Category: 1222780-33-7

Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model was written by Trindade-da-Silva, Carlos A.;Clemente-Napimoga, Juliana T.;Abdalla, Henrique B.;Rosa, Sergio Marcolino;Ueira-Vieira, Carlos;Morisseau, Christophe;Verri, Waldiceu A. Jr;Montalli, Victor Angelo Martins;Hammock, Bruce D.;Napimoga, Marcelo H.. And the article was included in FASEB Journal in 2020.Application of 1222780-33-7 The following contents are mentioned in the article:

Epoxyeicosatrienoic acids (EET) and related epoxy fatty acids (EpFA) are endogenous anti-inflammatory compounds, which are converted by the soluble epoxide hydrolase (sEH) to dihydroxylethersatrienoic acids (DHETs) with lessened biol. effects. Inhibition of sEH is used as a strategy to increase EET levels leading to lower inflammation. Rheumatoid arthritis is a chronic autoimmune disease that leads to destruction of joint tissues. This pathogenesis involves a complex interplay between the immune system, and environmental factors. Here, we investigate the effects of inhibiting sEH with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) on a collagen-induced arthritis model. The treatment with TPPU ameliorates hyperalgesia, edema, and decreases the expression of important pro-inflammatory cytokines of Th1 and Th17 profiles, while increasing Treg cells. Considering the challenges to control RA, this study provides robust data supporting that inhibition of the sEH is a promising target to treat arthritis. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Application of 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) 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. 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.Application of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Soluble epoxide hydrolase inhibitor mediated analgesia lacks tolerance in rat models was written by Wagner, Karen M.;Atone, Jogen;Hammock, Bruce D.. And the article was included in Brain Research in 2020.Related Products of 1222780-33-7 The following contents are mentioned in the article:

Effectively treating chronic pain remains a therapeutic challenge in the clinic. Recent evidence has shown the inhibition of the soluble epoxide hydrolase (sEH) to be an effective strategy to limit chronic pain in preclin. models, horses and companion animals. Determining the safety of sEH inhibition in addition to this demonstrated efficacy is a critical step to the further development of sEH inhibitors (sEHI) as analgesics. Here we describe a comparison of the sEHI TPPU with other first in class analgesics for human chronic pain. We assess the development of tolerance to the analgesia mediated by TPPU with extended use. We also assess for CNS effects by measuring changes in motor control and functioning. The sEHI are multimodal analgesics that have demonstrated potent efficacy against chronic pain. They have previously been tested and show no reward potential using operant methods. The results of the current experiments show that they lack motor function effects and also lack the development of tolerance with extended dosing. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Related Products of 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. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising 伪-glucosidase inhibitors. The former are analogs of DNJ with an improved 伪-glucosidase inhibitory profile than that of DNJ. Boisson et al.Related Products of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Drug-Target Residence Time Affects in Vivo Target Occupancy through Multiple Pathways was written by Lee, Kin Sing Stephen;Yang, Jun;Niu, Jun;Ng, Connie J.;Wagner, Karen M.;Dong, Hua;Kodani, Sean D.;Wan, Debin;Morisseau, Christophe;Hammock, Bruce D.. And the article was included in ACS Central Science in 2019.Reference of 1222780-33-7 The following contents are mentioned in the article:

The drug discovery and development process is greatly hampered by difficulties in translating in vitro potency to in vivo efficacy. Recent studies suggest that the long-neglected drug-target residence time parameter complements classical drug affinity parameters (K_I, K_d, IC₅₀, or EC₅₀) and is a better predictor of in vivo efficacy. Compounds with a long drug-target residence time are often more efficacious in vivo. The impact, however, of the drug-target residence time on in vivo efficacy remains controversial due to difficulties in exptl. determining the in vivo target occupancy during drug treatment. To tackle this problem, an in vivo displacement assay was developed using soluble epoxide hydrolase as a biol. model. In this report, we exptl. demonstrated that drug-target residence time affects the duration of in vivo drug-target binding. In addition, the drug-target residence time plays an important role in modulating the rate of drug metabolism which also affects the efficacy of the drug. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Reference of 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. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Reference of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Probing the orientation of inhibitor and epoxy-eicosatrienoic acid binding in the active site of soluble epoxide hydrolase was written by Lee, Kin Sing Stephen;Henriksen, Niel M.;Ng, Connie J.;Yang, Jun;Jia, Weitao;Morisseau, Christophe;Andaya, Armann;Gilson, Michael K.;Hammock, Bruce D.. And the article was included in Archives of Biochemistry and Biophysics in 2017.Product Details of 1222780-33-7 The following contents are mentioned in the article:

Soluble epoxide hydrolase (sEH) is an important therapeutic target of many diseases, such as chronic obstructive pulmonary disease (COPD) and diabetic neuropathic pain. It acts by hydrolyzing and thus regulating specific bioactive long chain polyunsaturated fatty acid epoxides (lcPUFA), like epoxyeicosatrienoic acids (EETs). To better predict which epoxides could be hydrolyzed by sEH, one needs to dissect the important factors and structural requirements that govern the binding of the substrates to sEH. This knowledge allows further exploration of the physiol. role played by sEH. Unfortunately, a crystal structure of sEH with a substrate bound has not yet been reported. In this report, new photoaffinity mimics of a sEH inhibitor and EET regioisomers were prepared and used in combination with peptide sequencing and computational modeling, to identify the binding orientation of different regioisomers and enantiomers of EETs into the catalytic cavity of sEH. Results indicate that the stereochem. of the epoxide plays a crucial role in dictating the binding orientation of the substrate. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Product Details of 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 derivatives are being utilized in different ways as anticancer, antiviral, antimalarial, antimicrobial, antifungal, antihypertension, analgesic, anti-inflammatory, anti-Alzheimer, antipsychotic and/or anticoagulant agents.Product Details of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

A Supervised Molecular Dynamics Approach to Unbiased Ligand-Protein Unbinding was written by Deganutti, Giuseppe;Moro, Stefano;Reynolds, Christopher A.. And the article was included in Journal of Chemical Information and Modeling in 2020.Application of 1222780-33-7 The following contents are mentioned in the article:

The recent paradigm shift toward the use of the kinetics parameters in place of thermodn. constants is leading the computational chem. community to develop methods for studying the mechanisms of drug binding and unbinding. From this standpoint, mol. dynamics (MD) plays an important role in delivering insight at the mol. scale. However, a known limitation of MD is that the time scales are usually far from those involved in ligand-receptor unbinding events. Here, we show that the algorithm behind supervised MD (SuMD) can simulate the dissociation mechanism of druglike small mols. while avoiding the input of any energy bias to facilitate the transition. SuMD was tested on seven different intermol. complexes, covering four G protein-coupled receptors: the A_2A and A₁ adenosine receptors, the orexin 2 and the muscarinic 2 receptors, and the soluble globular enzyme epoxide hydrolase. SuMD well-described the multi-step nature of ligand-receptor dissociation, rationalized previous exptl. data and produced valuable working hypotheses for structure-kinetics relationships. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Application of 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. 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.Application of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption was written by Napimoga, M. H.;Rocha, E. P.;Trindade-da-Silva, C. A.;Demasi, A. P. D.;Martinez, E. F.;Macedo, C. G.;Abdalla, H. B.;Bettaieb, A.;Haj, F. G.;Clemente-Napimoga, J. T.;Inceoglu, B.;Hammock, B. D.. And the article was included in Journal of Periodontal Research in 2018.Category: piperidines The following contents are mentioned in the article:

In the current study we used the sEH inhibitor (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea [TPPU]) to investigate the immunomodulatory effects in a mouse periodontitis model. Mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 6) that were treated orally, daily for 15 days, with 1 mg/kg of TPPU. Then, the mice were killed and their jaws were analyzed for bone resorption using morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by microarray PCR or western blotting. Infected mice treated with TPPU showed lower bone resorption than infected mice without treatment. Interestingly, infected mice showed increased expression of sEH; however, mice treated with TPPU had a reduction in expression of sEH. Besides, several proinflammatory cytokines and mol. markers were downregulated in the gingival tissue in the group treated with 1 mg/kg of TPPU. The sEH inhibitor, TPPU, showed immunomodulatory effects, decreasing bone resorption and inflammatory responses in a bone resorption mouse model. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Category: piperidines).

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鈥揌 bond in an axial position, and the other in an equatorial position.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Eicosanoid regulation of debris-stimulated metastasis was written by Deng, Jianjun;Yang, Haixia;Haak, Victoria M.;Yang, Jun;Kipper, Franciele C.;Barksdale, Chantal;Hwang, Sung Hee;Gartung, Allison;Bielenberg, Diane R.;Subbian, Selvakumar;Ho, Koc-Kan;Ye, Xiang;Fan, Daidi;Sun, Yongkui;Hammock, Bruce D.;Panigrahy, Dipak. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2021.Synthetic Route of C16H20F3N3O3 The following contents are mentioned in the article:

Cancer therapy reduces tumor burden via tumor cell death (debris), which can accelerate tumor progression via the failure of inflammation resolution Thus, there is an urgent need to develop treatment modalities that stimulate the clearance or resolution of inflammation-associated debris. Here, we demonstrate that chemotherapy-generated debris stimulates metastasis by up-regulating soluble epoxide hydrolase (sEH) and the prostaglandin E2 receptor 4 (EP4). Therapy-induced tumor cell debris triggers a storm of proinflammatory and proangiogenic eicosanoid-driven cytokines. Thus, targeting a single eicosanoid or cytokine is unlikely to prevent chemotherapy-induced metastasis. Pharmacol. abrogation of both sEH and EP4 eicosanoid pathways prevents hepato-pancreatic tumor growth and liver metastasis by promoting macrophage phagocytosis of debris and counterregulating a protumorigenic eicosanoid and cytokine storm. Therefore, stimulating the clearance of tumor cell debris via combined sEH and EP4 inhibition is an approach to prevent debris-stimulated metastasis and tumor growth. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Synthetic Route of C16H20F3N3O3).

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. Piperidine derivatives bearing a masked aldehyde function in the 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Synthetic Route of C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Movement to the Clinic of Soluble Epoxide Hydrolase Inhibitor EC5026 as an Analgesic for Neuropathic Pain and for Use as a Nonaddictive Opioid Alternative was written by Hammock, Bruce D.;McReynolds, Cindy B.;Wagner, Karen;Buckpitt, Alan;Cortes-Puch, Irene;Croston, Glenn;Lee, Kin Sing Stephen;Yang, Jun;Schmidt, William K.;Hwang, Sung Hee. And the article was included in Journal of Medicinal Chemistry in 2021.Synthetic Route of C16H20F3N3O3 The following contents are mentioned in the article:

This report describes the development of an orally active analgesic that resolves inflammation and neuropathic pain without the addictive potential of opioids. EC5026 (I) acts on the cytochrome P 450 branch of the arachidonate cascade to stabilize epoxides of polyunsaturated fatty acids (EpFA), which are natural mediators that reduce pain, resolve inflammation, and maintain normal blood pressure. EC5026 is a slow-tight binding transition-state mimic that inhibits the soluble epoxide hydrolase (sEH) at picomolar concentrations The sEH rapidly degrades EpFA; thus, inhibiting sEH increases EpFA in vivo and confers beneficial effects. This mechanism addresses disease states by shifting endoplasmic reticulum stress from promoting cellular senescence and inflammation toward cell survival and homeostasis. We describe the synthesis and optimization of EC5026 and its development through human Phase 1a trials with no drug-related adverse events. Addnl., we outline fundamental work leading to discovery of the analgesic and inflammation-resolving CYP450 branch of the arachidonate cascade. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Synthetic Route of C16H20F3N3O3).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. 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.Synthetic Route of C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Oral treatment of rodents with soluble epoxide hydrolase inhibitor 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU): Resulting drug levels and modulation of oxylipin pattern was written by Ostermann, Annika I.;Herbers, Jan;Willenberg, Ina;Chen, Rongjun;Hwang, Sung Hee;Greite, Robert;Morisseau, Christophe;Gueler, Faikah;Hammock, Bruce D.;Schebb, Nils Helge. And the article was included in Prostaglandins and Other Lipid Mediators in 2015.Formula: C16H20F3N3O3 The following contents are mentioned in the article:

Epoxides from polyunsaturated fatty acids (PUFAs) are potent lipid mediators. In vivo stabilization of these epoxides by blockade of the soluble epoxide hydrolase (sEH) leads to anti-inflammatory, analgesic and normotensive effects. Therefore, sEH inhibitors (sEHi) are a promising new class of drugs. Herein, we characterized pharmacokinetic (PK) and pharmacodynamic properties of a com. available potent sEHi 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU). Cell culture studies suggest its high absorption and metabolic stability. Following administration in drinking water to rats (0.2, 1, and 5 mg TPPU/L with 0.2% PEG400), TPPU’s blood concentration increased dose dependently within the treatment period to reach an almost steady state after 8 days. TPPU was found in all the tissues tested. The linoleic epoxide/diol ratios in most tissues were dose dependently increased, indicating significant sEH inhibition. Overall, administration of TPPU with the drinking water led to systemic distribution as well as high drug levels and thus makes chronic sEH inhibition studies possible. 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 structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Piperidine derivatives bearing a masked aldehyde function in the 蔚-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Formula: C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Protective effects of the soluble epoxide hydrolase inhibitor 1- trifluoromethoxyphenyl-3-(1- propionylpiperidin-4-yl) urea in a rat model of permanent middle cerebral artery occlusion was written by Zhang, Linlei;Xu, Shasha;Wu, Xiaoxiao;Muse, Farah Mohamed;Chen, Jiaou;Cao, Yungang;Yan, Jueyue;Cheng, Zicheng;Yi, Xingyang;Han, Zhao. And the article was included in Frontiers in Pharmacology in 2020.Related Products of 1222780-33-7 The following contents are mentioned in the article:

Acute ischemic stroke is a serious disease that endangers human health. In our efforts to develop an effective therapy, we previously showed that the potent, highly selective inhibitor of soluble epoxide hydrolase called 1-trifuoromethoxyphenyl-3-(1- propionylpiperidin-4-yl) urea (TPPU) protects the brain against focal ischemia in rats. Here we explored the mechanism of TPPU action by assessing whether it could preserve blood-brain barrier integrity and reduce apoptosis in the brain during permanent middle cerebral artery occlusion in male Sprague-Dawley rats. TPPU administration at the onset of stroke and once daily thereafter led to smaller infarct volume and brain edema as well as milder neurol. deficits. TPPU significantly inhibited the activity of soluble epoxide hydrolase and matrix metalloproteases 2 and 9, reducing 14,15-DHET levels, while increasing expression of tight junction proteins. TPPU decreased numbers of apoptotic cells by down-regulating the pro-apoptotic proteins BAX and Caspase-3, while upregulating the anti-apoptotic protein BCL-2. Our results suggest that TPPU can protect the blood-brain barrier and reduce the apoptosis of brain tissue caused by ischemia. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Related Products of 1222780-33-7).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N鈥揌 bond in an axial position, and the other in an equatorial position.Related Products of 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem