Search results for " Pyrazole"

Central nervous system involvement in ALK-rearranged NSCLC : promising strategies to overcome crizotinib resistance

2016

ABSTRACT: Introduction: ALK rearranged Non Small Cell Lung Cancers (NSCLCs) represent a distinct subgroup of patients with peculiar clinic-pathological features. These patients exhibit dramatic responses when treated with the ALK tyrosine kinase inhibitor Crizotinib, albeit Central Nervous System (CNS) activity is much less impressive than that observed against extracranial lesions. CNS involvement has become increasingly observed in these patients, given their prolonged survival. Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition. Areas covered: The CNS activity of Crizotinib and novel generation ALK inhibito…

COVID-19 in Philadelphia-negative myeloproliferative disorders: a GIMEMA survey

2020

Synthesis and in vitro antimicrobial activities of new (cyano-NNO-azoxy) pyrazole derivatives

2011

The antibacterial and antifungal activity of a series of products, in which the 1,5-dimethyl-4-(cyano- NNO-azoxy)pyrazol-3-yl and 1,3-dimethyl-4-(cyano-NNO-azoxy)pyrazol-5-yl moieties were linked to pyridine, pyrazole, isoxazole, thiophene and the furan ring, were examined. No molecule displayed activity against the Gram-negative bacteria tested. Conversely, some compounds displayed activity against two Staphylococcus aureus strains, including the methicillin resistant strain. All compounds displayed interesting antifungal activity, the most active compound of the series being the thiophene derivative 7a. This compound’s activity against Candida krusei and Candida glabrata (MIC = 0.25 and 0…

Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice.

2015

International audience; The endocannabinoid system (ECS) is associated with an alteration of glucose homeostasis dependent on cannabinoid receptor-1 (CB1R) activation. However, very little information is available concerning the consequences of ECS activation on intestinal glucose absorption. Mice were injected intraperitoneally with anandamide, an endocannabinoid binding both CB1R and CB2R. We measured plasma glucose and xylose appearance after oral loading, gastrointestinal motility, and glucose transepithelial transport using the everted sac method. Anandamide improved hyperglycemia after oral glucose charge whereas glucose clearance and insulin sensitivity were impaired, pointing out so…

Pyrazole[3,4-d]pyrimidine derivatives loaded into halloysite as potential CDK inhibitors

2021

Uncontrolled cell proliferation is a hallmark of cancer as a result of rapid and deregulated progression through the cell cycle. The inhibition of cyclin-dependent kinases (CDKs) activities is a promising therapeutic strategy to block cell cycle of tumor cells. In this work we reported a new example of nanocomposites based on halloysite nanotubes (HNTs)/pyrazolo[3,4-d]pyrimidine derivatives (Si306 and Si113) as anticancer agents and CDK inhibitors. HNTs/Si306 and HNTs/Si113 nanocomposites were synthesized and characterized. The release kinetics were also investigated. Antitumoral activity was evaluated on three cancer cell lines (HeLa, MDA-MB-231 and HCT116) and the effects on cell cycle ar…

Lack of nucleophilic addition in the isoxazole and pyrazole diketone modified analogs of curcumin; implications for their antitumor and chemosensitiz…

2009

Curcumin (CUR) can be considered as a good lead compound for the design of new anticancer drugs. Further, structure-activity relationship studies may clarify the importance of the redox activities in the antitumor effects of the drug. We have elaborated the alpha,beta-unsaturated 1,3-diketone moiety of CUR into the isoxazole (ISO) and pyrazole (PYR) derivatives. These derivatives should be much less prone to nucleophilic addition than CUR and benzyl mercaptan addition analyses showed that indeed they do not form isolable conjugated products. When compared with CUR, ISO and PYR exhibited increased cell growth inhibitory and pro-apoptotic effects in liver cancer HA22T/VGH cells as well as in …

The synthesis of fluorinated heteroaromatic compounds. Part 2. Five-membered rings with two heteroatoms. A review

2007

Synthesis, and Molecular Structure Investigations of a New s-Triazine Derivatives Incorporating Pyrazole/Piperidine/Aniline Moieties

2021

In this work, we synthesized two new s-triazine incorporates pyrazole/piperidine/aniline moieties. Molecular structure investigations in the light of X-ray crystallography combined with Hirshfeld and DFT calculations were presented. Intermolecular interactions controlling the molecular packing of 4-(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-6-(piperidin-1-yl)-1,3,5-triazin-2-amine; 5a and N-(4-bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-amine; 5b were analyzed using Hirshfeld calculations. The most dominant interactions are the H...H, N...H and H...C contacts in both compounds. The N...H and H...C interactions in 5a and the N...H, Br...H and H...H interacti…

Unexpected synthesis by a non-classical Pschorr reaction of 3,5-dimethyl-1-phenyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one, with binding affinity…

2014

The reaction of the diazonium salt 12 derived from N-(2-aminophenyl)-N,3-dimethyl-1-phenyl-1H-pyrazole-5-carboxamide with copper sulfate and sodium chloride in the presence of ascorbic acid afforded the unexpected products 3,5-dimethyl-1-phenyl-1,5-dihydro-4H-pyrazolo[4,3-c]¬quinolin-4-one (17) and N-methyl-2-(3-methyl-1-phenyl-1H-pyrazol-5-yl)aniline (19), accompanied by N-(2-chlorophenyl)-N,3-dimethyl-1-phenyl-1H-pyrazole-5-carboxamide (18). Products 17 and 19 are formed via a non-classical Pschorr reaction. The formation of 17 represents an alternative to the literature synthesis of this biologically active compound. The molecular structure of 18 was confirmed by single-crystal X-ray ana…

New 2-Methoxy Acetylenic Acids and Pyrazole Alkaloids from the Marine Sponge Cinachyrella sp.

2017

Three new 2-methoxy acetylenic acids (1–3) and a known derivative (4), in addition to three new natural pyrazole alkaloids (5–7) were isolated from an Indonesian marine sponge of the genus Cinachyrella. Compounds 5 and 6 have previously been reported as synthetic compounds. The structures of the new compounds were established on the basis of one- and two-dimensional NMR spectroscopy as well as by mass spectrometric data. The absolute configuration of the new acetylenic acid derivatives (1–3) was established by ECD spectroscopy. All isolated compounds were evaluated for their cytotoxicity against L5178Y mouse lymphoma cells. Compounds 1–4 exhibited strong activity with an IC50 value of 0.3 µ…