Physicochemical Properties
| Molecular Formula | C21H24F3N5O2 |
| Molecular Weight | 435.442774772644 |
| Exact Mass | 435.188 |
| CAS # | 2410393-15-4 |
| PubChem CID | 146386401 |
| Appearance | White to yellow solid powder |
| LogP | 2.8 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 31 |
| Complexity | 631 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC(C1=CC=CC(C(NC2=CC3=CN(CCN(C)C)N=C3C=C2C(C)(C)O)=O)=N1)(F)F |
| InChi Key | QAOWCAZEVIIQTF-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H24F3N5O2/c1-20(2,31)14-11-16-13(12-29(27-16)9-8-28(3)4)10-17(14)26-19(30)15-6-5-7-18(25-15)21(22,23)24/h5-7,10-12,31H,8-9H2,1-4H3,(H,26,30) |
| Chemical Name | N-[2-[2-(dimethylamino)ethyl]-6-(2-hydroxypropan-2-yl)indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide |
| 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
| Targets | IRAK4 7.2 μM (IC50) |
| ln Vivo | Rat models of LPS-induced TNFα generation and collagen-induced arthritis were used to assess the substantial in vivo antiinflammatory effectiveness of HS271 (15-150 mg/kg)[1]. HS271 has a Cmax of 2107 ng/mL and a t1/2 of 3.3 h[1]. In liver microsome experiments, HS271 remains stable in rat, mouse, monkey, and human species[1]. In mice, rats, dogs, and monkeys, HS271 has an oral bioavailability of 67.3%, 58.2%, 14.4%, and 49%, respectively[1]. |
| Animal Protocol |
Animal/Disease Models: A rat model of collagen induced arthritis (CIA)[1]. Doses: 15, 50, 150 mg/kg. Route of Administration: PO, one time/day. Experimental Results: Led to a significant reduction in paw swelling as compared to vehicle control, with a minimum effective dose at 15 mg/kg QD. Notably, at 150 mg/kg QD, HS271 eliminated the paw swelling. |
| References |
[1]. Discovery and optimization of a potent and selective indazolamine series of IRAK4 inhibitors. Bioorg Med Chem Lett. 2020 Nov 24;31:127686. |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (229.65 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.74 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 25.0 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 3: ≥ 2.5 mg/mL (5.74 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 25.0 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 | 2.2965 mL | 11.4826 mL | 22.9653 mL | |
| 5 mM | 0.4593 mL | 2.2965 mL | 4.5931 mL | |
| 10 mM | 0.2297 mL | 1.1483 mL | 2.2965 mL |