214470-78-7

Basic information

• Product Name: 6-ethoxy-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile
• Synonyms: 6-Ethoxy-7-methoxy-4-oxo-1,4-dihydrochinolin-3-carbonitril
• CAS NO: 214470-78-7
• Molecular Formula: C₁₃H₁₂N₂O₃
• Molecular Weight: 244.246
• Mol File: 214470-78-7.mol

Chemical Properties

• Boiling Point: 398.404°C at 760 mmHg
• Flash Point: 194.748°C
• Density: 1.292g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.592
• CAS DataBase Reference: 6-ethoxy-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 6-ethoxy-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile(214470-78-7)
• EPA Substance Registry System: 6-ethoxy-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile(214470-78-7)

Safety Data

• Hazardous Substances Data: 214470-78-7(Hazardous Substances Data)

Upstream product

• 109-72-8 n-butyllithium 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 214470-85-6 2-amino-5-ethoxy-4-methoxybenzoic acid methyl ester 
• 463-52-5 formamidine 
• 645-08-9 Isovanillic acid 
• 75-05-8 acetonitrile 
• 214470-90-3 5-ethoxy-4-methoxy-2-nitrobenzoic acid methyl ester 
• 97966-31-9 3-ethoxy-4-methoxybenzoic acid methyl ester 
• 6702-50-7 3-hydroxy-4-methoxybenzoate 
• 1026844-87-0 2-(dimethylamino-methyleneamino)-5-ethoxy-4-methoxy-benzoic acid methyl ester 

Downstream Products

• 214470-75-4 4-chloro-6-ethoxy-7-methoxyquinoline-3-carbonitrile 

Relevant articles and documents

USE OF CYANOQUINOLINES FOR TREATING OR INHIBITING COLONIC POLYPS

This invention provides a method of treating or inhibiting colonic polyps which comprises providing a compound of formula (1); wherein R1, R2, R3, R4, X, Y, and n are defined hereinbefore, or a pharmaceutically acceptable salt thereof.

SUBSTITUTED 3-CYANO QUINOLINES

This invention provides compounds having formula (1), wherein: X is cycloalkyl which may be optionally substituted; or is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally substituted; n is 0-1; Y is -NH-, -O-, -S-, or -NR-; R is alkyl of 1-6 carbon atoms; R1, R2, R3 and R4 are each, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkenyloxy, alkynyloxy, hydroxymethyl, halomethyl, alkanoyloxy, alkenoyloxy, alkynoyloxy, alkanoyloxymethyl, alkenoyloxymethyl, alkynoyloxymethyl, alkoxymethyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfonamido, alkenylsulfonamido, alkynylsulfonamido, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy, carboalkyl, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino, alkylamino, dialkylamino, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, phenylamino, benzylamino, formulae (a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p, q or r); R5 is alkyl which may be optionally substituted, or phenyl which may be optionally substituted; R6 is hydrogen, alkyl, or alkenyl; R7 is chloro or bromo; R8 is hydrogen, alkyl, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, N-cycloalkylaminoalkyl, N-cycloalkyl-N-alkylaminoalkyl, N,N-dicycloalkylaminoalkyl, morpholino-N-alkyl, piperidino-N-alkyl, N-alkyl-piperidino-N-alkyl, azacycloalkyl-N-alkyl, hydroxyalkyl, alkoxyalkyl, carboxy, carboalkoxy, phenyl, carboalkyl +, chloro, fluoro, or bromo; Z is amino, hydroxy, alkoxy, alkylamino, dialkylamino, morpholino, piperazino, N-alkylpiperazino, or pyrrolidino; m = 1-4, q = 1-3, and p = 0-3; any of the substituents R1, R2, R3 or R4 that are located on contiguous carbon atoms can together be the divalent radical -O-C(R8)2-O-; or a pharmaceutically acceptable salt thereof with the proviso that when Y is -NH-, R1, R2, R3 and R4 are hydrogen, and n is O, X is not 2-methylphenyl, which are inhibitors of protein tyrosine kinase.

SUBSTITUTED 3-CYANOQUINOLINES AS PROTEIN TYROSINE KINASES INHIBITORS

This invention provides compounds of formula (1) wherein R1, G1, G2, R4, Z, X and n are defined herein, or a pharmaceutically acceptable salt thereof, which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.

Method of treating or inhibiting colonic polyps

This invention provides a method of treating or inhibiting colonic polyps which comprises providing a compound of formula 1 wherein:R1, R2, R3, R4, X, Y, and n are as defined hereinbefore, or a pharmaceutically acceptable salt thereof.

4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor kinase and their bioisosteric relationship to the 4-anilino-6,7-dialkoxyquinazoline inhibitors

The synthesis and SAR of a series of 4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor (EGF-R) kinase are described. Condensation of 3,4-dialkoxyanilines with ethyl (ethoxymethylene)cyanoacetate followed by thermal cyclization gave, regiospecifically, 6,7-dialkoxy-4-oxo-1,4-dihydroquinoline-3-carbonitriles. Chlorination (POCl3) followed by the reaction with substituted anilines furnished the 4-anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of EGF-R kinase. An alternate synthesis of these compounds starts with a methyl 3,4-dialkoxybenzoate. Nitration followed by reduction (Fe, NH4Cl, MeOH-H2O) gave a methyl 2-amino-4,5-dialkoxybenzoate. Amidine formation using DMF-acetal followed by cyclization using LiCH2CN furnished a 6,7-dialkoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile, which was transformed as before. Compounds containing acid, ester, amide, carbinol, and aldehyde groups at the 3-position of the quinoline ring were also prepared for comparison, as were several 1-anilino-6,7-dimethoxyisoquinoline-4-carbonitriles. The compounds were evaluated for their ability to inhibit the autophosphorylation of the catalytic domain of EGF-R. The SAR of these inhibitors with respect to the nature of the 6,7-alkoxy groups, the aniline substituents, and the substituent at the 3-position was studied. The compounds were further evaluated for their ability to inhibit the growth of cell lines that overexpress EGF-R or HER-2. It was found that 4-anilinoquinoline-3-carbonitriles are effective inhibitors of EGF-R kinase with activity comparable to the 4-anilinoquinazoline-based inhibitors. A new homology model of EGF-R kinase was constructed based on the X-ray structures of Hck and FGF receptor-1 kinase. The model suggests that with the quinazoline-based inhibitors, the N3 atom is hydrogen-bonded to a water molecule which, in turn, interacts with Thr 830. It is proposed that the quinoline-3-carbonitriles bind in a similar manner where the water molecule is displaced by the cyano group which interacts with the same Thr residue.