Pharmaceutical composition and method for modulating the immune reaction

A pharmaceutical composition of formula I or II, ##STR23## wherein R.sup.1 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, or an acyl group of the formula ##STR24## wherein R.sup.4 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, an aryl group or a cycloalkyl group,

• Z is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group or an aryl group, and
• X and Y represent independently from each other hydrogen atoms, alkyl groups, cycloalkyl groups, aryl groups, hydroxy groups, halogen atoms, nitro groups, ether groups of the formula
• --O--R.sup.2,
• ester groups of the formula ##STR25## or ester groups of the formula ##STR26## wherein R.sup.4 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, an aryl group or a cycloalkyl group;
• R.sup.2 is an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group or an aryl group or groups, or
• X and Y together represent a group of the formula
• --O--(CH.sub.2).sub.n --O--
• in which n is an integer between 1-4, and
• R is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, an aryl group, a hexose group linked as an ester, or a chain of 2-6 hexose groups,
• provided firstly that in those compounds of the formula I or II where R is a hydrogen atom, a methyl group, or an ethyl group, and R.sup.1 is hydrogen or a methyl group, and Z is hydrogen, then the groups X and Y are not collectively two hydrogen atoms, two chlorine atoms, two bromine atoms, two methoxy groups, or a group of the formula --O--CH.sub.2 --O--, and where X is hydrogen then Y is not an iodine atom, a hydroxy group, a methoxy group, or a methyl group,
• provided secondly that in those compounds of the formula I or II, where Z, X and Y are hydrogen atoms and R is hydrogen, a methyl group, an ethyl group, or a butyl group, then R.sup.1 is not a methyl group, a butyl group, a benzyl group, an acetyl group or a 4-chlorobenzoyl group, and
• provided thirdly that in those 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acids of formula II where Z is an ethyl group, then at least one of R, R.sup.1, X and Y is not a hydrogen atom.

A pharmaceutical composition including as the pharmaceutically active agent 2-oxindole-3-acetic acid of formula I ##STR28## wherein R.sup.1 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, or an acyl group of the formula ##STR29## wherein R.sup.4 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, an aryl group, or a cycloalkyl group,

• Z is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, or an aryl group, and
• X and Y represent independently of one other hydrogen atoms, alkyl groups, cycloalkyl groups, aryl groups, hydroxy groups, halogen atoms, nitro groups, ether groups of the formula
• --O--R.sup.2,
• ester groups of the formula ##STR30## or ester groups of the formula ##STR31## wherein R.sup.4 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, an aryl group, or a cycloalkyl group;
• R.sup.2 is an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, or an aryl group or groups, or
• X and Y together represent a group of the formula
• --O--(CH.sub.2).sub.n --)--
• in which n is an integer in the range of 1-4, and
• R is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, an aryl group, a hexose group linked as an ester, or a chain of 2-6 hexose groups.

A method of modulating the immune reaction of a warm-blooded animal including the step of administering to the animal a daily dosage of between 0.02 and 0.06 milligram per kilogram of body weight of a pharmaceutical composition comprising as the pharmaceutically active agent 2-oxindole-3-acetic acid of formula I or 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid of formula II ##STR33## wherein R.sup.1 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, or an acyl group of the formula ##STR34## wherein R.sup.4 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, an aryl group or a cycloalkyl group;

• Z is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, or an aryl group, and
• X and Y represent independently from each other hydrogen atoms, alkyl groups, cycloalkyl groups, aryl groups, hydroxy groups, halogen groups, nitro groups, ether groups of the formula
• --O--R.sup.2,
• ester groups of the formula ##STR35## or ester groups of the formula ##STR36## wherein R.sup.4 is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, an aryl group or a cycloalkyl group;
• R.sup.2 is an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, or an aryl group or groups, or
• X and Y together represent a group of the formula
• --O--(CH.sub.2).sub.n --O--
• in which n is an integer between 1-4, and
• R is a hydrogen atom, an alkyl group with 1-6 carbon atoms, an aralkyl group with 1-6 carbon atoms in the alkyl portion, a cycloalkyl group, an aryl group, a hexose group linked by an ester, or a chain of 2-6 hexose groups.