Month: December 2022

Lei, Hanqi published the artcileCRISPR screening identifies CDK12 as a conservative vulnerability of prostate cancer, HPLC of Formula: 1702809-17-3, the publication is Cell Death & Disease (2021), 12(8), 740, database is CAplus and MEDLINE.

Androgen receptor (AR) signaling inhibitors provide limited survival benefits to patients with prostate cancer (PCa), and worse, few feasible genomic lesions restrict targeted treatment to PCa. Thus, a better understanding of the critical dependencies of PCa may enable more feasible therapeutic approaches to the dilemma. We performed a kinome-scale CRISPR/Cas9 screen and identified cyclin-dependent kinase 12 (CDK12) as being conservatively required for PCa cell survival. Suppression of CDK12 by the covalent inhibitor THZ531 led to an obvious anti-PCa effect. Mechanistically, THZ531 downregulated AR signaling and preferentially repressed a distinct class of CDK12 inhibition-sensitive transcripts (CDK12-ISTs), including prostate lineage-specific genes, and contributed to cellular survival processes. Integration of the super-enhancer (SE) landscape and CDK12-ISTs indicated a group of potential PCa oncogenes, further conferring the sensitivity of PCa cells to CDK12 inhibition. Importantly, THZ531 strikingly synergized with multiple AR antagonists. The synergistic effect may be driven by attenuated H3K27ac signaling on AR targets and an intensive SE-associated apoptosis pathway. In conclusion, we highlight the validity of CDK12 as a druggable target in PCa. The synergy of THZ531 and AR antagonists suggests a potential combination therapy for PCa.

Cell Death & Disease 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, HPLC of Formula: 1702809-17-3.

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

Yi, Hailing published the artcileUltrasonic treatment enhances the formation of oxygen vacancies and trivalent manganese on α-MnO₂ surfaces: Mechanism and application, Synthetic Route of 826-36-8, the publication is Journal of Colloid and Interface Science (2022), 629-638, database is CAplus and MEDLINE.

Catalytic activity is the main obstacle limiting the application of peroxymonosulfate (PMS) activation on transition metal oxide catalysts in organic pollutant removal. Herein, ultrasonic treatment was applied to α-MnO₂ to fabricate a new u-α-MnO₂ catalyst for PMS activation. Di-Me phthalate (DMP, 10 mg/L) was almost completely degraded within 90 min, and the pseudofirst-order rate constant for DMP degradation in the u-α-MnO₂/PMS system was âˆ? times that in the initial α-MnO₂/PMS system. The ultrasonic treatment altered the crystalline and pore structures of α-MnO₂ and produced defects on the u-α-MnO₂ catalyst. According to the XPS, TG, and EPR results, higher contents of trivalent Mn and oxygen vacancies (OVs) were produced on the catalyst surfaces. The OVs induced the decomposition of PMS to produce ¹O₂, which was identified as the main reactive oxygen species (ROS) responsible for DMP degradation The u-α-MnO₂ catalyst presented great reusability, especially by ultrasonic regeneration of OVs toward the used catalyst. This study provides new insights into regulating OVs generation and strengthening catalyst activity in the PMS activation process for its application in water purification

Journal of Colloid and Interface Science 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 C6H12N2O, Synthetic Route of 826-36-8.

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

Dong, Yuxiang published the artcileStructure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439), Quality Control of 39546-32-2, the publication is Journal of Medicinal Chemistry (2017), 60(7), 2654-2668, database is CAplus and MEDLINE.

Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pK_a and lower log D_7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, addnl. functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D_7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associated with high and prolonged plasma exposure, but exposure on its own did not explain the presence or absence of either curative efficacy or in vivo toxicity.

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 C6H12N2O, Quality Control of 39546-32-2.

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

Huang, Zhiyan published the artcileCoagulation treatment of swine wastewater by the method of in-situ forming layered double hydroxides and sludge recycling for preparation of biochar composite catalyst, COA of Formula: C9H17NO, the publication is Chemical Engineering Journal (Amsterdam, Netherlands) (2019), 784-792, database is CAplus.

In order to achieve enhanced treatment of swine wastewater as well as resource recycle, in this work, we applied coagulation treatment on swine wastewater by adding Fe and Mg ions, MgFe layered double hydroxides (LDHs) was yielded during coagulation process and the coagulation sludge was recycled to prepare biochar composite catalyst. The removal rates of total phosphorus (TP) and COD (COD) by Mg-Fe coagulation could achieve 82.55% and 98.51%, which is higher than that by coagulation with individual Mg²⁺ or individual Fe³⁺. Finely dispersed MgFe-LDHs flocculation was formed during the coagulation process and was embedded within zoogloea, suspended particles, organic matters, etc. The obtained coagulation sludge was recycled to prepare biochar composite catalyst by oxygen-limited pyrolysis. Redox reaction of iron compounds and electron shuttles capacity of biochar in the catalyst could activate potassium peroxymonosulfate (PMS) to generate ·OH, ·OOH and ¹O₂, which was responsible for catalysis potential. The as-prepared biochar composite catalyst showed satisfactory catalytic degradation capacity on tylosin and rhodamine B (pH value varied from 3 to 10), and the maximum degradation rate achieved 92.2% for tylosin and 81.9% for rhodamine B (RhB). Coagulation treatment of swine wastewater and in-situ formed layered double hydroxides recycling was suitable in wastewater treatment and resource recycling, of which the degradation rates of RhB were above 83% after five cycling experiments In general, the combined process exhibits great potential for the deep treatment of swine wastewater and resource recycling for sludge.

Chemical Engineering Journal (Amsterdam, Netherlands) 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 C9H17NO, COA of Formula: C9H17NO.

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

Wu, Chun-Feng published the artcileSynthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer, HPLC of Formula: 39546-32-2, the publication is European Journal of Medicinal Chemistry (2022), 114055, database is CAplus and MEDLINE.

The development of inhibitors targeting the PI3K-Akt-mTOR signaling pathway has been greatly hindered by the on-target AEs, such as hyperglycemia and hepatotoxicities. In this study, a series of diaryl urea derivatives has been designed and synthesized based on clin. candidate gedatolisib, and most of the newly synthesized derivatives showed kinase inhibitory and antiproliferative activities within nanomolar and submicromolar level, resp. The terminal L-proline amide substituted derivative I showed 8.6-fold more potent PI3Kα inhibitory activity (0.7 nM) and 4.6-fold more potent antiproliferative effect against HCT116 cell lines (0.11μM) compared with control gedatolisib. The potential antitumor mechanism and efficacy of I in HCT116 xenograft models have also been evaluated, and found I showed comparable in vivo antitumor activity with gedatolisib. The safety investigations revealed that compound I exhibited more safer profiles in the selectivity of liver cells (selectivity index: >6.6 vs 1.85) and blood glucose regulation than gedatolisib. In addition, the in vitro stability assays also indicated that developed compound I possessed good metabolic stabilities.

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 C9H9BO2, HPLC of Formula: 39546-32-2.

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

Long, Jiao published the artcileNickel/Bronsted Acid-Catalyzed Chemo- and Enantioselective Intermolecular Hydroamination of Conjugated Dienes, Safety of Piperidine-4-carboxamide, the publication is iScience (2019), 369-379, database is CAplus and MEDLINE.

A novel nickel/Bronsted acid-catalyzed asym. hydroamination of acyclic 1,3-dienes was established. A wide array of primary and secondary amines were transformed into allylic amines with high yields and high enantioselectivities under very mild conditions. Moreover, this method was compatible with various functional groups and heterocycles, allowing for late-stage functionalization of biol. active complex mols. Remarkably, this protocol exhibited good chemoselectivity with respect to amines bearing two different nucleophilic sites. Mechanistic studies revealed that the enantioselective carbon-nitrogen bond-forming step was reversible.

iScience 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, Safety of Piperidine-4-carboxamide.

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

He, Yuan published the artcileCatalytic ozonation for metoprolol and ibuprofen removal over different MnO₂ nanocrystals: Efficiency, transformation and mechanism, Formula: C9H17NO, the publication is Science of the Total Environment (2021), 147328, database is CAplus and MEDLINE.

Manganese dioxide has been widely recognized as catalyst in catalytic ozonation for organic pollutants removal from wastewater in recent decades. However, few studies focus on the structure-activity relationship of MnO₂ and catalytic ozonation mechanism in water. In the present study, the oxidative reactivity of three different crystal phases of MnO₂ corresponding to α-MnO₂, β-MnO₂ and γ-MnO₂ towards metoprolol (MET) and ibuprofen (IBU) were evaluated. α-MnO₂ was found to contain the most abundant oxygen vacancy and readily reducible surface adsorbed oxygen (O^2-, O^–, OH^–), which facilitated an increase of ozone utilization and the highest catalytic performance with 99% degradation efficiency for IBU and MET. α-MnO₂ was then selected to investigate the optimum key operating parameters with a result of catalyst dosage 0.1 g/L, ozone dosage 1 mg/min and an initial pH 7. The introduction of α-MnO₂ promoted reactive oxygen species (O^2-, O^–, OH^–) generation which played significant roles in IBU degradation Probable degradation pathways of MET and IBU were proposed according to the organic intermediates identified and the reaction sites based on d. function theory (DFT) calculations The present study deepened our understanding on the MnO₂ catalyzed ozonation and provided reference to enhance the process efficiency.

Science of the Total Environment 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 C9H17NO, Formula: C9H17NO.

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

Wang, Yujiao published the artcileFeOx@graphitic carbon core-shell embedded in microporous N-doped biochar activated peroxydisulfate for removal of Bisphenol A: Multiple active sites induced non-radical/radical mechanism, Formula: C9H17NO, the publication is Chemical Engineering Journal (Amsterdam, Netherlands) (2022), 135552, database is CAplus.

The development of novel carbocatalysts with high activity and stability is important for the rapid degradation of emerging pollutants. Fe/N co-doped biochar (FeOx@GC-NBC) was innovatively synthesized with a pyrolytic carbonization method and then used as a functional peroxydisulfate (PDS) activator to degrade Bisphenol A (BPA). FeOx@GC-NBC with an optimized Fe/N ratio modification exhibited 23.16 and 8.65-fold great activity for BPA removal compared to pristine BC and N-doped BC, resp. Approx. 93% of total organic carbon (TOC) could be removed in the heterogeneous activation system. We attributed the excellent performance of FeOx@GC-NBC to the following attributes: i) a microporous carbon matrix with larger sp. surface area (1691.81 m²·g^-1) was favorable for adsorption, exposure of catalyst active sites (e.g., Fe-Nx, Graphitic N) and electron-transfer; ii) the C-O-Fe bond and highly core-shell structure of graphitic nanosheets (FeOx@GC) enhanced the N retention ability and durability of the catalyst; iii) organics adsorption dominated by a “pore-filling and π-π interaction” mechanism effectively promoted BPA oxidation In acidic and neutral solutions, the radical oxidation (SO·-4and ·OH) processes were responsible for BPA decomposition In alk. solution, electron transfer, instead of 1O2 or a high-valent iron species, was the dominant pathway. This study proposes a simple and feasible strategy to synthesize the FeOx@GC-NBC catalyst, which provides insights into catalyst design and the internal active sites involved in the purification mechanism of refractory organics

Chemical Engineering Journal (Amsterdam, Netherlands) 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 C22H23ClN4, Formula: C9H17NO.

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

Peng, Hui published the artcileSuppression of NRF2-ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells, SDS of cas: 39546-32-2, the publication is Toxicology and Applied Pharmacology (2016), 1-7, database is CAplus and MEDLINE.

Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chem. detoxification in normal and tumor cells. Consistent with previous findings that NRF2-ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As₂O₃), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2-ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As₂O₃-challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2-ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As₂O₃-induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As₂O₃-induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2-ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents.

Toxicology and Applied Pharmacology 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, SDS of cas: 39546-32-2.

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

Mao, Fei published the artcileDesign, Synthesis, and Biological Evaluation of Orally Available First-Generation Dual-Target Selective Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) for the Treatment of Alzheimer’s Disease, Safety of Piperidine-4-carboxamide, the publication is ACS Chemical Neuroscience (2018), 9(2), 328-345, database is CAplus and MEDLINE.

Through drug discovery strategies of repurposing and redeveloping existing drugs, a series of novel tadalafil derivatives were rationally designed, synthesized, and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs for Alzheimer’s disease (AD). Among these derivatives, (6R,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-(2-(1-benzylpiperidin-4yl)ethyl)-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione (1p, I) and (6R,12aS)-6-(benzo[d][1,3]dioxol-5-yl)-2-(2-(1-benzylpiperidin-4yl)ethyl)-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione (1w, II) exhibited excellent selective dual-target AChE/PDE5 inhibitory activities and improved blood-brain barrier (BBB) penetrability. Importantly, II·Cit (citrate of II) could reverse the cognitive dysfunction of scopolamine-induced AD mice and exhibited an excellent effect on enhancing cAMP response element-binding protein (CREB) phosphorylation in vivo, a crucial factor in memory formation and synaptic plasticity. Moreover, the mol. docking simulations of II with hAChE and hPDE5A confirmed that the design strategy was rational. In summary, the research provides a potential selective dual-target AChE/PDE5 inhibitor as a good candidate drug for the treatment of AD, and it could also be regarded as a small mol. probe to validate the novel AD therapeutic approach in vivo.

ACS Chemical Neuroscience 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, Safety of Piperidine-4-carboxamide.

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