Tag: M.W=300-350

Charwat, Verena published the artcileValidating the Arrhythmogenic Potential of High-, Intermediate-, and Low-Risk Drugs in a Human-Induced Pluripotent Stem Cell-Derived Cardiac Microphysiological System, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is ACS Pharmacology & Translational Science (2022), 5(8), 652-667, database is CAplus and MEDLINE.

Evaluation of arrhythmogenic drugs is required by regulatory agencies before any new compound can obtain market approval. Despite rigorous review, cardiac disorders remain the second most common cause for safety-related market withdrawal. On the other hand, false-pos. preclin. findings prohibit potentially beneficial candidates from moving forward in the development pipeline. Complex in vitro models using cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) have been identified as a useful tool that allows for rapid and cost-efficient screening of proarrhythmic drug risk. Currently available hiPSC-CM models employ simple two-dimensional (2D) culture formats with limited structural and functional relevance to the human heart muscle. Here, we present the use of our 3D cardiac microphysiol. system (MPS), composed of a hiPSC-derived heart micromuscle, as a platform for arrhythmia risk assessment. We employed two different hiPSC lines and tested seven drugs with known ion channel effects and known clin. risk: dofetilide and bepridil (high risk); amiodarone and terfenadine (intermediate risk); and nifedipine, mexiletine, and lidocaine (low risk). The cardiac MPS successfully predicted drug cardiotoxicity risks based on changes in action potential duration, beat waveform (i.e., shape), and occurrence of proarrhythmic events of healthy patient hiPSC lines in the absence of risk cofactors. We showcase examples where the cardiac MPS outperformed existing hiPSC-CM 2D models.

ACS Pharmacology & Translational Science published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Tauskela, Joseph S. published the artcileNeuroprotection against supra-lethal ′stroke in a dishâ€?insults by an anti-excitotoxic receptor antagonist cocktail, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Neurochemistry International (2022), 105381, database is CAplus and MEDLINE.

The goal of this study was to identify cocktails of drugs able to protect cultured rodent cortical neurons against increasing durations of oxygen-glucose deprivation (OGD). As expected, a cocktail composed of an NMDA and AMPA receptor antagonists and a voltage gated Ca²⁺ channel blocker (MK-801, CNQX and nifedipine, resp.) provided complete neuroprotection against mild OGD. Increasingly longer durations of OGD necessitated increasing the doses of MK-801 and CNQX, until these cocktails ultimately failed to provide neuroprotection against supra-lethal OGD, even at maximal drug concentrations Surprisingly, supplementation of any of these cocktails with blockers of TRPM7 channels for increasing OGD durations was not neuroprotective, unless these blockers possessed the ability to inhibit NMDA receptors. Supplementation of the maximally effective cocktail with other NMDA receptor antagonists augmented neuroprotection, suggesting insufficient NMDAR blockade by MK-801. Substitution of MK-801 in cocktails with high concentrations of a glycine site NMDA receptor antagonist caused the greatest improvements in neuroprotection, with the more potent SM-31900 superior to L689,560. Substitution of CQNX in cocktails with AMPA receptor antagonists at high concentrations also improved neuroprotection, particularly with the combination of SYM2206 and NBQX. The most neuroprotective cocktail was thus composed of SM-31900, SYM2206, NBQX, nifedipine and the antioxidant trolox. Thus, the cumulative properties of antagonist potency and concentration in a cocktail dictate neuroprotective efficacy. The central target of supra-lethal OGD is excitotoxicity, which must be blocked to the greatest extent possible to minimize ion influx.

Neurochemistry International published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C11H24O3, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Bohme, Horst published the artcileAddition compounds of triphenylboron and thioethers or tertiary amines, Product Details of C23H20BN, the publication is Zeitschrift fuer Anorganische und Allgemeine Chemie (1957), 160-3, database is CAplus.

cf. C.A. 51, 13739e. NaBPh₄ in MeOH with Me₂SBr₂ at 5-10° precipitated Me₂SBPh₃ (I), m. 180°; with (iso-Pr)₂S and Br at 0° (iso-Pr)₂SBPh₃, m. 165° (decomposition); with tetrahydrothiophene dibromide at -5-0° unstable (C₄H₈S)₂BPh₃, m. 132-3°; and with PhCH₂SBr₂ at -70° in a closed system, PhCH₂SBPh₃, decomposed at room temperature With pyridine dibromide at 0° and with Et₃NBr₂, the products were colorless C₅H₅NBPh₃, m. 214° (decomposition), and Et₃NBPh₃, m. 177-8°, resp. Ph₂SBPh₃ could not be prepared in this way, nor could the thioether addition compounds be prepared by direct combination. I was insoluble in H₂O and most organic solvents and was not attacked in the cold by dilute acids or alkalies.

Zeitschrift fuer Anorganische und Allgemeine Chemie published new progress about 971-66-4. 971-66-4 belongs to pyridine-derivatives, auxiliary class Pyridine,Benzene, name is Triphenyl(pyridin-1-ium-1-yl)borate, and the molecular formula is C23H20BN, Product Details of C23H20BN.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Largeau, Berenger published the artcileGabapentinoid-induced peripheral edema and acute heart failure: A translational study combining pharmacovigilance data and in vitro animal experiments, Category: pyridine-derivatives, the publication is Biomedicine & Pharmacotherapy (2022), 112807, database is CAplus and MEDLINE.

Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac. All cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between Jan. 1, 1994 and Apr. 30, 2020 were included to describe their onset patterns (e.g., time to onset). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries and on the electrophysiol. properties of rat ventricular cardiomyocytes. A total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57-85, range 32-95). The median time to onset were 23 days (IQR 10-54) and 17 days (IQR 3-30) for non-cardiogenic edema and acute heart failure, resp. Cardiogenic and non-cardiogenic peripheral edema occurred frequently after a dose escalation (27/45, 60%), and the course was rapidly favorable after discontinuation of gabapentinoid (median 7 days, IQR 5-13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Acute application of gabapentinoids had no significant effect on Cav1.2 currents of ventricular cardiomyocytes. Gabapentinoids can cause concentration-dependent peripheral edema of early onset. The primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Cav1.2 blockade under the exptl. conditions tested.

Biomedicine & Pharmacotherapy published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Lim, Xin Rui published the artcileFast voltage-dependent sodium (Na_v) currents are functionally expressed in mouse corpus cavernosum smooth muscle cells, Synthetic Route of 21829-25-4, the publication is British Journal of Pharmacology (2022), 179(5), 1082-1101, database is CAplus and MEDLINE.

Corpus cavernosum smooth muscle (CCSM) exhibits phasic contractions that are coordinated by ion channels. Mouse models are commonly used to study erectile dysfunction, but there are few published electrophysiol. studies of mouse CCSM. We describe the voltage-dependent sodium (NaV) currents in mouse CCSM and investigate their function. We used electrophysiol., pharmacol. and immunocytochem. methods to study the NaV currents in isolated CCSM cells from C57BL/6 mice. Tension measurements were carried out using crural sections of the corpus cavernosum in whole tissue. Fast, voltage-dependent, sodium currents in mouse CCSM were induced by depolarising steps. Steady-state activation and inactivation curves revealed a window current between -60 and -30 mV. Two populations of NaV currents, ′TTX-sensitiveâ€?and ′TTX-insensitiveâ€? were identified. TTX-sensitive currents showed 48% block with the NaV channel subtype-specific blockers ICA-121431 (NaV1.1-1.3), PF-05089771 (NaV1.7) and 4,9-anhydro-TTX (NaV1.6). TTX-insensitive currents were resistant to blockade by A803467, specific for NaV1.8 channels. Immunocytochem. confirmed expression of NaV1.5 and NaV1.4 in freshly dispersed CCSM cells. Veratridine, a NaV channel activator, reduced time-dependent inactivation of NaV currents and increased duration of evoked action potentials. Veratridine induced phasic contractions in CCSM strips, reversible with TTX and nifedipine but not KB-R7943. There are fast, voltage-dependent, sodium currents in mouse CCSM. Stimulation of these currents increased contractility of CCSM in vitro, suggesting an involvement in detumescence and potentially providing a clin. relevant target in erectile dysfunction. Further work will be necessary to define its role.

British Journal of Pharmacology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Synthetic Route of 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Roth, H. J. published the artcileRing formation and β-elimination by the reaction of triphenylboron on tertiary amines, SDS of cas: 971-66-4, the publication is Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft (1964), 297(12), 766-72, database is CAplus.

Tertiary amino alcs. and tertiary amines of the Mannich-base types were treated with Ph₃B to yield a boron-containing heterocyclic N compound and elimination of an unsaturated moiety. Freshly-prepared, moist Ph₃B (3 g.) in 5 ml. EtOH was added to 2.05 g. 1-phenyl-2-piperidino-l-ethanol in 20 ml. EtOH, and the mixture heated several min. on a steam bath and cooled to give 81% the triphenylboroxazolidine (I), m. 190-1°. N-Methyl-L-ephedrin (1.8 g.), and 1.1 g. 1-phenyl-3-piperidino-1-propanol gave 89% II, m. 207-8°, and 78% III, m. 198-200°, resp. Concentrated EtOH solutions of Et₃N and Ph₃B (stoichiometric equivalents) were allowed to react in the cold and kept a short time to give quant. B,B,B-triphenyl-N,N,N-triethylaminoborane, m. 108-12°. B,B,B-Triphenyl-1-ethylpiperidineborane, m. 114-16°, was similarly prepared from 1-ethylpiperidine. The pyridinyl analog C₅H₅NBPh₃, m. 214-15° (decomposition), was prepared from pyridine and Ph₃B. A solution of 3 g. Ph₃B in 10 ml. absolute EtOH was added to 1.56 g. 2-piperidinomethylcyclohexanone (Mannich base) in 10 ml. EtOH and the solution was evaporated to half its volume on a steam bath and cooled several hrs. to precipitate 85% B,B,B-triphenylpiperidineborane (IV), m. 213-14°. The mother liquor was evaporated in vacuo to a sirup which was dissolved in glacial HOAc and the solution treated with 1 ml. HCl to give 88% the hydrated dimeric cyclohexanone (V), m. 153°. Ph₃B (1.5 g.) in 5 ml. EtOH was added to 5 ml. of an EtOH solution of 2-diethylaminomethylphenol, prepared from 1 g. of the HCl salt by usual procedures. The precipitate, C₄₆H₅₀B₂N₂O, m. 169° (EtOH-acetone). No phenolic, other OH, or NH groups were present, as shown by ir. A similar reaction was carried out with 2-piperidinomethyl-4-methylphenol and Ph₃B. The compound, C₅₀H₅₄B₂N₂O, m. 230° (decomposition), likewise showed no OH or NH groups. IV was obtained by similar reaction of piperidinomethylbenzamide or piperidinomethylsalicylamide with Ph₃B along with BzNH₂, or salicylamide, resp.

Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft published new progress about 971-66-4. 971-66-4 belongs to pyridine-derivatives, auxiliary class Pyridine,Benzene, name is Triphenyl(pyridin-1-ium-1-yl)borate, and the molecular formula is C23H20BN, SDS of cas: 971-66-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Hawlitschek, Christina published the artcileAntihypertensive and cardioprotective effects of different monotherapies and combination therapies in young spontaneously hypertensive rats – A pilot study, Product Details of C17H18N2O6, the publication is Saudi Journal of Biological Sciences (2022), 29(1), 339-345, database is CAplus and MEDLINE.

Spontaneously hypertensive rats (SHR) are an established animal model for antihypertensive treatment. The aim of this pilot study was a systematic search for two lines of antihypertensive treatment – a monotherapy and a combination of two drugs – to be applied in a future study on old SHR. Originally, representatives of three drug classes recommended for antihypertensive therapy in humans should be applied, namely captopril (CAP) as an antagonist of the renin-angiotensin-aldosterone system, nifedipine (NIF) as calcium channel blocker and propranolol (PROP) as β-adrenergic blocker. As we observed that PROP had been poorly ingested, all groups with PROP therapy were excluded from the study. CAP (60 mg kg^-1 d^-1), NIF (10 mg kg^-1 d^-1) or both were administered orally to seven-week-old SHR over 3 wk. A further group of SHR received no treatment (SHR/CTRL). Age-matched normotensive Wistar-Kyoto rats served as normotensive controls. We examined the effect of the antihypertensive therapies on systolic blood pressure, heart weight and on histol. and biochem. markers of cardiac hypertrophy and fibrosis. CAP proved to be the most effective treatment reducing blood pressure and relative heart weight significantly compared to SHR/CTRL without reaching normotensive values. Beginning cardiac fibrosis observed in SHR/CTRL was completely abrogated with CAP treatment. Similar effects were achieved with a combination of CAP and NIF. CAP as monotherapy and CAP + NIF as combination therapy were chosen for the forthcoming study on old SHR.

Saudi Journal of Biological Sciences published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Product Details of C17H18N2O6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Yao, Xin published the artcileSurfactants Accelerate Crystallization of Amorphous Nifedipine by Similar Enhancement of Nucleation and Growth Independent of Hydrophilic-Lipophilic Balance, Computed Properties of 21829-25-4, the publication is Molecular Pharmaceutics (2022), 19(7), 2343-2350, database is CAplus and MEDLINE.

Amorphous formulations, increasingly employed to deliver poorly soluble drugs, generally contain surfactants to improve wetting and dissolution These surfactants are often liquids and can potentially increase the mobility of the drug and reduce its stability, but little is known about this effect. Here we investigate the effect of four common nonionic surfactants (Tween 80, Span 80, Triton X-100, and Poloxamer 407) on the crystallization of amorphous nifedipine (NIF). We find that the surfactants significantly enhance the rates of crystal nucleation and growth even at low concentrations, by up to 2 orders of magnitude at 10 wt %. The surfactants tested show similar enhancement effects independent of their structural details and hydrophilic-lipophilic balance (HLB), suggesting that surfactant adsorption at solid/liquid interfaces does not play a major role in crystal nucleation and growth. Importantly, the surfactants accelerate crystal nucleation and growth by a similar factor. This result mirrors the previous finding that a polymer dopant in a mol. glass-former causes similar slowdown of nucleation and growth. These results indicate that nucleation and growth in a deeply supercooled liquid are both mobility-limited, and a dopant mainly functions as a mobility modifier (enhancer or suppressor depending on the dopant). The common surfactants tested are all mobility enhancers and destabilize the amorphous drug, and this neg. effect must be managed using stabilizers such as polymers. The effect of surfactants on nucleation can be predicted from the effect on crystal growth and the crystallization kinetics of the pure system, using the same principle previously established for drug-polymer systems. We show how the independently measured nucleation and growth rates enable predictions of the overall crystallization rates.

Molecular Pharmaceutics published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C9H7NO2, Computed Properties of 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Lazcano-Perez, Fernando published the artcileA Sea Anemone Lebrunia neglecta Venom Fraction Decreases Boar Sperm Cells Capacitation: Possible Involvement of HVA Calcium Channels, Computed Properties of 21829-25-4, the publication is Toxins (2022), 14(4), 261, database is CAplus and MEDLINE.

Sea anemones produce venoms characterized by a complex mixture of low mol. weight compounds, proteins and peptides acting on voltage-gated ion channels. Mammal sperm cells, like neurons, are characterized by their ion channels. Calcium channels seem to be implicated in pivotal roles such as motility and capacitation. In this study, we evaluated the effect of a low mol. weight fraction from the venom of the sea anemone Lebrunia neglecta on boar sperm cells and in HVA calcium channels from rat chromaffin cells. Spermatozoa viability seemed unaffected by the fraction whereas motility and sperm capacitation were notoriously impaired. The sea anemone fraction inhibited the HVA calcium current with partial recovery and no changes in chromaffin cells’ current kinetics and current-voltage relationship. These findings might be relevant to the pharmacol. characterization of cnidarian venoms and toxins on voltage-gated calcium channels.

Toxins published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Computed Properties of 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Gawri, Rahul published the artcileThe anabolic effect of inorganic polyphosphate on chondrocytes is mediated by calcium signalling, Synthetic Route of 21829-25-4, the publication is Journal of Orthopaedic Research (2022), 40(2), 310-322, database is CAplus and MEDLINE.

Inorganic polyphosphates (polyP) are polymers composed of phosphate residues linked by energy-rich phosphoanhydride bonds. As polyP can bind calcium, the hypothesis of this study is that polyP enters chondrocytes and exerts its anabolic effect by calcium influx through calcium channels. PolyP treatment of cartilage tissue formed in 3D culture by bovine chondrocytes showed an increase in proteoglycan accumulation but only when calcium was also present at a concentration of 1.5 mM. This anabolic effect could be prevented by treatment with either ethylene glycol-bis(β-aminoethyl ether)-N,N,N,N-tetraacetic acid or the calcium channel inhibitors gadolinium and nifedipine. Calcium and polyP cotreatment of chondrocytes in monolayer culture resulted in calcium oscillations that were polyP chain length specific and were inhibited by gadolinium and nifedipine. The calcium influx resulted in increased gene expression of sox9, collagen type II, and aggrecan which was prevented by treatment with either calphostin, an inhibitor of protein kinase C, and W7, an inhibitor of calmodulin; suggesting activation of the protein kinase C-calmodulin pathway. Tracing studies using 4,6-diamidino-2-phenylindole, Mitotracker Red, and/or Fura-AM staining showed that polyP was detected in the nucleus, mitochondria, and intracellular vacuoles suggesting that polyP may also enter the cell. PolyP colocalizes with calcium in mitochondria. This study demonstrates that polyP requires the influx of calcium to regulate chondrocyte matrix production, likely via activating calcium signaling. These findings identify the mechanism regulating the anabolic effect of polyP in chondrocytes which will help in its clin. translation into a therapeutic agent for cartilage repair.

Journal of Orthopaedic Research published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Synthetic Route of 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem