118430-73-2

Usage

Uses

Used in Pharmaceutical Industry:
5-Amino-3-tert-butyl-1-methylpyrazole is used as a chemical intermediate for the synthesis of various pharmaceuticals. Its unique structure allows it to be incorporated into the development of new drugs, particularly those targeting specific enzymes, making it a valuable asset in drug discovery and medicinal chemistry.
Used in Agrochemical Industry:
In the agrochemical sector, 5-amino-3-tert-butyl-1-methylpyrazole is utilized as an intermediate in the production of agrochemicals. Its ability to inhibit certain enzymes can be harnessed to create compounds that protect crops from pests and diseases, thereby contributing to agricultural productivity and food security.
Used in Chemical Research:
5-Amino-3-tert-butyl-1-methylpyrazole is employed as a building block in the synthesis of a wide range of organic compounds. Its versatility in chemical reactions and its capacity to form stable complexes with various molecules make it an essential component in the advancement of organic chemistry and the creation of novel chemical entities.
Used in Enzyme Inhibition Studies:
As a compound with enzyme-inhibiting properties, 5-amino-3-tert-butyl-1-methylpyrazole is used in research to understand and develop inhibitors for specific enzymes. This application is crucial in the study of enzyme mechanisms, the development of enzyme-targeted therapies, and the exploration of potential drug candidates for various diseases and conditions.

Upstream product

• 59997-51-2 trimethylacetylacetonitrile 
• 60-34-4 methylhydrazine 
• 32064-64-5 methylhydrazine oxalic acid salt 
• 3938-95-2 2,2-dimethyl-propanoic acid ethyl ester 
• 29586-83-2 (2Z)-3-chloro-4,4-dimethylpent-2-enenitrile 
• 302-15-8 methylhydrazine sulfuric acid 
• 75-97-8 3,3-dimethyl-butan-2-one 

Downstream Products

• 403608-38-8 5,6,7,8-tetrafluoro-3-tert-butyl-1-methyl-1H-pyrazolo[3,4-b]quinoline 
• 857266-62-7 phenyl (3-(tert-butyl)-1-methyl-1H-pyrazol-5-yl)carbamate 
• 857266-35-4 N-(3-tert-butyl-1-methyl-1H-pyrazol-5-yl)-N'-{3-[(2-chloropyrimidin-5-yl)ethynyl]phenyl}urea 
• 857287-55-9 N-(3-tert-butyl-1-methyl-1H-pyrazol-5-yl)-N'-(3-ethynylphenyl)urea 
• 756839-38-0 1-(2-Aminobenzyl)-3-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-urea 
• 229002-10-2 N-[3-(tert-butyl)-1-methylpyrazol-5-yl][(4-(4-pyridyloxy)phenyl)amino]carboxamide 
• 1427282-58-3 4-bromo-2-(3-(tert-butyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenol 
• 1353570-18-9 C₂₁H₂₃FN₆S 
• 1353570-14-5 C₁₆H₂₀N₄OS 
• 1255040-29-9 N-((3-tert-butyl-1-methyl-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-(methylsulphonamido)phenyl)propanamide 

Relevant academic research and scientific papers

Synthesis and pharmacological characterization of a potent, orally active p38 kinase inhibitor.

Inhibitors of the MAP kinase p38 provide a novel approach for the treatment of osteoporosis, inflammatory disorders, and cancer. We have identified N-(3-tert-butyl-1-methyl-5-pyrazolyl)-N'-(4-(4-pyridinylmethyl)phenyl)urea as a potent and selective p38 ki

Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators

The evolution of gamma-secretase modulators (GSMs) through the introduction of novel heterocycles with the goal of aligning activity for reducing the levels of Aβ42 and properties consistent with a drug-like molecule are described. The insertion of a methoxypyridine motif within the tetracyclic scaffold provided compounds with improved activity for arresting Aβ42 production as well as improved properties, including solubility. In vivo pharmacokinetic analysis demonstrated that several compounds within the novel series were capable of crossing the BBB and accessing the therapeutic target. Treatment with methoxypyridine-derived compound 64 reduced Aβ42 levels in the plasma of J20 mice, in addition to reducing Aβ42 levels in the plasma and brain of Tg2576 mice.

Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists

A series of 1-substituted 3-(t-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for hTRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the S-configuration, providing exceptionally potent antagonists 13S and 16S with Ki(CAP) = 0.1 nM. Particularly significant, 13S exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for rTRPV1, blocking in vivo the hypothermic action of capsaicin, consistent with their in vitro mechanism. The docking study of compounds 13S and 16S in our hTRPV1 homology model indicated that the binding modes differed somewhat, with that of 13S more closely resembling that of GRT12360.

Drug Discovery against Psoriasis: Identification of a New Potent FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor, 1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-fluorophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea, That Showed Potent Activity in a Psoriatic Animal Model

Psoriasis is a chronic T-cell-mediated autoimmune disease, and FMS-like tyrosine kinase 3 (FLT3) has been considered as a potential molecular target for the treatment of psoriasis. In this investigation, structural optimization was performed on a lead compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (1), which showed a moderate inhibitory activity againt FLT3. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis led to the discovery of a number of potent FLT3 inhibitors. One of the most active compounds, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(5-tert-butylisoxazol-3-yl)urea (18b), was then chosen for in-depth antipsoriasis studies because this compound displayed the highest potency in a preliminary antipsoriasis test. Compound 18b exhibited significant antipsoriatic effects in the K14-VEGF transgenic mouse model of psoriasis, and no recurrence was found 15 days later after the last administration. Detailed mechanisms of action of compound 18b were also investigated. Collectively, compound 18b could be a potential drug candidate for psoriasis treatment.

Design and synthesis of aminothiazole modulators of the gamma-secretase enzyme

The design and construction of a series of novel aminothiazole-derived γ-secretase modulators is described. The incorporation of heterocyclic replacements of the terminal phenyl D-ring of lead compound 1 was conducted in order to align potency with favorable drug-like properties. γ-Secretase modulator 28 displayed good activity for in vitro inhibition of Aβ42, as well as substantial improvement in ADME and physicochemical properties, including aqueous solubility. Pharmacokinetic evaluation of compound 28 in mice revealed good brain penetration, as well as good clearance, half-life, and volume of distribution which collectively support the continued development of this class of compounds.

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.

PYRAZOLYL PYRROLINONES AND THEIR USE AS HERBICIDES

The invention relates to pyrrolone compounds of the formula (I) wherein X, Ra, Rb, Rc, R1, R2 and R3 are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds to control plant growth.

DIHYDRO-HYDANTOIN DERIVATIVES WITH HERBICIDAL ACTIVITY

The invention relates to substituted dihydro-hydantoin derivatives of the formula (I) wherein X, Ra, Rb, Rc, R1, R2 and R3 are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds 10 to control or inhibit plant growth.

Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1, 1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E

The Ras/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway plays a central role in the regulation of cell growth, differentiation, and survival. Expression of mutant BRAFV600E results in constitutive activation of the MAPK pathway, which can lead to uncontrolled cellular growth. Herein, we describe an SAR optimization campaign around a series of quinazoline derived BRAFV600E inhibitors. In particular, the bioisosteric replacement of a metabolically sensitive tert-butyl group with fluorinated alkyl moieties is described. This effort led directly to the identification of a clinical candidate, compound 40 (CEP-32496). Compound 40 exhibits high potency against several BRAFV600E-dependent cell lines and selective cytotoxicity for tumor cell lines expressing mutant BRAFV600E versus those containing wild-type BRAF. Compound 40 also exhibits an excellent PK profile across multiple preclinical species. In addition, significant oral efficacy was observed in a 14-day BRAFV600E-dependent human Colo-205 tumor xenograft mouse model, upon dosing at 30 and 100 mg/kg BID.

COMPOUNDS AND USES THEREOF IN MODULATING LEVELS OF VARIOUS AMYLOID BETA PEPTIDE ALLOFORMS

The invention provides a novel compound having a structure corresponding to Formula (I): (A)-(B)-(C)-(D) or a pharmaceutically acceptable salt or prodrug thereof and methods for using them.