.65±1.4 4095±552 95.0±29 Kaog Gliptin (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 Protocol |
Animal/Disease Models: ob/ob mice[2] Doses: 3 mg/kg, 10 mg/kg, 30 mg/kg. Route of Administration: single dose, oral administration, 3 mg/kg, 10 mg/kg, 30 mg/kg. Experimental Results: It demonstrated strong inhibitory ability on plasma DPP-4 in a dose-dependent manner. Animal/Disease Models: Rhesus monkey[2] Doses: 10 mg/kg Route of Administration: Single oral administration, 10 mg/kg Experimental Results:It has more than 80% plasma DPP-4 inhibition ability, which lasts for at least 12 days. The plasma DPP-4 inhibition rates at the second and third weeks after administration were 76.16% and 43.41% respectively. |
| References |
[1]. International Nonproprietary Names for Pharmaceutical Substances (INN). [2]. 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. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~214.39 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1439 mL | 10.7197 mL | 21.4394 mL | |
| 5 mM | 0.4288 mL | 2.1439 mL | 4.2879 mL | |
| 10 mM | 0.2144 mL | 1.0720 mL | 2.1439 mL |