848133-14-2

Upstream product

• 848133-76-6 7-ethoxy-6-acetylamino-4-chloro-quinoline-3-carbonitrile 
• 443882-99-3 3-chloro-4-(3-fluorobenzyloxy)nitrobenzene 
• 619-08-9 2-chloro-4-nitrophenol 
• 456-41-7 1-(Bromomethyl)-3-fluorobenzene 
• 214476-08-1 7-Ethoxy-4-hydroxy-6-nitro-quinoline-3-carbonitrile 
• 116435-75-7 3-(ethyloxy)-4-nitroaniline 
• 202197-26-0 3-chloro-4-(3-fluorobenzyloxy)aniline 
• 848133-87-9 6-amino-4-chloro-7-ethoxyquinoline-3-carbonitrile 
• 848133-75-5 3-cyano-4-hydroxyl-6-acetamido-7-ethoxyquinoline 
• 214476-09-2 4-Chloro-7-ethoxy-6-nitro-quinoline-3-carbonitrile 
• 915942-03-9 6-amino-4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-3-cyano-7-ethoxyquinoline hydrochloride 

Downstream Products

• 848133-17-5 (E)-N-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(dimethylamino)but-2-enamide 

Relevant academic research and scientific papers

Phenylacrylamide quinoline derivative and preparation method and application thereof

The invention belongs to the field of anti-cancer drugs, and particularly relates to a phenylacrylamide quinoline derivative and a preparation method and application thereof. The invention provides a compound shown as a formula I, a stereoisomer or a pharmaceutically acceptable salt thereof. Compared with the existing antitumor drugs, the compound has excellent antitumor activity on A431, SKOV3, SK-BR3, BT474 and the like, and has a good application prospect. Moreover, the preparation method of the compound is low in cost, simple in step, mild in reaction condition, high in yield and easy for post-treatment.

Quinoline derivative containing furyl and preparation method and application thereof

The invention belongs to the field of anti-cancer drugs, and particularly relates to a furyl-containing quinoline derivative and a preparation method and application thereof. The invention provides a compound as shown in the formula I, and a stereoisomer or pharmaceutically acceptable salt thereof. Compared with an existing antitumor drug, the compound disclosed by the invention has excellent antitumor activity on A431, SKOV3, SK-BR-3, BT474 and the like, and has a very good application prospect. In addition, the preparation method of the compound is low in cost, simple in step, mild in reaction condition, high in yield and easy for post-treatment.

Pyridyl-substituted quinoline derivative as well as preparation method and application thereof

The invention belongs to the field of anti-cancer drugs, and particularly relates to a pyridyl substituted quinoline derivative as well as a preparation method and application thereof. The invention provides a compound shown as a formula I, a stereoisomer or a pharmaceutically acceptable salt thereof. Compared with the existing antitumor drugs, the compound provided by the invention has excellent antitumor activity on A431, SK-BR-3, BT474 and the like, and has a good application prospect. Moreover, the preparation method of the compound is low in cost, simple in step, mild in reaction condition, high in yield and easy for post-treatment.

1,2-DITHIOLANE AND DITHIOL COMPOUNDS USEFUL IN TREATING MUTANT EGFR-MEDIATED DISEASES AND CONDITIONS

Compositions of the invention comprise 1,2-dithiolane, dithiol and related compounds useful as therapeutic agents for the treatment and prevention of diseases and conditions associated with aberrant EGFR activity.

Quinoline and quinazoline derivatives, preparation method, intermediate, composition and use thereof (by machine translation)

The invention discloses a quinoline and quinazoline derivative I, a preparation method, an intermediate C, composition and an application. The preparation method comprises two methods, wherein the first method comprises steps as follows: 1, a compound A and a compound B react in a solvent under the action of alkali 1 to obtain a compound C; and 2, the product C obtained in the step 1 reacts with a compound D under the action of alkali 2; and the second comprises step as follows: the compound A and a compound E react in the solvent under the action of the alkali 1. The invention further provides the application of the compound represented in formula I or medicine composition in preparation of an EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor, an A431 or H1975 cell proliferation inhibitor or medicine for preventing or treating tumor diseases. The provided compound has better antitumor activity.

Method of preparing 3-cyano-quinolines and intermediates made thereby

The present invention relates to methods for preparing substituted 3-cyanoquinolines and intermediates obtained by the methods of the present invention. The methods of the invention comprise reacting an N-aryl-2-propanimide with phosphoryl chloride to produce the substituted 3-cyanoquinolines. The methods further comprise reacting arylamines, orthoformates and active methylenes to produce the N-aryl-2-propenamide.

Methods of synthesizing substituted 3-cyanoquinolines and intermediates thereof

The invention is directed to methods of making substituted 3-cyanoquinolines, including compounds according to the following formula: The methods are amenable to large scale manufacture, avoid the use of chromatographic separations, and provide stable, high purity product more efficiently than in the prior art.

SUBSTITUTED QUINOLINES AS PROTEIN TYROSINE KINASE ENZYME INHIBITORS

This invention provides compounds of formula (I), having the structure wherein R1, R2, R3 are described within the specification. The compounds act as anti-cancer agents by inhibition of HER-2 and EGFR.

Protein tyrosine kinase enzyme inhibitors

This invention provides compounds of formula 1, having the structure wherein R1, R2, R3, R4, and R5 are described within the specification.

Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase activity

A series of new 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitrile derivatives that function as irreversible inhibitors of human epidermal growth factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) kinases have been prepared. These compounds demonstrated enhanced activities for inhibiting HER-2 kinase and the growth of HER-2 positive cells compared to our EGFR kinase inhibitor 86 (EKB-569). Three synthetic routes were used to prepare these compounds. They were prepared mostly by acylation of 6-amino-4-(arylamino) quinoline-3-carbonitriles with unsaturated acid chlorides or by amination of 4-chloro-6-(crotonamido)-quinoline-3-carbonitriles with monocyclic or bicyclic anilines. The third route was developed to prepare a key intermediate, 6-acetamido-4-chloroquinoline-3-carbonitrile, that involved a safer cyclization step. We show that attaching a large lipophilic group at the para position of the 4-(arylamino) ring results in improved potency for inhibiting HER-2 kinase. We also show the importance of a basic dialkylamino group at the end of the Michael acceptor for activity, due to intramolecular catalysis of the Michael addition. This, along with improved water solubility, resulted in compounds with enhanced biological properties. We present molecular modeling results consistent with the proposed mechanism of inhibition. Binding studies of one compound, 25o (C-14 radiolabeled), showed that it binds irreversibly to HER-2 protein in BT474 cells. Furthermore, it demonstrated excellent oral activity, especially in HER-2 overexpressing xenografts. Compound 25o (HKI-272) was selected for further studies and is currently in phase I clinical trials for the treatment of cancer.