Tag: M.W=200-350

Micucci, Matteo published the artcileNeutral/negative α1-AR antagonists and calcium channel blockers at comparison in functional tests on guinea-pig smooth muscle and myocardium, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is smooth muscle myocardium left atrium benzodioxane alpha1 AR antagonist; Calcium channel blockers; Inverse agonism; WB4101; alpha1-antagonists.

In the present exptl. approach, we compared the activity of three calcium channel blockers (nifedipine, diltiazem and verapamil) and of three potent benzodioxane-based α1-AR antagonists, differing for subtype selectivity and inverse agonist properties, in producing smooth muscle relaxation and neg. inotropy under the same test conditions. We selected, as benzodioxane derivatives, (S)-WB4101, inverse agonist with slight α1A/α1B-α1D AR selectivity, and two previously developed analogs. Both of these are potent antagonists at α1D-AR, that is the α1- AR subtype suspected of the highest susceptibility to inverse agonists for its high degree of basal activity, but only one is inverse agonist. We found that all the three benzodioxane-related α1-AR antagonists have significant intrinsic relaxant activity on non-vascular smooth muscle and moderate neg. inotropic effect, while they do not relax aorta. Their potency is always lower than that of three calcium channel blockers. Intrinsic myorelaxant and neg. inotropic activity of the three benzodioxane-based α1-AR antagonist is related neither to a particular profile of α1-AR subtype selectivity nor to whether or not being an inverse agonist, but it parallels the calcium antagonists effects indicating a direct interaction of the three α1-AR antagonists with L-type Ca2+ channels.

Pharmacological Reports published new progress about Adrenoceptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Gonzalez-Montelongo, Maria del Carmen published the artcileNeuropeptide Y facilitates P2X1 receptor-dependent vasoconstriction via Y1 receptor activation in small mesenteric arteries during sympathetic neurogenic responses, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Neuropeptide Y P2X1 Suramin vasoconstriction NF449 Calcium channel; Calcium channel; Neurogenic; Neuropeptide Y; P2X receptors; Vasoconstriction.

Investigate effect of NPY on P2X1-dependent vasoconstriction in mesenteric arteries. Suramin or P2X1 antagonist NF449 abolished α,β-meATP evoked vasoconstrictions. Y1 receptor inhibition (BIBO3304) reversed NPY facilitation of α,β-meATP-evoked vasoconstriction. L-type Ca2+ channel antagonism (nifedipine) had no effect on α,β-meATP-evoked vasoconstrictions, but completely reversed NPY. Elec. field stimulation evoked sympathetic neurogenic vasoconstriction. Neurogenic responses dependent upon dual α1-adrenergic (prazosin) and P2X1 (NF449) receptor activation. Y1 receptor antagonism reduced neurogenic vasoconstriction. Isolation of P2X1 component by α1-adrenergic blockade faciliatory effects of Y1 receptor activation explored. Y1 receptor antagonism reduced P2X1 receptor component during neurogenic vasoconstriction. α1-adrenergic and P2X1 receptors post-junctional receptors during sympathetic neurogenic vasoconstriction in mesenteric arteries. Identified that NPY lacks direct vasoconstrictor effect in mesenteric arteries but can vasoconstriction by enhancing activity of P2X1, activation by exogenous agonists or during sympathetic nerve stimulation. Mechanism of P2X1 facilitation by NPY involved activation of NPY Y1 receptor and L-type Ca2+ channel.

Vascular Pharmacology published new progress about Adrenoceptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Pang, Yefei published the artcileRole of mPRα (PAQR7) in progesterone-induced Ca2+ decrease in human vascular smooth muscle cells, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is progesterone mPRalpha PAQR7 umbilical artery vascular smooth muscle cell; VSMC; calcium; mPRα; signaling.

We have shown progesterone exerts a direct action on vascular smooth muscle cells (VSMCs) to induce relaxation through activation of membrane progesterone receptor alpha (mPRα)-dependent signaling pathways, but information on downstream events is lacking. Progesterone-induced changes in calcium concentrations in human umbilical artery VSMCs through mPRα-dependent signaling pathways and the involvement of Rho/ROCK signaling were investigated. Acute in vitro treatment with progesterone and the selective mPRα agonist 10-ethenyl-19-norprogesterone (Org OD 02-0, 02-0) blocked the rapid prostaglandin F2α-induced calcium increase. This inhibitory progesterone action was prevented by knockdown of mPRα but not by knockdown of the nuclear progesterone receptor, confirming it is mediated through mPRα. The decrease in calcium levels and VSMC relaxation were abolished by treatment with FPL64176 (Ca2+ channel activator), supporting a role for decreased calcium channel activity in this progesterone action. The reduction in calcium was attenuated by pretreatment with pertussis toxin, 8-Bromo-cAMP and forskolin, indicating this progesterone action involves activation of an inhibitory G protein and downregulation of cAMP-dependent signaling. Inhibition of MAPK and Akt signaling with PD98059 and ML-9, resp., prevented the progesteroneinduced calcium concentration decrease and VSMC relaxation. Forskolin decreased progesterone-induced MAPK and Akt phosphorylation which suggests that the cAMP status influences calcium levels indirectly through altering these signaling pathways. Progesterone and 02-0 treatments decreased RhoA activity and ROCK phosphorylation, which suggests that reduced RhoA/ROCK signaling is a component of the mPRα-mediated progesterone actions on VSMCs. The results suggest that progesterone induces VSMC relaxation by reducing cellular calcium levels through mPRα-induced alterations in multiple signaling pathways.

Journal of Molecular Endocrinology published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ponnusamy, Parasuraman published the artcileMolecular modeling and molecular docking studies on the derivatives of 1,4-dihydropyridine towards Cytochrome P450 for structure based drug design, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is dihydropyridine14 cytochromeP450 cardioprotective agent cardiovascular disease.

Protein-ligand interactions are instrumental for the structure based drug design in the human health care systems to cure problematic diseases especially cardiovascular diseases. To treat the cardiovascular disease, the Calcium Channel Blockers (CCBs) such as 1,4-dihydropyridine (DHP) derivatives have been used in a effective way. In this study, the series of nine DHP derivatives (DHP I-DHP IX) have been docked in the binding pocket of Cytochrome P 450. Among these nine DHP-P 450 complexes, the DHP-III [N-(4-methoxy phenyl)-3,5 dicarbethoxy-2,6-dimethyl-4-(3-nitro phenyl)-1,4-Dihydropyridine] and DHP-VI [2,6-Dimethyl-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid di-Et ester] exhibits lowest binding energy of -11.89 and -11.14 kcal/mol resp., which indicates that these two mols. strongly bind to the binding pocket amino acid residues of P 450 when compared with the other DHP derivatives An anal. of hydrogen bonding interactions shows that Arg212 is essential for high affinity ligand binding. Subsequently, the C(8) atom in the DHPIII-P 450 complex forms strong hydrophobic interaction with Ala3l0 while the C(8) atom in the DHPVI-P 450 complex makes strong hydrogen bonding interaction with Arg212. Comparatively, the C(8) atom was not interacting with neighboring amino acids in other DHP – P 450 complexes. Further, in the DHPIII-P 450 complex, the ligand makes more hydrophobic interactions with the amino acids of Ala370, Phe304, Phe213, Ile369, Met371 and Ser119. The DHP-VI mol. forms strong hydrogen bonding interactions with P 450 whereas in the amlodipine-P 450 complex, amlodipine reduces the better chance of making hydrogen bonding interactions due to the absence of N-Ph ring. Thus the binding of two DHP derivatives such as DHP-III and DHP-VI are found to be higher and exhibit increased binding affinities towards Cytochrome P 450. These two mols. may be considered as a drug candidate for the treatment of cardio vascular diseases as well as in vivo and in vitro studies in future.

Materials Today: Proceedings published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Modvig, Ida M. published the artcilePeptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors, Application In Synthesis of 21829-25-4, the main research area is GLP1 glucagon like peptide1 calcium sensing receptor review; Amino acid sensing; Calcium-Sensing Receptor; glucagon-like peptide 1; peptide transporter 1; peptone.

Protein intake robustly stimulates the secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1) but the mol. mechanisms involved are not well understood. In particular, it is unknown whether proteins stimulate secretion by activation of luminal or basolateral sensors. We characterized the mechanisms using a physiol. relevant model – the isolated perfused proximal rat small intestine. Intraluminal protein hydrolyzates derived from meat (peptone; 50 mg/mL) increased GLP-1 secretion 2.3-fold (from a basal secretion of 110 ± 28 fmol/min). The sensory mechanisms underlying the response depended on di/tripeptide uptake through Peptide Transporter 1 (PepT1) and subsequent basolateral activation of the amino acid sensing receptor, Calcium-Sensing Receptor (CaSR), since inhibition of PepT1 as well as CaSR both attenuated the peptone-induced GLP-1 response. Supporting this, intraluminal peptones were absorbed efficiently by the perfused intestine (resulting in increased amino acid concentrations in the venous effluent) and infusion of amino acids robustly stimulated GLP-1 secretion. Inhibitors of voltage-gated L-type Ca2+ channels had no effect on secretion suggesting that peptone-mediated GLP-1 secretion is not mediated by L-cell depolarization with subsequent opening of these channels. Specific targeting of CaSR could serve as a target to stimulate the endogenous secretion of GLP-1.

Physiological Reports published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zou, Xiaohan published the artcileBmK NSP, a new sodium channel activator from Buthus martensii Karsch, promotes neurite outgrowth in primary cultured spinal cord neurons, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Buthus neurite spinal cord neuron; Neurite outgrowth; Scorpion toxin; Sodium channel.

In the current study, guided by a Ca2+ mobilization assay, we purified a new neuroactive peptide designated as BmK NSP (Buthus martensii Karsch neurite-stimulating peptide). The primary structure of BmK NSP was determined by Edman degradation BmK NSP concentration-dependently elevated intracellular Ca2+ concentration ([Ca2+]i) with an EC50 value of 4.18 μM in primary cultured spinal cord neurons (SCNs). Depletion of extracellular Ca2+ abolished BmK NSP-triggered Ca2+ response. Moreover, we demonstrated that BmK NSP-induced Ca2+ response was partially suppressed by the inhibitors of L-type Ca2+ channels, Na+-Ca2+ exchangers and NMDA receptors and was abolished by voltage-gated sodium channel (VGSC) blocker, tetrodotoxin. Whole-cell patch clamp recording demonstrated that BmK NSP delayed VGSC inactivation (EC50 = 1.10 μM) in SCNs. BmK NSP enhanced neurite outgrowth in a non-monotonic manner that peaked at âˆ?0 nM in SCNs. BmK NSP-promoted neurite outgrowth was suppressed by the inhibitors of L-type Ca2+ channels, NMDA receptors, and VGSCs. Considered together, these data demonstrate that BmK NSP is a new α-scorpion toxin that enhances neurite outgrowth through main routes of Ca2+ influx. Modulation of VGSC activity by α-scorpion toxin might represent a novel strategy to regulate the neurogenesis in SCNs.

Toxicon published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, 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:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yao, Jun published the artcileNifedipine inhibits oxidative stress and ameliorates osteoarthritis by activating the nuclear factor erythroid-2-related factor 2 pathway, Synthetic Route of 21829-25-4, the main research area is osteoarthritis nifedipine oxidative stress Nrf2; Inflammation; Nifedipine; Nrf2/HO-1 pathway; Osteoarthritis; Oxidative stress.

Nifedipine is a voltage-gated calcium channel inhibitor widely used in the treatment of hypertension. Nifedipine has been reported to have antioxidant and anti-apoptotic effects and promotes cell proliferation. However, the effects of nifedipine on oxidative stress and apoptosis in osteoarthritic (OA) chondrocytes are still unclear. In this study, we sought to investigate whether nifedipine alleviates oxidative stress and apoptosis in OA through nuclear factor erythroid-2-related factor 2 (Nrf2) activation. The cytotoxicity of nifedipine against human chondrocytes was detected using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) kit, whereas mRNA and protein expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, resp. The oxidative stress level was analyzed by measuring reactive oxygen species (ROS), glutathione peroxidase (GSH-px), catalase (CAT) and superoxide dismutase (SOD) activities. The role of Nrf2 in the effect of nifedipine on OA was analyzed using an Nrf2 inhibitor brusatol (BR). The result showed that nifedipine inhibited the expression of matrix metalloprotein(MMP)-13, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, inducible nitric oxide (NO) synthase (iNOS), and prostaglandin E2 (PGE2), as well as reduced ROS production in human OA chondrocytes, which was partially reversed by BR. Nifedipine prevented cartilage degeneration and contributed to the expression of Nrf-2 in chondrocytes. These results indicate that nifedipine inhibited inflammation and oxidative stress in chondrocytes via activation of Nrf-2/HO-1 signaling.

Life Sciences published new progress about Aggrecans Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, 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:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Asante, Du-Bois published the artcileAnti-inflammatory, anti-nociceptive and antipyretic activity of young and old leaves of Vernonia amygdalina, SDS of cas: 21829-25-4, the main research area is Vernonia leaf anti inflammatory nociceptive antipyretic; Aspirin; Cold allodynia; Diclofenac; Edema; Mast cells; Paw withdrawal; Pyrexia; Vernonia amygdalina.

Both young and old leaves of Vernonia amygdalina (VA) are traditionally used to treat inflammation, pain and fever. However, the efficacy of young and old leaves for treating these ailments have not been compared till date. To ascertain the effect of young and old leaves of VA in managing inflammation, pain and fever. Both quant. and qual. phytochem. screening of ethanol extracts of young (EthYL) and old (EthOL) leaves of VA were performed. The anti-inflammatory activity of orally administered Et and EthOL (50-200 mg/kg) and Diclofenac (10 mg/kg) were evaluated in carrageenan-induced inflammation model in rats. Antipyretic activity of Et, EthOL and Aspirin (25 mg/kg) were assessed in the Baker’s yeast-induced pyrexia model. Anti-allodynic effect of both extracts were evaluated by inserting inflamed paws of rats in cold water. Antinociceptive property of the extracts were assessed using tail withdrawal and formalin-induced nociception test. Histopathol. examination of the paws was performed, in addition to formalin test to understand the possible mechanism of action of the extracts Neg. control rats received 2 mL/kg normal saline in all tests. The amount of flavonoids, alkaloids, tannins, and phenolics were significantly (p < 0.05) higher in EthOL than Et, while saponins were significantly higher (p < 0.05) in Et than EthOL. The antioxidant ability and total antioxidant capacity were significantly (p < 0.05) higher in Et than EthOL. However, this was significantly (p < 0.05) lower than the anti-oxidant activity of Ascorbic acid. A dose-dependent increase in anti-inflammatory, antipyretic and antinociceptive properties were observed in both Et and EthOL, similar to the standard drugs. Mast cell degranulation accompanied by vasodilatation and high leukocytosis were observed in the neg. control, but were markedly low in extract treated groups. Both extracts mediated their analgesic effect through opioidergic and nitric oxide pathways with Et addnl. implicating the muscarinic cholinergic system. Although both Et and EthOL alleviate inflammation, pyrexia and nociception, Et of VA was found to be more potent than EthOL. Biomedicine & Pharmacotherapy published new progress about Alkaloids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, SDS of cas: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Nakayama, Yohei published the artcileFollicular dendritic cell-secreted protein gene expression is upregulated and spread in nifedipine-induced gingival overgrowth, HPLC of Formula: 21829-25-4, the main research area is gingival dendritic cell gene expression; AMTN; FDC-SP; Gingival overgrowth; Junctional epithelium; Nifedipine.

Abstract: Follicular dendritic cell-secreted protein (FDC-SP) is secreted protein expressed in follicular dendritic cells, periodontal ligament and junctional epithelium (JE). Its expression could be controlled during inflammatory process of gingiva; however, responsible mechanism for gingival overgrowth and involvement of FDC-SP in clin. condition is still unclear. We hypothesized that JE-specific genes are associated with the initiation of drug-induced gingival enlargement called gingival overgrowth, and investigated the changes of JE-specific genes expression and their localization in overgrown gingiva from the patients. Immunohistochem. anal. revealed that the FDC-SP localization was spread in overgrown gingival tissues. FDC-SP mRNA levels in GE1 and Ca9-22 cells were increased by time-dependent nifedipine treatments, similar to other JE-specific genes, such as Amelotin (Amtn) and Lamininβ3 subunit (Lamβ3), whereas type 4 collagen (Col4) mRNA were decreased. Immunocytochem. anal. showed that FDC-SP, AMTN, and Lamβ3 protein levels were increased in GE1 and Ca9-22 cells. Transient transfection analyses were performed using luciferase constructs including various lengths of human FDC-SP gene promoter, nifedipine increased luciferase activities of -345 and -948FDC-SP constructs. These results raise the possibility that the nifedipine-induced FDC-SP may be related to the mechanism responsible for gingival overgrowth does not occur at edentulous jaw ridges.

Odontology published new progress about Amelotins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, HPLC of Formula: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wang, Xinxin published the artcileDiltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is diltiazem antiviral agent cell attachment internalization SARS CoV2 infection.

The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2 α1c) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Cav1.2 α1c interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Cav1.2 α1c is a promising target for antiviral drug development for COVID-19.

PLoS Pathogens published new progress about 28S rRNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem