100516-88-9

Usage

Chemical Properties

Light yellow or pink powder

InChI:InChI=1/C10H9NO/c12-7-8-3-4-10-9(6-8)2-1-5-11-10/h1-6,12H,7H2

Upstream product

• 73987-38-9 quinoline-6-carboxylic acid ethyl ester 
• 38896-30-9 6-(methoxycarbonyl)quinoline 
• 100-74-3 N-ethylmorpholine; 
• 10349-57-2 Quinoline-6-carboxylic acid 
• 541-41-3 chloroformic acid ethyl ester 
• 4113-04-6 quinoline-6-carbaldehyde 
• 173089-80-0 quinolin-6-yl triflate 
• 612-57-7 6-chloroquinoline 
• 77934-75-9 2-Methyl-benzoic acid quinolin-6-ylmethyl ester 

Downstream Products

• 2644-82-8 6-(chloromethyl)quinoline 
• 101279-39-4 6-bromomethyl quinoline 
• 4113-04-6 quinoline-6-carbaldehyde 
• 133739-16-9 6-[(3-fluoro-5-[4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl]phenoxy)methyl]quinoline 
• 1234580-83-6 C₁₉H₁₃NO₂ 
• 54884-99-0 6-benzylquinoline 

Relevant academic research and scientific papers

Design, synthesis, and LFA-1/ICAM-1 antagonist activity evaluation of Lifitegrast analogues

The interaction between Lymphocyte function-associated antigen 1 (LFA-1) and intercellular-adhesion molecule-1 (ICAM-1) plays important roles in the cell-mediated immune response and inflammation associated with dry eye disease. LFA-1/ICAM-1 antagonists can be used for the treatment of dry eye disease, such as Lifitegrast which has been approved by the FDA in 2016 as a new drug for the treatment of dry eye disease. In this study, we designed and synthesized some new structure compounds that are analogues to Lifitegrast, and their biological activities were evaluated by in vitro cell-based assay and also by in vivo mouse dry eye model. Our results demonstrated that one of these analogues of Lifitegrast (compound 1b) showed good LFA-1/ICAM-1 antagonist activity in in vitro assay; meanwhile, it also significantly reduced ocular surface epithelial cells damage, increased goblet cell density in dry eye mouse and highly improved the symptoms of dry eye mouse. [Figure not available: see fulltext.]

Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery

Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phoxSH3A-B) with KD values of 400-600 μM. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phoxSH3A-B and these competed with p22phox for binding to p47phoxSH3A-B. Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phoxSH3A-B-p22phox interaction (Ki of 20 μM). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.

Imidazopyridine-fused [1,3]diazepinones: modulations of positions 2 to 4 and their impacts on the anti-melanoma activity

A series of 19 novel pyrido-imidazodiazepinones, with modulations of positions 2, 3 and 4 of the diazepine ring were synthesised and screened for their in vitro cytotoxic activities against two melanoma cell lines (A375 and MDA-MB-435) and for their poten

Catalytic Reductions Without External Hydrogen Gas: Broad Scope Hydrogenations with Tetrahydroxydiboron and a Tertiary Amine

Facile reduction of aryl halides with a combination of 5% Pd/C, B2(OH)4, and 4-methylmorpholine is reported. Aryl bromides, iodides, and chlorides were efficiently reduced. Aryl dihalides containing two different halogen atoms underwent selective reduction: I over Br and Cl, and Br over Cl. Beyond these, aryl triflates were efficiently reduced. This combination was broadly general, effectuating reductions of benzylic halides and ethers, alkenes, alkynes, aldehydes, and azides, as well as for N-Cbz deprotection. A cyano group was unaffected, but a nitro group and a ketone underwent reduction to a low extent. When B2(OD)4 was used for aryl halide reduction, a significant amount of deuteriation occurred. However, H atom incorporation competed and increased in slower reactions. 4-Methylmorpholine was identified as a possible source of H atoms in this, but a combination of only 4-methylmorpholine and Pd/C did not result in reduction. Hydrogen gas has been observed to form with this reagent combination. Experiments aimed at understanding the chemistry led to the proposal of a plausible mechanism and to the identification of N,N-bis(methyl-d3)pyridin-4-amine (DMAP-d6) and B2(OD)4 as an effective combination for full aromatic deuteriation. (Figure presented.).

TRIAZOLOPYRIDINE INHIBITORS OF MYELOPEROXIDASE

The present invention provides compounds of Formula (I): wherein A is as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.

Tunable Ligand Effects on Ruthenium Catalyst Activity for Selectively Preparing Imines or Amides by Dehydrogenative Coupling Reactions of Alcohols and Amines

Selective dehydrogenative synthesis of imines from a variety of alcohols and amines was developed by using the ruthenium complex [RuCl2(dppea)2] (6 a: dppea=2-diphenylphosphino-ethylamine) in the presence of catalytic amounts of Zn(OCOCF3)2 and KOtBu, whereas the selective dehydrogenative formation of amides from the same sources was achieved by using another ruthenium complex, [RuCl2{(S)-dppmp}2] [6 d: (S)-dppmp=(S)-2-((diphenylphosphenyl)methyl)pyrrolidine], in the presence of catalytic amounts of Zn(OCOCF3)2 and potassium bis(trimethylsilyl)amide (KHMDS). Our previously reported ruthenium complex, [Ru(OCOCF3)2(dppea)2] (8 a), was the catalyst precursor for the imine synthesis, whereas [Ru(OCOCF3)2{(S)-dppmp}2] (8 d), which was derived from the treatment of 6 d with Zn(OCOCF3)2 and characterized by single-crystal X-ray analysis, was the pre-catalyst for the amide formation. Control experiments revealed that the zinc salt functioned as a reagent for replacing chloride anions with trifluoroacetate anions. Plausible mechanisms for both selective dehydrogenative coupling reactions are proposed based on a time-course study, Hammett plot, and deuterium-labeling experiments.

Unique nanocages of 12CaO·7Al2O3 boost heterolytic hydrogen activation and selective hydrogenation of heteroarenes over ruthenium catalyst

The chemoselective hydrogenation of heteroarenes is one of the most important synthetic reactions for the production of key intermediates in agrochemicals, pharmaceuticals and various fine chemicals. The development of new heterogeneous catalysts for the environmentally benign synthesis of heterocycle hydrogenated products is a fundamental objective for chemists. Here, we report that 12CaO·7Al2O3 with a unique sub-nanocage structure loaded with Ru nanoparticles exhibits higher activity, chemoselectivity and sustainability for the hydrogenation of heteroarenes in a solvent-free system than traditional oxide-supported metal catalysts. Conversion of >99% and a selectivity close to 99% were achieved for the hydrogenation of quinoline under mild conditions. This catalyst was also successfully applied to the hydrogenation of a variety of N- and O-heteroarenes with high yields. The superior catalytic performance can be attributed to a cooperative effect between the hydrogen-storage ability and large amount of strong basic sites on the surface of the support, which promotes heterolytic H2 cleavage and prevents poisoning of the metal surface caused by the adsorption of heteroarenes.

6-O-SUBSTITUTED KETOLIDES HAVING ANTIBACTERIAL ACTIVITY

PROBLEM TO BE SOLVED: To provide 6-O-substituted ketolides with antibacterial activity, having acid stability and enhanced activity toward gram negative bacteria and macrolide resistant gram positive bacteria. SOLUTION: This invention provides 6-O-substituted erythromycin ketolide derivatives such as formula (II) and compositions comprising the compounds. [Y and Z together form a group X; X is ketone, hydroxyimino or the like; or, one of Y and Z is H and the other is hydrogen, hydroxy or the like; Ra is H, hydroxy; Rc is H or a hydroxy protective group; R is a substituted methyl group]. COPYRIGHT: (C)2015,JPOandINPIT

Design, synthesis and evaluation of novel HDAC inhibitors as potential antitumor agents

Phenyl imidazolidin-2-one was introduced as the linker for novel HDAC inhibitors. A focused library of 20 compounds was designed and synthesized, among which eight compounds showed equivalent or higher potencies against HDAC1 as compared to vorinostat. In vitro antitumor activity assays in HCT-116, PC-3 and HL-60 cancer cells revealed six compounds with potent antitumor activities, and compound 1o showed 6- to 9-fold higher potencies compared to vorinostat. In an HCT-116 nude mice xenograft model, compound 1o displayed significant antitumor activity in both continuous and intermittent dosing schedules.

Palladium-catalyzed direct hydroxymethylation of aryl halides and triflates with potassium acetoxymethyltrifluoroborate

Suzuki-Miyaura cross-coupling reactions of aryl halides and triflates with potassium acetoxymethyltrifluoroborate afforded the corresponding aryl and heteroaryl methanol products in moderate to excellent yields.