A5101803643- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Radical Photochemical Reactions
- Catalytic C–H Functionalization Methods
- Sulfur-Based Synthesis Techniques
- Chemical Synthesis and Analysis
- Cancer, Hypoxia, and Metabolism
- Fluorine in Organic Chemistry
- Cancer Mechanisms and Therapy
- Cancer therapeutics and mechanisms
- Synthesis and biological activity
- Chronic Lymphocytic Leukemia Research
- Chemical Synthesis and Reactions
- Enzyme function and inhibition
- X-ray Diffraction in Crystallography
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Synthesis and Biological Activity
- Synthesis and Biological Evaluation
- Inorganic Fluorides and Related Compounds
- Histiocytic Disorders and Treatments
- Asymmetric Hydrogenation and Catalysis
- Oxidative Organic Chemistry Reactions
- Lymphoma Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
Henan Normal University
2017-2024
Green Chemistry
2017-2020
Xinxiang University
2017
La Roche College
2005-2014
Restoration of p53 activity by inhibition the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, hydrophobic protein-protein surface represents a significant challenge development small-molecule inhibitors with desirable pharmacological profiles. RG7112 was first inhibitor in clinical development. Here, we report discovery and characterization second generation MDM2 inhibitor, RG7388, superior potency selectivity.
The p53 tumor suppressor is a potent transcription factor that plays key role in the regulation of cellular responses to stress. It controlled by its negative regulator MDM2, which binds directly and inhibits transcriptional activity. MDM2 also targets for degradation proteasome. Many tumors produce high levels thereby impairing function. Restoration activity inhibiting p53-MDM2 interaction may represent novel approach cancer treatment. RG7112 (2g) first clinical small-molecule inhibitor...
Abstract With ethylene glycol as a green solvent, general transition metal‐free photocatalytic system using 9‐mesityl‐10‐methylacridinium perchlorate (Acr + −Mes ⋅ ClO 4 − ) catalyst was developed for the synthesis of sulfone‐containing heterocycles including thioflavones, oxindoles, and quinoline‐2,4(1 H ,3 )‐diones through cascade sulfonation/cyclization reactions under irradiation blue light at room temperature. magnified image
The cyclin-dependent kinases (CDKs) and their cyclin partners are key regulators of the cell cycle. Since deregulation CDKs is found with high frequency in many human cancer cells, pharmacological inhibition small molecules has potential to provide an effective strategy for treatment cancer. 2,4-diamino-5-ketopyrimidines 6 reported here represent a novel class potent ATP-competitive inhibitors that selectively target kinase family. This diaminopyrimidine core substituted 4-piperidine moiety...
The development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents a novel approach for cancer treatment. In previous communication, the efforts leading identification non-imidazoline inhibitor, RG7388, was disclosed and revealed desirable in vitro vivo pharmacological properties that this class pyrrolidine-based possesses. Given richness critical need wide variety chemical structures ensure success clinic, research expanded evaluate additional derivatives....
2,1,3-Benzothiadiazole is widely used as a privileged scaffold in pharmaceuticals and organic functional materials. Nonetheless, many current methods for the functionalization of 2,1,3-benzothiadiazole rely on preactivation, transition metal catalysts/promoters, or an elevated reaction temperature. Herein we disclose transition-metal-free visible-light-induced photocatalytic method direct C–H alkylation using readily accessible carboxylic acid derivatives, i.e., N-hydroxyphthalimide esters...
Bruton's tyrosine kinase (BTK) inhibitors suppressing the aberrant activation of BTK have led to a paradigm shift in therapy B-cell malignancies. However, there is an urgent need discover more selective covalent owing off-target adverse effects approved inhibitor, ibrutinib. Herein, we disclose discovery and preliminary activity studies novel carrying 1-amino-1H-imidazole-5-carboxamide as hinge binder. The most potent inhibitor 26 demonstrates impressive selectivity, favorable...
Abstract Low‐energy light, endowing with excellent characteristics of lower energy, fewer side reactions, more abundance in solar light. The scenario has been developed for the fabrication indenone through a low‐energy green light driven radical annulation reaction between α‐keto acids and internal alkynes using Rhodamine 6G as photocatalyst. Various kinds substrates are suitable this methodology, affording corresponding indenones greener efficient manner.
Pulmonary fibrosis (PF) is a fatal interstitial lung disease associated with declining pulmonary function but currently few effective drugs. Cellular senescence has been implicated in the pathogenesis of PF and could be potential therapeutic target. Emerging evidence suggests wogonin, bioactive compound isolated from Scutellaria baicalensis , owns anti-senescence properties, however, possible impact wogonin on mechanisms remain unclear. In this study, well-established mouse model was...
The sustainable construction of spirocyclic compounds is important to the scientific community and pharmaceutical industries. Herein, we demonstrate a carbamoyl radical-initiated intramolecular dearomative spirocyclization access spiro-cyclohexadiene oxindoles under visible light irradiation, which constitutes first example accessing I-substituted derivatives that facilitate diversified transformations. Additionally, scalability, late-stage modification drugs, significant antitumor activity...
A set of transition-metal-free NaI/TBHP-mediated sulfonylation cyclization reactions methylthiolated alkynones with sulfonyl hydrazides was developed, by which various 3-sulfonylated thioflavones were prepared under mild reaction conditions.
A variety of terminal alkenes were converted to the corresponding amides in yields 25 86% water <italic>via</italic> treatment with 1,3-dibromo-5,5-dimethylhydantoin, followed by reaction molecular iodine and aq. NH<sub>3</sub> (or amine) one pot.
3123 Background: VTAs now undergoing clinical trials include those that interact with tubulin (e.g. combretastatins and ZD6126) the distinct tubulin-independent based flavonoid DMXAA (AS1404). induces both direct apoptosis of tumor vascular endothelial cells a secondary induction vasoactive agents such as serotonin (from platelets aggregating to damaged vasculature) necrosis factor (TNFα). The study objective was determine whether plasma levels metabolite, 5HIAA, correlated induced blood...
A series of 5,6,7,8‐tetrahydro‐1,6‐naphthyridin‐2(1 H )‐one derivatives hydrochloride were obtained using a convenient and mild method from 4‐piperidone monohydrate hydrochloride. The newly synthesized compounds their characterized by 1 NMR, 13 C high‐resolution mass spectrometry. Furthermore, cytotoxicity in vitro the screened MTT or CCK8 assay. results showed that some potential antitumor activity. Among them, compound 10a had effects against tumor cells (MOLM‐13), half maximal inhibitory...
Reported is a one-pot combination of metal (AgOTf) and organo (proline) catalysis for the synthesis 1,2-dihydroisoquinolines from three-component reaction 2-alkynylbenzaldehyde, amines, ketones. The scope was explored with few 2-alkynylbenzaldehydes, selected EWG/EDG group anilines, limited Although chiral proline catalyst used, only racemic products were obtained. Aprotic solvents (THF, toluene, dichloroethane) led to very low yields products.