Month: November 2022

Du, Fangyu published the artcileStructure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is neuropathic pain epoxide hydrolase inhibitor drug discovery; Analgesia; Inhibitor; Neuropathic pain; Soluble epoxide hydrolase; Synthesis.

Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (±)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.

Acta Pharmaceutica Sinica B published new progress about Body weight. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Franco, Francisco M. published the artcileStructure-based discovery of small molecule hepsin and HGFA protease inhibitors: Evaluation of potency and selectivity derived from distinct binding pockets, Computed Properties of 478646-32-1, the main research area is structure hepsin HGFA protease inhibitor; Benzamidine; Cancer; Cell-signaling; Enzyme inhibitor; Growth factor; HGF; HGFA; Hepsin; MSP; Matriptase; Peptidomimetic; RON; Receptor tyrosine kinase; Serine protease; Small-molecule; Structure-based drug design; Therapeutic; c-MET.

Hepatocyte growth factor activator (HGFA), matriptase and hepsin are all S1 trypsin-like serine endopeptidases. HGFA is a plasma protease while hepsin and matriptase are type II transmembrane proteases (TTSPs). Upregulated expression and activity of all three proteases is associated with aberrant cancer cell signaling through c-MET and RON tyrosine kinase cell-signaling pathways in cancer. The authors modeled known benzamidine protease inhibitor scaffolds into the active sites of matriptase, hepsin and HGFA to design new nonpeptide inhibitors of hepsin and HGFA. First, the authors used a docking model of the irreversible inhibitor, Nafamostat, bound to the active site of HGFA in order to explore structure activity relationships (SAR). Compounds were screened for inhibition of HGFA activity in a kinetic enzyme assay using a chromogenic substrate. Next, the authors designed matched pair compound libraries of 3-amidino and 4-amidino phenylalanine (benzamidine) arginine peptidomimetics based on the structure of matriptase inhibitor, CJ-672. Compounds were screened for inhibition of HGFA, matriptase, and hepsin enzyme activity using fluorogenic substrates. Using this strategy the authors have discovered the first reported nonpeptide small mol. inhibitors of both HGFA and hepsin. These inhibitors have differential potency and selectivity towards all three proteases. A subset of piperazinyl ureas highlighted by I, have excellent potency and selectivity for hepsin over matriptase and HGFA.

Bioorganic & Medicinal Chemistry published new progress about Homo sapiens. 478646-32-1 belongs to class piperidines, name is (R)-Benzyl piperidin-3-ylcarbamate, and the molecular formula is C13H18N2O2, Computed Properties of 478646-32-1.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Nishizawa, Naoki published the artcileDesign and Synthesis of an Investigational Nonapeptide KISS1 Receptor (KISS1R) Agonist, Ac-D-Tyr-Hydroxyproline (Hyp)-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH2 (TAK-448), with Highly Potent Testosterone-Suppressive Activity and Excellent Water Solubility, SDS of cas: 158922-07-7, the main research area is nonapeptide KISS1 receptor agonist testosterone.

Metastin/kisspeptin is an endogenous ligand of KISS1R. Metastin and KISS1R are suggested to play crucial roles in regulating the secretion of GnRH and continuous administration of metastin derivatives attenuated the plasma testosterone levels in male rats. The optimization studies of metastin derivatives led to the discovery of Ac-D-Tyr-D-Trp-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH2, TAK-683, (I), which suppressed plasma testosterone in rats at lower doses than those of leuprolide. Although I possessed an extremely potent pharmacol. activity, 20-mg/mL aqueous solution of I has a gel formation property. In order to improve this physicochem. property, the authors substituted D-Trp at position 47 with a variety of amino acids; the authors identified that substitution with cyclic amino acids, which could change peptide conformation, retained its potency. Especially, Hyp47 analog TAK-448 (II) showed not only superior pharmacol. activity to I, but also excellent water solubility Furthermore, 20-mg/mL aqueous solution of 24 did not show a gel formation up to five days.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 158922-07-7 belongs to class piperidines, name is 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, and the molecular formula is C21H21NO4, SDS of cas: 158922-07-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Schwaid, Adam G. published the artcileDevelopment of a selective activity-based probe for glycosylated LIPA, Synthetic Route of 959918-19-5, the main research area is lysosomal acid lipase glycosylation activity probe; Activity based protein profiling; Glycosylation; LAL; LIPA; Lysosomal acid lipase; Serine hydrolase.

Loss of LIPA activity leads to diseases such as Wolman’s Disease and Cholesterol Ester Storage Disease. While it is possible to measure defects in LIPA protein levels, it is difficult to directly measure LIPA activity in cells. In order to measure LIPA activity directly we developed a LIPA specific activity based probe. LIPA is heavily glycosylated although it is unclear how glycosylation affects LIPA activity or function. Our probe is specific for a glycosylated form of LIPA in cells, although it labels purified LIPA regardless of glycosylation.

Bioorganic & Medicinal Chemistry Letters published new progress about Homo sapiens. 959918-19-5 belongs to class piperidines, name is 3-Ethynylpiperidine hydrochloride, and the molecular formula is C7H12ClN, Synthetic Route of 959918-19-5.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pasqualetto, Gaia published the artcileLigand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is rhodopsin binding site chromophore preparation chem chaperone opsin; cyclohexene preparation rhodopsin binding site chromophore chem chaperone opsin; Molecular modelling; Rhodopsin; Severe inherited blinding diseases; Small-molecule agents; Synthetic organic chemistry.

Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber’s congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin mols., which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chem. chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analog 11-cis-6mr-retinal. Following mol. docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds, e.g., I, were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new mols. displayed an effect in at least one assay, acting either as chem. chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.

European Journal of Medicinal Chemistry published new progress about Cytotoxicity. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Tomoda, Shuji published the artcileOrigin of π-facial diastereoselection in hydride reduction of piperidones. The importance of ground-state effects, Recommanded Product: 3-Methylpiperidin-4-one, the main research area is facial stereoselectivity hydride reduction piperidinone FMO steric effect.

The exterior frontier orbital extension model (the EFOE Model) strongly suggested that the ground-state conformation (steric effects) and the anisotropic frontier orbital (LUMO) extension over π-faces may be the origin of the π-facial diastereoselection in hydride reductions of substituted piperidones.

Chemistry Letters published new progress about Conformation. 5773-58-0 belongs to class piperidines, name is 3-Methylpiperidin-4-one, and the molecular formula is C6H11NO, Recommanded Product: 3-Methylpiperidin-4-one.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wong, Siu Wai published the artcileDevelopment of [18F]MIPS15692, a radiotracer with in vitro proof-of-concept for the imaging of MER tyrosine kinase (MERTK) in neuroinflammatory disease, HPLC of Formula: 73874-95-0, the main research area is neuroinflammatory disease MER tyrosine kinase 18F MIPS15692 radiotracer; Autoradiography; CNS radiotracer; MER tyrosine Kinase; Multiple sclerosis; Positron emission tomography; X-ray crystallography.

MER tyrosine kinase (MERTK) upregulation is associated with M2 polarization of microglia, which plays a vital role in neuroregeneration following damage induced by neuroinflammatory diseases such as multiple sclerosis (MS). Therefore, a radiotracer specific for MERTK could be of great utility in the clin. management of MS, for the detection and differentiation of neuroregenerative and neurodegenerative processes. This study aimed to develop an [18F] ligand with high affinity and selectivity for MERTK as a potential positron emission tomog. (PET) radiotracer. MIPS15691 and MIPS15692 were synthesized and kinase assays were utilized to determine potency and selectivity for MERTK. Both compounds were shown to be potent against MERTK, with resp. IC50 values of 4.6 nM and 4.0 nM, and were also MERTK-selective. Plasma and brain pharmacokinetics were measured in mice and led to selection of MIPS15692 over MIPS15691. X-ray crystallog. was used to visualize how MIPS15692 is recognized by the enzyme. [18F]MIPS15692 was synthesized using an automated iPHASE FlexLab module, with a molar activity (Am) of 49 ± 26 GBq/μmol. The radiochem. purity of [18F]MIPS15692 was >99% and the decay-corrected radiochem. yields (RCYs) were determined as 2.45 ± 0.85%. Brain MERTK protein d. was measured by a saturation binding assay in the brain slices of a cuprizone mouse model of MS. High levels of specific binding of [18F]MIPS15692 to MERTK were found, especially in the corpus callosum/hippocampus (CC/HC). The in vivo PET imaging study of [18F]MIPS15692 suggested that its neuroPK is sub-optimal for clin. use. Current efforts are underway to optimize the neuroPK of our next generation PET radiotracers for maximal in vivo utility.

European Journal of Medicinal Chemistry published new progress about Blood plasma. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, HPLC of Formula: 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Nakatani, Hisayuki published the artcileNovel Recycling System of Polystyrene Water Debris with Polymer Photocatalyst and Thermal Treatment, COA of Formula: C28H52N2O4, the main research area is polystyrene hindered amine light stabilizer polymer photocatalyst thermal treatment.

A poly(styrene-block-acrylic acid) containing TiO2 gel (PS-b-PAA/TiO2) polymer photocatalyst had the same d. as PS and could provoke photocatalytic activity to PS particles in water. It showed photocatalytic activity to a PS containing a N-H type hindered amine light stabilizer (PS/LA-77) in water under the UV irradiation The mol. weight decrease was ca. 10%, showing that a weaker light source and different kind of hindered amine light stabilizer (HALS) should be employed. The phthalocyanine modified photocatalyst had the activity under visible light irradiation In addition, a N-OR type HALS (LA-81) loading worked as radical scavenger, showing that the PS autoxidation was certainly controlled. After the 144 h irradiation, the mol. weight was drastically decreased with the increases of heating temperature and time. When the heat treatment was performed by the enclosed sample with the aluminum foil, the mol. weight change behavior was considerably different between the PS and PS/LA-81. The difference was due to the chain scission mechanism. The intra-alkyl radical production in PS chain allowed controlling mol. weight by the heat treatment.

Journal of Polymers and the Environment published new progress about Autoxidation. 52829-07-9 belongs to class piperidines, name is Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, and the molecular formula is C28H52N2O4, COA of Formula: C28H52N2O4.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Gajdosova, Veronika published the artcilePro-oxidant activity of biocompatible catechin stabilizer during photooxidation of polyolefins, HPLC of Formula: 52829-07-9, the main research area is oxidative biocompatible catechin stabilizer photooxidation polyolefin.

Polymer plaques made of high-d. polyethylene (HDPE) or cycloolefin copolymer (COC) were stabilized with natural phenolic stabilizer (+)-catechin (CAT) and aged using accelerated weathering technique (WOM; accelerated photooxidation). The efficiency of the phenolic stabilizer was compared with a well-established hindered amine stabilizer (HAS) Tinuvin770 (Tin770). In pursuit of the stabilization and identification of short-living radicals generated in the process of photooxidation of the polymers, a spin trapping agent 2,4,6-tri-tert-butylnitrosobenzene (TTBNB) was added to selected samples. Profiles of oxidation products and crystallinity inside the HDPE plaques were determined by IR microspectroscopy, oxidation products in COC copolymers were identified using ATR spectroscopy, concentration profiles of radicals generated inside polymer plaques during WOM exposure were determined by ESRI, the changes of local mech. properties at the surface of polymer plaques were characterized using microindentation hardness testing (MHI), and the surface morphol. changes were studied by light and/or SEM. All methods are in accordance with the conclusion that the natural phenolic stabilizer CAT exhibited pro-oxidant activity during accelerated photooxidation of both polymers, i.e. higher concentration of oxidation products, bigger changes of local mech. properties and/or more microcracks on the exposed surfaces in comparison with non-stabilized systems and systems stabilized with Tin770.

Polymer Degradation and Stability published new progress about Antioxidants. 52829-07-9 belongs to class piperidines, name is Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, and the molecular formula is C28H52N2O4, HPLC of Formula: 52829-07-9.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Twigg, Christopher published the artcilePeroxide-initiated chemical modification of polyolefins: In search of a latent antioxidant, Formula: C28H52N2O4, the main research area is peroxide initiated polyolefin antioxidant.

The ability of piperidine-based compounds to confer oxidative stability to polyolefin thermosets without compromising the yields of peroxide-initiated crosslinking and monomer grafting is demonstrated. Unlike phenolic, nitroxyl and phosphite antioxidants that lower the concentration of macroradical intermediates that support polyolefin modifications, additives based upon 2,2,6,6-tetramethylpiperidine (TEMPH) are shown to have little to no effect on the extent of LLDPE crosslinking or the conversion of vinyltriethoxysilane (VTEOS) to grafted hydrocarbon adducts. Notwithstanding this lack of interference in radical-mediated polymer modification, this class of hindered light stabilizer (HAS) compounds are shown to limit the extent of radical oxidation of linear low-d. polyethylene (LLDPE) in an accelerated aging test. The origins of this paradox are discussed in terms of the current state of knowledge regarding HAS activation. The latent antioxidant concept is extended to an alternate approach, wherein 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-N-oxyl (AOTEMPO) is used as an alkyl radical scavenger bearing an oligomerizable functional group. When added at a fraction of the peroxide loading used to produce an LLDPE thermoset, ATEMPO is shown to provide a predictable induction delay without impacting ultimate crosslink d., and produces polymer-bound alkoxyamine functionality that stabilizes the product against oxidation

Polymer published new progress about Antioxidants. 52829-07-9 belongs to class piperidines, name is Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, and the molecular formula is C28H52N2O4, Formula: C28H52N2O4.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem