Category: 1222780-33-7

Inhibition of Soluble Epoxide Hydrolase Attenuates Bosutinib-Induced Blood Pressure Elevation was written by Cui, Zhen;Li, Bochuan;Zhang, Yanhong;He, Jinlong;Shi, Xuelian;Wang, Hui;Zhao, Yinjiao;Yao, Liu;Ai, Ding;Zhang, Xu;Zhu, Yi. And the article was included in Hypertension in 2021.Formula: C16H20F3N3O3 The following contents are mentioned in the article:

Endothelial cells play a critical role in maintaining homeostasis of vascular function, and endothelial activation is involved in the initial step of atherogenesis. Previously, we reported that Abl kinase mediates shear stress-induced endothelial activation. Bosutinib, a dual inhibitor of Src and Abl kinases, exerts an atheroprotective effect; however, recent studies have demonstrated an increase in the incidence of side effects associated with bosutinib, including increased arterial blood pressure (BP). To understand the effects of bosutinib on BP regulation and the mechanistic basis for novel treatment strategies against vascular dysfunction, we generated a line of mice conditionally lacking c-Abl in endothelial cells (endothelial cell-Abl^KO). Knockout mice and their wild-type littermates (Abl^f/f) were orally administered a clin. dose of bosutinib, and their BP was monitored. Bosutinib treatment increased BP in both endothelial cell-Abl^KO and Abl^f/f mice. Furthermore, acetylcholine-evoked endothelium-dependent relaxation of the mesenteric arteries was impaired by bosutinib treatment. RNA sequencing of mesenteric arteries revealed that the CYP (cytochrome P 450)-dependent metabolic pathway was involved in regulating BP after bosutinib treatment. Addnl., bosutinib treatment led to an upregulation of soluble epoxide hydrolase in the arteries and a lower plasma content of eicosanoid metabolites in the CYP pathway in mice. Treatment with 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, a soluble epoxide hydrolase inhibitor, reversed the bosutinib-induced changes to the eicosanoid metabolite profile, endothelium-dependent vasorelaxation, and BP. Thus, the present study demonstrates that upregulation of soluble epoxide hydrolase mediates bosutinib-induced elevation of BP, independent of c-Abl. The addition of soluble epoxide hydrolase inhibitor in patients treated with bosutinib may aid in preventing vascular side effects. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Formula: C16H20F3N3O3).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. 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.Formula: C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model was written by Shen, Yijun;Peng, Weifeng;Chen, Qinglan;Hammock, Bruce D.;Liu, Junyan;Li, Dongyang;Yang, Jun;Ding, Jing;Wang, Xin. And the article was included in Brain, Behavior, and Immunity in 2019.Recommanded Product: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

This study aimed to investigate whether 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor with anti-inflammatory effects, could alleviate spontaneous recurrent seizures (SRS) and epilepsy-associated depressive behaviors in the lithium chloride (LiCl)-pilocarpine-induced post-status epilepticus (SE) rat model. The rats were i.p. (IP) injected with LiCl (127 mg/kg) and pilocarpine (40 mg/kg) to induce SE. A video surveillance system was used to monitor SRS in the post-SE model for 6 wk (from the onset of the 2nd week to the end of the 7th week after SE induction). TPPU (0.1 mg/kg/d) was intragastrically given for 4 wk from the 21st day after SE induction in the SRS + 0.1 TPPU group. The SRS + PEG 400 group was given the vehicle (40% polyethylene glycol 400) instead, and the control group was given LiCl and PEG 400 but not pilocarpine. The sucrose preference test (SPT) and forced swim test (FST) were conducted to evaluate the depression-like behaviors of rats. Immunofluorescent staining, ELISA, and western blot anal. were performed to measure astrocytic and microglial gliosis, neuronal loss, and levels of soluble epoxide hydrolase (sEH), cytokines [tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6], and cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB). The frequency of SRS was significantly decreased at 6 wk and 7 wk after SE induction in the 0.1TPP U group compared with the SRS + PEG 400 group. The immobility time (IMT) evaluated by FST was significantly decreased, whereas the climbing time (CMT) was increased, and the sucrose preference rate (SPR) evaluated by SPT was in an increasing trend. The levels of sEH, TNF-α, IL-1β, and IL-6 in the hippocampus (Hip) and prefrontal cortex (PFC) were all significantly increased in the SRS + PEG 400 group compared with the control group; neuronal loss, astrogliosis, and microglial activation were also observed The astrocytic and microglial activation and levels of the pro-inflammatory cytokines in the Hip and PFC were significantly attenuated in the TPPU group compared with the SRS + PEG 400 group; moreover, neuronal loss and the decreased CREB expression were significantly alleviated as well. TPPU treatment after SE attenuates SRS and epilepsy-associated depressive behaviors in the LiCl-pilocarpine induced post-SE rat model, and it also exerts anti-inflammatory effects in the brain. Our findings suggest a new therapeutic approach for epilepsy and its comorbidities, especially depression. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Recommanded Product: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. 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.Recommanded Product: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Unbiased Molecular Dynamics of 11 min Timescale Drug Unbinding Reveals Transition State Stabilizing Interactions was written by Lotz, Samuel D.;Dickson, Alex. And the article was included in Journal of the American Chemical Society in 2018.Electric Literature of C16H20F3N3O3 The following contents are mentioned in the article:

Ligand (un)binding kinetics is being recognized as a determinant of drug specificity and efficacy in an increasing number of systems. However, the calculation of kinetics and the simulation of drug unbinding is more difficult than computing thermodn. quantities, such as binding free energies. Here we present the first full simulations of an unbinding process at pharmacol. relevant time scales (11 min), without the use of biasing forces, detailed prior knowledge, or specialized processors using the weighted ensemble based algorithm, WExplore. These simulations show the inhibitor TPPU unbinding from its enzyme target soluble epoxide hydrolase, which is a clin. relevant target that has attracted interest in kinetics optimization in order to increase efficacy. We make use of conformation space networks that allow us to conceptualize unbinding not just as a linear process, but as a network of interconnected states that connect the bound and unbound states. This allows us to visualize patterns in hydrogen-bonding, solvation, and nonequilibrium free energies, without projection onto progress coordinates. The topol. and layout of the network reveal multiple unbinding pathways, and other rare events, such as the reversal of ligand orientation within the binding site. Furthermore, we make a prediction of the transition state ensemble, using transition path theory, and identify protein-ligand interactions which are stabilizing to the transition state. Addnl., we uncover trends in ligand and binding site solvation that corroborate exptl. evidence from more classical structure kinetics relationships and generate new questions as to the role of drug modifications in kinetics optimization. Finally, from only 6 μs of simulation time we observed 75 unbinding events from which we calculate a residence time of 42 s, and a standard error range of 23 to 280 s. This nearly encompasses the exptl. residence time 11 min (660 s). In addition to the insights to sEH inhibitor unbinding, this study shows that simulations of complex processes on timescales as long as minutes are becoming feasible for more researchers to perform. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Electric Literature of C16H20F3N3O3).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Piperidine derivatives are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Electric Literature of C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Inhibition of soluble epoxide hydrolase offers protection against fructose-induced diabetes and related metabolic complications in rats was written by Shah, S. Ali;Mehmood, M. H.;Khan, M.;Bukhari, I. Ali;Alorainey, B. I.;Vohra, F.. And the article was included in Journal of Physiology and Pharmacology in 2020.Name: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

Stabilization of epoxyeicosatrienoic acids (EETs) levels via soluble epoxide hydrolase (sEH) deletion or its pharmacol. inhibition have been shown to have beneficial effects on inflammation, ischemia, hypertension and diabetes. Owing to the diverse role of EETs, current study was designed to evaluate the therapeutic potential of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl) urea (TPPU), a novel sEHI against fructose-induced diabetes and related complications in rats. Sprague-Dawley rats (200 – 230 g) were divided into four different groups, each containing 10 animals. One group served as a normal control and received standard diet and drinking water. The second group served as a diseased control and received standard diet, 25% fructose in drinking water and was treated with vehicle only. The third and fourth groups received standard diet, 25% fructose in drinking water and TPPU (2 mg/kg) or metformin (150 mg/kg), resp. All treatments were given orally for 12 wk. At the end of the study, blood samples were collected to measure serum insulin levels and other biochem. parameters. Animals were dissected to collect tissue specimens for histol. and immunohistochem. anal. Animals fed on fructose and treated with vehicle demonstrated elevated blood insulin and glucose levels as well as high levels (P < 0.001) of triglycerides (TGs), cholesterol, low-d. lipoprotein (LDL) and homeostatic model assessment of insulin resistance (HOMA-IR) compared to naive rats. Similarly, the levels of alk. phosphatase (ALP), alanine aminotransferase (ALT), urea and uric acid were significantly (P < 0.001) increased in vehicle treated fructose fed animals. TPPU (2 mg/kg p.o.) and simultaneously fed on fructose for 12 wk substantially decreased HOMA-IR levels, lowered blood glucose, serum cholesterol, LDLs and TGs while high-d. lipoproteins (HDL) levels were increased compared to untreated animals. Metformin, a standard reference drug showed similar results. Microscopic studies of liver and pancreatic sections of TPPU treated animals showed marked improvement in cellular architecture compared to untreated animals. Current study demonstrated profound therapeutic potential of TPPU against fructose induced-diabetes and related metabolic complications which was evident by its attenuating effect fructose-induced hyperglycemia, hyperlipidemia and impaired renal and hepatic serum markers. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Name: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. 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.Name: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem