SD-06 is an inhibitor of p38 alpha MAP kinase which inhibits p38α with an IC50 value of 170 nM and inhibits LPS-stimulated TNF-release in rats with 83% inhibition at an oral dose of 1mg/kg. It could be applied to the treatment of arthritis.
Physicochemical Properties
| Molecular Formula | C20H20CLN5O2 | |
| Molecular Weight | 397.86 | |
| Exact Mass | 397.13 | |
| Elemental Analysis | C, 60.38; H, 5.07; Cl, 8.91; N, 17.60; O, 8.04 | |
| CAS # | 271576-80-8 | |
| Related CAS # | 271576-80-8; | |
| PubChem CID | 9865587 | |
| Appearance | White to off-white solid powder | |
| Density | 1.4±0.1 g/cm3 | |
| Boiling Point | 652.6±55.0 °C at 760 mmHg | |
| Flash Point | 348.5±31.5 °C | |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C | |
| Index of Refraction | 1.638 | |
| LogP | 1.5 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 5 | |
| Rotatable Bond Count | 4 | |
| Heavy Atom Count | 28 | |
| Complexity | 523 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | OCC(N1CCC(CC1)C2=NNC(C3=CC=C(C=C3)Cl)=C2C4=NC=NC=C4)=O |
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| InChi Key | CATQHDWESBRRQA-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C20H20ClN5O2/c21-15-3-1-13(2-4-15)19-18(16-5-8-22-12-23-16)20(25-24-19)14-6-9-26(10-7-14)17(28)11-27/h1-5,8,12,14,27H,6-7,9-11H2,(H,24,25) | |
| Chemical Name | 1-[4-[3-(4-chlorophenyl)-4-pyrimidin-4-yl-1H-pyrazol-5-yl]piperidin-1-yl]-2-hydroxyethanone | |
| Synonyms |
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| 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 |
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| 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 | p38 MAPK (IC50 = 110 nM) |
| ln Vitro | SD0006 is selective for p38α kinase over 50 other kinases screened (including p38γ and p38δ with modest selectivity over p38β). In cellular studies, it reduces the release of inflammatory mediators. Multiple proinflammatory proteins are expressed less frequently when SD0006 is present, both at the transcriptional and translational levels. While SD0006 has no direct COX-1 or COX-2 inhibitory activity in RASFs, it was able to completely inhibit the release of IL-1β-stimulated PGE2 with an IC50 of 96.2 nmol/l[1]. |
| ln Vivo | In animal models of chronic inflammation and disease, SD0006 is successful in vivo. It has significant protective effects on bone density and paw joint integrity in the rat streptococcal-cell-wall induced arthritis model, demonstrating its efficacy. Additionally, SD0006 exhibits good oral anti-inflammatory efficacy and excellent interspecies agreement in rats, cynomolgus monkeys, and humans. In a rodent model of acute inflammation, it reduces pain and swelling[1]. |
| Animal Protocol |
8- to 12-week-old DBA/1 mice 3.75, 7.5 and 15 mg/kg. Orally twice daily. |
| References |
[1]. SD0006: a potent, selective and orally available inhibitor of p38 kinase. Pharmacology. 2009;84(1):42-60. [2]. Identification of SD-0006, a potent diaryl pyrazole inhibitor of p38 MAP kinase. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2634-8. |
| Additional Infomation | SD-06 is a member of the class of pyrazoles that is 1H-pyrazole in which the hydrogens at positions 3, 4, and 5 are replaced by N-(hydroxyacetyl)piperidin-4-yl, pyrimidin-4-yl and p-chlorophenyl groups, respectively. It is a member of pyrazoles, a member of pyrimidines, a N-acylpiperidine, a member of monochlorobenzenes and a primary alcohol. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~80 mg/mL ( ~201.1 mM) Water: <2 mg/mL Ethanol: Insoluble |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.28 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 (6.28 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 (6.28 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 | 2.5134 mL | 12.5672 mL | 25.1345 mL | |
| 5 mM | 0.5027 mL | 2.5134 mL | 5.0269 mL | |
| 10 mM | 0.2513 mL | 1.2567 mL | 2.5134 mL |