337533-96-7

Usage

Uses

Used in Pharmaceutical Industry:
3-TERT-BUTYL-1-(2-METHYLPHENYL)-1H-PYRAZOL-5-AMINE is used as a potential candidate for the development of new drugs due to its unique structural features and potential biological activities.
Used in Agrochemical Industry:
3-TERT-BUTYL-1-(2-METHYLPHENYL)-1H-PYRAZOL-5-AMINE is used as a potential candidate for the development of new pesticides, leveraging its chemical properties for pest control.
Used in Medicinal Chemistry Research:
3-TERT-BUTYL-1-(2-METHYLPHENYL)-1H-PYRAZOL-5-AMINE is used as a subject of interest for studying its biological activities and exploring its potential as a therapeutic agent.
Used in Chemical Biology Research:
3-TERT-BUTYL-1-(2-METHYLPHENYL)-1H-PYRAZOL-5-AMINE is used to investigate its interactions with biological systems and understand its role in various biological processes.
Used as a Synthesis Intermediate:
3-TERT-BUTYL-1-(2-METHYLPHENYL)-1H-PYRAZOL-5-AMINE is used as a valuable intermediate for the synthesis of other complex organic molecules, taking advantage of its reactivity and structural features.

Upstream product

• 59997-51-2 trimethylacetylacetonitrile 
• 635-26-7 o-tolylhydrazine hydrochloride 
• 213257-69-3 N-(2-methylphenyl)benzophenone hydrazone 
• 529-27-1 2-methylphenylhydrazine 

Downstream Products

• 705275-20-3 2-{[3-tert-butyl-1(2-methylphenyl)-1H-pyrazol-5yl]amino}-5-methoxybenzoic acid 
• 705277-81-2 methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-fluorobenzoate 
• 705278-95-1 4-bromo-3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-amine 
• 705279-10-3 N,N-dibenzyl-2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzenesulfonamide 
• 848149-96-2 C₃₂H₃₆N₄O₄ 
• 1163730-90-2 1-(3-tert-butyl-1-o-tolyl-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea 

Relevant academic research and scientific papers

Biophysical investigation and conformational analysis of p38α kinase inhibitor doramapimod and its analogues

Doramapimod (BIRB 796) is a potent inhibitor of p38α mitogen-activated protein kinase. It contains an aryl-pyrazole scaffold as a pharmacophore critical for binding. The aryl-pyrazole scaffold is not planar and adopts an out-of-plane conformation, which is described by the torsion angle θ. In this letter, we report the chemical synthesis and biophysical characterization of different analogues of doramapimod (3-12) exhibiting distinctly different aryl-pyrazole torsion angle θ values. The torsion angle θ values of the synthesized analogues (3-6) were determined by crystal structural analysis and the binding affinities to p38α kinase investigated by microscale thermophoresis. Our results unveil a clear correlation between kinase binding and the torsion angle θ of tested doramapimod analogues, highlighting the importance of inhibitor conformation for protein binding.

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.

The design and synthesis of novel α-ketoamide-based p38 MAP kinase inhibitors

We have identified a novel series of potent p38 MAP kinase inhibitors through structure-based design which due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME and in vivo PK studies show these compounds to have drug-like characteristics which could result in the development of an oral treatment for inflammatory conditions.

PHENYLACETAMIDES SUITABLE AS PROTEIN KINASE INHIBITORS

The invention relates to compounds of the formula (I) wherein the moieties R1 , R2, R3, R9, R10 and Q and X, Y and Z are as defined in the specification, and salts thereof; as well as their use, methods of use for them and method of their synthesis, and the like. The compounds are protein kinase inhibitors and can, inter alia, be used in the treatment of various proliferative diseases.

Heteroarylaminopyrazole derivatives useful for the treatment of diabetes

The present invention relates to heteroarylaminopyrazole compounds, pharmaceutical compositions, and methods for treating diabetes and related disorders.

ANILINOPYRAZOLE DERIVATIVES USEFUL FOR THE TREATMENT OF DIABETES

The present invention relates to anilinopyrazole compounds, pharmaceutical compositions, and methods for treating diabetes and related disorders.

Pyrazole urea-based inhibitors of p38 MAP kinase: From lead compound to clinical candidate

We report on a series of N-pyrazole, N′-aryl ureas and their mode of binding to p38 mitogen activated protein kinase. Importantly, a key binding domain that is distinct from the adenosine 5′-triphoshate (ATP) binding site is exposed when the conserved activation loop, consisting in part of Asp168-Phe169-Gly170, adopts a conformation permitting lipophilic and hydrogen bonding interactions between this class of inhibitors and the protein. We describe the correlation of the structure-activity relationships and crystallographic structures of these inhibitors with p38. In addition, we incorporated another binding pharmacophore that forms a hydrogen bond at the ATP binding site. This modification affords significant improvements in binding, cellular, and in vivo potencies resulting in the selection of 45 (BIRB 796) as a clinical candidate for the treatment of inflammatory diseases.

Novel application of the palladium-catalyzed N-arylation of hydrazones to a versatile new synthesis of pyrazoles

A versatile synthesis of pyrazoles from aryl benzophenone hydrazones was demonstrated with a variety of 1,3-bifunctional substrates under acidic conditions. The obtained regioselectivity is consistent with transhydrazonation followed by subsequent cycliza

1-Phenyl-5-pyrazolyl ureas: Potent and selective p38 kinase inhibitors

Inhibitors of the MAP kinase p38 are potentially useful for the treatment of arthritis and osteoporosis. Several 2,3-dichlorophenyl ureas were identified as small-molecule inhibitors of p38 by a combinatorial chemistry effort. Optimization for cellular potency led to the discovery of a new class of potent and selective p38 kinase inhibitors, exemplified by the 1-phenyl-5-pyrazolyl urea 7 (IC50 = 13 nM). (C) 2000 Elsevier Science Ltd.