Category: 73874-95-0

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

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

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

Liu, Qian published the artcileDesign, Synthesis, and Biological Evaluation of APN and AKT Dual-Target Inhibitors, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is APN AKT dual inhibitor CD13 kinase antitumor polypharmacol.

Herein a novel series of APN and AKT dual inhibitors were derived from the clin. AKT inhibitor AZD5363. It was demonstrated that most compounds exhibited remarkable APN inhibitory activities with the most potent compound 8b (I) (IC50 = 0.05 ± 0.01 μM) being over 70-fold more potent than the approved APN inhibitor bestatin (IC50 = 3.64 ± 0.56 μM). The moderate AKT inhibitory potencies of target compounds were also confirmed, with 5f (II) and 5h (III) possessing AKT1 IC50 values of 0.12 and 0.27 μM, resp. More importantly, the APN IC50 values of 5f and 5h were 0.96 and 0.21 μM, resp., indicating their balanced APN and AKT dual inhibition. HUVEC tube formation assays confirmed the superior APN inhibitory activities of 5f and 5h relative to bestatin at the cellular level. Western blot anal. demonstrated that 5h could effectively inhibit the phosphorylation of GSK3β, the intracellular substrate of AKT.

ACS Medicinal Chemistry Letters published new progress about Drug design. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Name: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Tavares, Ines G. published the artcileIntramolecular interchromophore singlet-singlet and triplet-singlet energy transfer in a metal-free donor-acceptor emitter, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is intramol interchromophore singlet triplet energy transfer donor acceptor emitter.

In this work we demonstrate the occurrence of singlet to singlet, and triplet to singlet, intramol. energy transfer between two thiophene-comprising donors (D) and a central perylene bisimide acceptor (A) covalently linked to each other trough a linker that separates the donor and acceptor moieties in a D-A-D structure. The designed metal-free organic tandem luminophore is herein designated as ARC-1467. Energy transfer from the excited triplet state of the thiophene donor to the singlet state of the perylene bisimide acceptor is observed in solution and in solid films of ARC-1467 dispersed in polystyrene. When the perylene bisimide acceptor is directly excited, the fluorescence decays with 4.9 ns lifetime. However, upon excitation of the donor unit in the near-UV region, delayed fluorescence of perylene bisimide with 5.7 μs lifetime is distinctly observed demonstrating the occurrence of energy transfer from the triplet state of the D unit to the perylene bisimide acceptor.

Journal of Luminescence published new progress about Absorption. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Name: tert-Butyl piperidin-4-ylcarbamate.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Liu, Wenjie published the artcileDesign, synthesis and biological evaluation of novel coumarin derivatives as multifunctional ligands for the treatment of Alzheimer’s disease, SDS of cas: 73874-95-0, the main research area is coumarin preparation docking antitumor enzyme inhibitor ADME Alzheimer disease; AChE; Alzheimer’s disease; BACE1; Coumarin; GSK-3β.

Herein, a series of novel coumarin derivatives such as I and II [R = 3-pyridinyl, 4-pyridinyl, 2-F-4-pyridinyl, 6-F-3-pyridinyl, 4-FC6H4, 2-(cyclopropylcarbonylamino)-4-pyridinyl, 2-(benzoylamino)-4-pyridinyl] was explored, synthesized, and assessed their inhibitory effects on cholinesterase (AChE, BuChE), GSK-3β, and BACE1. Among these compounds, compound II (R = pyridin-3-yl) displayed the multifunctional profile of targeting the AChE (IC50 = 1.313 ± 0.099μM) with a good selectivity over BuChE (SI = 24.623), GSK-3β (19.30% inhibition at 20μM), BACE1 (IC50 = 1.227 ± 0.112μM), along with moderate HepG2 cytotoxicity, SH-SY5Y cytotoxicity, low HL-7702 cytotoxicity, as well as good blood-brain barrier (BBB) permeability. Kinetic and docking studies indicated that compound II (R = pyridin-3-yl) was a competitive AChE inhibitor. Furthermore, acute toxicity experiments revealed that it was non-toxic at a dosage of 1000 mg/kg. The ADME prediction results indicate that II (R = pyridin-3-yl) has acceptable physicochem. properties. Collectively, these findings demonstrated that compound II (R = pyridin-3-yl) would be a potential multifunctional candidate for AD therapy.

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

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wu, Lei published the artcileBromination-induced spirocyclization of rhodamine dyes affording a FRET-based ratiometric fluorescent probe for visualization of hypobromous acid (HOBr) in live cells and zebrafish, Synthetic Route of 73874-95-0, the main research area is rhodamine dye fluorescent probe hypobromous acid zebrafish bromination spirocyclization.

Hypobromous acid (HOBr) has been implicated in many physiol. and pathol. conditions. Therefore, real-time monitoring of HOBr fluctuations in biosystem plays a key role for understanding pathophysiol. processes. To date, it remains a challenge to design fluorescent probes specific toward HOBr, because HOBr and HOCl have similar chem. properties and the former has a relatively lower concentration in comparison with the former in living system. Herein, a Forster resonance energy transfer (FRET)-based ratiometric fluorescent HOBr probe (Cou-RhB) was developed. The probe consists of a coumarin donor and a rhodamine acceptor. Upon treatment of Cou-RhB with HOBr, the electrophilic bromination of xanthene ring occurs, which shifts the equilibrium of rhodamine from the highly absorbing and fluorescent zwitterion form to the colorless and non-fluorescent spirolactone form, thus decreasing the FRET efficiency within the probe. The above reaction affords a large emission wavelength shift (ca. 89 nm), and ratiometric sensing of HOBr can be realized by measuring the ratio of coumarin- to rhodamine-type intensities (I491/I580). Cou-RhB responds to HOBr with a fast kinetics (∼ 10 s), high sensitivity and excellent specificity and has been applied for ratiometric imaging of HOBr inside live cells and zebrafish.

Sensors and Actuators, B: Chemical published new progress about Absorption. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Synthetic Route of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Ishida, Akiharu published the artcileDiscovery and SAR Studies of Orally Active Somatostatin Receptor Subtype-2 (SSTR2) Agonists for the Treatment of Acromegaly, Synthetic Route of 73874-95-0, the main research area is acromegaly somatostatin SSTR2 GPCR acromegaly nonpeptidic orally active SAR; GPCR; SSTR2; Somatostatin; acromegaly; nonpeptidic; orally active.

Acromegaly is a disease caused by the oversecretion of growth hormone. It is currently treated by i.v. injection with cyclic peptide drugs that activate somatostatin receptor subtype 2 (SSTR2). Here, novel nonpeptidic, small-mol., and orally active SSTR2 agonists were identified from a hit compound (13). Pharmacophore studies enabled scaffold hopping to obtain a unique 3,4,5-trisubstituted pyridine motif. Further optimization conferred potent SSTR2 agonistic activity and metabolic stability. Several compounds were evaluated and these showed good oral pharmacokinetic profiles in rats, and one representative compound (25)(I) showed highly potent inhibition of growth hormone secretion induced by growth hormone-releasing hormone in rats. Based on these results, 25 was identified as a promising lead for further optimization. A structure-activity relationship (SAR) study and the metabolic stability data for this compound are also described.

ACS Chemical Neuroscience published new progress about Acromegaly. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Synthetic Route of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Lv, Kai published the artcileDesign, synthesis and anti-HBV activity of NVR3-778 derivatives, Application In Synthesis of 73874-95-0, the main research area is preparation antiviral hepatitis B HBV NVR3 778 derivative; Anti-HBV activity; Capsid assembly modulators; NVR3-778; Structure modification; Sulfamoylbenzamides.

NVR3-778, one of the most advanced capsid assembly modulators (CAMs), is currently in phase II clin. trial for the treatment of HBV infection. In this study, we reported the first structure optimization of NVR3-778. Compound 2d was found to exhibit more potent anti-HBV activity (IC50: 0.25μM), lower cytotoxicity (CC50: 10.68μM) and higher selectivity index (SI: 40.72) than NVR3-778 (IC50: 0.33μM; CC50: 5.14μM; SI: 18.36) in vitro, and also display similar inhibitory effect on the assembly of HBV capsids as NVR3-778. Mol. docking further suggested that compound 2d might form a stronger interaction with core protein. Moreover, compound 2d also showed acceptable pharmacokinetic profiles. Currently compound 2d was selected as a new lead for further modifications, and studies to determine the in vivo anti-HBV studies of 2d will begin soon.

Bioorganic Chemistry published new progress about Antiviral agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Application In Synthesis of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Hendrick, Charles E. published the artcileDirect-to-Biology Accelerates PROTAC Synthesis and the Evaluation of Linker Effects on Permeability and Degradation, Product Details of C10H20N2O2, the main research area is proteolysis targeting chimera preparation linker effect.

A platform to accelerate optimization of proteolysis targeting chimeras (PROTACs) had been developed using a direct-to-biol. (D2B) approach with a focus on linker effects. A large number of linker analogs-varying length, polarity, and rigidity-were rapidly prepared and characterized in four cell-based assays by streamlining time-consuming steps in synthesis and purification The expansive data set informs on linker structure activity relationships for in-cell E3 ligase target engagement, degradation, permeability, and cell toxicity. Unexpected aspects of linker SAR were discovered, consistent with literature reports on “”linkerol.””, and the method dramatically speeds up empirical optimization. Physicochem. property trends emerged, and the platform had the potential to rapidly expand training sets for more complex prediction models. In-depth validation studies were carried out and confirm the D2B platform was a valuable tool to accelerate PROTAC design-make-test cycles.

ACS Medicinal Chemistry Letters published new progress about Chemical library. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Product Details of C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem