77103-47-0

Upstream product

• 27914-73-4 4-acetoxybenzoyl chloride 
• 2345-34-8 4-acetyloxy-benzoic acid 
• 2881-83-6 ethyl 4-methoxybenzoylacetate 
• 623-73-4 diazoacetic acid ethyl ester 
• 123-08-0 4-hydroxy-benzaldehyde 
• 99-93-4 4-Hydroxyacetophenone 
• 105-58-8 Diethyl carbonate 

Downstream Products

• 3813-93-2 2-(4-hydroxy-phenyl)-1H-quinolin-4-one 
• 1361006-01-0 (E)-ethyl 3-(4-hydroxyphenyl)-3-(phenylamino)acrylate 
• 1449521-91-8 3-(tert-butyldimethylsilyloxy)-3-(4-(tert-butyldimethylsilyloxy) phenyl)-N-methoxy-N-methylpropanamide 
• 1449521-90-7 6-(tert-butyldimethylsilyloxy)-6-(4-(tert-butyldimethylsilyloxy)phenyl)-1-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)hexane-2,4-dione 
• 1449521-92-9 3-(methoxy(methyl)amino)-1-(4-methoxyphenyl)-3-oxopropyl 2-(2-(tert-butyldimethylsilyloxy)-2-(4-(tert-butyldimethylsilyloxy)phenyl)ethyl)-4,6-dihydroxybenzoate 
• 1462352-06-2 ethyl 3-[4-(4'-propoxy)benzoyloxyphenyl]-3-oxo-propanoate 
• 1462352-07-3 C₂₂H₂₄O₆ 
• 1462352-08-4 C₂₃H₂₆O₆ 
• 1462352-09-5 C₂₄H₂₈O₆ 
• 1462352-10-8 C₂₅H₃₀O₆ 
• 1462352-11-9 C₂₆H₃₂O₆ 
• 1462352-12-0 C₂₇H₃₄O₆ 

Relevant academic research and scientific papers

Allosteric Inhibition of the Tumor-Promoting Interaction between Exon 2–Depleted Splice Variant of Aminoacyl–Transfer RNA Synthetase-Interacting Multifunctional Protein 2 and Heat Shock Protein 70

Although protein-protein interactions (PPIs) have emerged as an attractive therapeutic target space, the identification of chemicals that effectively inhibit PPIs remains challenging. Here, we identified through library screening a chemical probe (compound 1) that can inhibit the tumor-promoting interaction between the oncogenic factor exon 2–depleted splice variant of aminoacyl–transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) and heat shock protein 70 (HSP70). We found that compound 1 binds to the N-terminal subdomain of glutathione S-transferase (GST-N) of AIMP2-DX2, causing a direct steric clash with HSP70 and an intramolecular interaction between the N-terminal flexible region and the GST-N of AIMP2-DX2, which induces masking of the HSP70 binding region during molecular dynamics and mutation studies. Compound 1 thus interferes with the AIMP2-DX2 and HSP70 interaction and suppresses the growth of cancer cells that express high levels of AIMP2-DX2 in vitro and in preliminary in vivo experiment. This work provides an example showing that allosteric conformational changes induced by chemicals can be a way to control pathologic PPIs. SIGNIFICANCE STATEMENT Compound 1 is a promising protein-protein interaction inhibitor between AIMP2-DX2 and HSP70 for cancer therapy by the mechanism with allosteric modulation as well as competitive binding. It seems to induce allosteric conformational change of AIMP2-DX2 proteins and direct binding clash between AIMP2-DX2 and HSP70. The compound reduced the level of AIMP2-DX2 in ubiquitin-dependent manner via suppression of binding between AIMP2-DX2 and HSP70 and suppressed the growth of cancer cells highly expressing AIMP2-DX2 in vitro and in preliminary in vivo experiment.

Design, Synthesis, and Biochemical Characterization of Non-Native Antagonists of the Pseudomonas aeruginosa Quorum Sensing Receptor LasR with Nanomolar IC50 Values

Quorum sensing (QS), a bacterial cell-to-cell communication system mediated by small molecules and peptides, has received significant interest as a potential target to block infection. The common pathogen Pseudomonas aeruginosa uses QS to regulate many of its virulence phenotypes at high cell densities, and the LasR QS receptor plays a critical role in this process. Small molecule tools that inhibit LasR activity would serve to illuminate its role in P. aeruginosa virulence, but we currently lack highly potent and selective LasR antagonists, despite considerable research in this area. V-06-018, an abiotic small molecule discovered in a high-throughput screen, represents one of the most potent known LasR antagonists but has seen little study since its initial report. Herein, we report a systematic study of the structure-activity relationships (SARs) that govern LasR antagonism by V-06-018. We synthesized a focused library of V-06-018 derivatives and evaluated the library for bioactivity using a variety of cell-based LasR reporter systems. The SAR trends revealed by these experiments allowed us to design probes with 10-fold greater potency than that of V-06-018 and 100-fold greater potency than other commonly used N-acyl-l-homoserine lactone (AHL)-based LasR antagonists, along with high selectivities for LasR. Biochemical experiments to probe the mechanism of antagonism by V-06-018 and its analogues support these compounds interacting with the native ligand-binding site in LasR and, at least in part, stabilizing an inactive form of the protein. The compounds described herein are the most potent and efficacious antagonists of LasR known and represent robust probes both for characterizing the mechanisms of LuxR-type QS and for chemical biology research in general in the growing QS field.

Synthesis of new metallomesogens based on 3-ketoesters

Ethyl 3-(4-hydroxyphenyl)-3-ketopropionate was synthesized by acylation of acetoacetic ester with 4-acetoxybenzoyl chloride, followed by cleavage of aroylacetoacetic ester and hydrolysis of the protecting acetate group. Further esterification of the pheno

Synthetic studies towards tragoponol: Preparation of a highly functionalized resorcylate

Studies on the synthesis of racemic tragoponol are described. The western resorcylate unit of tragoponol was efficiently constructed from appropriate diketo-dioxinone and secondary alcohol intermediates using a ketene generation-trapping and aromatization

Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:Quinone oxidoreductase (PfNDH2)

A program was undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a dehydrogenase of the mitochondrial electron transport chain of the malaria parasite Plasmodium falciparum. PfNDH2 has only one known inhibitor, hydroxy-2-dodecyl-4-(1H)-quinolone (HDQ), and this was used along with a range of chemoinformatics methods in the rational selection of 17 000 compounds for high-throughput screening. Twelve distinct chemotypes were identified and briefly examined leading to the selection of the quinolone core as the key target for structure-activity relationship (SAR) development. Extensive structural exploration led to the selection of 2-bisaryl 3-methyl quinolones as a series for further biological evaluation. The lead compound within this series 7-chloro-3-methyl-2-(4-(4-(trifluoromethoxy)benzyl)phenyl) quinolin-4(1H)-one (CK-2-68) has antimalarial activity against the 3D7 strain of P. falciparum of 36 nM, is selective for PfNDH2 over other respiratory enzymes (inhibitory IC50 against PfNDH2 of 16 nM), and demonstrates low cytotoxicity and high metabolic stability in the presence of human liver microsomes. This lead compound and its phosphate pro-drug have potent in vivo antimalarial activity after oral administration, consistent with the target product profile of a drug for the treatment of uncomplicated malaria. Other quinolones presented (e.g., 6d, 6f, 14e) have the capacity to inhibit both PfNDH2 and P. falciparum cytochrome bc1, and studies to determine the potential advantage of this dual-targeting effect are in progress.

MEDICINAL COMPOSITION

The present invention is composed of a pharmaceutical composition for the therapy of nephritis which comprises an amide derivative represented by the following formula [1] or pharmaceutically acceptable salt thereof, as an active ingredient: ???wherein R1 and R2 may be the same or different and each is hydrogen, alkyl which may be substituted, acyl, aryl which may be substituted, or an aromatic heterocyclic group which may be substituted; R3, R4, R5 and R6 may be the same or different and each is hydrogen, halogen, hydroxy, amino which may be substituted, alkyl which may be substituted, alkoxy or nitro and the like; and R7 represents cyclic amino which may be substituted or azabicycloalkylamino which may be substituted. The pharmaceutical composition of the invention is useful for the therapy of nephritis.

AMIDE DERIVATIVES AND DRUG COMPOSITIONS

The present invention is composed of an amide derivative represented by the following formula [1] or pharmaceutically acceptable salt thereof: ???wherein R1 and R2 may be the same or different and each is hydrogen, alkyl which may be substituted, acyl, aryl which may be substituted, or an aromatic heterocyclic group which may be substituted; R3, R4, R5, and R6 may be the same or different and each is hydrogen, halogen, hydroxy, amino which may be substituted, alkyl which may be substituted, alkoxy, or nitro and the like; and R7 represents cyclic amino which may be substituted or azabicycloalkylamino which may be substituted, and a pharmaceutical composition which comprises it as an active ingredient. The compound of the invention is useful as an inhibitor of TGF-β production or an antagonist of TGF-β.

Acyclovir diester derivatives

Disclosed are novel prodrugs represented by the following structural formula: Z is oxygen or sulfur; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a substituted benzyl group with one or more protected hydroxy or protected amine groups in the ortho or para positions, relative to the phosphate ester, which can be converted in vivo to a hydroxy or amino group. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.

Flavonoids Syntheses. VI. Synthesis and Spectral Properties of 4-Arylcoumarins (Neoflavones)

Eight neoflavones were synthesized for examination of their spectral properties.In the mass spectra, 2'-oxygenated neoflavones showed characteristic fragments owing to dehydrxylation or demethoxylation.Other spectral data ultraviolet, proton and carbon-13 nuclear magnetic resonance, however, showed no specific features that could be used to characterize the structures.Keywords--neoflavone synthesis; 4-arylcoumarin; 2'-oxygenated neoflavone; mass spectrum