Category: 1222780-33-7

Computer-Aided Fragment Growing Strategies to Design Dual Inhibitors of Soluble Epoxide Hydrolase and LTA4 Hydrolase was written by Hefke, Lena;Hiesinger, Kerstin;Zhu, W. Felix;Kramer, Jan S.;Proschak, Ewgenij. And the article was included in ACS Medicinal Chemistry Letters in 2020.Formula: C16H20F3N3O3 The following contents are mentioned in the article:

Multitarget ligands are interesting candidates for drug discovery and development due to improved safety and efficacy. However, rational design and optimization of multitarget ligands is tedious because affinity optimization for two or more targets has to be performed simultaneously. In this study, we demonstrate that, given a mol. fragment, which binds to two targets of interest, computer-aided fragment growing can be applied to optimize compound potency, relying on either ligand- or structure-derived information. This methodol. is applied to the design of dual inhibitors of soluble epoxide hydrolase and leukotriene A4 hydrolase. 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. 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.Formula: C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pharmacophoric modeling and atom-based 3D-QSAR of novel 1-aryl-3-(1-acylpiperidin-4-yl) urea as human soluble epoxide hydrolase inhibitors (sEHIs) was written by Das, Nirupam;Dhanawat, Meenakshi;Kulshrestha, Akanksha;Shrivastava, Sushant K.. And the article was included in Medicinal Chemistry in 2011.Computed Properties of C16H20F3N3O3 The following contents are mentioned in the article:

Soluble Epoxide Hydrolase (sEH) is an important and promising new pharmacol. target for the treatment of acute systemic inflammation. Inhibition of sEH by a highly selective and potent sEH inhibitor (sEHI) elevates the epoxyeicosatrienoic acids (EETs) level in vivo leading to decreased inflammation. To explore the necessary structural requirement of 1, 3-disubstituted ureas as sEH inhibitors for anti-inflammatory activity, the mol. modeling studies have been pursued. A ligand-based pharmacophoric model and atom-based 3D-QSAR have been generated by Phase. Binding interaction as determined by the docking study revealed that these inhibitors interact at active site (ASP 335 & TYR 383) of sEH enzyme. The pharmacophore model was further used as a 3D query for virtual screening to retrieve potential inhibitors. 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. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. 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

1-Aryl-3-(1-acylpiperidin-4-yl)urea Inhibitors of Human and Murine Soluble Epoxide Hydrolase: Structure-Activity Relationships, Pharmacokinetics, and Reduction of Inflammatory Pain was written by Rose, Tristan E.;Morisseau, Christophe;Liu, Jun-Yan;Inceoglu, Bora;Jones, Paul D.;Sanborn, James R.;Hammock, Bruce D.. And the article was included in Journal of Medicinal Chemistry in 2010.Synthetic Route of C16H20F3N3O3 The following contents are mentioned in the article:

1,3-Disubstituted ureas possessing a piperidyl moiety have been synthesized to investigate their structure-activity relationships as inhibitors of the human and murine soluble epoxide hydrolase (sEH). Oral administration of 13 1-aryl-3-(1-acylpiperidin-4-yl)urea inhibitors in mice revealed substantial improvements in pharmacokinetic parameters over previously reported 1-adamantylurea based inhibitors. For example, 1-(1-(cyclopropanecarbonyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea showed a 7-fold increase in potency, a 65-fold increase in C_max, and a 3300-fold increase in AUC over its adamantane analog 1-(1-adamantyl)-3-(1-propionylpiperidin-4-yl)urea. This novel sEH inhibitor showed a 1000-fold increase in potency when compared to morphine by reducing hyperalgesia as measured by mech. withdrawal threshold using the in vivo carrageenan induced inflammatory pain model. 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 has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. 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.Synthetic Route of C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Development of multitarget inhibitors for the treatment of pain: Design, synthesis, biological evaluation and molecular modeling studies was written by Wilt, Stephanie;Kodani, Sean;Le, Thanh N. H.;Nguyen, Lato;Vo, Nghi;Ly, Tanya;Rodriguez, Mark;Hudson, Paula K.;Morisseau, Christophe;Hammock, Bruce D.;Pecic, Stevan. And the article was included in Bioorganic Chemistry in 2020.Application In Synthesis of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

Multitarget-directed ligands are a promising class of drugs for discovering innovative new therapies for difficult to treat diseases. In this study, we designed dual inhibitors targeting the human fatty acid amide hydrolase (FAAH) enzyme and human soluble epoxide hydrolase (sEH) enzyme. Targeting both of these enzymes concurrently with single target inhibitors synergistically reduces inflammatory and neuropathic pain; thus, dual FAAH/sEH inhibitors are likely to be powerful analgesics. Here, we identified the piperidinyl-sulfonamide moiety as a common pharmacophore and optimized several inhibitors to have excellent inhibition profiles on both targeted enzymes simultaneously. In addition, several inhibitors show good predicted pharmacokinetic properties. These results suggest that this series of inhibitors has the potential to be further developed as new lead candidates and therapeutics in pain management. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Application In Synthesis 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. 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.Application In Synthesis of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Designing a small fluorescent inhibitor to investigate soluble epoxide hydrolase engagement in living cells was written by Brunst, Steffen;Schoenfeld, Julia;Breunig, Peter;Burgers, Luisa D.;DeMeglio, Murphy;Ehrler, Johanna H. M.;Lillich, Felix F.;Weizel, Lilia;Hefendehl, Jasmin K.;Fuerst, Robert;Proschak, Ewgenij;Hiesinger, Kerstin. And the article was included in ACS Medicinal Chemistry Letters in 2022.Formula: C16H20F3N3O3 The following contents are mentioned in the article:

Soluble epoxide hydrolase (sEH) is a promising target for a number of inflammation-related diseases. In addition, inhibition of sEH has been shown to reduce neuroinflammation, which plays a critical role in the development of central nervous system (CNS) diseases such as Alzheimer’s disease. In this study, we present the rational design of a small fluorescent sEH inhibitor. Starting from the clin. candidate GSK2256294A, we replaced the triazine moiety with the 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) fluorophore. The resulting fluorescent sEH inhibitor displayed excellent potency in an in vitro enzyme activity assay (IC₅₀ < 2 nM). The developed inhibitor is applicable in a NanoBRET-based assay system suitable for studying sEH target engagement in living cells. Furthermore, the inhibitor can be used to visualize sEH in sEH-transfected HEK293 cells and in primary mouse astrocytes by fluorescence microscopy. 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 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. 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.Formula: C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway was written by Wu, Qiong;Song, Jingfang;Meng, Danxin;Chang, Quanzhong. And the article was included in Journal of Molecular Neuroscience in 2019.Recommanded Product: 1222780-33-7 The following contents are mentioned in the article:

High level of corticosterone (CORT) is toxic to neurons and plays an important role in depression-like behavior and chronic stress. Our previous study showed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor (sEHI), induces an antidepressant effect in animal models. However, the underlying mechanism is not clear. In this study, we investigated the protective effect of TPPU on PC12 cells against CORT-induced cytotoxicity and its underlying mechanism. We found that TPPU and the sEH substrate epoxyeicosatrienoic acids (EETs) protected PC12 cells from the CORT-induced injury by increasing cell viability and inhibiting apoptosis. Furthermore, TPPU and EETs also blocked the CORT-mediated downregulation of BDNF. Blocking the BDNF-TrkB pathway by the TrkB inhibitor K252a abolished the protective effect of TPPU. Taken together, our results suggest that sEHI could protect PC12 cells against the CORT-induced cytotoxicity via the BDNF-TrkB signaling pathway. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Recommanded Product: 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. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Recommanded Product: 1222780-33-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Peripheral FAAH and soluble epoxide hydrolase inhibitors are synergistically antinociceptive was written by Sasso, Oscar;Wagner, Karen;Morisseau, Christophe;Inceoglu, Bora;Hammock, Bruce D.;Piomelli, Daniele. And the article was included in Pharmacological Research in 2015.Category: piperidines The following contents are mentioned in the article:

We need better medicines to control acute and chronic pain. Fatty acid amide hydrolase (FAAH) and soluble epoxide hydrolase (sEH) catalyze the deactivating hydrolysis of two classes of bioactive lipid mediators – fatty acid ethanolamides (FAEs) and epoxidized fatty acids (EpFAs), resp. – which are biogenetically distinct but share the ability to attenuate pain responses and inflammation. In these experiments, we evaluated the antihyperalgesic activity of small-mol. inhibitors of FAAH and sEH, administered alone or in combination, in two pain models: carrageenan-induced hyperalgesia in mice and streptozocin-induced allodynia in rats. When administered sep., the sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea (TPPU) and the peripherally restricted FAAH inhibitor URB937 were highly active in the two models. The combination TPPU plus URB937 was markedly synergistic, as assessed using isobolog. analyses. The results of these experiments reveal the existence of a possible functional crosstalk between FAEs and EpFAs in regulating pain responses. Addnl., the results suggest that combinations of sEH and FAAH inhibitors might be exploited therapeutically to achieve greater analgesic efficacy. 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 metabolite of cadaverine, a polyamine found in the human intestine. 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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers was written by Goswami, Sumanta Kumar;Rand, Amelia Ann;Wan, Debin;Yang, Jun;Inceoglu, Bora;Thomas, Melany;Morisseau, Christophe;Yang, Guang-Yu;Hammock, Bruce D.. And the article was included in Life Sciences in 2017.Category: piperidines The following contents are mentioned in the article:

This research was conducted to evaluate the hypothesis that gastric ulcers caused by the NSAID diclofenac sodium (DCF) can be prevented by the soluble epoxide hydrolase inhibitor TPPU. Mice were administered a single dose of 10, 30 or 100 mg/kg of DCF. Once an ulcerative dose of DCF was chosen, mice were pretreated with TPPU for 7 days at 0.1 mg/kg to evaluate anti-ulcer effects of the sEH inhibitor on anatomy, histopathol., pH, inflammatory markers and epithelial apoptosis of stomachs. Diclofenac caused ulceration of the stomach at a dose of 100 mg/kg and a time post dose of 6 h. Ulcers generated under these conditions were associated with a significant increase in the levels of TNF-α and IL-6 in serum and increased apoptosis compared to control mice. Pretreatment with TPPU resulted in a decrease of ulceration in mice treated with DCF with a significant decrease in the level of apoptosis, TNF-α and IL-6 in the serum in comparison to diclofenac-treated mice. TPPU did not affect the pH of the stomach, whereas omeprazole elevated the pH of the stomach as expected. A similar anti-ulcer effect was observed in sEH gene knockout mice treated with DCF. The sEH inhibitor TPPU decreases the NSAID-induced stomach ulcers. 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 metabolite of cadaverine, a polyamine found in the human intestine. 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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Correction to Optimized Inhibitors of Soluble Epoxide Hydrolase Improve in Vitro Target Residence Time and in Vivo Efficacy [Erratum to document cited in CA161:346388] was written by Lee, Kin Sing Stephen;Liu, Jun-Yan;Wagner, Karen M.;Pakhomova, Svetlana;Dong, Hua;Morisseau, Christophe;Fu, Samuel H.;Yang, Jun;Wang, Peng;Ulu, Arzu;Mate, Christina A.;Nguyen, Long V.;Hwang, Sung Hee;Edin, Matthew L.;Mara, Alexandria A.;Wulff, Heike;Newcomer, Marcia E.;Zeldin, Darryl C.;Hammock, Bruce D.. And the article was included in Journal of Medicinal Chemistry in 2018.Computed Properties of C16H20F3N3O3 The following contents are mentioned in the article:

In the legend within Figure S11, the yellowish green line with solid triangle should be inhibitor 21 instead of inhibitor 19, while green line with open triangle should be inhibitor 19 instead of inhibitor 21. The corresponding structures should be swapped too. The correct Figure S11 is provided here. 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 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.Computed Properties of C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Combined Cardioprotective and Adipocyte Browning Effects Promoted by the Eutomer of Dual sEH/PPAR纬 Modulator was written by Hartmann, Markus;Bibli, Sofia-Iris;Tews, Daniel;Ni, Xiaomin;Kircher, Theresa;Kramer, Jan S.;Kilu, Whitney;Heering, Jan;Hernandez-Olmos, Victor;Weizel, Lilia;Scriba, Gerhard K. E.;Krait, Sulaiman;Knapp, Stefan;Chaikuad, Apirat;Merk, Daniel;Fleming, Ingrid;Fischer-Posovszky, Pamela;Proschak, Ewgenij. And the article was included in Journal of Medicinal Chemistry in 2021.Category: piperidines The following contents are mentioned in the article:

The metabolic syndrome (MetS) is a constellation of cardiovascular and metabolic symptoms involving insulin resistance, steatohepatitis, obesity, hypertension, and heart disease, and patients suffering from MetS often require polypharmaceutical treatment. PPAR纬 agonists are highly effective oral antidiabetics with great potential in MetS, which promote adipocyte browning and insulin sensitization. However, the application of PPAR纬 agonists in clinics is restricted by potential cardiovascular adverse events. We have previously demonstrated that the racemic dual sEH/PPAR纬 modulator RB394 (3) simultaneously improves all risk factors of MetS in vivo. In this study, we identify and characterize (R)-3 (I), the eutomer of 3. We provide structural rationale for mol. recognition of the eutomer. Furthermore, we could show that the dual sEH/PPAR纬 modulator is able to promote adipocyte browning and simultaneously exhibits cardioprotective activity which underlines its exciting potential in treatment of MetS. 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 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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem