168273-05-0

Basic information

• Product Name: 1H-Pyrazole-3-carbonyl chloride, 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-
• CAS NO: 168273-05-0
• Molecular Formula: C17H10Cl4N2O
• Molecular Weight: 400.091
• Mol File: 168273-05-0.mol

Chemical Properties

• CAS DataBase Reference: 1H-Pyrazole-3-carbonyl chloride, 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-Pyrazole-3-carbonyl chloride, 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-(168273-05-0)
• EPA Substance Registry System: 1H-Pyrazole-3-carbonyl chloride, 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-(168273-05-0)

Safety Data

• Hazardous Substances Data: 168273-05-0(Hazardous Substances Data)

Upstream product

• 162758-35-2 rimonabant acid 
• 6285-05-8 4'-chloropropiophenone 
• 169544-41-6 4-(4-chlorophenyl)-3-methyl-2,4-dioxobutyric acid ethyl ester 
• 877-37-2 2-bromo-1-(4-chlorophenyl)-1-propanone 
• 554-00-7 2,4-Dichloroaniline 
• 13617-98-6 2,4-dichlorophenyldiazonium chloride 
• 162758-34-1 ethyl [2-acetyl-4-(4-chlorophenyl)-3-methyl-4-oxo]butyrate 
• 1034980-65-8 C₁₈H₁₃Cl₃N₂O₂ 
• 170937-37-8 4-(4-chlorophenyl)-2-[(2,4-dichlorophenyl)-hydrazono]-3-methyl-4-oxobutyric acid ethyl ester 
• 5446-18-4 2,4-dichlorophenyl hydrazine hydrochloride 
• 13123-92-7 (2,4-dichlorophenyl)hydrazine 
• 1012314-40-7 ethyl 4-(4-chlorophenyl)-3-methyl-4-oxydo-2-oxobuten-3-oate lithium salt 

Downstream Products

• 168273-06-1 rimonabant 
• 336615-69-1 O-1399 
• 158940-64-8 CHASR 
• 443141-90-0 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazide 

Relevant articles and documents

"Photo-Rimonabant": Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar " Cis-On" CB1R Antagonist

Human cannabinoid receptor type 1 (hCB1R) plays important roles in the regulation of appetite and development of addictive behaviors. Herein, we describe the design, synthesis, photocharacterization, molecular docking, and in vitro characterization of "photo-rimonabant", i.e., azo-derivatives of the selective hCB1R antagonist SR1411716A (rimonabant). By applying azo-extension strategies, we yielded compound 16a, which shows marked affinity for CB1R (Ki (cis form) = 29 nM), whose potency increases by illumination with ultraviolet light (CB1R Kitrans/cis ratio = 15.3). Through radioligand binding, calcium mobilization, and cell luminescence assays, we established that 16a is highly selective for hCB1R over hCB2R. These selective antagonists can be valuable molecular tools for optical modulation of CBRs and better understanding of disorders associated with the endocannabinoid system.

MMPL3 INHIBITORS, COMPOSITIONS AND USES THEREOF

Disclosed are inhibitors of mycobacterial membrane protein MmpL3, compositions comprising the inhibitors, and methods of preparation and use thereof.

Rimonaban derivative as well as preparation method and application thereof

The invention discloses a derivative of a CB1 receptor antagonist rimonabant as well as a preparation method and application of the derivative. The structural formula of the derivative is shown as a formula I in the specification. Pharmacodynamic tests sh

Divalent cannabinoid-1 receptor ligands: A linker attachment point survey of SR141716A for development of high-affinity CB1R molecular probes

The cannabinoid-1 receptor (CB1R) inverse agonist SR141716A has proven useful for study of the endocannabinoid system, including development of divalent CB1R ligands possessing a second functional motif attached via a linker unit. These have predominantly employed the C3 position of the central pyrazole ring for linker attachment. Despite this precedent, a novel series of C3-linked CB1R-D2R divalent ligands exhibited extremely high affinity at the D2R, but only poor affinity for the CB1R. A systematic linker attachment point survey of the SR141716A pharmacophore was therefore undertaken, establishing the C5 position as the optimal site for linker conjugation. This linker attachment survey enabled the identification of a novel divalent ligand as a lead compound to inform ongoing development of high-affinity CB1R molecular probes.

1,5-Diarylpyrazole and vanillin hybrids: Synthesis, biological activity and DFT studies

Herein, we report the design and synthesis of 13 diarylpyrazole hybrids with vanillin constructed as dual compounds against oxidative stress and diabetes. Compounds were tested in two different antioxidant assays. It was found that all compounds showed an

Discovery of rimonabant and its potential analogues as anti-TB drug candidates

Rimonabant and its analogues have been synthesized in moderate to good yields using a simple synthetic route. All the newly synthesized compounds were subjected to in vitro screening against M. tuberculosis and M. smegmatis. The most potent analogue JMG-14 exhibits MIC value of 3.13 compared to 3.25 and 50 μ/ml for ethambutol and pyrazinamide, respectively. The molecular docking reveals that pyrazole ring, number and position of halogen atoms play a crucial role in deciding interactions with MTCYP-121. These findings open up a new avenue in the search of potent anti-TB drugs with rimonabant and its novel analogue JMG-14 as lead molecules.

The pentafluorosulfanyl group in cannabinoid receptor ligands: Synthesis and comparison with trifluoromethyl and tert-butyl analogues

An array of cannabinoid ligands, bearing meta- and para-substituted pentafluorosulfanyl (SF5) aniline groups in position 3 of the pyrazole ring, was efficiently synthesised and compared with the exact trifluoromethyl and tert-butyl analogues. In general, the SF5 substituted ligands showed higher lipophilicity (i.e. logP values) than the CF3 counterparts and lower lipophilicity than the tert-butyl ones. In terms of pharmacological activity, SF5 pyrazoles generally showed slightly higher or equivalent CB1 receptor affinity (Ki), always in the nanomolar range, and selectivity towards the CB2 relative to both CF3 and tert-butyl analogues. Functional β-arrestin recruitment assays were used to determine equilibrium dissociation constants (Kb) and showed that all of the tested SF 5 and CF3 compounds are CB1 neutral antagonists. These results confirm the possibility of successfully using an aromatic SF5 group as a stable, synthetically accessible and effective bioisosteric analogue of the electron-withdrawing CF3 group, and possibly also of bulky aliphatic groups, for drug discovery and development applications. This journal is the Partner Organisations 2014.

Design, synthesis and in vitro evaluation of novel uni- and bivalent ligands for the cannabinoid receptor type 1 with variation of spacer length and structure

Using rimonabant, a potent inverse agonist for cannabinoid receptor type 1 (CB1R), as parent ligand, a series of novel univalent and bivalent ligands were designed by variation of spacer length and its chemical structure. The ligands synthesized were evaluated for affinity and selectivity by radioligand displacement and a functional steady-state GTPase assay. The results showed the nature of the spacer influences the biological readout. Albeit all compounds show significantly lower affinities than rimonabant, this fact could be used to demonstrate that affinities and selectivity are influenced by the chemical structure and length of the spacer and might be helpful for designing bivalent probes for other GPCR receptors.

PYRAZOLE CARBOXYLIC ACID ANALOGUES AS ANTI-MYCOBACTERIAL DRUG CANDIDATES

The present invention relates to the pyrazole carboxylic acid analogues of Formula (1) or stereoisomers, or esters or pharmaceutically acceptable salts thereof, as potent anti- mycobacterial agents. Formula Further it discloses the pharmaceutical composition comprising compounds of Formula-I for the treatment of mycobacterial infections.

Synthesis, hypoglycemic activity and molecular modeling studies of pyrazole-3-carbohydrazides designed by a CoMFA model

Diabetes and obesity are two universal health problems that constitute a research objective of several groups due to the lack of efficient and safe drug treatment. In this sense, cannabinoid receptor 1 (CB1) has attracted interest because of its role in food intake and metabolic balance, two targets in the control of metabolic syndrome. In this work, novel 1,5-diaryl pyrazole derivatives were synthesized in accordance with the pKi prediction of a previously reported CoMFA model by our group. To further investigate the biological activity of these compounds in metabolic disorders, their hypoglycemic activity in an in vivo model was tested. Interestingly, a high degree of correlation was observed between the predicted pKi and hypoglycemic effect 7 h after administration. Compounds 4, 9 and 13 showed the most significant plasma glucose reduction with decreases of 60%, 64% and 60% respectively. This result not only surpasses the activity of the lead rimonabant, but also that of the reference drug glibenclamide. Moreover, PASS prediction and molecular docking in an excellent validated homology model of CB1 suggest that these compounds would probably act as CB1 antagonists/inverse agonists and therefore, anti-obesity agents. The ligand-receptor complexes demonstrate that 1,5-diaryl pyrazole derivatives bind to the proposed binding site where a hydrophobic moiety interacts with the phenyl rings in the pyrazole nucleus and Lys192 forms a hydrogen bond with the oxygen of the carbonyl group. Dynamics simulations were also carried out to study the stability of the ligand-receptor complexes where the most active compounds showed smaller ΔG values and more hydrogen bonds throughout the simulation. These compounds are considered useful leads for further optimization in the treatment of such metabolic illnesses.