Category: 1222780-33-7

Vasodilator effect of 1-trifluoromethoxyphenyl-3-(1- propionylpiperidin-4-yl) urea is predominantly mediated through activation of voltage-dependent K+ channels was written by Shah, Shafiq Ali;Mehmood, Malik Hassan;Khan, Munasib;Bukhari, Ishfaq Ali;Gilani, Anwarul Hassan. And the article was included in Tropical Journal of Pharmaceutical Research in 2018.Recommanded Product: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

To determine the mechanism of vasorelaxant effect of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea in cardiovascular diseases, including hypertension. Isolated rat thoracic aortic tissue preparations were mounted in an organ bath set up integrated with isometric transducer and a Power Lab assembly. TPPU was tested for vasorelaxant effect against low K⁺ (25 mM) and high K⁺ (80 mM)-induced contractions and its mechanism was determined in the presence of different antagonists (glibenclamide, 4- aminopyridine and tetra-Et ammonium). In rat aortic preparations, TPPU showed a concentration-dependent (0.3 – 100μM) and significant (p < 0.001) inhibition of low K⁺ induced contractions with complete inhibition obtained at 100μM. TPPU produced significant inhibition of high K⁺ induced contractions with maximum relaxation of 15.36 ± 1.95% and 15.85 ± 3.35% at 30 and 100μM, resp. Glibenclamide (Gb,10μM) pretreatment partially inhibited the vasorelaxant effect of TPPU against low K⁺ in a concentration range of 1 – 30μM. 4-Aminopyridine (4-AP, 1 mM) and tetra-Et ammonium markedly inhibited the vasorelexant effect of TPPU against low K⁺ induced contractions with maximum relaxation of 20.09 ± 2.40 and 21.67 ± 0.88%, resp., at 100μM. TPPU possesses marked vasorelaxant properties which provides sound pharmacol. evidence for its use as a potential drug candidate in the management of hypertension. 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 has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. 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.Recommanded Product: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Target-Mediated Drug Disposition-A Class Effect of Soluble Epoxide Hydrolase Inhibitors was written by An, Guohua;Lee, Kin Sing Stephen;Yang, Jun;Hammock, Bruce D.. And the article was included in Journal of Clinical Pharmacology in 2021.Recommanded Product: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

A review. Pharmacol. target-mediated drug disposition (TMDD) represents a special source of nonlinear pharmacokinetics, and its occurrence in large-mol. compounds has been well recognized because numerous protein drugs have been reported to have TMDD due to specific binding to their pharmacol. targets. Although TMDD can also happen in small-mol. compounds, it has been largely overlooked. In this mini-review, we summarize the occurrence of TMDD that we discovered recently in a series of small-mol. soluble epoxide hydrolase (sEH) inhibitors. Our journey started with an accidental discovery of target-mediated kinetics of 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU), a potent sEH inhibitor, in a pilot clin. study. To confirm what we observed in humans, we conducted a series of mechanism experiments in animals, including pharmacokinetic experiments using sEH knockout mice as well as in vivo displacement experiments with co-administration of another potent sEH inhibitor. Our mechanism studies confirmed that the TMDD of TPPU is due to its pharmacol. target sEH. We further expanded our evaluation to various other sEH inhibitors and found that TMDD is a class effect of this group of small-mol. sEH inhibitors. In addition to summarizing the occurrence of TMDD in sEH inhibitors, in this mini-review we also highlighted the importance of recognizing TMDD of small-mol. compounds and its impact in clin. development as well as using pharmacometric modeling in facilitating quant. understanding of TMDD. 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. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Recommanded Product: 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

TPPU enhanced exercise-induced epoxyeicosatrienoic acid concentrations to exert cardioprotection in mice after myocardial infarction was written by Guo, Yuan;Luo, Fei;Zhang, Xv;Chen, Jingyuan;Shen, Li;Zhu, Yi;Xu, Danyan. And the article was included in Journal of Cellular and Molecular Medicine in 2018.SDS of cas: 1222780-33-7 The following contents are mentioned in the article:

Exercise training (ET) is a safe and efficacious therapeutic approach for myocardial infarction (MI). Given the numerous benefits of exercise, exercise-induced mediators may be promising treatment targets for MI. C57BL/6 mice were fed 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl) urea (TPPU), a novel soluble epoxide hydrolase inhibitor (sEHI), to increase epoxyeicosatrienoic acid (EET) levels, for 1 wk before undergoing MI surgery. After 1-wk recovery, the mice followed a prescribed exercise program. Bone marrow-derived endothelial progenitor cells (EPCs) were isolated from the mice after 4 wk of exercise and cultured for 7 days. Angiogenesis around the ischemic area, EPC functions, and the expression of microRNA-126 (miR-126) and its target gene Spred1 were measured. The results were confirmed in vitro by adding TPPU to EPC culture medium. ET significantly increased serum EET levels and promoted angiogenesis after MI. TPPU enhanced the effects of ET to reduce the infarct area and improve cardiac function after MI. ET increased EPC function and miR-126 expression, which were further enhanced by TPPU, while Spred1 expression was significantly down-regulated. Addnl., the protein kinase B/glycogen synthase kinase 3β (AKT/GSK3β) signalling pathway was activated after the administration of TPPU. EETs are a potential mediator of exercise-induced cardioprotection in mice after MI. TPPU enhances exercise-induced cardiac recovery in mice after MI by increasing EET levels and promoting angiogenesis around the ischemic area. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7SDS of cas: 1222780-33-7).

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. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.SDS of cas: 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Epoxyeicosatrienoic acids alleviate methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in mice was written by Wang, Xiaojing;Li, Lan;Wang, Hongwu;Xiao, Fang;Ning, Qin. And the article was included in Scandinavian Journal of Immunology in 2019.SDS of cas: 1222780-33-7 The following contents are mentioned in the article:

The epoxyeicosatrienoic acids (EETs) are products of cytochrome P 450 epoxygenases and have recently been found to have an anti-inflammatory activity. However, the role of EETs in non-alc. steatohepatitis has not been fully understood. In this study, we investigated the protective role of EETs in methionine-choline-deficient (MCD) diet-induced non-alc. steatohepatitis (NASH) in mice and the potential mechanisms. We used 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea(TPPU), a soluble epoxide hydrolase inhibitor, to increase the endogenous EET level in mice. Upon TPPU treatment, the liver steatosis and inflammatory damage were significantly ameliorated in mice with steatohepatitis, paralleled by the downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) as well as chemokines (CXCL1, MCP-1). Compared with untreated NASH mice, mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and inflammation relevant adhesion mols. (ICAM-1, VCAM-1) were downregulated, whereas mRNA level of peroxisome proliferator-activated receptor α(PPAR-α) was elevated in TPPU-treated mice. In vitro, 11,12-EET treatment remarkably attenuated free fatty acid (FFA)-induced inflammation in HepG2 and THP-1 cells. Further, 11,12-EET inhibited the activation of NF-kappaB signalling pathway in macrophages from mice with steatohepatitis. Collectively, these results suggest that EETs play a protective role and alleviate the MCD diet-induced steatohepatitis in mice mainly by downregulating activation of NF-κB pathway in macrophages. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7SDS of cas: 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. 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.SDS of cas: 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Chronic Ethanol-Induced Cardiac Fibrosis by Restoring Autophagic Flux was written by Zhou, Chi;Huang, Jin;Li, Qing;Zhan, Chenao;He, Ying;Liu, Jinyan;Wen, Zheng;Wang, Dao Wen. And the article was included in Alcoholism: Clinical & Experimental Research in 2018.Safety of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

Background : Chronic drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, and cardiac fibrosis is a consequence of these alc. injuries. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) to less bioactive diols, and EETs have cardioprotective properties. However, the effects of sEH inhibition in ethanol (EtOH)-induced cardiac fibrosis are unknown. Methods : This study was designed to investigate the role and underlying mechanisms of sEH inhibition in chronic EtOH feeding-induced cardiac fibrosis. C57BL/6J mice were fed a 4% Lieber-DeCarli EtOH diet for 8 wk, and the sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered throughout the exptl. period. Results : The results showed that chronic EtOH intake led to cardiac dilatation, collagen deposition, and autophagosome accumulation, while TPPU administration ameliorated these effects. In vitro, treating primary cardiac fibroblasts (CFs) with EtOH resulted in CF activation, including alpha smooth muscle actin overexpression, collagen synthesis, and cell migration. Moreover, EtOH disturbed CF autophagic flux, as evidenced by the increased LC3 II/I ratio and SQSTM1 expression, and by the enhanced autophagosome accumulation. TPPU treatment prevented the activation of CF induced by EtOH and restored the impaired autophagic flux by suppressing mTOR activation. Conclusions : Taken together, these findings suggest that sEH pharmacol. inhibition may be a unique therapeutic strategy for treating EtOH-induced cardiac fibrosis. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Safety of 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 has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Safety of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

A soluble epoxide hydrolase inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, ameliorates experimental autoimmune encephalomyelitis was written by Jonnalagadda, Deepa;Wan, Debin;Chun, Jerold;Hammock, Bruce D.;Kihara, Yasuyuki. And the article was included in International Journal of Molecular Sciences in 2021.Computed Properties of C16H20F3N3O3 The following contents are mentioned in the article:

Polyunsaturated fatty acids (PUFAs) are essential FAs for human health. Cytochrome P 450 oxygenates PUFAs to produce anti-inflammatory and pain-resolving epoxy fatty acids (EpFAs) and other oxylipins whose epoxide ring is opened by the soluble epoxide hydrolase (sEH/Ephx2), resulting in the formation of toxic and pro-inflammatory vicinal diols (dihydroxy-FAs). Pharmacol. inhibition of sEH is a promising strategy for the treatment of pain, inflammation, cardiovascular diseases, and other conditions. We tested the efficacy of a potent, selective sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), in an animal model of multiple sclerosis (MS), exptl. autoimmune encephalomyelitis (EAE). Prophylactic TPPU treatment significantly ameliorated EAE without affecting circulating white blood cell counts. TPPU accumulated in the spinal cords (SCs), which was correlated with plasma TPPU concentration Targeted lipidomics in EAE SCs and plasma identified that TPPU blocked production of dihydroxy-FAs efficiently and increased some EpFA species including 12(13)-epoxy-octadecenoic acid (12(13)-EpOME) and 17(18)-epoxy-eicosatrienoic acid (17(18)-EpETE). TPPU did not alter levels of cyclooxygenase (COX-1/2) metabolites, while it increased 12-hydroxyeicosatetraenoic acid (12-HETE) and other 12/15-lipoxygenase metabolites. These anal. results are consistent with sEH inhibitors that reduce neuroinflammation and accelerate anti-inflammatory responses, providing the possibility that sEH inhibitors could be used as a disease modifying therapy, as well as for MS-associated pain relief. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Computed Properties of C16H20F3N3O3).

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. 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.Computed Properties of C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Simultaneous target-mediated drug disposition model for two small-molecule compounds competing for their pharmacological target: soluble epoxide hydrolase was written by Wu, Nan;Hammock, Bruce D.;Lee, Kin Sing Stephen;An, Guohua. And the article was included in Journal of Pharmacology and Experimental Therapeutics in 2020.SDS of cas: 1222780-33-7 The following contents are mentioned in the article:

1-(1-Propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU) and 1-(4-trifluoro-methoxy-phenyl)-3-(1-cyclopropanecarbonyl-piperidin-4-yl)-urea (TCPU) are potent inhibitors of soluble epoxide hydrolase (sEH) that have much better efficacy in relieving nociceptive response than the Food and Drug Administration-approved drug gabapentin in a rodent model of diabetic neuropathy. Experiments conducted in sEH knockout mice or with coadministration of a potent sEH displacer demonstrated that the pharmacokinetics of TPPU and TCPU were influenced by the specific binding to their pharmacol. target sEH, a phenomenon known as target-mediated drug disposition (TMDD). To quant. characterize the complex pharmacokinetics of TPPU and TCPU and gain better understanding on their target occupancy, population pharmacokinetics anal. using a nonlinear mixed-effect modeling approach was performed in the current study. The final model was a novel simultaneous TMDD interaction model, in which TPPU and TCPU compete for sEH, with TCPU binding to an addnl. unknown target pool with larger capacity that we refer to as a refractory pool. The total amount of sEH enzyme in mice was predicted to be 16.2 nmol, which is consistent with the exptl. value of 10 nmol. The dissociate rate constants of TPPU and TCPU were predicted to be 2.24 and 2.67 h-1, resp., which is close to the values obtained from in vitro experiments Our simulation result predicted that 90% of the sEH will be occupied shortly after a low dose of 0.3 mg/kg TPPU administration, with ≥40% of sEH remaining to be bound with TPPU for at least 7 days. Further efficacy experiments are warranted to confirm the predicted target occupancy. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7SDS of cas: 1222780-33-7).

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. 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.SDS of cas: 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK was written by Luo, Ying;Wu, Ming-Yu;Deng, Bing-Qing;Huang, Jian;Hwang, Sung Hee;Li, Meng-Yuan;Zhou, Chun-Yu;Zhang, Qian-Yun;Yu, Hai-Bo;Zhao, Da-Ke;Zhang, Guodong;Qin, Ling;Peng, Ai;Hammock, Bruce D.;Liu, Jun-Yan. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2019.HPLC of Formula: 1222780-33-7 The following contents are mentioned in the article:

A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and mol. levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1, and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. Also, 14(15)-EET (a major substrate of sEH), but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1, and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may pos. regulate Ampk transcriptionally in mRMCs. This study provides insights into and therapeutic target for the HFD-mediated renal injury. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7HPLC of Formula: 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.HPLC of Formula: 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) Urea, a Selective and Potent Dual Inhibitor of Soluble Epoxide Hydrolase and p38 Kinase Intervenes in Alzheimer’s Signaling in Human Nerve Cells was written by Liang, Zhibin;Zhang, Bei;Xu, Meng;Morisseau, Christophe;Hwang, Sung Hee;Hammock, Bruce D.;Li, Qing X.. And the article was included in ACS Chemical Neuroscience in 2019.Safety of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Neuroinflammation is a prevalent pathogenic stress leading to neuronal death in AD. Targeting neuroinflammation to keep neurons alive is an attractive strategy for AD therapy. 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) is a potent inhibitor of soluble epoxide hydrolase (sEH) and can enter into the brain. It has a good efficacy on a wide range of chronic inflammatory diseases in preclin. animal models. However, the anti-neuroinflammatory effects and mol. mechanisms of TPPU for potential AD interventions remain elusive. With an aim to develop multi-target therapeutics for neurodegenerative diseases, we screened TPPU against sEH from different vertebrate species and a broad panel of human kinases in vitro for potential new targets relevant to neuroinflammation in AD. TPPU inhibits both human sEH and p38β kinase, two key regulators of inflammation, with nanomolar potencies and distinct selectivity. To further elucidate the mol. mechanisms, differentiated SH-SY5Y human neuroblastoma cells were used as an AD cell model and investigated the neuroprotection of TPPU against amyloid oligomers. We found that TPPU effectively prevents neuronal death by mitigating amyloid neurotoxicity, tau hyperphosphorylation and mitochondrial dysfunction, promoting neurite outgrowth, and suppressing activation and nuclear translocation of NF-κB for inflammatory responses in human nerve cells. The results indicate that TPPU is a potent and selective dual inhibitor of sEH and p38β kinase, showing a synergistic action in multiple AD signaling pathways. Our study sheds light upon TPPU and other sEH/p38β dual inhibitors for potential pharmacol. interventions in AD. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Safety of 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.Safety of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pharmacokinetics and in vivo potency of soluble epoxide hydrolase inhibitors in cynomolgus monkeys was written by Ulu, A.;Appt, S. E.;Morisseau, C.;Hwang, S. H.;Jones, P. D.;Rose, T. E.;Dong, H.;Lango, J.;Yang, J.;Tsai, H. J.;Miyabe, C.;Fortenbach, C.;Adams, M. R.;Hammock, B. D.. And the article was included in British Journal of Pharmacology in 2012.Safety of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

Soluble epoxide hydrolase inhibitors (sEHIs) possess anti-inflammatory, antiatherosclerotic, antihypertensive and analgesic properties. The pharmacokinetics (PK) and pharmacodynamics in terms of inhibitory potency of sEHIs were assessed in non-human primates (NHPs). Development of a sEHI for use in NHPs will facilitate investigations on the role of sEH in numerous chronic inflammatory conditions. PK parameters of 11 sEHIs in cynomolgus monkeys were determined after oral dosing with 0.3 mg/kg^-1. Their phys. properties and inhibitory potency in hepatic cytosol of cynomolgus monkeys were examined Dose-dependent effects of the two inhibitors 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the related acetyl piperidine derivative, 1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl) urea (TPAU), on natural blood eicosanoids, were determined Among the inhibitors tested, TPPU and two 4-(cyclohexyloxy) benzoic acid urea sEHIs displayed high plasma concentrations (>10 × IC₅₀), when dosed orally at 0.3 mg/kg^-1. Although the 4-(cyclohexyloxy) benzoic acid ureas were more potent against monkey sEH than piperidyl ureas (TPAU and TPPU), the latter compounds showed higher plasma concentrations and more drug-like properties. The C_max increased with dose from 0.3 to 3 mg/kg^-1 for TPPU and from 0.1 to 3 mg/kg^-1 for TPAU, although it was not linear over this range of doses. As an indication of target engagement, ratios of linoleate epoxides to diols increased with TPPU administration. Our data indicate that TPPU is suitable for investigating sEH biol. and the role of epoxide-containing lipids in modulating inflammatory diseases in NHPs. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Safety of 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. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Safety of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem