GB1036274A - 1-oxo-isoindoline derivatives - Google Patents

Abstract

The invention comprises isoindoline derivatives of the formula <FORM:1036274/C2/1> wherein Hal represents a halogen atom, preferably chlorine or fluorine, and R represents a hydroxyalkyl group, a cycloalkyl group containing 5 to 8 carbon atoms, or a carboxyalkyl carbonyloxyalkyl group, and, where R represents a carboxyalkylcarbonyloxyalkyl group, alkali metal and ammonium salts thereof (alkyl in all the above cases containing up to six carbon atoms), and the preparation thereof either by reduction of a compound of formula <FORM:1036274/C2/2> or by the reaction of a diazonium salt of a compound of formula <FORM:1036274/C2/3> with a cuprous halide such as cuprous chloride, or, in the case where R represents a carboxyalkylcarbonyloxyalkyl group, by the monoesterification of the appropriate dibasic acid, e.g. succinic or adipic acid, or anhydride thereof, by a compound of the first general formula above wherein R is hydroxy, in the presence of a base, e.g. pyridine, optionally followed by the formation of an alkali metal, amine or ammonium salt of the resulting acid. Amino-1-oxo-isoindolines of the third general formula above are prepared by the reduction of 1-oxo-iso-indolines of the formula <FORM:1036274/C2/4> wherein R is protected hydroxyalkyl or cycloalkyl. Nitro compounds of the last general formula above may be prepared by nitration, for example with concentrated sulphuric acid and sodium nitrate, of a compound of formula <FORM:1036274/C2/5> wherein R is a protected hydroxyalkyl group, e.g. an acetoxy group, or is a cycloalkyl group. Other methods of preparation of compounds of the invention are outlined. Pharmaceutical compositions in conventional forms for oral administration, having use in the treatment of hypertension, comprise a compound of the first general formula above and an inert diluent or exipient.