Thiazolidinone compounds and composition for angina pectoris comprising the compounds as an active ingredient

A pharmaceutical composition for the treatment or prophylaxis of angina pectoris comprising an effective amount of an active compound in admixture with a pharmacologically acceptable carrier or diluent, wherein said active compound is selected from the group consisting of thiazolidinone compounds having the general formula:

• ##STR9## wherein:
• W represents a sulfur atom or an oxygen atom, and X represents a group having the formula --N(R.sup.1)--;
• or
• X represents a sulfur atom or an oxygen atom, and W represents a group having the formula --N(R.sup.1)--;
• R.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below;
• R.sup.2 and R.sup.3 may be the same or different and each represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below, an aryl group as defined below, or a 5- or 6-membered aromatic heterocyclic group containing 1 to 3 hetero groups selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms, said aromatic heterocyclic group being unsubstituted or being substituted by a substituent selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms, halogen atoms, amino groups and mono- and di-alkylamino groups wherein the or each alkyl group has from 1 to 6 carbon atoms;
• R.sup.4 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below;
• R.sup.5 represents a cycloalkyl group having from 3 to 8 carbon atoms, said group optionally containing a ring nitrogen atom, said group being substituted by a group having the formula --B--ONO.sub.2 and said group further optionally being substituted by an alkyl group having from 1 to 6 carbon atoms, wherein B represents a single bond or an alkylene group having from 1 to 6 carbon atoms;
• A represents a single bond or an alkylene group having from 1 to 6 carbon atoms;
• and said aryl group represents an aryl group having from 6 to 10 carbon atoms which may optionally be substituted by a substituent selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms, alkoxy groups having from 1 to 6 carbon atoms, halogen atoms, amino groups, mono- and di- alkylamino groups wherein the or each alkyl group has from 1 to 6 carbon atoms, and nitro groups;
• and pharmacologically acceptable salts thereof.

A method for the treatment or prophylaxis of angina pectoris comprising administering to a patient an effective amount of an active compound in admixture with a pharmacologically acceptable carrier or diluent, wherein said active compound is selected from the group consisting of thiazolidinone compounds having the general formula:

• ##STR10## wherein:
• W represents a sulfur atom or an oxygen atom, and X represents a group having the formula --N(R.sup.1)--;
• or
• X represents a sulfur atom or an oxygen atom, and W represents a group having the formula --N(R.sup.1)--;
• R.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below;
• R.sup.2 and R.sup.3 may be the same or different and each represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below, an aryl group as defined below, or a 5- or 6-membered aromatic heterocyclic group containing 1 to 3 hetero groups selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms, said aromatic heterocyclic group being unsubstituted or being substituted by a substituent selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms, halogen atoms, amino groups and mono- and di-alkylamino groups wherein the or each alkyl group has from 1 to 6 carbon atoms;
• R.sup.4 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below;
• R.sup.5 represents a cycloalkyl group having from 3 to 8 carbon atoms, said group optionally containing a ring nitrogen atom, said group being substituted by a group having the formula --B--ONO.sub.2 and said group further optionally being substituted by an alkyl group having from 1 to 6 carbon atoms, wherein B represents a single bond or an alkylene group having from 1 to 6 carbon atoms;
• A represents a single bond or an alkylene group having from 1 to 6 carbon atoms;
• and said aryl group represents an aryl group having from 6 to 10 carbon atoms which may optionally be substituted by a substituent selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms, alkoxy groups having from 1 to 6 carbon atoms, halogen atoms, amino groups, mono- and di- alkylamino groups wherein the or each alkyl group has from 1 to 6 carbon atoms, and nitro groups;
• and pharmacologically acceptable salts thereof.

A process for preparing a thiazolidinone compound having the general formula:

• ##STR11## wherein:
• W represents a sulfur atom or an oxygen atom, and X represents a group having the formula --N(R.sup.1)--;
• or
• X represents a sulfur atom or an oxygen atom, and W represents a group having the formula --N(R.sup.1)--;
• R.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below;
• R.sup.2 and R.sup.3 may be the same or different and each represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below, an aryl group as defined below, or a 5- or 6-membered aromatic heterocyclic group containing 1 to 3 hetero groups selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms, said aromatic heterocyclic group being unsubstituted or being substituted by a substituent selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms, halogen atoms, amino groups and mono- and di- alkylamino groups wherein the or each alkyl group has from 1 to 6 carbon atoms;
• R.sup.4 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms or an alkyl group having from 1 to 4 carbon atoms substituted by an aryl group as defined below;
• R.sup.5 represents a cycloalkyl group having from 3 to 8 carbon atoms, said group optionally containing a ring nitrogen atom, said group being substituted by a group having the formula --B--ONO.sub.2 and said group further optionally being substituted by an alkyl group having from 1 to 6 carbon atoms, wherein B represents a single bond or an alkylene group having from 1 to 6 carbon atoms;
• A represents a single bond or an alkylene group having from 1 to 6 carbon atoms;
• and said aryl group represents an aryl group having from 6 to 10 carbon atoms which may optionally be substituted by a substituent selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms, alkoxy groups having from 1 to 6 carbon atoms, halogen atoms, amino groups, mono- and di- alkylamino groups wherein the or each alkyl group has from 1 to 6 carbon atoms, and nitro groups;
• or a pharmacologically acceptable salt thereof, which comprises reacting a compound having the following general formula or a reactive derivative thereof:
• ##STR12## wherein Wa, Xa, R.sup.2 a and R.sup.3 a have the same meanings as W, X, R.sup.2 and R.sup.3, as defined above, respectively except that an amino group or an imino group (--NH--) in any of said groups may be optionally protected,
• with a compound having the general formula, or an acid addition salt thereof:
• ##STR13## wherein A has the same meaning as defined above, and R.sup.4 a and R.sup.5 a have the same meanings as R.sup.4 and R.sup.5, as defined above, respectively except that an amino group or an imino group (--NH--) in either of said groups may be optionally protected;
• and
• if desired, eliminating a protective group such as an amino protecting group from the compound thus obtained.