611168-85-5

Basic information

• Product Name: 1-[2-(3-nitrophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea
• Synonyms: 1-[2-(3-nitrophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea
• CAS NO: 611168-85-5
• Molecular Weight: 558.637
• Mol File: 611168-85-5.mol

Chemical Properties

• CAS DataBase Reference: 1-[2-(3-nitrophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea(CAS DataBase Reference)
• NIST Chemistry Reference: 1-[2-(3-nitrophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea(611168-85-5)
• EPA Substance Registry System: 1-[2-(3-nitrophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea(611168-85-5)

Safety Data

• Hazardous Substances Data: 611168-85-5(Hazardous Substances Data)

Upstream product

• 317806-90-9 4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-ylamine 
• 611168-84-4 [5-tert-butyl-2-(3-nitrophenyl)-2H-pyrazol-3-yl]-carbamic acid phenyl ester 
• 476637-05-5 2-(3-nitrophenyl)-5-tert-butyl-2H-pyrazol-3-yl-amine 
• 1012883-12-3 C₁₆H₁₇Cl₃N₄O₄ 
• 317806-89-6 C₁₆H₂₀N₂O₂*ClH 

Downstream Products

• 1609257-17-1 1-(3-(tert-butyl)-1-(3-((2-ethoxyethyl)amino)phenyl)-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea 

Relevant articles and documents

Identification of type II and III DDR2 inhibitors

Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.

Structure-Activity Relationships of the p38α 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)

We report on the structure-activity relationships (SAR) of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy) naphthalen-1-yl]urea (BIRB 796), an inhibitor of p38α MAP kinase which has advanced into human clinical trials for the treatment of autoimmune diseases. Thermal denaturation was used to establish molecular binding affinities for this class of p38α inhibitors. The tert-butyl group remains a critical binding element by occupying a lipophilic domain in the kinase which is exposed upon rearrangement of the activation loop. An aromatic ring attached to N-2 of the pyrazole nucleus provides important π-CH 2 interactions with the kinase. The role of groups attached through an ethoxy group to the 4-position of the naphthalene and directed into the ATP-binding domain is elucidated. Pharmacophores with good hydrogen bonding potential, such as morpholine, pyridine, and imidazole, shift the melting temperature of p38α by 16-17 °C translating into Kd values of 50-100 pM. Finally, we describe several compounds that potently inhibit TNF-α production when dosed orally in mice.