285983-48-4

Usage

Uses

1. Used in Pharmaceutical Industry:
Doramapimod is used as an immunomodulator for the treatment of inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis. It helps in modulating the immune response and reducing inflammation.
2. Used in Inflammatory Disease Treatment:
Doramapimod is used as an anti-inflammatory agent, blocking the upregulation of p38 MAPK and Hsp27 phosphorylation, which contributes to enhanced cytotoxicity and caspase activation in inflammatory conditions.
3. Used in Research and Development:
Doramapimod is used as a research tool for studying the role of p38 MAPK in various cellular processes and its potential as a therapeutic target for inflammatory diseases.
Chemical Properties:
Doramapimod is a pale beige solid with potent and selective inhibitory activity against p38 MAPK.

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].

References

1) Pargellis?et al. (2002),?Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site; Nat. Struct. Biol.,?9?268 2) Branger?et al.?(2002),?Anti-inflammatory effects of a p38 mitogen-activated protein kinase inhibitor during human endotoxemia; J. Immunol.,?168?4070 3) Joos?et al. (2010),?Differential effects of p38MAP kinase inhibitors on the expression of inflammation-associated genes in primary, interleukin-1 beta-stimulated human chondrocytes; Br. J. Pharmacol.,?160?1252

InChI:InChI=1/C31H37N5O3/c1-22-9-11-23(12-10-22)36-29(21-28(34-36)31(2,3)4)33-30(37)32-26-13-14-27(25-8-6-5-7-24(25)26)39-20-17-35-15-18-38-19-16-35/h5-14,21H,15-20H2,1-4H3,(H2,32,33,37)

Upstream product

• 75-44-5 phosgene 
• 317806-90-9 4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-ylamine 
• 317806-86-3 3-amino-5-tert-butyl-2-(p-tolyl)-2H-pyrazole hydrochloride 
• 5720-05-8 4-methylphenylboronic acid 
• 142-71-2 copper diacetate 
• 59997-51-2 trimethylacetylacetonitrile 
• 24424-99-5 di-tert-butyl dicarbonate 
• 637-60-5 p-tolylhydrazine hydrochloride 
• 317806-87-4 2,2,2-trichloroethyl 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate 
• 285984-25-0 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine 
• 285984-50-1 1-amino-4-(2-morpholin-4-yl-ethoxy)naphthalene dihydrochloride 
• 317806-88-5 4-nitro-1-(2-morpholinethoxy)naphthalene 
• 3647-69-6 4-(2-chloroethyl)morpholine hydrochride 
• 605-62-9 4-nitro-1-naphthol 

Downstream Products

• 285984-10-3 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{4-[2-(4-oxy-morpholin-4-yl)-ethoxy]-naphthalen-1-yl}-urea 
• 489432-49-7 2-methyl-2-(5-{3-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-ureido}-1-p-tolyl-1H-pyrazol-3-yl)-propionic acid 
• 1283526-53-3 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea.hydrochloride 

Relevant academic research and scientific papers

2,3-DIHYDRO-1H-INDENE-2-YL UREA DERIVATIVE AND PHARMACEUTICAL APPLICATION OF SAME

A 2,3-dihydro-1H-indene-2-yl urea derivative represented by Formula (Ia) or a pharmaceutically acceptable salt thereof:

Synthesis of p38 MAP kinase inhibitor BIRB 796 and analogs via copper-mediated N-arylation reaction

Direct N-arylation of urea (5) with various arylboronic acids mediated by cupric acetate furnished BIRB796 and a range of N-substituted BIRB796 analogs in good to moderate yields in one step. Urea (5) was readily synthesized from commercially available compounds.

Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors

Kinase disregulation disrupts the intricate network of intracellular signaling pathways and contributes to the onset of diseases such as cancer. Although several kinase inhibitors are on the market, inhibitor selectivity and drug resistance mutations persist as fundamental challenges in the development of effective long-term treatments. Chemical entities binding to less conserved allosteric sites would be expected to offer new opportunities for scaffold development. Because no high-throughput method was previously available, we developed a fluorescence-based kinase binding assay for identifying and characterizing ligands which stabilize the inactive kinase conformation. Here, we present a description of the development and validation of this assay using the serine/threonine kinase p38R. By covalently attaching fluorophores to the activation loop of the kinase, we were able to detect conformational changes and measure the Kd, kon, and koff associated with the binding and dissociation of ligands to the allosteric pocket. We report the SAR of a synthesized focused library of pyrazolourea derivatives, a scaffold known to bind with high affinity to the allosteric pocket of p38R. Additionally, we used protein X-ray crystallography together with our assay to examine the binding and dissociation kinetics to characterize potent quinazoline- and quinoline-based type II inhibitors, which also utilize this binding pocket in p38α. Last, we identified the b-Raf inhibitor sorafenib as a potent low nanomolar inhibitor of p38α and used protein X-ray crystallography to confirm a unique binding mode to the inactive kinase conformation.

Microwave-assisted synthesis of N-pyrazole ureas and the p38α inhibitor BIRB 796 for study into accelerated cell ageing

Microwave irradiation of substituted hydrazines and β-ketoesters gives 5-aminopyrazoles in excellent yield, which can be transformed to the corresponding N-carbonyl derivatives by treatment with an isocyanate or chloroformate. Derivatization of 4-nitronaphth-1-ol using predominantly microwave heating methods and reaction with an N-pyrazole carbamate provides a rapid route to the N-pyrazole urea BIRB 796 in high purity, as a potent and selective inhibitor of p38α mitogen-activated protein kinase for the study of accelerated ageing in Werner syndrome cells. The Royal Society of Chemistry 2006.

BENZIMIDAZOLONES AND THEIR USE AS CYTOKINE INHIBITORS

Disclosed are benzimidazolone compounds of formulas (II) wherein X is O, S or NR5. The compounds inhibit production of cytokines involved in inflammatory processes and are thus useful for treating diseases and pathological conditions involving inflammatio

Synthesis of deuterium, tritium, and carbon-14 labeled BIRB 796, a p38 MAP kinase inhibitor

1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy) naphthalen-1-yl]urea (BIRB 796), currently in clinical trials for the treatment of inflammatory diseases, is a potent inhibitor of p38 MAP kinase. Labeled BIRB 796 with stable and r

Anticoagulant and fibrinolytic therapy uning p38 MAP kinase inhibitors

Disclosed are methods for a treating a disease or condition relating to blood coagulation and fibrinolysis using p38 MAP kinase inhibitors.

Polymorph and process for preparing same

Disclosed are processes, polymorph and intermediate compounds for preparing aryl- and heteroaryl-substituted urea compounds of the formula(I) wherein Ar1, Ar2, L, Q and X are described herein. The product compounds are useful in pharmaceutic compositions for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. 1

Methods of treating cytokine mediated diseases

Disclosed are methods of treating certain cytokine mediated diseases or conditions using novel aromatic heterocyclic compounds of the formula(I) wherein Ar1,Ar2,L,Q and X are described herein.

Aromatic heterocyclic compounds as antiinflammatory agents

Disclosed are novel aromatic heterocyclic compounds of the formula(I) wherein Ar1,Ar2,L,Q and X are described herein. The compounds are useful in pharmaceutic compositions for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are processes of making such compounds.