Carbostyril derivatives

Various bioisosteric replacements for a phenolic hydroxyl have been explored. One such, a lactam NH, is incorporated into the design of the 3-adrenergic blocker, carteolol O)- The fundamental synthon is carbostyril derivative K This is reacted in the usual manner with epichlorohydrin to give which is in turn reacted with t-butylamine to complete the synthesis of carteolol (3 ), a drug that appears to have relatively reduced nonspecific myocardial depressant action. Carrying this de-... 

Ge, P., and Selvin, P.R. (2004) Carbostyril derivatives as antenna molecules for luminescent lanthanide chelates. Bioconjugate Chem. 15, 1088-1094. 

N. J. Thumar, M. P. Patel, Saudi Pharm. J. 2011, 19, 75-83. Synthesis, characterization, and antimicrobial evaluation of carbostyril derivatives of l//-pyrazole. 

The reaction between aryl Grignard compounds and 5-methoxy-6-nitroquinoline derivatives in THF has been found to proceed in a chemodivergent mode that depended on the functional groups present in the heterocyclic ring. Thus, the reactions that started from carbostyril derivatives afforded 6-(arylamino)carbostyrils as the major products, whereas those that started with 2-alkoxyquinolines gave exclusively 5-aryl-quinolines. 

Examples from preparative chemistry indicate the possible occurrence of special alpha-e ects in several other cases. The different reaction of 2- and 4-ethoxy quinolines with a thiol yielding carbostyril and a 4-arylthio derivative, respectively, may indicate the intervention of structures such as 17 in the transition state of the 2-isomer. 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

Of the lactam derivatives of quinoline and isoquinoline, 2(1 H)-quinolinones and 1 (2//)-isoquinolinones (carbostyrils and isocarbostyrils) have long been known. Although over 100 years have passed since Gabriel discussed the tautomerism of 3(2//)-isoquinolinone derivatives (1) (3-isoquinolones, 3-hydroxyisoquinolines or 3-isoquinolinols), these com-... 

Subsequent development in all industrialized countries was rapid, especially during the period 1945-1975, and led to more than 1000 commercial products by 1989. Almost 400 compounds of distinct chemical structure or composition are registered in the Colour Index. Many of these compounds, including 3 and heterocycles such as imidazolone, dibenzothiophene-5,5 -dioxides, methine derivatives, dihydrocollidine, pyrazine, carbostyrils, pyrazolo[3,4-6]quinolines, and 5,6-benzocoumarins are no longer used and have been replaced by others. 

The phenyliodonium salt of carbostyril on reaction with phenol, in the absence of solvent, was converted into a phenolic derivative [57] ... 

Hydrogenation to Dihydro Derivatives. Similarly to 2-hydroxy-pyridines, 2-hydroxyquinoline (carbostyril) and 1-hydroxyisoquinoline (isocarbo-styril) are hydrogenated to the 3,4-dihydro compounds over palladium black (Willstatter) in ethanol or dioxane at 55°C and 0.1-0.3 MPaH2 (Scheme 12.13), while 3-, 5-, 6-, 7-, and 8-hydroxyquinolines are hydrogenated to yield the corresponding 1,2,3,4-tetrahydroquinolines.39 4-Hydroxy-, 4-hydroxy-2-methyl-, and 2-hydroxy-4-methylquinolines were not hydrogenated under the conditions employed. 

Carbostyril.—If in the Baeyer and Drewsen synthesis cinnamic acid is used instead of cinnamic aldehyde the or//fo-amino derivative, by loss of water, yields a hydroxy quinoline known as carbostyril. 

The photochemical behavior of the W-oxides of the Cinchona alkaloids has been examined 49). Photolysis (> 300 nm) of the aromatic mono-iV-oxides 183 of the dihydro derivatives of quinine, quinidine, cincho-nidine, and cinchonine in alcoholic solvents gave the expected carbo-styrils 186 in yields of 70-85%. The same results were obtained with the corresponding AjiV-dioxides 184. An interesting rearrangement was observed in the case of the iV,A -dioxides of dihydrocinchonine and dihydrocinchonidine. Photolysis in benzene solution afforded, in addition to the carbostyrils, the iV -formylindole methanols 188 in 30% yield. The hydrolysis-sensitive benz[d]-l,3-oxazepines 185 were proposed as the probable intermediates. 

A Quinoline is derived from naphthalene by replacement of one of its a-CH groups by nitrogen. 2-and 3-Methylquinoline (quinaldine and lepidine), 2-quinolone (carbostyril), 4-quinolone and the quinolinium ion are important derivatives of quinoline. 

Coumarins. A soln. of 3-(2-hydroxy-5-methylphenyl)-2-phenylcyclopropenone in te-tralin heated at 200° under N2 for 1 h - 6-methyl-3-phenylcoumarin. Y 72%. F.e. and carbostyrils from the corresponding o-aminoaryl derivs. s. T. Richer, V. Schneider Synthesis 1989, 372-8. 

Photochemical [2+2] cycloaddition of cyclohexene to carbostyril, 3-, and 4-methylcarbostyril, and 3,4-dimethylcarbostyril have been shown to involve the T state of the carbostyrils as the reactive species. The unsubstituted carbostyril, and the 4-methyl and 3,4-dimethyl derivatives gave [2+ 2] adducts with high stereospecificity, but the 4-methyl derivative gave mixtures. Reaction of 3-acetyl and 3-carbomethoxycoumarin with vinylpyridine, 1,1-dichloroethylene, vinylene carbonate, and cyclohexene gave the corresponding [2+ 2] adducts. ... 

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