Doramapimod

Base Information

• Chemical Name: Doramapimod
• CAS No.: 285983-48-4
• Molecular Formula: C31H37N5O3
• Molecular Weight: 527.666
• Hs Code.: 2934999090
• UNII: HO1A8B3YVV
• DSSTox Substance ID: DTXSID2048957
• Nikkaji Number: J1.719.293K
• Wikidata: Q27077098
• NCI Thesaurus Code: C76770
• Pharos Ligand ID: YYY6KR6VBYVL
• Metabolomics Workbench ID: 147585
• ChEMBL ID: CHEMBL103667
• Mol file: 285983-48-4.mol

Synonyms:1-(3-(1,1-dimethylethyl)-1-(4-methylphenyl)-1H-pyrazol-5-yl)-3-(4-(2-(morpholin-4-yl)ethoxy)naphthalen-1-yl)urea;1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3(4-(2-morpholin-4-yl-ethoxy)naph- thalen-1-yl)urea;BIRB 796;BIRB 796 BS;BIRB-796;BIRB-796 BS;BIRB796;doramapimod

Chemical Property of Doramapimod

Chemical Property:

• Vapor Pressure: 7.36E-16mmHg at 25°C
• Melting Point: 142-143 °C
• Refractive Index: 1.619
• Boiling Point: 631.6 °C at 760 mmHg
• PKA: 13.47±0.70(Predicted)
• Flash Point: 335.8 °C
• PSA: 80.65000
• Density: 1.2 g/cm³
• LogP: 6.07030
• 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).
• XLogP3: 5.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 8
• Exact Mass: 527.28964006
• Heavy Atom Count: 39
• Complexity: 777

Purity/Quality:

99% ^*data from raw suppliers

Doramapimod ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CC=C(C=C1)N2C(=CC(=N2)C(C)(C)C)NC(=O)NC3=CC=C(C4=CC=CC=C43)OCCN5CCOCC5
• Recent ClinicalTrials: Efficacy, Safety and Pharmacokinetics of BIRB 796 BS Tablets in Patients With Active Rheumatoid Arthritis
• 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.
• 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 bo rtezomib-triggered upregulation of p38 MAPK and Hsp27 phosphorylation leading to enhanced cytotoxicity and caspase activation. 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.

Technology Process of Doramapimod

There total 18 articles about Doramapimod which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

phosgene (75-44-5) + 4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-ylamine (317806-90-9) + 3-amino-5-tert-butyl-2-(p-tolyl)-2H-pyrazole hydrochloride (317806-86-3) → BIRB-796 (285983-48-4) + 1,3-bis-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea

Guidance literature:

phosgene; 3-amino-5-tert-butyl-2-(p-tolyl)-2H-pyrazole hydrochloride; With sodium hydrogencarbonate; In dichloromethane; water; toluene; at 0 ℃; for 4h;

4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-ylamine; In dichloromethane; water; toluene; at 0 - 20 ℃;

DOI:10.1002/jlcr.873

Reference yield: 91.0%

1-(3-tert-butyl-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea + 4-methylphenylboronic acid (5720-05-8) → (4,4'-dimethyl-1,1'-biphenyl) (613-33-2) + BIRB-796 (285983-48-4)

Guidance literature:

With pyridine; copper diacetate; In dichloromethane; at 21 ℃; for 17h; Molecular sieve; Inert atmosphere;

DOI:10.1016/j.tetlet.2010.06.109

Reference yield: 69.0%

2,2,2-trichloroethyl 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate (317806-87-4) + 4-nitro-1-(2-morpholinethoxy)naphthalene (317806-88-5) → BIRB-796 (285983-48-4)

Guidance literature:

4-nitro-1-(2-morpholinethoxy)naphthalene; With hydrogen; 5%-palladium/activated carbon; In tetrahydrofuran; methanol; dimethyl sulfoxide; at 20 ℃;

2,2,2-trichloroethyl 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate; With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 60 ℃;

upstream raw materials:

3-(tert-butyl)-5-isocyanato-1-(p-tolyl)-1H-pyrazole

4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-ylamine

phosgene

3-amino-5-tert-butyl-2-(p-tolyl)-2H-pyrazole hydrochloride

Downstream raw materials:

1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea.hydrochloride

2-methyl-2-(5-{3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-ureido}-1-p-tolyl-1H-pyrazol-3-yl)-propionic acid

1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{4-[2-(4-oxy-morpholin-4-yl)-ethoxy]-naphthalen-1-yl}-urea

Refernces

• 1、 Tan, Zhulin,Song, Jinhua J.,Reeves, Jonathan T.,Fandrick, Daniel R.,Lee, Heewon,Campbell, Scot,Yee, Nathan K.. "Synthesis of p38 MAP kinase inhibitor BIRB 796 and analogs via copper-mediated N-arylation reaction". supporting information; experimental part. p. 4547 - 4551. Retrieved 2010/10/02.
• 2、 Bagley, Mark C.,Davis, Terence,Dix, Matthew C.,Widdowson, Caroline S.,Kipling, David. "Microwave-assisted synthesis of N-pyrazole ureas and the p38α inhibitor BIRB 796 for study into accelerated cell ageing". . p. 4158 - 4164. Retrieved 2008/09/19.