85870-47-9

Usage

Chemical Properties

Yellow solid

Upstream product

• 17422-56-9 diethyl 2-(2-nitrobenzylidene)malonate 
• 529-23-7 o-aminobenzaldehyde 
• 105-53-3 diethyl malonate 
• 552-89-6 2-nitro-benzaldehyde 
• 132416-65-0 diethyl 2-(2-azido-benzylidene)-malonate 
• 16714-25-3 2-azidobenzaldehyde 
• 55552-69-7 2-ethylmalonyl dichloride 
• 59-31-4 2-quinolone 
• 541-41-3 chloroformic acid ethyl ester 

Downstream Products

• 85870-48-0 1,2-dihydro-6-nitro-2-oxo-3-quinolinecarboxylic acid ethyl ester 
• 2003-79-4 2-oxo-1,2-dihydro-quinoline-3-carboxylic acid 
• 1239164-02-3 3-(2-hydroxy-6-oxo-1-cyclohexenecarbonyl)-1-methylquinolin-2(1H)-one 
• 1239164-54-5 3-oxo-1-cyclohexenyl 1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate 
• 1375112-59-6 N-cyclohexyl-2-(p-fluorobenzyloxy)-quinoline-3-carboxamide 
• 1203801-74-4 N-cyclohexyl-1-(p-fluorobenzyl)-quinolin-2(1H)-one-3-carboxamide 
• 1203801-73-3 N-cyclohexyl-1-benzyl-quinolin-2(1H)-one-3-carboxamide 
• 1203801-76-6 N-cyclohexyl-1-(2-(morpholin-4-yl)ethyl)-quinolin-2(1H)-one-3-carboxamide 
• 1203801-81-3 N-cycloheptyl-1-(p-fluorobenzyl)-quinolin-2(1H)-one-3-carboxamide 

Relevant academic research and scientific papers

Discovery of the Bruton's Tyrosine Kinase Inhibitor Clinical Candidate TAK-020 (S)-5-(1-((1-Acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-2,4-dihydro-3 H-1,2,4-triazol-3-one, by Fragment-Based Drug Design

This publication details the successful use of FBDD (fragment-based drug discovery) principles in the invention of a novel covalent Bruton's tyrosine kinase inhibitor, which ultimately became the Takeda Pharmaceuticals clinical candidate TAK-020. Describe

Amide compounds and uses thereof

Provided herein are novel amide compounds of formula (I), pharmaceutical compositions comprising same, methods for preparing same, and uses thereof, wherein the definition of each symbol is as described in the description.

FLUORESCENT DYE AGENT AND CARBOSTYRIL COMPOUND

PROBLEM TO BE SOLVED: To provide a novel fluorescent dye agent. SOLUTION: A fluorescent dye agent contains a carbostyril compound represented by formula (1) [in the formula (1), R1 is H, a halogen atom, a hydroxyl group, a cyano group, a nitro group or the like; R2 is O; R3 is a halogen atom, a carboxyl group, an ester group, an amide group or the like; R4-R6 and R8 independently represent H, a halogen atom, a nitro group, a cyano group or the like, where mutually adjacent groups of R4-R8 may be bound to form a ring; R7 is H, a substituted or unsubstituted aliphatic group or the like]. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

Formation or Cleavage of Rings via Sulfide-Mediated Reduction Offers Background-Free Detection of Sulfide

A set of three highly selective probes for sulfide detection has been developed. Two novel mechanistic strategies for the detection, including (a) transformation of a pro-fluorophore into an active fluorophore and (b) destruction of a fused ring to activate a fluorophore, have been explored. The structural features of the probes including azido groups ("active" and "latent") and leaving groups (with or without being attached to the fluorophore) have been investigated. During the course of the mechanistic studies, the single-crystal structures of all the probes and the products were obtained. One of the probes proved to be superior in terms of its ability to detect sulfide in pure water via an in situ formation of a fluorophore from a nonfluorescent precursor. These cheap and easy-to-prepare probes offer practical applications of sulfide recognition in environmental water samples and in the ovaries of fruit flies. A detection and quantification method using one of these probes and analysis with a smartphone enabled nonspecialists to detect sulfide reliably.

Antifungal activity, mode of action variability, and subcellular distribution of coumarin-based antifungal azoles

Azole antifungals inhibit the biosynthesis of ergosterol, the fungal equivalent of cholesterol in mammalian cells. Here we report an investigation of the activity of coumarin-substituted azole antifungals. Screening against a panel of Candida pathogens, including a mutant lacking CYP51, the target of antifungal azoles, revealed that this enzyme is inhibited by triazole-based antifungals, whereas imidazole-based derivatives have more than one mode of action. The imidazole-bearing antifungals more effectively reduced trailing growth associated with persistence and/or recurrence of fungal infections than triazole-based derivatives. The imidazole derivatives were more toxic to mammalian cells and more potently inhibited the activity of CYP3A4, which is one of the main causes of azole toxicity. Using live cell imaging, we showed that regardless of the type of azole ring fluorescent 7-diethylaminocoumarin-based azoles localized to the endoplasmic reticulum, the organelle that harbors CYP51. This study suggests that the coumarin is a promising scaffold for development of novel azole-based antifungals that effectively localize to the fungal cell endoplasmic reticulum.

The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors

Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool molecule 20 (AM-1488), which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Additional structural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with human GlyRα3cryst to afford the first described potentiator-bound X-ray cocrystal structure within this class of ligand-gated ion channels (LGICs).

Photochemistry of ortho -Azidocinnamoyl Derivatives: Facile and Modular Synthesis of 2-Acylated Indoles and 2-Substituted Quinolines under Solvent Control

The light-promoted potential of ortho -azidocinnamoyl compounds is evaluated for heterocycle synthesis. Depending on the nature of the solvent, 2-acylated indoles were obtained under aprotic conditions, whereas the use of a protic medium led to 2-substituted quinolines. The synthetic significance of this metal-free method is that, by simply changing the solvent, the reaction outcome can be directed towards different key heterocyclic scaffolds.

2-Anilino-3-Aroylquinolines as Potent Tubulin Polymerization Inhibitors

Several 2-anilino-3-aroylquinolines were designed, synthesized, and screened for their cytotoxic activity against five human cancer cell lines: HeLa, DU-145, A549, MDA-MB-231, and MCF-7. Their IC50values ranged from 0.77 to 23.6 μm. Among the s

Visible-Light-Driven Intermolecular [2+2] Cycloadditions between Coumarin-3-Carboxylates and Acrylamide Analogs

This paper reports a room temperature visible-light-driven protocol for the intermolecular [2+2] cycloadditions between coumarin-3-carboxylates and acrylamides analogs by an energy-transfer process. Using an iridium complex FIrPic as a photosensitizer and a 3W blue LED as a light source, an array of cyclobutabenzocypyranones were prepared in moderate to excellent yields.

Rational design, synthesis and anti-proliferative properties of new CB2 selective cannabinoid receptor ligands: An investigation of the 1,8-naphthyridin-2(1H)-one scaffold

CB2 receptor ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Using our previously described series of 1,8-naphthyridin-2(1H)-on-3-carboxamides as a lead class, several nitrogen heterocyclic derivatives, characterized by different central cores, were synthesized and tested for their affinity toward the human CB1 and CB2 cannabinoid receptors. The obtained results suggest that the new series of quinolin-2(1H)-on-3-carboxamides, 4-hydroxy-2-oxo-1,2-dihydro- 1,8-naphthyridine-3-carboxamides and 1,2-dihydro-2-oxopyridine-3-carboxamides represent novel scaffolds very suitable for the development of promising CB2 ligands. Furthermore, the newly synthesized CB2 ligands inhibit proliferation of several cancer cell lines. In particular, it was demonstrated that in DU-145 cell line these ligands exert a CB2-mediated anti-proliferative action and decrease the CB2 receptor expression levels.