1-bolizazepin-2,5-diones

A method for the treatment of stroke, hypoglycemia ischemic attack or anoxia comprising administering to a mammal in need of such treatment an effective amount of a compound of formula I, wherein:

• ##STR2## R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently selected from:
• hydrogen,
• (1-3C)perfluoroalkyl,
• halo, nitro and cyano;
• R.sup.6 and R.sup.7 are independently selected from hydrogen,
• CH.sub.2 Y wherein Y is selected from (CH.sub.2).sub.m OH and (CHOH).sub.n CH.sub.2 OH wherein m is 0 to 5 and n is 1 to 5,
• aryl, and aryl(1-6C)alkyl wherein each aryl moiety is selected from phenyl and naphthyl each of which may be substituted with 0-2 substituents selected from halo, cyano, hydroxyl, nitro, (1-6C)alkyl, (1-6C)alkoxy, vinyl, and allyl;
• and
• heteroaryl, and heteroaryl(1-6C)alkyl wherein each heteroaryl moiety is selected from pyridyl, pyrrolo, pyrazinyl, pyrimidinyl, pyridazinyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl and triazolyl;
• or R.sup.6 and R.sup.7, together with the nitrogen atom to which they are attached, form a 5-, 6- or 7-membered heterocyclic ring which is bonded to said compound through said nitrogen atom, said heterocyclic ring optionally containing one additional heteroatom selected from nitrogen, oxygen and sulfur;
• R.sup.8 is selected from
• hydrogen,
• (1-6C)alkyl which may optionally bear a substituent selected from amino, formyl, acetyl, propanoyl, isopropanoyl, butyryl, isobutyryl, pentanoyl, pivaloyl, carboxy, and carboxamido;
• and
• aryl(1-6C)alkyl;
• or a pharmaceutically acceptable salt thereof.

A compound of formula I or formula II, and pharmaceutically acceptable salts thereof, wherein. ##STR3## R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently selected from hydrogen, (1-3C)perfluoroalkyl, halo, nitro and cyano;

• R.sup.5 is selected from hydrogen and (1-6C)alkyl;
• R.sup.6 and R.sup.7 are independently selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (3-7C)cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl, and heteroaryl(1-6C)alkyl and CH.sub.2 Y wherein Y is selected from (CHOH).sub.n CH.sub.2 OH and (CH.sub.2).sub.m R.sup.c wherein m is 0 to 5 n is 1 to 5 and R.sup.c is selected from hydroxy, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, carboxy, (3-7C)cycloalkyl, and NR.sup.d R.sup.e in which R.sup.d and R.sup.e are independently selected from hydrogen and (1-4C)alkyl or R.sup.d and R.sup.e together with the nitrogen atom to which they are attached, form a 5-, 6- or 7-membered heterocyclic ring which optionally contains one additional heteroatom selected from nitrogen, oxygen and sulfur;
• or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached, form a 5-, 6- or 7-membered heterocyclic ring which is bonded to said compound through said nitrogen atom, said heterocyclic ring optionally containing one additional heteroatom selected from nitrogen, oxygen and sulfur, and wherein said heterocyclic ring may be substituted with 0-2 substituents selected from (1-6C)alkyl, phenyl, phenyl(1-4C)alkyl, phenoxy, phenyl(1-4C)alkoxy;
• R.sup.8 is selected from hydrogen, halo, (1-6C)alkyl which may optionally bear a substituent selected from amino, formyl, acetyl, propanoyl, isopropanoyl, butyryl, isobutyryl, pentanoyl, pivaloyl, carboxy and carboxamido, aryl(1-6C)alkyl and heteroaryl(1-6C)alkyl;
• and wherein each aryl moiety is selected from phenyl and naphthyl;
• each heteroaryl moiety is selected from pyridyl, pyrrolo, pyrazinyl, pyrimidinyl, pyridazinyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl and triazolyl;
• and wherein each aryl or heteroaryl moiety may be substituted with 0-2 substituents selected from halo, cyano, hydroxy, carboxy, nitro, (1-6C)alkyl, (1-6C)alkoxy, (2-6C)alkenyl, phenyl, phenyl(1-4C)alkyl, phenoxy, phenyl(1-4C)alkoxy and (1-6C)alkoxycarbonyl;
• provided that in compounds of formula II, R.sup.8 is not hydrogen;
• and excluding the compound of formula II in which R.sup.1 -R.sup.4 are each hydrogen, R.sup.8 is bromo and R.sup.5 is hydrogen;
• the compounds of formula I wherein R.sup.1 -R.sup.4 and R.sup.6 -R.sup.7 are each hydrogen and R.sup.8 is hydrogen or methyl;
• the compounds of formula I in which R.sup.1 -R.sup.4 and R.sup.8 are each hydrogen and R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached, form a 5- or 6-membered ring;
• the compounds of formula I in which R.sup.1 -R.sup.4 and R.sup.8 are each hydrogen, R.sup.6 is hydrogen and R.sup.7 is CH.sub.2 Y in which Y is (CH.sub.2).sub.m R.sup.c and R.sup.c is NR.sup.d R.sup.e in which R.sup.d and R.sup.e are (1-4C)alkyl;
• and their pharmaceutically acceptable salts.

A process for producing a compound of formula I wherein R.sup.1 -R.sup.4 are selected from H or halo;

• R.sup.8 is selected from H or (1-6C)alkyl or (1-6C)alkylphenyl, comprising reacting a compound of formula II wherein R.sup.1 -R.sup.4 are selected from H or halo;
• R.sup.8 is selected from H or (1-6C)alkyl or (1-6C)alkylphenyl and wherein R.sup.5 is selected from (1-6C)alkyl with an amine of formula HNR6R.sup.7 wherein R.sup.6 and R.sup.7 are independently selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (3-7C) cycloalkyl, (3-7C)cycloalkyl (1-6C)alkyl, aryl, aryl (1-6C) alkyl, heteroaryl, heteroaryl (1-6C)alkyl and CH.sub.2 Y wherein Y is selected from (CHOH).sub.n CH.sub.2 OH and (CH.sub.2).sub.m R.sup.c wherein m is 0 to 5 n is 1 to 5 and R.sup.c is selected from hydroxy, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, carboxy, (3-7C)cycloalkyl, and NR.sup.d R.sup.e in which R.sup.d and R.sup.e are independently selected from hydrogen and (1-4C)alkyl or R.sup.d and R.sup.e, together with the nitrogen atom to which they are attached, form a 5-, 6- or 7-membered heterocyclic ring which optionally contains one additional heteroatom selected from nitrogen, oxygen and sulfur;
• or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached, form a 5-, 6- or 7-membered heterocyclic ring which is bonded to said compound through said nitrogen atom, said heterocyclic ring optionally containing one additional heteroatom selected from nitrogen, oxygen and sulfur, and wherein said heterocyclic ring may be substituted with 0-2 substituents selected from (1-6C)alkyl, phenyl, phenyl(1-4C)alkyl, phenoxy and phenyl (1-4C) alkoxyl;
• and wherein each aryl moiety is selected from phenyl and naphthyl;
• each heteroaryl moiety is selected from pyridyl, pyrrolo, pyrazinyl, pyrimidinyl, pyridazinyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl and triazolyl;
• and wherein each aryl or heteroaryl moiety may be substituted with 0-2 substituents selected from halo, cyano, hydroxy, carboxy, nitro, (1-6C) alkyl, (1-6C) alkoxy, (2-6.0 alkenyl, phenyl, phenyl(1-4C) alkyl, phenoxy, phenyl(1-4C) alkoxy and (1-6C)alkoxycarbonyl.