214470-72-1

Basic information

• Product Name: 4-chloro-7-(2-chloroethoxy)-6-methoxyquinoline-3-carbonitrile
• Synonyms: 4-Chlor-7-(2-chlorethoxy)-6-methoxychinolin-3-carbonitril
• CAS NO: 214470-72-1
• Molecular Formula: C₁₃H₁₀Cl₂N₂O₂
• Molecular Weight: 297.1367
• Mol File: 214470-72-1.mol

Chemical Properties

• Boiling Point: 457.259°C at 760 mmHg
• Flash Point: 230.342°C
• Density: 1.412g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.618
• CAS DataBase Reference: 4-chloro-7-(2-chloroethoxy)-6-methoxyquinoline-3-carbonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 4-chloro-7-(2-chloroethoxy)-6-methoxyquinoline-3-carbonitrile(214470-72-1)
• EPA Substance Registry System: 4-chloro-7-(2-chloroethoxy)-6-methoxyquinoline-3-carbonitrile(214470-72-1)

Safety Data

• Hazardous Substances Data: 214470-72-1(Hazardous Substances Data)

Upstream product

• 214470-61-8 7-(2-chloro-ethoxy)-6-methoxy-4-oxo-1,4-dihydro-quinoline-3-carbonitrile 
• 263149-10-6 4-chloro-7-hydroxy-6-methoxyquinolin-3-carbonitrile 
• 107-07-3 2-chloro-ethanol 
• 3943-74-6 4-hydroxy-3-methoxybenzoic acid methyl ester 
• 214470-61-8 7-(2-Chloro-ethoxy)-4-hydroxy-6-methoxy-quinoline-3-carbonitrile 
• 214470-58-3 4-(2-chloroethoxy)-5-methoxy-2-nitrobenzoic acid methyl ester 
• 214470-60-7 2-amino-4-(2-chloroethoxy)-5-methoxybenzoic acid methyl ester 
• 214470-56-1 4-(2-Chloro-ethoxy)-5-methoxy-benzoic acid methyl ester 
• 79-37-8 oxalyl dichloride 

Downstream Products

• 863029-96-3 7-(2-chloroethoxy)-6-methoxy-4-(4-phenoxyphenylamino)quinoline-3-carbonitrile 
• 380844-42-8 7-(2-chloroethoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile 
• 214484-55-6 7-(2-Chloro-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-6-methoxy-quinoline-3-carbonitrile 
• 214484-57-8 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(2-chloro-ethoxy)-6-methoxy-quinoline-3-carbonitrile 

Relevant articles and documents

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.

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.

Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity

Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino] -6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM) several additional analogues were prepared. Optimization of the C-4 anilino group of la led to lc which contains a 2,4-dichloro-5-methoxy- substituted aniline. Replacement of the methoxy group at C-7 of 1c with a 3-(morpholin-4-yl)propoxy group provided 2c resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c with other trisubstituted anilines at C-4 were also potent Src inhibitors and the propoxy group of 2c was preferred over ethoxy butoxy or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a which had an IC50 of 1.2 nM in the Src enzymatic assay an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a which had higher 1 and 4 h plasma levels than 2c effectively inhibited tumor growth in xenograft models.

Synthesis and structure-activity relationships of 3-cyano-4(phenoxyanilino)quinolines as MEK (MAPKK) inhibitors

A series of 3-cyano-4-(phenoxyanilino)cyanoquinolines has been prepared as MEK (MAP kinase kinase) inhibitors. The best activity is seen with alkoxy groups at both the 6- and 7-positions. The lead compounds show low nanomolar IC50's against MAP kinase kinase, and have potent inhibitory activity in tumor cells. (C) 2000 Elsevier Science Ltd.