52980-28-6Relevant articles and documents
Conformational restriction leading to a selective CB2 cannabinoid receptor agonist orally active against colitis
El Bakali, Jamal,Muccioli, Giulio G.,Body-Malapel, Mathilde,Djouina, Madjid,Klupsch, Frédérique,Ghinet, Alina,Barczyk, Amélie,Renault, Nicolas,Chavatte, Philippe,Desreumaux, Pierre,Lambert, Didier M.,Millet, Régis
, p. 198 - 203 (2015)
The CB2 cannabinoid receptor has been implicated in the regulation of intestinal inflammation. Following on from the promising activity of a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide, we developed constrained analogues based on a 2H-pyrazolo[4,3-c]quinolin-3(5H)-one scaffold, with improved affinity for the hCB2 receptor and had very high selectivity over the hCB1 receptor. Importantly, the lead of this series (26, hCB2: Ki = 0.39 nM, hCB1: Ki > 3000 nM) was found to protect mice against experimental colitis after oral administration.
The concept of hybrid molecules of tacrine and benzyl quinolone carboxylic acid (BQCA) as multifunctional agents for Alzheimer's disease
Hepnarova,Korabecny,Matouskova,Jost,Muckova,Hrabinova,Vykoukalova,Kerhartova,Kucera,Dolezal,Nepovimova,Spilovska,Mezeiova,Pham,Jun,Staud,Kaping,Kuca,Soukup
, p. 292 - 306 (2018)
Novel tacrine-benzyl quinolone carboxylic acid (tacrine-BQCA) hybrids were designed based on multi-target directed ligands (MTLDs) paradigm, synthesized and evaluated in vitro as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). Tacrine moiety is represented herein as 7-methoxytacrine, 6-chlorotacrine or unsubstituted tacrine forming three different families of seven members, i.e. 21 compounds in overall. Introducing BQCA, a positive modulator of M1 muscarinic acetylcholine receptors (mAChRs), the action of novel compounds on M1 mAChRs was evaluated via Fluo-4 NW assay on the Chinese hamster ovarian (CHO-M1WT2) cell line. All the novel tacrine-BQCA hybrids were able to block the action of hAChE and hBChE in micromolar to nanomolar range. The hAChE kinetic profile of 5p was found to be mixed-type which is consistent with our docking experiments. Moreover, selected ligands were assessed for their potential hepatotoxicity on HepG2 cell line and presumable permeation through the blood-brain barrier by PAMPA assay. Expected agonistic profile towards M1 mAChRs delivered by BQCA moiety was not confirmed. From all the hybrids, 5o can be highlighted as non-selective cholinesterase inhibitor (hAChE IC50 = 74.5 nM; hBChE IC50 = 83.3 nM) with micromolar antagonistic activity towards M1 mAChR (IC50 = 4.23 μM). A non-selective pattern of cholinesterase inhibition is likely to be valuable during the onset as well as later stages of AD.
Intermediate compound for synthesizing nitrogen-containing heterocyclic ring and preparation method and application thereof
-
, (2021/04/21)
The invention relates to an intermediate compound for synthesizing a nitrogen-containing heterocyclic ring and a preparation method and application thereof, and the chemical structural formula of the intermediate compound is as follows: amide, azodicarboxylate and carboxylic acid are used as raw materials, and under the action of a catalyst, the intermediate compound is prepared through direct carbon-hydrogen bond bifunctionalization synthesis. Compared with the prior art, the method has the advantages that the intermediate compound is synthesized through the direct carbon-hydrogen bond bifunctionalization process, the substrate can be expanded in a large range, different nitrogen-containing heterocycles can be obtained through different subsequent treatment, the structural diversity is achieved, and a new method is provided for industrial production of the nitrogen-containing heterocycles.
Quinolone-N-acylhydrazone hybrids as potent Zika and Chikungunya virus inhibitors
Marra, Roberta K.F.,Kümmerle, Arthur E.,Guedes, Guilherme P.,Barros, Caroline de S.,Gomes, Rafaela S.P.,Cirne-Santos, Claudio C.,Paix?o, Izabel Christina N.P.,Neves, Amanda P.
, (2019/12/25)
This work reports the synthesis of quinolone-N-acylhydrazone hybrids, namely 6-R-N'-(2-hydxoxybenzylidene)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide (R = H: 5a, F: 5b, Cl: 5c and Br: 5d), which exhibited excellent activity against arbovirus Zika (ZIKV) and Chikungunya (CHIKV). In vitro screening towards ZIKV and CHIKV inhibition revealed that all substances have significant antiviral activity, most of them being more potent than standard Ribavirin (5a-d: EC50 = 0.75–0.81 μM, Ribavirin: EC50 = 3.95 μM for ZIKV and 5a-d: 1.16–2.85 μM, Ribavirin: EC50 = 2.42 μM for CHIKV). The quinolone-N-acylhydrazone hybrids were non-toxic against Vero cells, in which compounds 5c and 5d showed the best selectivities (SI = 1410 and 630 against ZIKV and CHIKV, respectively). Antiviral activity was identified by inhibition of viral RNA production in a dose-dependent manner. In the evaluation of the time of addition of the compounds, we observed that 5b and 5c remain with strong effect even in the addition for 12 h after infection. The above results indicate that quinolone-N-acylhydrazones represent a new and promising class to be further investigated as anti-ZIKV and anti-CHIKV agents.
