ES269692A1 - Process for the production of new carbostyril derivatives - Google Patents

Abstract

The invention comprises compounds of general formula <FORM:0988776/C2/1> wherein R1 represents a hydrocarbon radical with 1 to 10 carbon atoms which can be substituted at aryl nuclei by halogen or low alkoxy (low = C1- 4) radicals, or a polymethyleneiminoalkyl or morpholinoalkyl group, or a low dialkylaminoalkyl group R2 represents hydrogen or a hydrocarbon radical with 1 to 10 carbon atoms R3 represents hydrogen, a halogen atom, a low alkyl or alkoxy group, the nitro group, cyano group or trifluoromethyl group R4 represents hydrogen, a halogen atom or a low alkyl or alkoxy group, or, together with R3, the methylenedioxy group R5 represents hydrogen or a radical corresponding to the definition of R1 and R6 represents hydrogen or a low alkyl radical, or the alkyl radicals R5 and R6 can be bound to each other direct: and their acid addition salts and their preparation by (1) reacting a compound of formula <FORM:0988776/C2/2> wherein Hal represents chlorine or bromine, with ammonia or an amine of formula HNR5R6 (separating if necessary a mixture of primary and secondary amines formed when using a dialkylamine HNR5R6) and possibly converting the compounds so obtained when these are primary or secondary amines into other compounds I by (A) reaction in the presence of an acid binding agent with a reactive ester of a compound of formula R15-OH or/and by reaction with a reactive ester of a compound of formula R51-OH wherein R51 and R61 have the meanings given above for R5 and R6 with the exception of hydrogen, or by (B) reaction of those compounds in which R2 is not a hydrogen atom with a low oxo alkane under reducing conditions, or (2) reacting a compound I in which R1 is replaced by hydrogen, (A) in the presence of an acid binding agent or after conversion into a salt of a metal, with a reactive ester of a compound R11OH wherein R11 has the meaning given for R1 with the exception of aromatic radicals, or (B) with a diazo alkane. 4 - Chloro - or bromo - carbostyril derivatives II are obtainable from the 4-hydroxy-compounds with halogenating agents. Compounds I having R1 replaced by hydrogen and their enol tautomers are obtainable by heating 2,4-dioxo-tetrahydroquinolines with monoamides or diamines. Pharmaceutical compositions comprise compounds I and their acid addition salts together with carriers. Oral and parenteral administration is mentioned. The compounds have analgetic, antiphlogistic and antipyretic activity.