Month: November 2022

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

Rathinamoorthy, R. published the artcileDisposable tri-layer masks and microfiber pollution – An experimental analysis on dry and wet state emission, Synthetic Route of 52829-07-9, the main research area is disposable trilayer mask microfiber pollution dry wet emission; Freshwater; Microfiber shedding; Polypropylene; Rubbing; Seawater; Tri-layer mask.

The use of masks as a personal protective material is the new normal in the post-pandemic. The higher use of masks triggers immediate disposal of synthetic textile fibers leading to environmental pollution. This research is aimed to analyze the level of mask-related pollution and its impact on microfiber release. Microfiber emission characteristics of the tri-layer nonwoven mask (Polypropylene-based disposable mask) are analyzed in the dry and wet stages. The individual layers of the mask and the entire mask are evaluated by subjecting them to static immersion and mech. agitation against freshwater and seawater in the wet stage. The results of the study showed a higher microfiber shedding at dry state (14,031.97-177,601.58 fibers/mask) than the wet state (2557.65-22,525.89 fibers/mask). The increased fuzz formation in the dry state than the wet state is noted as the main reason. In the case of wet state, when the freshwater and seawater are compared, both in a static and agitated state, seawater degraded the mask highly (3358.03-27,348.9 fibers/mask) than the freshwater (1757.26-17,702.86 fibers/mask). Higher salinity and d. of the seawater were noted as influencing parameters over the freshwater. When the results of naturally weathered masks are compared with the new mask, weathered masks released significantly (p < 0.05) higher amount of fibers at the evaluation stages. Similar to the new masks, the weathered masks also showed a higher amount of shedding in the dry state and presence of seawater. When the individual layers of the disposable masks were evaluated, at dry and wet states, all the layers showed a similar shedding (no significant difference between individual layers) in the case of a new mask. Whereas, after weathering, a significant amount of higher shedding (p < 0.05) is noted in the middle layer of the mask followed by the outer and inner layer. The difference in fiber composition is noted as the main reason for the strength difference of the nonwoven structure. Statistical anal. confirmed the significant impact of the natural weathering process and seawater on the microfiber shedding. Science of the Total Environment published new progress about Environmental pollution. 52829-07-9 belongs to class piperidines, name is Bis(2,2,6,6-tetramethylpiperidin-4-yl) decanedioate, and the molecular formula is C28H52N2O4, Synthetic Route of 52829-07-9.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Hamper, Bruce C. published the artcileSolid Phase Synthesis of β-Peptoids: N-Substituted β-Aminopropionic Acid Oligomers, Recommanded Product: 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid, the main research area is solid phase preparation peptoid combinatorial library; substituted aminopropionic acid oligomer library preparation.

A solid-phase organic synthesis method has been developed for the preparation of N-substituted-β-aminopropionic acid oligomers or β-peptoids I. Treatment of polymer-bound 4-(benzyloxy)benzyl acrylate with primary amines afforded N-substituted β-alanines. Polymer loadings and product conversions were determined by direct cleavage of resin-bound materials and measurement by 1H NMR with an internal standard The NMR method was used to establish loading of all resin-bound intermediates including acrylic acid. Acylation with acryloyl chloride followed by Michael addition of primary amines to the acrylamide allowed preparation of di-β-peptoids. By a linear set of seven reactions, trimeric N-benzyl-β-aminopropionic acid was prepared in 67% overall yield. Single-bead FT-IR microspectroscopy was used to acquire spectra of the resin bound mono-β-peptoids, di-β-peptoids, and acrylamide intermediates. A combinatorial library of defined mixtures of tri-β-peptoids was prepared by mixing equimolar amounts of the mono-β-peptoid resins and carrying them through two sequences of the acylation-Michael addition The identity of a sample mixture II (R = Me, CH2Ph, CH2CH2Ph, CH2C6H4OMe-4, allyl, CH2CHMe2, CHMeEt, CHMe2) was determined by LC-MS anal. of the cleavage product.

Journal of Organic Chemistry published new progress about Combinatorial chemistry. 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, Recommanded Product: 1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-3-carboxylic acid.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Dolle, Roland E. published the artcileA statistical-based approach to assessing the fidelity of combinatorial libraries encoded with electrophoric molecular tags. Development and application of tag decode-assisted single bead LC/MS analysis, COA of Formula: C21H21NO4, the main research area is statistical sampling mol tag encoded combinatorial library statine amide; combinatorial library QA method tag decoding single bead LCMS; statine peptide library preparation inhibition screening cathepsin plasmepsin.

A statistical sampling protocol is described to assess the fidelity of libraries encoded with mol. tags. The methodol., termed library QA, is based on the combined application of tag decode anal. and single bead LC/MS. The phys. existence of library compounds eluted from beads is established by comparing the mol. weight predicted by tag decode with empirical measurement. The goal of sampling is to provide information on overall library fidelity and an indication of the performance of individual library synthons. The minimal sampling size n for library QA is 10× the largest synthon set. Data are reported as proportion (p) ± lower and upper boundary (lb-ub) computed at the 95% confidence level (α = 0.05). As a practical demonstration, library QA was performed on a 25 200-member library of statine-containing peptide amides (size = 40 × 63 × 10). Sampling was conducted three times at n ∼ 630 beads per run for a total of 1902 beads. The overall proportions found for the three runs were consistent with one another: p = 84.4%, lb-ub = 81.5-87.2%; p = 83.1%, lb-ub = 80.2-85.95; and p = 84.5%, lb-ub = 81.8-87.3%, suggesting the true value of p is close to 84% compound confirmation. The performance pi of individual synthons was also computed. Corroboration of QA data with biol. screening results obtained from assaying the library against cathepsin D and plasmepsin II is discussed.

Journal of Combinatorial Chemistry published new progress about Combinatorial chemistry. 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, COA of Formula: C21H21NO4.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kamakolanu, Uma Gayathri published the artcileDiscovery and Structure-Activity Relationships of Nociceptin Receptor Partial Agonists That Afford Symptom Ablation in Parkinson’s Disease Models, SDS of cas: 73874-95-0, the main research area is piperdinylindole synthesis antiparkinson SAR nociceptin opioid receptor Parkinsons dyskinesia.

A novel series of C(3)-substituted piperdinylindoles were developed as nociceptin opioid receptor (NOP) partial agonists to explore a pharmacol. hypothesis that NOP partial agonists would afford a dual pharmacol. action of attenuating Parkinson’s disease (PD) motor symptoms and development of levodopa-induced dyskinesias. SAR around the C-3 substituents investigated effects on NOP binding, intrinsic activity, and selectivity and showed that while the C(3)-substituted indoles are selective, high affinity NOP ligands, the steric, polar, and cationic nature of the C-3 substituents affected intrinsic activity to afford partial agonists with a range of efficacies. Compounds 4, 5, and 9 with agonist efficacies between 25% and 35% significantly attenuated motor deficits in the 6-OHDA-hemilesioned rat model of PD. Further, unlike NOP antagonists, which appear to worsen dyskinesia expression, these NOP partial agonists did not attenuate or worsen dyskinesia expression. The NOP partial agonists and their SAR reported here may be useful to develop nondopaminergic treatments for PD.

Journal of Medicinal Chemistry published new progress about Antiparkinsonian agents. 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

Tiwari, Shashi B. published the artcileSynthesis of 3-(5-bromo-2,3-dimethoxy-phenyl)-[1, 2, 4] oxadiazole analogues and their evaluation as anti-Parkinson’s agents, Computed Properties of 1690-74-0, the main research area is bromo dimethoxyphenyl oxadiazole preparation antiparkinson activity.

A series of 3-(5-bromo-2,3-dimethoxy-phenyl)-[1, 2, 4] oxadiazole derivatives, e.g., I, was prepared and their evaluation for anti-Parkinson’s activity was measured in vivo using albino rats. The result of the biol. activity studies indicated that some of the synthesized compounds have good agonistic activity on the dopamine receptors and a few of them were also found to be free from neurotoxicity. Thus these compounds might be useful ligands for studying the functional role of dopamine receptors in vivo. The high log P value of the compounds indicates that they should easily cross the blood-brain barrier (log P > 2.6).

Medicinal Chemistry Research published new progress about Antiparkinsonian agents. 1690-74-0 belongs to class piperidines, name is Methyl 1-methylpiperidine-2-carboxylate, and the molecular formula is C8H15NO2, Computed Properties of 1690-74-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem