US RE30,420 E · Pyrazol-5-ones

Abstract

1-Substituted pyrazole-5-ones of the formula ##STR1## and pharmaceutically acceptable, nontoxic salts thereof, wherein R is hydrogen or amino; R.sup.1 is hydrogen, alkyl, alkenyl, unsubstituted or substituted aryl or unsubstituted or substituted aralky; X is a. ethylene, ethylene wherein 1 hydrogen atom on one of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by alkyl of 1 to 4 carbon atoms or said ethylene which is linked to R.sup.2 via an oxygen or sulphur atom; b. propenyl, propenyl wherein 1 hydrogen atom on one, two or three of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, said propenyl being linked to the N.sup.1 atom of the pyrazol ring via its methylene moiety; or c. methylene; provided that when X is methylene, R.sup.1 is not hydrogen if R is amino; R.sup.2 is aryl unsubstituted or substituted by: a. 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, and lower alkoxy; b. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms; c. alkylamino, dialkylamino, cyano, trifluoromethoxy, nitro, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, or said carbamoyl wherein the nitrogen atom is a member of a heterocyclic ring, sulphamyl, alkylsulphamyl, dialkylsulphamyl, or said sulphamyl wherein the nitrogen is a member of a heterocyclic ring, or --SO.sub.n alkyl wherein n is 0, 1 or 2; d. alkylamino, dialkylamino, cyano, trifluoromethoxy, nitro, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, or said carbamoyl wherein the nitrogen atom is a member of a heterocyclic ring, sulphamyl, alkylsulphamyl, dialkylsulphamyl or said sulphamyl wherein the nitrogen is a member of a heterocyclic ring, or --SO.sub.n -- alkyl wherein n is 0, 1 or 2, and 1 or 2 of the same or different substituents selected from the group consisting of alkyl, alkenyl, alkoxy, halogen, and trifluoromethyl; or e. a fused, saturated or unsaturated 5-, 6-, or 7-membered ring or said ring containing 1 or 2 oxygen or sulphur atoms; are useful for their diuretic, saluretic, antihypertensive and antithrombotic effects.

Claims27

Dependent claims

A pharmaceutical composition useful for effecting diuresis or saluresis in humans and animals and for treating hypertension in humans and animals which comprises a diuretically effective amount, a saluretically effective amount or an antihypertensive amount of a compound of the formula ##STR48## or a pharmaceutically acceptable nontoxic salt thereof, wherein R is amino;

R.sup.1 is [hydrogen,] lower alkyl or lower alkenyl;
X is
ethylene, ethylene wherein 1 hydrogen atom on 1 of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, linked to R.sup.2 via an oxygen or sulphur atom;
R.sup.2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by:
a. 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms and lower alkoxy;
b. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms;
c. nitro or
d. nitro, and 1 or 2 of the same or different substituents selected from the group consisting of lower alkyl, lower alkenyl, lwer alkoxy, halogen and trifluoromethyl
in combination with a pharmaceutically-acceptable, nontoxic, inert diluent or carrier.

6 more elements

[20. A composition according to claim 1 wherein the compound is ##STR59##

21. A method of effecting diuresis and saluresis in humans and animals and treating hypertension in humans and animals which comprises administering to such human or animal a diuretically effective amount, a saluretically effective amount or an antihypertensive amount of a compound of the formula ##STR60## or a pharmaceutically acceptable nontoxic salt thereof, wherein R is amino;
R.sup.1 is [hydrogen,] lower alkyl or lower alkenyl;
X is ethylene, ethylene wherein 1 hydrogen atom on 1 of the carbon atoms is substituted by alkyl of 1 to 4 carbon atoms or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by alkyl of 1 to 4 carbon atoms, linked to R.sup.2 via an oxygen or sulphur atom;
R.sup.2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by:
a. 1 to 2 of the same or different substitutents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms and lower alkoxy;
b. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms;
c. nitro;
or
d. nitro and 1 or 2 of the same or different substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkoxy, halogen and trifluoromethyl;
in combination with a pharmaceutically-acceptable, nontoxic, inert diluent
or carrier. 22. A method according to claim 21 wherein
R.sup.2 is aryl of 6 to 10 carbon atoms unsubstituted or substituted by:
a. 1 or 2 of the same or different substituents selected from the group consisting of halogen, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms;
b. nitro;
or
c. nitro and 1 or 2 of the same or different substituents selected from the group consisting of alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon
atoms, alkoxy of 2 to 4 carbon atoms, halogen and trifluoromethyl. 23. A method according to claim 21 wherein
R.sup.1 is [hydrogen,] alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms;
and
R.sup.2 is phenyl;
naphthyl;
or phenyl substituted by:
a. 1 or 2 straight or branched-chain alkyl moieties of 1 to 8 carbon atoms, or alkenyl moieties of 2 to 8 carbon atoms;
b. 1 or 2 alkoxy moieties or 1 to 6 carbon atoms;
c. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms;
d. 1 or 2 halogens;
e. 1 or 2 trifluoromethyl moieties;
or
f. nitro. 24. A method according to claim 21 wherein
R.sup.1 is [hydrogen,] alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms;
and
R.sup.2 phenyl;
naphthyl;
or phenyl substituted by:
a. 1 or 2 straight or branched-chain alkyl moieties of 1 to 4 carbon atoms or alkenyl moieties of 2 to 4 carbon atoms;
b. 1 or 2 alkoxy moieties of 1 to 4 carbon atoms;
c. cycloalkyl of 5, 6 or 7 carbon atoms or cycloalkenyl of 5, 6 or 7 carbon atoms;
d. 1 or 2 fluoro, chloro or bromo moieties;
e. 1 or 2 trifluoromethyl moieties;
or
f. nitro. 25. A method according to claim 21 wherein
R.sup.1 is [hydrogen,] alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms;
and
R.sup.2 is phenyl;
naphthyl or phenyl substituted by:
a. 1 or 2 members selected from the group consisting of straight or branched-chain alkyl and trifluoromethyl moieties of 1 to 4 carbon atoms;
b. alkoxy of 1 to 4 carbon atoms;
c. cycloalkyl of 5 to 6 carbon atoms;
d. 1 or 2 fluoro, chloro, bromo or iodo moieties;
e. chloro or bromo and alkyl of 1 or 2 carbon atoms, trifluoromethyl;
or
f. nitro. 26. A method according to claim 21 wherein
R.sup.1 is [hydrogen,] methyl or ethyl;
X is ethylene, ethylele wherein 1 hydrogen atom on one of the carbon atoms is substituted by alkyl of 1 or 2 carbons or ethylene wherein 1 hydrogen atom on each of the two carbon atoms are substituted by alkyl of 1 or 2 carbon atoms, linked to R.sup.2 via an oxygen or sulphur atom;
and
R.sup.2 is phenyl;
naphthyl;
or phenyl substituted by fluorine, chlorine, bromine, iodine, trifluoromethyl, nitro, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cyclohexyl, dichlorine, chlorine and methyl, chlorine and bromine, chlorine and fluorine, chlorine and
trifluoromethyl, dibromine or methyl and trifluoromethyl. 27. A method according to claim 21 wherein
X is ethylene, ethylene wherein 1 hydrogen on one of the carbon atoms is substituted by methyl or ethyl or ethylene wherein 1 hydrogen atom on each of the two carbon atoms is substituted by methyl, linked to R.sup.2 via an
oxygen or sulphur atom. 28. A method according to claim 21 wherein
R.sup.1 is [hydrogen or] alkyl or 1 to 4 carbon atoms;
X is ethylene or ethylene wherein 1 hydrogen atom on one of the carbon atoms is substituted by methyl and linked to R.sup.2 via an oxygen or sulphur atom;
and
R.sup.2 is phenyl;
naphthyl;
or phenyl substituted by 1 or 2 chlorine,
methyl, ethyl or trifluoromethyl moieties. 29. A method according to claim 21 wherein
R.sup.1 is [hydrogen or] alkyl of 1 to 4 carbon atoms;
X is ethylene or ethylene wherein 1 hydrogen atom of one of the carbon atoms is substituted by methyl, linked to R.sup.2 via an oxygen or sulphur atom;
and
R.sup.2 is naphthyl;
phenyl;
or phenyl substituted by chlorine, methyl, trifluoromethyl, dichlorine, dimethyl, methyl and ethyl or methyl and
trifluoromethyl.

72 more elements

Dependencies are inferred from the claim text.

Pyrazol-5-ones

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Pyrazol-5-ones

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Abstract

Claims27