848133-75-5

Usage

Uses

Since the provided materials do not specify any particular applications for Acetamide, N-(3-cyano-7-ethoxy-4-hydroxy-6-quinolinyl)-, it is not possible to list specific uses for Acetamide, N-(3-cyano-7-ethoxy-4-hydroxy-6-quinolinyl)- based on the information given. However, given its complex structure and the presence of various functional groups, it is plausible that Acetamide, N-(3-cyano-7-ethoxy-4-hydroxy-6-quinolinyl)- could be used in the following hypothetical applications:
Used in Pharmaceutical Industry:
Acetamide, N-(3-cyano-7-ethoxy-4-hydroxy-6-quinolinyl)could be used as a pharmaceutical intermediate for the synthesis of drugs targeting specific biological pathways or receptors, given its unique structure and functional groups.
Used in Chemical Research:
Acetamide, N-(3-cyano-7-ethoxy-4-hydroxy-6-quinolinyl)might serve as a research tool in the development of new chemical reactions or as a probe to understand the interactions between molecules in various chemical and biological systems.
Used in Material Science:
Acetamide, N-(3-cyano-7-ethoxy-4-hydroxy-6-quinolinyl)-'s structural features could potentially be exploited in the design of new materials with specific properties, such as in the development of advanced polymers or coatings.

InChI:InChI=1/C14H13N3O3/c1-3-20-13-5-11-10(4-12(13)17-8(2)18)14(19)9(6-15)7-16-11/h4-5,7H,3H2,1-2H3,(H,16,19)(H,17,18)

Upstream product

• 75-05-8 acetonitrile 
• 1571-72-8 3-amino-4-hydroxybenzoic acid 
• 91004-38-5 3-acetamido-4-hydroxybenzoic acid 
• 1356916-92-1 3-acetamido-4-ethoxybenzoic acid 
• 1201080-23-0 methyl 5-acetamido-4-ethoxy-2-nitrobenzoate 
• 1222172-49-7 methyl 5-acetamido-2-amino-4-ethoxybenzoate 
• 1222172-50-0 methyl 5-acetamido-2-[(2-cyanovinyl)amino]-4-ethoxybenzoate 
• 28443-50-7 2-amino-5-chlorophenol 
• 860742-51-4 N-(4-chloro-2-ethoxyphenyl)acetamide 
• 16323-09-4 N-(4-chloro-2-hydroxyphenyl)acetamide 
• 54255-50-4 3-amino-4-hydroxyacetophenone 
• 74896-30-3 1-<3-(acetylamino)-4-hydroxyphenyl>ethanone 
• 544-92-3 copper(I) cyanide 
• 1201079-13-1 1-(5-acetamido-4-ethoxy-2-nitrophenyl)-2-bromoethanone 

Downstream Products

• 214476-09-2 4-Chloro-7-ethoxy-6-nitro-quinoline-3-carbonitrile 
• 848133-14-2 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-amino-7-ethoxyquinoline-3-carbonitrile 
• 848655-77-6 N-(4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinolin-6-yl)acetamide 
• 1360430-63-2 N-(4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl)acrylamide 
• 1360430-64-3 N-(4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(dimethylamino)propanamide 
• 1360430-72-3 3-chloro-N-(4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl)propanamide 
• 1360430-65-4 N-(4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl)-3-piperidin-1-ylpropanamide 
• 1360430-66-5 N-(4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl)-3-morpholinopropanamide 
• 1360430-67-6 N-(4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)acrylamide 
• 1233953-81-5 N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)anilino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(dimethylamino)propanamide 
• 1233953-83-7 N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)anilino)-3-cyano-7-ethoxyquinolin-6-yl)-3-piperidin-1-ylpropanamide 
• 1360430-68-7 N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)anilino)-3-cyano-7-ethoxyquinolin-6-yl)-3-morpholinopropanamide 
• 848139-78-6 6-amino-4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-7-ethoxyquinoline-3-carbonitrile 
• 1233953-82-6 3-chloro-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)anilino)-3-cyano-7-ethoxyquinolin-6-yl)propanamide 

Relevant academic research and scientific papers

Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro

The discovery and development of a novel HER-2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer are presented in this article. EGFR family has been recognized as a crucial meditator in the cancer progression; HER-2 tyrosine kinase was one of the members among them. In the effort to explore potent HER-2 inhibitors, a novel series of 4-anilino-3-cyanoquinoline derivatives have been designed, synthesized and evaluated. Most compounds possessed modest proliferation inhibition on SK-BR-3 cell line and HER-2 kinase. Compound 16 appeared to be the most potent compound (HER-2 kinase IC50: 19.4?nM, SK-BR-3 IC50: 94?nM). In the experiment of cellular cytotoxicity assay, compound 16 shows a much lower cytotoxicity than neratinib on Beas-2b cell line (Human bronchial epithelial cells). In conclusion, compound 16 would be a promising lead compound for further anti-breast cancer drug discovery.

Preparation method of Neratinib intermediate

The invention relates to the field of chemical synthesis, and specifically relates to a preparation method of a Neratinib intermediate. A compound (I) is taken as the raw material, and through a series of reactions, the intermediate compound (VIII) of a novel antitumor drug Neratinib is obtained. A high efficient synthesis route is provided and has the characteristics of low cost, few byproducts, high yield, and little environmental pollution.

New and practical synthesis of N-(3-Cyano-7-ethoxy-4-oxo-1,4- dihydroquinolin-6-yl)acetamide

New and practical synthetic route of N-(3-cyano-7-ethoxy-4-oxo-1,4- dihydroquinolin-6-yl)acetamide (1) is described, through the cyclization of 2-aminophenyl-ethanone (12) with N,N-dimethylformamide dimethylacetal. The overall yield of 1 obtained from this process is 46% (five steps) with a purity of >99% (HPLC).

New synthesis of N-(4-chloro-3-cyano-7-ethoxyquinolin- 6-yl)acetamide

New synthetic route of N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl)- acetamide (1) is described on a hectogram scale. The key steps include the intramolecular cyclization of 3-amino-2-(2-chlorobenzoyl)acrylonitrile 22 to give the 3-cyano-4-quinolone 7, which was chlorinated by POCl3 to give the final product 1 in 36.9% yield over 9 steps and 98.9% purity (HPLC). Purification methods of 7 and 1 were also given.

A new and improved process for N -(4-chloro-3-cyano-7-ethoxyquinolin-6-yl) acetamide

A new and improved synthetic route to N-(4-chloro-3-cyano-7-ethoxyquinolin- 6-yl)acetamide (1) is described on a kilogram scale. The key step is the basic cyclization of o-[(2-cyanovinyl)amino]benzoate (14) in tBuONa/ tBuOH system to give the 3-cyano-4-hydroxyquinoline (7). The final product 1 is obtained with 49% overall yield (seven steps) and 98.9% purity (HPLC), which makes it a cost-effective and commercially friendly process for scale-up operations.

Irreversible inhibition of epidermal growth factor receptor activity by 3-aminopropanamides

Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off-targets. We describe here a new series of irreversible inhibitors containing a 3-aminopropanamide linked in position 6 to 4-anilinoquinazoline or 4-anilinoquinoline-3- carbonitrile driving portions. Some of these compounds proved to be as efficient as their acrylamide analogues in inhibiting EGFR-TK (TK = tyrosine kinase) autophosphorylation in A549 lung cancer cells. Moreover, several 3-aminopropanamides suppressed proliferation of gefitinib-resistant H1975 cells, harboring the T790M mutation in EGFR, at significantly lower concentrations than did gefitinib. A prototypical compound, N-(4-(3-bromoanilino)quinazolin-6- yl)-3-(dimethylamino)propanamide (5), did not show covalent binding to cell-free EGFR-TK in a fluorescence assay, while it underwent selective activation in the intracellular environment, releasing an acrylamide derivative which can react with thiol groups.

Synthesis of n-(3-cyano-7-ethoxy-1,4-dihydro-4-oxoquinolin-6-yl)acetamide

New route for the preparation of N-(3-cyano-7-ethoxy-1,4-dihydro-4- oxoquinolin-6-yl)acetamide (1), a key intermediate for the synthesis of selective EGFR kinase inhibitors, was described.

PREPARATION METHODS OF 6-SUBSTITUTED AMINO-3-CYANOQUINOLINE COMPOUNDS AND THE INTERMEDIATES THEREOF

The present invention relates to a method for preparing 6-substituted amino-3-cyanoquinoline compounds (compound A for short) and the intermediates thereof, more particularly, to a compound of the following formula (I), the preparation method thereof, the intermediates thereof and use thereof for preparing the compound A. The compound of the formula (I) is cyclized in the presence of an alkali to give a compound of formula A, wherein W is OH; or the compound of the formula (I) is cyclized in the presence of an alkali, and then chlorinated to give a compound of the formula A, wherein W is Cl. Compared with the known methods in the literature, the method for preparing the compound A from the compound of formula (I) according to the present invention can avoid using high-temperature condition and high boiling point solvents, and is safe and environment-friendly, mild in reaction condition, easy in operation with a high yield and high product purity.

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.