Doramapimod CAS 285983-48-4
Doramapimod Basic information
| Product Name: | Doramapimod |
| Synonyms: | 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholinoethoxy)-1-naphthyl]urea;1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea;BIRB 796; BIRB-796; BIRB796;;CS-379;BIRB 796 - BIRB 0796 | Doramapimod;CS-1863;BIBR-796;1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea |
| CAS: | 285983-48-4 |
| MF: | C31H37N5O3 |
| MW: | 527.66 |
| EINECS: | 1308068-626-2 |
| Product Categories: | Anti-cancer&immunity;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators;MAPK;Inhibitors |
| Mol File: | 285983-48-4.mol |
Doramapimod Chemical Properties
| Melting point | 142-143 °C |
| Boiling point | 631.6±55.0 °C(Predicted) |
| density | 1.20±0.1 g/cm3(Predicted) |
| storage temp. | Sealed in dry,Store in freezer, under -20°C |
| solubility | Soluble in DMSO (up to 50 mg/ml) or in Ethanol (up to 30 mg/ml). |
| pka | 13.47±0.70(Predicted) |
| form | solid |
| color | White or off-white |
| Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 2 months. |
| InChIKey | MVCOAUNKQVWQHZ-UHFFFAOYSA-N |
| SMILES | CC1=CC=C(N2C(NC(NC3=CC=C(OCCN4CCOCC4)C5=C3C=CC=C5)=O)=CC(C(C)(C)C)=N2)C=C1 |
Safety Information
| WGK Germany | WGK 3 |
| HS Code | 2934999090 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Oral |
| Description | Doramapimod (285983-48-4) potently and selectively inhibits p38 MAPK by simultaneously binding to the ATP-binding domain and an allosteric site.1?(IC50=18 nM). Displays anti-inflammatory activity2?but differential effects on inflammatory genes3. Cell permeable. |
| Chemical Properties | Pale Beige Solid |
| Uses | Doramapimod is a highly potent inhibitor of p38 mitogen-activated protein kinase (MAPK). Doramapimod is a potential agent for the treatment of inflammatory diseases. Doramapimod blocks baseline and bortezomib-triggered upregulation of p38 MAPK and Hsp27 phosphorylation leading to enhanced cytotoxicity and caspase activation. |
| Definition | ChEBI: A member of the class of pyrazoles that is an immunomodulator used for treatment of rheumatoid arthritis, Crohn's disease and psoriasis. |
| Synthesis | 317806-87-4 317806-88-5 285983-48-4 Step 4 Synthesis of 1-(3-tert-butyl-1-tosyl-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea (Compound 4): to a mixed solution of 4-(2-((4-nitronaphthalen-1-yl)oxy)ethyl)morpholine (11.18 g, 36.9 mmol) in methanol (90 mL) and THF (30 mL) , 5% palladium/activated carbon (0.500 g) was added. The resulting mixture was stirred at room temperature in a hydrogen atmosphere for 23 hours. Upon completion of the reaction, the insoluble material was removed by filtration and the solvent was evaporated under reduced pressure. The resulting residue was mixed with 2,2,2-trichloroethyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamate (16.1 g, 39.7 mmol), N,N-diisopropylethylamine (8.50 mL) and DMSO (30 mL) and stirred at 60 °C for 18 hours. After completion of the reaction, the reaction solution was cooled to room temperature and saturated brine was added. The aqueous layer was extracted with ethyl acetate and the organic phase was dried with anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=50/50 to ethyl acetate/methanol=90/10) to afford 13.58 g of the target product 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea in 69% yield. |
| in vitro | birb 796 is a picomolar inhibitor of human p38 map kinase with a 12,000-fold increase in binding affinity. moreover, birb 796 behavors as one of the most potent and slowest dissociating human p38 map kinase inhibitors now known [1]. |
| in vivo | in a lps-stimulated tnf-α synthesis mouse model, a 65% inhibition of tnf-α synthesis was observed when birb 796 was dosed orally at 10 mg/kg. in a model of established collagen-induced arthritis using b10.riii mice, birb 796 showed a 63% inhibition of arthritis severity when dosed orally at 30 mg/kg qd [2]. |
| storage | Store at -20°C |
| References | [1] CHRISTOPHER PARGELLIS. Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site[J]. Nature Structural & Molecular Biology, 2002, 9 4: 268-272. DOI:10.1038/nsb770 [2] J. BRANGER. Anti-Inflammatory Effects of a p38 Mitogen-Activated Protein Kinase Inhibitor During Human Endotoxemia1[J]. The Journal of Immunology, 2002, 1 1: 4070-4077. DOI:10.4049/jimmunol.168.8.4070 [3] H JOOS. Differential effects of p38MAP kinase inhibitors on the expression of inflammation-associated genes in primary, interleukin-1β-stimulated human chondrocytes[J]. British Journal of Pharmacology, 2010, 160 5: 1252-1262. DOI:10.1111/j.1476-5381.2010.00760.x |
Doramapimod Preparation Products And Raw materials
| Raw materials | 2,2,2-trichloroethyl 3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-ylcarbamate-->4-[2-(4-NITRONAPHTHALEN-1-YLOXY)ETHYL]MORPHOLINE-->Methanol-->Hydrogen-->N,N-Diisopropylethylamine-->Dimethyl sulfoxide-->Tetrahydrofuran |
