Category: piperidines

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

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

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

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

Rus, Anika Zafiah M. published the artcileDeterioration rate of renewable polyurethanes composites prior to ultra violet irradiation exposure, Application of Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, the main research area is polyurethane composite preparation UV irradiation deterioration.

Polyurethanes (PU’s) made from renewable and sustainable materials are one of the most important groups of polymers because of their versatility with wide range of grades, densities and stiffness. In this project, polymers based on renewable materials such as rapeseed (RS) and sunflower oil (SF) were synthesized and cross-linked to form polyurethanes. The effect of prolonged exposure up to 1000 h upon UVB light, in general promotes photodegradation for both RS and SF-based polyurethanes, both neat and also composites loaded with TiO2. The addition of 10% Degussa P25 TiO2 pigment, gives the greater degradation while PUs loaded with 5% Kronos 2220 show the slowest rates of degradation due to the effect of the coating of this pigment. The photostabilizer Tinuvin 770 offers high protection from UVB, thus lead the combination of Tinuvin 770 with Degussa P25 promotes the highest protection from UVB exposure. Moreover, addition of Tinuvin 770 at the stage of preparation of the PUs also greatly reduced the undesirable yellow coloration prevalent during PU synthesis.

Composites, Part B: Engineering published new progress about Absorption. 52829-07-9 belongs to class piperidines, name is Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, and the molecular formula is C28H52N2O4, Application of Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate.

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