Search results for "Pyrazole"
showing 10 items of 315 documents
Central functional response to the novel peptide cannabinoid, hemopressin.
2013
Hemopressin is the first peptide ligand to be described for the CB₁ cannabinoid receptor. Hemopressin acts as an inverse agonist in vivo and can cross the blood-brain barrier to both inhibit appetite and induce antinociception. Despite being highly effective, synthetic CB₁ inverse agonists are limited therapeutically due to unwanted, over dampening of central reward pathways. However, hemopressin appears to have its effect on appetite by affecting satiety rather than reward, suggesting an alternative mode of action which might avoid adverse side effects. Here, to resolve the neuronal circuitry mediating hemopressin's actions, we have combined blood-oxygen-level-dependent, pharmacological-ch…
Monitoring the hydrogen bond net configuration and the dimensionality of aniline and phenyloxamate by adding 1 H -pyrazole and isoxazole as substitue…
2019
This work describes the synthesis and characterization of a new class of oxamic acid derivatives containing pyrazole and isoxazole as substituents to investigate their ability to form hydrogen bonds aiming at applying them in crystal engineering and molecular self-recognition. In this respect, we report a new synthesis of 2-(4-nitrophenyl)-1,3-propanedial (1) in high yield using SOCl2 as a chlorinating agent. The new oxamic esters 4-(1H-pyrazol-4-yl)phenylene-N-(ethyloxamate) (2d) and 4-(1,2-oxazol-4-yl)phenylene-N-(ethyloxamate) (3d) were prepared from 1. The synthetic route consists of the cyclisation of 1 either with hydrazine to afford 4-(-aminophenyl)-1H-pyrazole (2a) or with hydroxyla…
Understanding the domino reaction between 1-diazopropan-2-one and 1,1-dinitroethylene. A molecular electron density theory study of the [3 + 2] cyclo…
2017
The reaction between 1-diazopropan-2-one and 1,1-dinitroethylene has been studied using the Molecular Electron Density Theory (MEDT) at the B3LYP/6-31G(d,p) computational level. This reaction comprises two domino processes initialised by a common [3 + 2] cycloaddition (32CA) reaction yielding a 1-pyrazoline, which participates in two competitive reaction channels. Along channel I, 1-pyrazoline firstly tautomerises to a 2-pyrazoline, which by a proton abstraction and spontaneous loss of nitrite anion yields the final pyrazole, while along channel II, the thermal extrusion of the nitrogen molecule in 1-pyrazoline gives a very reactive diradical intermediate which quickly yields the final gem-…
Non-Classical Transformation of Benzendiazonium Hydrogen Sulfates. Access to 1,3-Dimethylisochromeno[4,3-c]pyrazol-5(1H)-one, a Potential Benzodiazep…
2013
The compound 2-((1,3-dimethyl-1H-pyrazol-5-yl)(methyl)carbamoyl)benzene-diazonium hydrogen sulfate (10) was reacted with copper sulfate and sodium chloride, in the presence of ascorbic acid as reducing agent, to afford a mixture of the chlorinated epimers 4′-chloro-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (18) and (19), the epimers 4′-hydroxy-2,2′,5′-trimethyl-2′,4′-dihydrospiro[isoindoline-1,3′-pyrazol]-3-one (20) and (21), and N-(1,3-dimethyl-1H-pyrazol-5-yl)benzamide (22). Under the foregoing conditions, diazonium salt 10 affords neither the 2-chloro-N-(1,3-dimethyl-1H-pyrazol-5-yl)-N-methylbenzamide (23) nor the tricyclic derivative 24, the classical products…
Fluorinated Pyrazoles and Indazoles
2014
The synthesis of fluorine containing pyrazoles has been boosted in the past decades due to the interesting properties that confer these building blocks in pharmaceutical and agricultural active ingredients. There are two main methods for the synthesis of fluorine-containing organic compounds, namely, the direct replacement of an atom or functional group such as diazo, hydroxyl, halogen or hydrogen by fluorine, and the modification of fluorine-containing building blocks. In the case of fluorinated pyrazoles the latter approach is the most commonly applied. This chapter deals primarily with the pivotal procedures that allow the preparation of fluoro- and fluoroalkyl- pyrazoles. Their benzocon…
Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat.
2009
The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB(1) receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB(1) antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21mgkg(-1)) exerted an anticonvulsant effect, significantly reduced by the pre-treatme…
Synthesis of alkyl-5,8-dimethyl-6-phenyl-5,6-dihydropyrazolo[3,4-f] [1,2,3,5]tetrazepin-4(3H)-ones of pharmaceutical interest
2006
The multistep synthesis of two pyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one derivatives, a new class of fused 1,2,3,5-tetrazepinones with potential antiproliferative activity, has been carried out. Owing to the instability of the above compounds, the last step of the synthesis was performed at -5/0 degrees C. The obtained tetrazepinones, when allowed to stand at r.t. for 24 h, afforded quantitatively 1-phenyl-3,6-dimethylpyrazolo [3,4-d][1,2,3] triazole.
Trichosporon beigelii pneumonia in a neutropenic patient.
1989
A case of pulmonary infection caused by Trichosporon beigelii is reported in an asthmatic patient undergoing steroid treatment who developed fever and lung infiltrates. Arthroconidia and blastoconidia were isolated from repeated sputum, bronchial aspirate and telescopic catheter samples. The infection coincided with neutropenia resulting from pyrazolone treatment. The response to amphotericin B treatment was favourable.
Functional, Biochemical, and Morphological Hepatobiliary Effects in Rats Chronically Exposed to a Steroidal Antiandrogen
1996
Abstract Yellow–brown deposits in intrahepatic bile ducts and portal macrophages were observed for male, but not female, Sprague–Dawley rats fed zanoterone, a steroidal antiandrogen, for ≥3 months. The lesion did not affect biliary canaliculi and was associated with changes of biliary epithelium, portal chronic inflammation, and bile duct proliferation. Deposit formation was assumed to be related to a gender-related anomaly in bile composition and/or flow. Therefore, the pathogenesis of the lesion was investigated in male, female, and orchiectomized rats. Hepatobiliary structure and function were evaluated after 3 months of treatment and 3 months of reversibility. Drug biliary disposition w…
Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration.
2014
The RAF family of kinases mediates RAS signaling, and RAF inhibitors can be effective for treating tumors with BRAF V600E mutant protein. However, RAF inhibitors paradoxically accelerate metastasis in RAS -mutant tumors and become ineffective in BRAF V600E tumors because of reactivation of downstream mitogen-activated protein kinase (MAPK) signaling. We found that the RAF isoform ARAF has an obligatory role in promoting MAPK activity and cell migration in a cell type–dependent manner. Knocking down ARAF prevented the activation of MAPK kinase 1 (MEK1) and extracellular signal–regulated kinase 1 and 2 (ERK1/2) and decreased the number of protrusions from tumor cell spheroids in three-dimensi…