53977-02-9

Upstream product

• 52980-28-6 ethyl 4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 100-39-0 benzyl bromide 
• 62-53-3 aniline 
• 26892-90-0 ethyl 4-hydroxy-3-quinolinecarboxylate 
• 620-05-3 iodomethylbenzene 
• 1071-46-1 hydrogen ethyl malonate 
• 1479-24-9 ethyl 2-fluorobenzoylacetate 
• 393-52-2 2-Fluorobenzoyl chloride 
• 100-46-9 benzylamine 
• 445-29-4 o-fluoro-benzoic acid 
• 1207748-75-1 ethyl 3-(benzylamino)-2-(2-fluorobenzoyl)-2-propenoate 
• 19112-35-7 ethyl (2-chlorobenzoyl)acetate 
• 289706-52-1 ethyl 2-(2',2',2'-trichloro)ethylidene-3-oxo-3-(2''-chlorophenyl)propionate 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 

Downstream Products

• 35975-86-1 1-benzyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acide 
• 1141925-66-7 1-benzyl-N-(2-hydroxyethyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide 
• 1622228-86-7 N-(2,4-di-tert-butyl-5-hydroxyphenyl)-1-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide 
• 873054-44-5 ivacaftor 

Relevant academic research and scientific papers

AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE

The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of a cardiovascular disease or of an inflammatory disease or condition:

Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-Dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators

Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for assessment of all three modes of pharmacology at M1, including agonist, positive allosteric modulator, and antagonist activities in a single screening platform. We disclose a dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one hit (DBPQ, CID 915409) and examine N-benzyl pharmacophore/SAR relationships versus previously reported quinolin-3(5H)-ones and isatins, including ML137. SAR and consideration of recently reported crystal structures, homology modeling, and structure-function relationships using point mutations suggests a shared binding mode orientation at the putative common allosteric binding site directed by the pendant N-benzyl substructure.

A PROCESS FOR THE PREPARATION OF IVACAFTOR AND ITS INTERMEDIATES

The present invention provides novel intermediates of ivacaftor and process for its preparation. The present invention also provides process for the preparation of ivacaftor and pharmaceutically acceptable salt thereof using novel intermediates.

Ethyl 1,4-dihydro-4-oxo-3-quinolinecarboxylates by a tandem addition-elimination-SNAr reaction

The ethyl 1,4-dihydro-4-oxo-3-quinolinecarboxylate ring structure, important in several drug compounds, has been prepared in two steps from ethyl 2-(2-fluorobenzoyl)acetate. Treatment of this β-ketoester with N,N-dimethylformamide dimethyl acetal gives a

Design, synthesis, and biological evaluation of novel quinoline derivatives as HIV-1 Tat-TAR interaction inhibitors

Thirty-two quinoline derivatives were designed and synthesized as HIV-1 Tat-TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Nine of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells, indicating effective inhibitory activities of blocking the Tat-TAR interaction. Molecular modeling experiments indicated that these compounds may inhibit Tat-TAR interaction by binding to Tat protein instead of TAR RNA.

Pharmacomodulations around the 4-oxo-1,4-dihydroquinoline-3-carboxamides, a class of potent CB2-selective cannabinoid receptor ligands: Consequences in receptor affinity and functionality

CB2 receptor selective ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Thus, the development of our previously described series of 4-oxo-1,4-dihydroquinoline-3-carboxamides was pursued with the aim to further characterize the structure-affinity and structure-functionality relationships of these derivatives. The influence of the side chain was investigated by synthesizing compounds bearing various carboxamido and keto substituents. On the other hand, the role of the quinoline central scaffold was studied by synthesizing several 6-, 7-, or 8-chloro-4-oxo-1,4-dihydroquinolines, as well as 4-oxo-1,4-dihydronaphthyridine and 4-oxo-1,4-dihydrocinnoline derivatives. The effect of these modifications on the affinity and functionality at the CB2 receptor was studied and allowed for the characterization of new selective CB2 receptor ligands.

Novel 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives as new CB 2 cannabinoid receptors agonists: Synthesis, pharmacological properties and molecular modeling

Recent data indicated that the CB2 cannabinoid receptor constitutes an attractive drug target due to its potential functional role in several physiological and pathological processes. A set of 4-oxo-1,4- dihydroquinoline-3-carboxamide derivatives, characterized by the presence of some important structural requirements exhibited by other classes of cannabinoid ligands, such as an aliphatic or aromatic carboxamide group in position 3, and an alkyl or benzyl group in position 1, was synthesized and assayed to measure their respective affinity for both human CB1 and CB2 cannabinoid receptors. The results indicate that these 3-carboxamido-quinolones derivatives exhibited a CB2 receptor selectivity, particularly derivatives 28-30, and 32R. Moreover, in the [35S]-GTPγS binding assay, all the compounds behaved as CB2 receptor agonists. Molecular modeling studies showed that compound 30 interacts with the CB 2 receptor through a combination of hydrogen bond and aromatic/hydrophobic interactions. In conclusion, 4-oxo-1,4-dihydroquinoline-3- carboxamide derivatives constitute a new class of potent and selective CB 2 cannabinoid receptors agonists.

Synthesis and biological evaluation of 2,5-dihydropyrazolo[4,3-c]quinolin-3-ones, a novel series of PDE 4 inhibitors with low emetic potential and antiasthmatic properties

A novel series of 2,5-dihydropyrazolo[4,3-c]quinolin-3-ones has been prepared. These compounds showed good PDE 4 inhibitory activity and weak affinity for rolipram's binding site. They also exhibited a good anti-inflammatory profile without emetic side effects. (C) 2000 Published by Elsevier Science Ltd.

An efficient synthesis of N-alkyl-1,4-dihydro-4oxo-3-quinolinecarboxylic acid via 2-(2',2',2'-trichloro)ethylidene-3-oxo-3-(2''-chloro- phenyl)propionate

A clay catalyzed synthesis of 2-(2',2',2'-trichloro)ethylidene-3-oxo-3- (2-chlorophenyl)propionate (2) and its application for the preparation of various N-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids (5a-e) has been described.