Tag: 407.0355

In Vitro screening for seizure liability using microelectrode array technology was written by Bradley, Jenifer A.;Luithardt, Harry H.;Metea, Monica R.;Strock, Christopher J.. And the article was included in Toxicological Sciences in 2018.Quality Control of Thioridazine hydrochloride This article mentions the following:

Drug-induced seizure liabilities produce significant compound attrition during drug discovery. Currently available in vitro cytotoxicity assays cannot predict all toxicity mechanisms due to the failure of these assays to predict sublethal target-specific electrophysiol. liabilities. Identification of seizurogenic and other electrophysiol. effects at early stages of the drug development process is important to ensure that safe candidate compounds can be developed while chem. is taking place, long before these liabilities are discovered in costly preclin. in vivo studies. The development of a high throughput and reliable in vitro assay to screen compounds for seizure liabilities would de-risk compounds significantly earlier in the drug discovery process and with greater dependability. Here the authors describe a method for screening compounds that utilizes rat cortical neurons plated onto multiwell microelectrode array plates to identify compounds that cause neurophysiol. disruptions. Changes in 12 electrophysiol. parameters (spike train descriptors) were measured after application of known seizurogenic compounds and the response pattern was mapped relative to neg. controls, vehicle control and neurotoxic controls. Twenty chems. with a variety of therapeutic indications and targets, including GABAA antagonists, glycine receptor antagonists, ion channel blockers, muscarinic agonist, δ-opioid receptor agonist, dopaminergic D2/adrenergic receptor blocker and nonsteroidal anti-inflammatory drugs, were tested to assess this system. Sixteen of the seventeen seizurogenic/neurotoxic compounds tested pos. for seizure liability or neurotoxicity, moreover, different endpoint response patterns for firing rate, burst characteristics and synchrony that distinguished the chems. into groups relating to target and seizurogenic response emerged from the data. The neg. and vehicle control compounds had no effect on neural activity. In conclusion, the multiwell microelectrode array platform using cryopreserved rat cortical neurons is a highly effective high throughput method for reliably screening seizure liabilities within an early de-risking drug development paradigm. In the experiment, the researchers used many compounds, for example, Thioridazine hydrochloride (cas: 130-61-0Quality Control of Thioridazine hydrochloride).

Thioridazine hydrochloride (cas: 130-61-0) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Quality Control of Thioridazine hydrochloride

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Novel insight into antimicrobial resistance and sensitivity phenotypes associated to qac and norA genotypes in Staphylococcus aureus was written by Marchi, Emmanuela;Furi, Leonardo;Arioli, Stefania;Morrissey, Ian;Di Lorenzo, Valeria;Mora, Diego;Giovannetti, Luciana;Oggioni, Marco Rinaldo;Viti, Carlo. And the article was included in Microbiological Research in 2015.COA of Formula: C21H27ClN2S2 This article mentions the following:

Staphylococcus aureus strains harboring QacA, QacB, QacC, QacG transporters and norA promoter up-regulating mutations were characterized by phenotype microarray (PM), standard methods for susceptibility testing, and ethidium bromide efflux assays, in order to increase knowledge on phenotypes associated to efflux pumps and their substrates. PM data and standard susceptibility testing lead to the identification of new potential efflux targets, such as guanidine hydrochloride or 8-hydroxyquinoline for QacA and QacC pumps, resp. The identification of compounds to which the presence of efflux pumps induced increased susceptibility opens new perspectives for potential adjunct anti-resistance treatment (i.e. strains bearing QacB transporters showed increased susceptibility to thioridazine, amitriptyline and orphenadrine). Although the tested isolates were characterized by high degree of heterogeneity, a hallmark of clin. isolates, direct ethidium bromide efflux assays were effective in highlighting differences in efflux efficiency among strains. These data add to characterization of substrate specificity in the different classes of staphylococcal multidrug efflux systems conferring specific substrate profiles and efflux features to each of them. In the experiment, the researchers used many compounds, for example, Thioridazine hydrochloride (cas: 130-61-0COA of Formula: C21H27ClN2S2).

Thioridazine hydrochloride (cas: 130-61-0) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.COA of Formula: C21H27ClN2S2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Spectral methods in the analysis of phenothiazine derivatives was written by Shchepochkina, O. Yu.;Prokofyeva, V. I.. And the article was included in Farmatsiya (Moscow, Russian Federation) in 2012.Product Details of 130-61-0 This article mentions the following:

The methods of mass spectrometry and IR spectrometry of impaired complete internal reflection may be used for the rapid quality control of structurally related drugs of phenothiazine derivatives In the experiment, the researchers used many compounds, for example, Thioridazine hydrochloride (cas: 130-61-0Product Details of 130-61-0).

Thioridazine hydrochloride (cas: 130-61-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.Product Details of 130-61-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Thioridazine reverts the phenotype in cellular and Drosophila models of amyotrophic lateral sclerosis by enhancing TDP-43 aggregate clearance was written by Cragnaz, Lucia;Spinelli, Greta;De Conti, Laura;Bureau, Emilie A.;Brownlees, Janet;Feiguin, Fabian;Romano, Valentina;Skoko, Natasa;Klima, Raffaella;Kettleborough, Catherine A.;Baralle, Francisco E.;Baralle, Marco. And the article was included in Neurobiology of Disease in 2021.Synthetic Route of C21H27ClN2S2 This article mentions the following:

Brain inclusions mainly composed of misfolded and aggregated TAR DNA binding protein 43 (TDP-43), are characteristic hallmarks of amyotrophic lateral sclerosis (ALS). Irresp. of the role played by the inclusions, their reduction represents an important therapeutic pathway that is worth exploring. Their removal can either lead to the recovery of TDP-43 function by removing the self-templating conformers that sequester the protein in the inclusions, and/or eliminate any potential intrinsic toxicity of the aggregates. The model demonstrated efficient aggregation of endogenous TDP-43, and concomitant loss of its splicing regulation function. We provided a proof-of-principle for its eventual use in high-throughput screening using compounds of the tricyclic family and showed that recovery of TDP-43 function can be achieved by the enhanced removal of TDP-43 aggregates by these compounds We observed that the degradation of the aggregates occurs independent of the autophagy pathway beyond autophagosome-lysosome fusion, but requires a functional proteasome pathway. The in vivo translational effect of the cellular model was tested with two of these compounds in a Drosophila model expressing a construct analogous to the cellular model, where thioridazine significantly improved the locomotive defect. This study also highlights the importance of a two-stage, in vitro and in vivo model system to cross-check the search for small mols. that can clear TDP-43 aggregates in TDP-43 proteinopathies. In the experiment, the researchers used many compounds, for example, Thioridazine hydrochloride (cas: 130-61-0Synthetic Route of C21H27ClN2S2).

Thioridazine hydrochloride (cas: 130-61-0) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N–H bond in an axial position, and the other in an equatorial position.Synthetic Route of C21H27ClN2S2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem