91331-68-9

Usage

General Description

3-Methyl-1-(2-methylphenyl)-1H-pyrazol-5-amine is a chemical compound that belongs to the pyrazole family. It is a potentially biologically active molecule with potential applications in pharmaceutical and agrochemical industries. Its structure consists of a methyl group substituted at the 3-position of the pyrazole ring and a 2-methylphenyl group attached to the 1-position. 3-METHYL-1-(2-METHYLPHENYL)-1H-PYRAZOL-& is of interest for its potential pharmacological properties and could be used as a building block for the synthesis of pharmaceuticals and agrochemicals.

InChI:InChI=1/C11H13N3/c1-8-5-3-4-6-10(8)14-11(12)7-9(2)13-14/h3-7H,12H2,1-2H3

Upstream product

• 91331-62-3 3-o-tolylhydrazono-butyronitrile 
• 529-27-1 2-methylphenylhydrazine 
• 1118-61-2 3-Aminocrotononitrile 
• 95-53-4 o-toluidine 
• 2469-99-0 Cyanoaceton 
• 635-26-7 o-tolylhydrazine hydrochloride 
• 1118-60-1 3-iminobutyronitrile 

Downstream Products

• 1025822-85-8 4-chloro-3-methyl-1-o-tolyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 
• 1442467-67-5 (4S,6S)-3,6-dimethyl-1-(2-methylphenyl)-4-(4-phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one 
• 1442467-69-7 (4R,6R)-3,6-dimethyl-1-(2-methylphenyl)-4-(4-phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one 
• 1442467-70-0 (4S,6R)-3,6-dimethyl-1-(2-methylphenyl)-4-(4-phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one 
• 1442467-68-6 (4R,6S)-3,6-dimethyl-1-(2-methylphenyl)-4-(4-phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one 
• 1442467-75-5 (±)-3-methyl-1-(2-methylphenyl)-4-(4-phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one 

Relevant academic research and scientific papers

Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M

The cullin-RING ubiquitin ligases (CRLs) are ubiquitin E3 enzymes that play a key role in controlling proteasomal degradation and are activated by neddylation. We previously reported inhibitors that target CRL activation by disrupting the interaction of defective in cullin neddylation 1 (DCN1), a CRL neddylation co-E3, and UBE2M, a neddylation E2. Our first-generation inhibitors possessed poor oral bioavailability and fairly rapid clearance that hindered the study of acute inhibition of DCN-controlled CRL activity in vivo. Herein, we report studies to improve the pharmacokinetic performance of the pyrazolo-pyridone inhibitors. The current best inhibitor, 40, inhibits the interaction of DCN1 and UBE2M, blocks NEDD8 transfer in biochemical assays, thermally stabilizes cellular DCN1, and inhibits anchorage-independent growth in a DCN1 amplified squamous cell carcinoma cell line. Additionally, we demonstrate that a single oral 50 mg/kg dose sustains plasma exposures above the biochemical IC90 for 24 h in mice.

Microwave synthesis of 1-aryl-1H-pyrazole-5-amines

A microwave-mediated synthesis of 1H-pyrazole-5-amines utilizing 1 M HCl at 150 °C was developed in order to provide products in a matter of minutes with minimal purification. Most reactions are complete in only 10 min and can be isolated via a simple filtration without the need for further purification by column chromatography or recrystallization. This method tolerates a range of functional groups and can be performed on milligram to gram scales.

One-pot, telescoped synthesis of N-aryl-5-aminopyrazoles from anilines in environmentally benign conditions

An efficient synthetic approach to synthesize N-aryl-5-aminopyrazoles from anilines via a one-pot, telescoped reaction performed in entirely aqueous conditions has been developed. This protocol provides a rapid, convenient method to prepare N-aryl-5-aminopyrazoles, useful building blocks for the synthesis of several bicyclic nitrogen heterocycles, by avoiding the isolation of the toxic intermediate arylhydrazines and the use of a metallic reductant. The Royal Society of Chemistry 2014.

Asymmetric synthesis of the four diastereoisomers of a novel non-steroidal farnesoid X receptor (FXR) agonist: Role of the chirality on the biological activity

An asymmetric synthetic strategy was designed for the preparation of the four possible diastereoisomers of 3,6-dimethyl-1-(2-methylphenyl)-4-(4- phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one, a non-steroidal FXR agonist, we recently discovered following a virtual screening approach. The results obtained from an AlphaScreen assay clearly demonstrated that only the isomer endowed with 4R,6S absolute configuration is responsible for the biological activity. A deep investigation of the different putative binding modes adopted by these enantiomerically pure ligands using computational modeling studies confirmed the enantioselectivity of FXR towards this class of molecules.

Pyrazole[3,4-e][1,4]thiazepin-7-one derivatives as a novel class of Farnesoid X Receptor (FXR) agonists

A virtual screening procedure was applied to the discovery of structurally diverse non-steroidal Farnesoid X Receptor (FXR) agonists. From 117 compounds selected by virtual screening, a total of 47 compounds were found to be FXR agonists, with 34 of them showing activity below a concentration of 20 μM. 1H-Pyrazole[3,4-e][1,4]thiazepin-7-one-based hit compound 7 was chosen for hit-to-lead optimization. A large number of 1H-pyrazole[3,4-e][1,4]thiazepin-7- one derivatives was designed, synthesized, and evaluated by a cell-based luciferase transactivation assay for their agonistic activity against FXR. Most of them exhibited low micromolar range of potency and very high efficacy.

Approach to the library of fused pyridine-4-carboxylic acids by combes-type reaction of acyl pyruvates and electron-rich amino heterocycles

A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.

Identification and optimization of substituted 5-aminopyrazoles as potent and selective adenosine A1 receptor antagonists

Potent and selective adenosine A1 receptor antagonists were disclosed. SAR and pharmacological profile of selected compounds were discussed.

The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist

The identification of novel, potent, non-steroidal/small molecule functional GR antagonist GSK1564023A selective over PR is described. Associated structure-activity relationships and the process of optimisation of an initial HTS hit are also described.

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.

Discovery of new orally active phosphodiesterase (PDE4) inhibitors

A series of 4-anilinopyrazolopyridine derivatives were synthesized and biologically evaluated as inhibitors of phosphodiesterase (PDE4). Chemical modification of 3, a structurally new chemical lead that was found in our in-house library, was focused on 1- and 3-substituents. Full details of the discovery of a new orally active chemical lead 5 are presented. Structure-activity relationship data, pharmacological evaluation, and the subtype selectivity study are also presented.