Day: November 16, 2022

Malakoutikhah, Morteza published the artcileN-Methyl Phenylalanine-Rich Peptides as Highly Versatile Blood-Brain Barrier Shuttles, HPLC of Formula: 158922-07-7, the main research area is blood brain barrier delivery peptide drug.

Here we studied the capacity of N-MePhe-(N-MePhe)3-CONH2, Cha-(N-MePhe)3-CONH2, and 2Nal-(N-MePhe)3-CONH2 to carry various drugs (cargos) in in vitro blood-brain barrier (BBB) models in order to determine the versatility of these peptides as BBB-shuttles for drug delivery to the brain. Using SPPS, the peptides were coupled to GABA, Nip, and ALA to examine their passive BBB permeation by means of PAMPA and their lipophilicity by IAMC. Unaided, these nonpermeating drugs alone did not cross the PAMPA barrier and the BBB passively; however, the peptides tested as potential BBB shuttles transferred them by passive transfer through the PAMPA phospholipid. The permeability of peptides that showed the highest permeability in PAMPA, and Ac-N-MePhe-(N-MePhe)3-CONH2 as the parent peptide was also examined in bovine brain microvessel endothelial cells (BBMECs). These peptide-based BBB shuttles open up the possibility to overcome the formidable obstacle of the BBB, thereby achieving drug delivery to the brain.

Journal of Medicinal Chemistry published new progress about Biological permeation. 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, HPLC of Formula: 158922-07-7.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Xu, Xi published the artcileDiscovery of novel glutaminase 1 allosteric inhibitor with 4-piperidinamine linker and aromatic heterocycles, COA of Formula: C10H20N2O2, the main research area is piperidinamine linker aromatic heterocycle preparation design GLS1 glutaminase inhibitor; glutaminase GLS1 allosteric inhibitor SAR metabolic stability antitumor; 4-Piperidinamine; Allosteric inhibitors; GLS1; Glutaminase 1; Glutamine metabolism.

Glutaminase 1 (GLS1) is overexpressed in multiple types of malignant tumors and is viewed as a promising target in cancer therapy. Thus, the discovery for small-mol. GLS1 inhibitors is urgent. Based on the authors’ previous study of compound I, a potent GLS1 allosteric inhibitor yet with a limited metabolic stability, a structure-based optimization was carried out, with a series of novel GLS1 allosteric inhibitors rationally designed, synthesized and biol. evaluated. Such endeavor has culminated in the identification of compound II, a promising GLS1 allosteric inhibitor with a 4-piperidinamine linker and aromatic heterocycles. Compound II displayed robust GLS1 binding affinity, superior liver microsome metabolic stability, and moderate anti-tumor activity (TGI: 47.5%) in HCT116 xenograft model with no considerable toxicity in vivo. The mechanism underlying the anti-proliferative effect of compound II on HCT116 cells was studied, revealing that the compound blocked the glutamine metabolism, induced the production of ROS, and triggered apoptosis. These findings merit further investigation of compound II as a targeted cancer therapeutic.

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

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Le, Chen published the artcileReclaimed water application to vegetation restoration in mining area: determination of water quality standards and optimization of moderate treatment technology, Quality Control of 52829-07-9, the main research area is water quality standard determination vegetation restoration moderate treatment technol.

Water shortage severely restricts vegetation restoration of mining area in the northwest China. Moderate treatment of reclaimed water is essential for improving the local ecol. environment. In this study, relevant water quality standards issued by the states and research results were comprehensively considered to propose a reclaimed water quality standard suitable for vegetation restoration of mining area. The available domestic sewage and mine water was moderately treated by hybrid biol. reactor system and nanofiltration membrane system, resp. The effluent quality meet the requirement of reclaimed water quality standards in this study. This study provides theor. support for vegetation restoration of mining area.

E3S Web of Conferences published new progress about Chemical oxygen demand. 52829-07-9 belongs to class piperidines, name is Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, and the molecular formula is C28H52N2O4, Quality Control of 52829-07-9.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Song, Wanchao published the artcileNanofiltration desalination of reverse osmosis concentrate pretreated by advanced oxidation with ultrafiltration: Response surface optimization and exploration of membrane fouling, Formula: C28H52N2O4, the main research area is nanofiltration desalination reverse osmosis advanced oxidation ultrafiltration membrane fouling.

Reverse osmosis (RO) technique has been widely used in the advanced treatment of industrial water and wastewater. However, this process generates a large amount of reverse osmosis concentrate (ROC) which contain high salinity and organic contaminants, and therefore pose serious environmental problems. This study explored the potential of advanced oxidation processes-ultrafiltration (AOPs-UF) pretreatment system and nanofiltration (NF90, Dow Chems.) membrane system for ROC desalination. Under the optimal conditions, 78% of COD and 81% of UV254 pollutants were removed by using advanced oxidation processes with ultrafiltration pretreatment technol. Box-Behnken design (BBD) results showed that the maximum total soluble salts rejection of 97.75% was obtained under the optimized conditions of nanofiltration membrane (the 1.18 MPa operating pressure, 6.79°C feed temperature, 64.33 min filtration time). A combined membrane cleaning method was finally determined via surface morphol. characterization by the comparison of scanning electron microscope (SEM), X-ray energy dispersive anal. (EDS) and Fourier transform IR (FTIR) technique anal. The results confirmed the possibility of advanced oxidation coupled membrane treatment process to treat ROC and realize its reuse. Moreover, by evaluating the benefit calculation, it provides insights for the treatment of industrial wastewater.

Journal of Environmental Chemical Engineering published new progress about Chemical oxygen demand. 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

Rossino, Giacomo published the artcileNew Insights into the Opening of the Occluded Ligand-Binding Pocket of Sigma1 Receptor: Binding of a Novel Bivalent RC-33 Derivative, Recommanded Product: tert-Butyl piperidin-4-ylcarbamate, the main research area is human Sigma1 receptor ligand binding pocket opening RC33 derivative.

Significant progresses have been made to understand the mol. basis of the Sigma1 receptor (S1R) operating in normal and pathol. conditions. S1R is a transmembrane protein that participates in a wide variety of processes at the central nervous system; hence, its function has been associated with mental and neurol. disorders. Several ligands have been proposed to regulate the function of S1R revealing a high plasticity of the ligand-binding pocket. Previous drug-design studies have been mainly based on pharmacophore models; however, the recently revealed crystal structure of S1R provides an excellent opportunity for verifying previous predictions and for evaluating the binding of novel compounds Interestingly, the crystal structure shows that the binding pocket of S1R is highly occluded from solvent; therefore, it is not clear how ligands access this site. In the present work, we applied steered mol. dynamics (SMD) simulations to open the occluded ligand-binding pocket in the S1R crystal structure and to determine the preferred ligand pathway to enter and exit the binding site. The intracellular surface of the β-barrel ligand-binding region was found the most favorable route to accommodate ligands. This route supports the binding of RC-33 (our inhouse-developed S1R modulator) and a new bivalent derivative that constitutes the first divalent structure showed to interact with S1R. Free energy calculations of these compounds associated to S1R agree with exptl. Ki values and provide mol. insights of the binding mode of modulators that could access the S1R ligand-binding pocket through the cytoplasmic region.

Journal of Chemical Information and Modeling published new progress about Central nervous system. 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

Sluder, Ann published the artcileSpiroindolines identify the vesicular acetylcholine transporter as a novel target for insecticide action, HPLC of Formula: 637362-21-1, the main research area is spiroindoline insecticide target vesicular acetylcholine transporter.

The efficacy of all major insecticide classes continues to be eroded by the development of resistance mediated, in part, by selection of alleles encoding insecticide insensitive target proteins. The discovery of new insecticide classes acting at novel protein binding sites is therefore important for the continued protection of the food supply from insect predators, and of human and animal health from insect borne disease. Here we describe a novel class of insecticides (Spiroindolines) encompassing mols. that combine excellent activity against major agricultural pest species with low mammalian toxicity. We confidently assign the vesicular acetylcholine transporter as the mol. target of Spiroindolines through the combination of mol. genetics in model organisms with a pharmacol. approach in insect tissues. The vesicular acetylcholine transporter can now be added to the list of validated insecticide targets in the acetylcholine signaling pathway and we anticipate that this will lead to the discovery of novel mols. useful in sustaining agriculture. In addition to their potential as insecticides and nematocides, Spiroindolines represent the only other class of chem. ligands for the vesicular acetylcholine transporter since those based on the discovery of vesamicol over 40 years ago, and as such, have potential to provide more selective tools for PET imaging in the diagnosis of neurodegenerative disease. They also provide novel biochem. tools for studies of the function of this protein family.

PLoS One published new progress about Caenorhabditis elegans. 637362-21-1 belongs to class piperidines, name is tert-Butyl 5-chlorospiro[indoline-3,4′-piperidine]-1′-carboxylate, and the molecular formula is C17H23ClN2O2, HPLC of Formula: 637362-21-1.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhang, Shengrui published the artcileMerocyanine-based turn-on fluorescent probe for the sensitive and selective determination of thiophenols via a pKa shift mechanism, Formula: C10H20N2O2, the main research area is merocyanine fluorescent probe thiophenol acid dissociation constant shift mechanism; Fluorescent probe; Merocyanine; Thiophenol; pK(a) shift.

The development of fluorescent probes for the sensitive and selective determination of highly toxic thiophenols is considerably important in the fields of biol. and environmental sciences. Herein, a turn-on fluorescent probe for thiophenol, named MCSH, was constructed based on a pKa shift mechanism, employing merocyanine dye as the fluorophore and 2,-4-dinitrobenzenesulfonamide (DNBS) group as the recognition unit. The imine nitrogen of MCSH has a pKa value of 4.12, which renders its non-fluorescent Schiff base form exclusively under neutral conditions. However, after reacting with thiophenols, its DNBS group was removed to afford a merocyanine dye as the final product, whose pKa value upshifts to 8.11, and was present mainly as the fluorescent protonated Schiff base form under neutral media. Such drastic change in pKa values leads to a significant fluorescence enhancement and can be utilized for the detection of thiophenols. The fluorescence intensity at 627 nm increases linearly with thiophenol concentration in the range of 0.2-3μM with a detection limit of 15 nM (S/N = 3). MCSH displays high selectivity for the detection of thiophenols over a wide range of other analytes, including aliphatic thiols. Furthermore, the preliminary applications of MCSH for monitoring thiophenols in living cells and environmental have been carried out.

Talanta published new progress about Analytical test strips. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Formula: C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kanouni, Toufike published the artcileDiscovery of CC-90011: A Potent and Selective Reversible Inhibitor of Lysine Specific Demethylase 1 (LSD1), Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is CC90011 inhibitor lysine specific demethylase 1 LSD1.

Histone demethylase LSDl (KDMlA) belongs to the FAD dependent family of monoamine oxidases and is vital in regulation of mammalian biol. Dysregulation and overexpression of LSD1 are hallmarks of a number of human diseases, particularly cancers that are characterized as morphol. poorly differentiated. As such, inhibitors of LSD1 have potential to be beneficial as a cancer therapy. The most clin. advanced inhibitors of LSDl are covalent inhibitors derived from tranylcypromine (TCP). Herein, we report the discovery of a novel series of reversible and selective LSDl inhibitors. Exploration of structure-activity relationships (SARs) and optimization of ADME properties resulted in the identification of clin. candidate CC-90011. CC-90011 exhibits potent on-target induction of cellular differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cell lines, and antitumor efficacy in patient-derived xenograft (PDX) SCLC models. CC-90011 is currently in phase 2 trials in patients with first line, extensive stage SCLC (ClinicalTrials.gov identifier: NCT03850067).

Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 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

Dolbois, Aymeric published the artcile1,4,9-Triazaspiro[5.5]undecan-2-one Derivatives as Potent and Selective METTL3 Inhibitors, HPLC of Formula: 73874-95-0, the main research area is prostate cancer AML anticancer METTL3 inhibitors optimization crystallog ADME.

N6-methyladenosine (m6A) is the most frequent of the 160 RNA modifications reported so far. Accumulating evidence suggests that the METTL3/METTL14 protein complex, part of the m6A regulation machinery, is a key player in a variety of diseases including several types of cancer, type 2 diabetes, and viral infections. Here we report on a protein crystallog.-based medicinal chem. optimization of a METTL3 hit compound that has resulted in a 1400-fold potency improvement (IC50 of 5 nM for the lead compound 22 (UZH2)(I) in a time-resolved Forster resonance energy transfer (TR-FRET) assay). The series has favorable ADME properties as physicochem. characteristics were taken into account during hit optimization. UZH2 shows target engagement in cells and is able to reduce the m6A/A level of polyadenylated RNA in MOLM-13 (acute myeloid leukemia) and PC-3 (prostate cancer) cell lines.

Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 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

Martinez-Gonzalez, Sonia published the artcileDiscovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors, COA of Formula: C10H20N2O2, the main research area is triazolopyridazinylquinoline derivative PIM kinase inhibition antiproliferative anticancer; Anticancer agents; Antiproliferative activity; Chemical probes; PIM-1 inhibitors; Selective PIM-1/PIM-3 inhibitors; Synergistic effects; pan-PIM inhibitors.

PIM kinase family (PIM-1, PIM-2 and PIM-3) is an appealing target for the discovery and development of selective inhibitors, useful in various disease conditions in which these proteins are highly expressed, such as cancer. The significant effort put, in the recent years, towards the development of small mols. exhibiting inhibitory activity against this protein family has ended up with several mols. entering clin. trials. As part of our ongoing exploration for potential drug candidates that exhibit affinity towards this protein family, we have generated a novel chem. series of triazolo[4,3-b]pyridazine based tricycles by applying a scaffold hopping strategy over our previously reported potent pan-PIM inhibitor ETP-47453 (compound 2). The structure-activity relationship studies presented herein demonstrate a rather selective PIM-1/PIM-3 biochem. profile for this novel series of tricycles, although pan-PIM and PIM-1 inhibitors have also been identified. Selected examples show significant inhibition of the phosphorylation of BAD protein in a cell-based assay. Moreover, optimized and highly selective compounds, such as 42, did not show significant hERG inhibition at 20 μM concentration, and proved its antiproliferative activity and utility in combination with particular antitumoral agents in several tumor cell lines.

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

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem