Month: December 2022

Tang, Kai published the artcileStructure-based design, synthesis and biological evaluation of aminopyrazines as highly potent, selective, and cellularly active allosteric SHP2 inhibitors, Computed Properties of 39546-32-2, the publication is European Journal of Medicinal Chemistry (2022), 114106, database is CAplus and MEDLINE.

Src homol.-2-containing protein tyrosine phosphatase 2 (SHP2) encoded by the proto-oncogene PTPN11 is the first identified non-receptor protein tyrosine phosphatase. SHP2 dysregulation contributes to the pathogenesis of different cancers, making SHP2 a promising therapeutic target for cancer therapy. In this article, authors report the structure-guided design based on the well-characterized SHP2 inhibitor SHP099, extensive structure-activity relationship studies (SARs) of aminopyrazines, biochem. characterization and cellular potency. These medicinal chem. efforts lead to the discovery of the lead compound TK-453 I, which potently inhibits SHP2 (SHP2WT IC₅₀ = 0.023μM, ΔTm = 7.01°C) in a reversible and noncompetitive manner. Compound I exhibits high selectivity over SHP2PTP, SHP1 and PTP1B, and may bind at the “tunnel” allosteric site of SHP2 as SHP099. As the key pharmacophore, the aminopyrazine scaffold not only reorganizes the cationic-π stacking interaction with R111 via the novel hydrogen bond interaction between the S atom of thioether linker and T219, but also mediates a hydrogen bond with E250. In vitro studies indicate that I inhibits proliferation of HeLa, KYSE-70 and THP-1 cells moderately and induces apoptosis of Hela cells. Further mechanistic studies suggest that I can decrease the phosphorylation levels of AKT and Erk1/2 in HeLa and KYSE-70 cells.

European Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C7H13BN2O2, Computed Properties of 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Xin, Zhili published the artcileDiscovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors, Quality Control of 1032229-33-6, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(15), 4298-4302, database is CAplus and MEDLINE.

A series of structurally novel stearoyl-Co-A desaturase 1 (SCD1) inhibitors has been identified via mol. scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(Me carbamoyl)phenyl]piperidine-1-carboxamide (I) exhibited robust in vivo activity with dose-dependent desaturation index lowering effects.

Bioorganic & Medicinal Chemistry Letters published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C9H21NO3, Quality Control of 1032229-33-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Liu, Jian-Guo published the artcileDevelopment of Bisindole-Substituted Aminopyrazoles as Novel GSK-3β Inhibitors with Suppressive Effects against Microglial Inflammation and Oxidative Neurotoxicity, Formula: C18H24N2O2, the publication is ACS Chemical Neuroscience (2020), 11(20), 3398-3408, database is CAplus and MEDLINE.

Development of glycogen synthase kinase-3β (GSK-3β) inactivation-centric agents with polypharmacol. profiles is increasingly recognized as a promising therapeutic strategy against the multifactorial etiopathol. of Alzheimer’s disease (AD). In this respect, a series of disubstituted aminopyrazole derivatives were designed and synthesized as a new class of GSK-3β inhibitors. Most of these derivatives possess GSK-3β inhibitory activities with IC₅₀ values in the micromolar ranges, among which bisindole-substituted aminopyrazole derivative 6h displayed moderate GSK-3β inhibition (IC₅₀ = 1.76 ± 0.19μM), and alleviative effects against lipopolysaccharide (LPS)-induced glial inflammation in BV-2 cells and glutamate-induced oxidative neurotoxicity in HT-22 cells. Further in vivo studies indicated that compound 6h(I) had potent anti-inflammatory effect, by showing markedly reduced microglial activation and astrocyte proliferation in the brain of LPS-injected mice. Overall, the simultaneous modulation of 6h on multiple dysfunctions of disease network highlights this structural distinctively bisindole-substituted aminopyrazole could be a useful prototype for the discovery of novel therapeutic agents to tackle AD and other GSK-3β associated complex neurol. syndromes.

ACS Chemical Neuroscience published new progress about 170364-89-3. 170364-89-3 belongs to piperidines, auxiliary class Indole,Piperidine,Amide, name is tert-Butyl 4-(1H-indol-1-yl)piperidine-1-carboxylate, and the molecular formula is C18H24N2O2, Formula: C18H24N2O2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wu, Qi-Fan published the artcileDesign, synthesis and fungicidal activity of isothiazole-thiazole derivatives, Related Products of piperidines, the publication is RSC Advances (2018), 8(69), 39593-39601, database is CAplus and MEDLINE.

3,4-Dichloroisothiazoles can induce systemic acquired resistance (SAR) to enhance plant resistance against a subsequent pathogen attack, and oxathiapiprolin exhibits excellent anti-fungal activity against oomycetes targeting at the oxysterol-binding protein. To discover novel chems. with systemic acquired resistance and fungicidal activity, 21 novel isothiazole-thiazole derivatives were designed, synthesized and characterized according to the active compound derivatization method. Compound 6u, with EC₅₀ values of 0.046 mg L^-1 and 0.20 mg L^-1 against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo, might act at the same target as oxysterol binding protein (PcORP1) of oxathiapiprolin; this result was validated by cross-resistance and mol. docking studies. The expression of the systemic acquired resistance gene pr1 was significantly up-regulated after treating with compound 6u for 24 h (43-fold) and 48 h (122-fold). These results can help the development of isothiazole-thiazole-based novel fungicides.

RSC Advances published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C19H22BNO5, Related Products of piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wu, Qifan published the artcileDiscovery of Novel Piperidinylthiazole Derivatives As Broad-Spectrum Fungicidal Candidates, Category: piperidines, the publication is Journal of Agricultural and Food Chemistry (2019), 67(5), 1360-1370, database is CAplus and MEDLINE.

Oxathiapiprolin is one of the best active fungicides discovered for oomycetes control. To develop a fungicide candidate with a broad spectrum of activity, 22 new piperidinylthiazole derivatives were designed and synthesized. Compound (I) showed the best activity against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo with 100% and 80% of inhibition, resp., at 1 mg/L, and 72.87% of field efficacy against P. cubensis at 1 g ai/667 m² validated these results. Compound (II) exhibited a broad spectrum of excellent activity against Sclerotinia sclerotiorum with EC₅₀ = 0.30 mg/L (>10 times more active than oxathiapiprolin and azoxystrobin in vitro), good activity against Botrytis cinerea, Cercospora arachidicola, and Gibberella zeae with EC₅₀ of 14.54, 5.57, and 14.03 mg/L in vitro and against P. cubensis and P. infestans with 60% and 30% inhibition rates, resp., at 1 mg/L in vivo. Mode of action studies by RNA sequencing anal. discovered oxysterol-binding protein (OSBP), chitin synthase (CHS1), and (1,3)-β-glucan synthase (FKS2) as the potent target of II against S. sclerotiorum. Quenching studies validated that OSBP was the same target of both II and oxathiapiprolin; it was quenched by both of them. Our studies discovered isothiazole-containing piperidinylthiazole as an OSBP target-based novel lead for fungicide development.

Journal of Agricultural and Food Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C11H8O3, Category: piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Cai, Dong published the artcileExploring new structural features of the 18β-glycyrrhetinic acid scaffold for the inhibition of anaplastic lymphoma kinase, Application of Piperidine-4-carboxamide, the publication is Molecules (2019), 24(19), 3631pp., database is CAplus and MEDLINE.

Novel 18β-glycyrrhetinic acid derivatives possessing a carbamate moiety I [R = 4-ClC₆H₄, 3,4-di-ClC₆H₃, 4-Cl-3-CF₃C₆H₃, etc.; R¹ = OH, morpholino] and structurally similar ester derivatives II [R² = 4-ClC₆H₄CH₂, (4-methylpiperazin-1-yl)methyl, (4-formyl-1-piperidyl)methyl, etc.] were developed and evaluated for their efficacy as antitumor inhibitors. In the cellular assays, most of the N-substituted carbamate derivatives I at the C3-position exhibited potent activities. The results of SAR investigation revealed that the introduction of the morpholine group at the C30-COOH led to a significant loss of the inhibitory potency. Among the ester derivatives, the ester group at C3-position also determined a noticeable reduction in the efficacy. Compound I [R = 3-CF₃C₆H₄; R¹ = OH] exhibited the most prominent antiproliferative activity against six human cancer cells (A549, HT29, HepG2, MCF-7, PC-3, and Karpas299). Furthermore, compound I [R = 3-CF₃C₆H₄; R¹ = OH] exerted a moderate inhibiting effect on the ALK. The results of mol. docking analyses suggested that it could bind well to the active site of the receptor ALK, which was consistent with the biol. data. These results might inspire further structural optimization of 18β-glycyrrhetinic acid aiming at the development of potent antitumor agents. The structures I [R = 4-ClC₆H₄, 4-BrC₆H₄, 4-FC₆H₄, 3-CF₃C₆H₄, 4-CF₃OC₆H₄; R¹ = morpholino] were studied by X-ray crystallog. analyses.

Molecules published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Application of Piperidine-4-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wang, Gen published the artcileMonodispersed CuO nanoparticles supported on mineral substrates for groundwater remediation via a nonradical pathway, Computed Properties of 826-36-8, the publication is Journal of Hazardous Materials (2022), 128282, database is CAplus and MEDLINE.

Nonradical oxidation based on singlet oxygen (¹O₂) has attracted great interest in groundwater remediation due to the selective oxidation property and good resistance to background constituents. Herein, recoverable CuO nanoparticles (NPs) supported on mineral substrates (SiO₂) were prepared by calcination of surface-coated metal-plant phenolic networks and explored for peroxymonosulfate (PMS) activation to generate ¹O₂ for degrading organic pollutants in groundwater. CuO NPs with a close particle size (40 nm) were spatially monodispersed on SiO₂ substrates, allowing highly exposure of active sites and consequently leading to outstanding catalytic performance. Efficient removal of various organic pollutants was obtained by the supported CuO NPs/PMS system under wide operation conditions, e.g., working pH, background anions and natural organic matters. Chem. scavenging experiments, ESR tests, furfuryl alc. decay and solvent dependency experiments confirmed the formation of ¹O₂ and its dominant role in pollutants removal. In situ characterization with ATR-FTIR and Raman spectroscopy and computational calculation revealed that a redox cycle of surface Cu(II)-Cu(III)-Cu(II) was responsible for the generation of ¹O₂. The feasibility of the supported CuO NPs/PMS for actual groundwater remediation was evaluated via a flow-through test in a fixed-bed column, which manifested long-term durability, high mineralization ratio and low metal ion leaching.

Journal of Hazardous Materials published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C6H20Cl2N4, Computed Properties of 826-36-8.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Chen, Yang published the artcileFluorescent quantification of amino groups on silica nanoparticle surfaces, Application of 1-((9H-Fluoren-9-yl)methyl)piperidine, the publication is Analytical and Bioanalytical Chemistry (2011), 399(7), 2503-2509, database is CAplus and MEDLINE.

Functionalization of the surfaces of silica particles is often the first step in their various applications. An improved heterogeneous Fmoc-Cl fluorescent assay using an aqueous solution was developed to detect the number of amino groups on solid-phase supports. The fluorescent Fmoc-Cl method is 50-fold more sensitive than the current UV assay using an organic solvent. This method, together with the homogeneous fluorescamine and OPA assays, is used to detect amino groups on the silica particle surface. The accuracy and effect factors of these methods were examined and the assays were optimized. The results showed that the amine groups on silica particles can produce stronger fluorescence than small amine mols. in solution, because the porous structure of the particle surface is a more hydrophobic environment. The number of active amino groups that can be conjugated with biomols. is much less than the total number of amino groups on the silica particle. Compared with phys. methods, chem. assays involving direct reaction with amino groups would furnish the closest result to the number of active amino groups on the particle surface.

Analytical and Bioanalytical Chemistry published new progress about 35661-58-6. 35661-58-6 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-((9H-Fluoren-9-yl)methyl)piperidine, and the molecular formula is C19H21N, Application of 1-((9H-Fluoren-9-yl)methyl)piperidine.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Gao, Yang published the artcileOvercoming Resistance to the THZ Series of Covalent Transcriptional CDK Inhibitors, COA of Formula: C30H32ClN7O2, the publication is Cell Chemical Biology (2018), 25(2), 135-142.e5, database is CAplus and MEDLINE.

Irreversible inhibition of transcriptional cyclin-dependent kinases (CDKs) provides a therapeutic strategy for cancers that rely on aberrant transcription; however, lack of understanding of resistance mechanisms to these agents will likely impede their clin. evolution. Here, we demonstrate upregulation of multidrug transporters ABCB1 and ABCG2 as a major mode of resistance to THZ1, a covalent inhibitor of CDKs 7, 12, and 13 in neuroblastoma and lung cancer. To counter this obstacle, we developed a CDK inhibitor, E9, that is not a substrate for ABC transporters, and by selecting for resistance, determined that it exerts its cytotoxic effects through covalent modification of cysteine 1039 of CDK12. These results highlight the importance of considering this common mode of resistance in the development of clin. analogs of THZ1, identify a covalent CDK12 inhibitor that is not susceptible to ABC transporter-mediated drug efflux, and demonstrate that target deconvolution can be accomplished through selection for resistance.

Cell Chemical Biology published new progress about 1702809-17-3. 1702809-17-3 belongs to piperidines, auxiliary class Cell Cycle,CDK, name is (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide, and the molecular formula is C30H32ClN7O2, COA of Formula: C30H32ClN7O2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Cheng, Yarui published the artcileNew insights into the function of the proteins IsiC and IsiD from Synechocystis sp. PCC 6803 under iron limitation, Quality Control of 39546-32-2, the publication is Applied Microbiology and Biotechnology (2021), 105(11), 4693-4707, database is CAplus and MEDLINE.

Iron is a common cofactor in biol. processes such as respiration, photosynthesis, and nitrogen fixation. The genes isiC and isiD encode unknown proteins, and the growth of ΔisiC and ΔisiD mutants is inhibited under iron-deficient conditions. To study the regulatory mechanisms of IsiC and IsiD during iron starvation, we carried out transcriptome and metabolome sequencing. The Kyoto Encyclopedia of Genes and Genomes (KEGG) anal. showed that the photosynthesis, nitrogen metabolism, and ABC transporter pathways play a vital role in regulating iron deficiency. Upon iron repletion, IsiC and IsiD also have a regulatory effect on these pathways. Addnl., KEGG anal. of the differential metabolites of wild type (WT) and mutants showed that they were all enriched in starch and sucrose metabolism after iron limitation. Weighted gene co-expression network anal. (WGCNA) constructed a co-expression network of differentially expressed genes with phenotypes and metabolites, and finally identified five modules. The turquoise module was pos. correlated with iron deficiency. In contrast, the WT and blue module exhibited a neg. correlation, and the mutants ΔisiC and ΔisiD were pos. correlated with the gray and brown modules, resp. WGCNA also analyzed the relationship between metabolites and phenotypes, and the green module was related to iron starvation. The co-expression network determined the hub genes and metabolites of each module. This study lays a foundation for a better understanding of cyanobacteria in response to iron deficiency.

Applied Microbiology and Biotechnology published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Quality Control of 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem