6-Oxo-7-substituted and 7,7-disubstituted-6H-indeno-[5,4-b]furan (and thiophene) carboxylic acids

A pharmaceutical composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula:

• ##SPC15##
• wherein the dotted line indicates 1,2-saturated or unsaturated embodiments;
• A is oxygen or sulfur;
• R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo;
• R.sup.1 is lower alkyl;
• X.sup.1 is lower alkyl or halo;
• X.sup.2 is hydrogen, lower alkyl or halo;
• and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof;
• and a pharmaceutically acceptable carrier.

A composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula:

• ##SPC16##
• wherein the dotted line indicates 1,2-saturated or unsaturated embodiments;
• A is oxygen or sulfur;
• R is phenyl, substituted phenyl wherein the substituents is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo;
• R.sup.1 is lower alkyl;
• X.sup.1 is lower alkyl or halo;
• X.sup.2 is hydrogen, lower alkyl or halo;
• and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 50:1 to 1:1.

A composition useful for the treatment of edema associated with hypertension comprising an effective amount of an indenofuran or indenothiophene compound of the formula:

• ##SPC17##
• wherein the dotted line indicates 1,2-saturated or unsaturated embodiments;
• A is oxygen or sulfur;
• R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo;
• R.sup.1 is lower alkyl having 1 to 6 carbon atoms;
• X.sup.1 is lower alkyl or halo;
• X.sup.2 is hydrogen, lower alkyl or halo;
• and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 25:1 to 1:1.

A method of treatment of edema associated with hypertension in a patient in need of said treatment comprising the oral administration of a therapeutically effective amount in unitary dosage form of a compound having the formula:

• ##SPC18##
• wherein the dotted line indicates 1,2-saturated or unsaturated embodiments;
• A is oxygen or sulfur;
• R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo;
• R.sup.1 is lower alkyl;
• X.sup.1 is lower alkyl or halo;
• X.sup.2 is hydrogen, lower alkyl or halo;
• and the non-toxic, pharmacologically acceptable salt, lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof.

A method of treatment of edema associated with hypertension in a patient in need of said treatment comprising the oral administration of a therapeutically effective amount in a combination dosage form of a composition comprising an indenofuran or indenothiophene of the formula:

• ##SPC19##
• wherein the dotted line indicates 1,2-saturated or unsaturated embodiments;
• A is oxygen or sulfur;
• R is phenyl, substituted phenyl wherein the substituent is lower alkyl or halo, thienyl or substituted thienyl wherein the substituent is lower alkyl or halo;
• R.sup.1 is lower alkyl having 1 to 6 carbon atoms;
• X.sup.1 is lower alkyl or halo;
• X.sup.2 is hydrogen, lower alkyl or halo;
• and the non-toxic, pharmacologically acceptable salt lower alkyl ester and mono and di lower alkyl, piperidino and morpholino amide derivatives thereof and N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride wherein the mole ratio of the indenofuran or indenothiophene compound to N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride ranges from about 50:1 to 1:1.