Cyclopentane(ene) heptanoic or cyclopentane(ene) heptenoic acid, 2-hydrocarbyl phosphinyloxyalkyl or phosphonamidoalkyl as therapeutic agents
AssigneeAllergan, Inc.
InventorRobert M. Burk
Life of this patent
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Abstract
The present invention relates to cyclopentane (or cyclopentane) heptanoic or cyclopentane (or cyclopentene) heptenoic acid, 2-hydrocarbyl phosphinyloxyalkyl or phosphonamidoalkyl, 1-esters, and derivatives thereof, useful as therapeutic agents. In particular, the therapeutic agents of this invention are useful as ocular hypotensives.
Claims21
A method of treating cardiovascular, pulmonary-respiratory, gastrointestinal, reproductive, allergic disease, shock and ocular hypertension which comprises administering an effective amount of a cyclopentane(ene) heptanoic or cyclopentane(ene) heptenoic acid, 2-hydrocarbylphosphinyloxymethyl or phosphonamidomethyl compound or derivative thereof represented by the formula I ##STR18## wherein the dashed bonds represent a single bond or a double bond which can be in the cis or trans configuration;
- A is a radical selected from the group consisting of
- --N(R.sub.4)(R.sub.4), --SR.sub.4 and --OR.sub.4
- wherein R.sub.4 is hydrogen or C.sub.1 to C.sub.3 alkyl, Z is oxo or represents two hydrogen radicals, Y is O or N;
- x is 0 or 1, provided that x is 0 when Y is O and x is 1 when Y is N;
- B is an alkyl or an alkylcycloalkyl radical having from one to ten carbon atoms, or an arylalkyl radical, selected from the group consisting of hydrocarbyl arylalkyl and heteroarylalkyl radicals wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms and said arylalkyl radical may comprise up to twelve carbon atoms;
- R is selected from the group consisting of hydrogen;
- lower alkyl and alkenyl radicals having from 1 to 10 carbon atoms, aromatic radicals and heteroaromatic radicals having from 1 to 10 carbon atoms, wherein said heteroatom is selected from the group consisting of oxygen, nitrogen, and sulfur;
- and substituted derivatives thereof wherein said substituent is selected from the group consisting of halo, nitro, amino, thiol, hydroxy, alkyl, alkyloxy, alkyl carboxy and halo substituted alkyl radicals wherein said alkyl comprises from 1 to 3 carbon atoms, R.sub.3 is hydrogen or a lower alkyl radical having from 1 to 3 carbon atoms;
- and one of R.sub.1 and R.sub.2 is .dbd.O, --OH or a --O(CO)R.sub.6 group, and the other one is --OH or --O(CO)R.sub.6, or R.sub.1 is .dbd.O and R.sub.2 is H, wherein R.sub.6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or --(CH.sub.2).sub.m R.sub.7 wherein m is 0-10;
- and R.sub.7 is an aliphatic ring from about 3 to about 7 carbon atoms, or an aryl or heteroaryl ring, and pharmaceutically-acceptable salts thereof.
A composition useful for treating cardiovascular, pulmonary-respiratory, gastrointestinal, reproductive, allergic disease, shock and ocular hypertension which comprises administering an effective amount of a cyclopentane(ene) heptanoic or cyclopentane(ene) heptenoic acid, 2-hydrocarbylphosphinyloxy methyl or phosphonamidomethyl compound or derivative thereof represented by the formula I ##STR23## wherein the dashed bonds represent a single bond or a double bond which can be in the cis or trans configuration;
- A is a radical selected from the group consisting of
- --N(R.sub.4)(R.sub.4), --SR.sub.4 and --OR.sub.4
- wherein R.sub.4 is hydrogen or C.sub.1 to C.sub.3 alkyl. Z is oxo or represents two hydrogen radicals, Y is O or N;
- x is 0 or 1, provided that x is 0 when Y is 0 and x is 1 when Y is N;
- B is an alkyl or an alkylcycloalkyl radical having from one to ten carbon atoms, or an arylalkyl radical, selected from the group consisting of hydrocarbyl arylalkyl and heteroarylalkyl radicals wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms and said arylalkyl radical may comprise up to twelve carbon atoms;
- R is selected from the group consisting of hydrogen;
- lower alkyl and alkenyl radicals having from 1 to 10 carbon atoms, aromatic radicals and heteroaromatic radicals having from 1 to 10 carbon atoms, wherein said heteroatom is selected from the group consisting of oxygen, nitrogen, and sulfur;
- and substituted derivatives thereof wherein said substituent is selected from the group consisting of oxygen, nitrogen, and sulfur;
- and substituted derivatives thereof wherein said substituent is selected from the group consisting of halo, nitro, amino, thiol, hydroxy, alkyl, alkyloxy, alkyl carboxy and halo substituted alkyl radicals wherein said alkyl comprises from 1 to 3 carbon atoms;
- R.sub.3 is hydrogen or a lower alkyl radical having from 1 to 3 carbon atoms;
- and one of R.sub.1 and R.sub.2 is .dbd.O, --OH or a --O(CO)R.sub.6 group, and the other one is --OH or --O(CO)R.sub.6, or R.sub.1 is .dbd.O and R.sub.2 is H, wherein R.sub.6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or --(CH.sub.2).sub.m R.sub.7 wherein m is 0-10, and R.sub.7 is an aliphatic ring from about 3 to about 7 carbon atoms, or an aryl or heteroaryl ring, and pharmaceutically-acceptable salts thereof.
A compound useful for treating cardiovascular, pulmonary-respiratory, gastrointestinal, reproductive, allergic disease, shock and ocular hypertension which comprises administering an effective amount of a cyclopentane(ene) heptanoic or cyclopentane(ene) heptenoic acid, 2-hydrocarbylphosphinyloxymethyl or phosphonamidomethyl compound or derivative thereof represented by the formula I ##STR24## wherein the dashed bonds represent a single bond or a double bond which can be in the cis or trans configuration;
- A is a radical selected from the group consisting of
- --N(R.sub.4)(R.sub.4), --SR.sub.4 and --OR.sub.4
- wherein R.sub.4 is hydrogen or C.sub.1 to C.sub.3 alkyl. Z is oxo or represents two hydrogen radicals, Y is O or N;
- x is 0 or 1, provided that x is 0 when Y is 0 and x is 1 when Y is N;
- B is an alkyl or an alkylcycloalkyl radical having from one to ten carbon atoms, or an arylalkyl radical, selected from the group consisting of hydrocarbyl arylalkyl and heteroarylalkyl radicals wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms and said arylalkyl radical may comprise up to twelve carbon atoms;
- R is selected from the group consisting of hydrogen;
- lower alkyl and alkenyl radicals having from, 1 to 10 carbon atoms, aromatic radicals and heteroaromatic radicals having from 1 to 10 carbon atoms, wherein said heteroatom is selected from the group consisting of oxygen, nitrogen, and sulfur;
- and substituted derivatives thereof wherein said substituent is selected from the group consisting of oxygen, nitrogen, and sulfur;
- and substituted derivatives thereof wherein said substituent is selected from the group consisting of halo, nitro, amino, thiol, hydroxy, alkyl, alkyloxy, alkyl carboxy and halo substituted alkyl radicals wherein said alkyl comprises from 1 to 3 carbon atoms;
- R.sub.3 is hydrogen or a lower alkyl radical having from 1 to 3 carbon atoms;
- and one of R.sub.1 and R.sub.2 is .dbd.O, --OH or a --O(CO)R.sub.6 group, and the other one is --OH or --O(CO)R.sub.6, or R.sub.1 is .dbd.O and R.sub.2 is H, wherein R.sub.6 is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or --(CH.sub.2).sub.m R.sub.7 wherein m is 0-10, and R.sub.7 is an aliphatic ring from about 3 to about 7 carbon atoms, or an aryl or heteroaryl ring, and pharmaceutically-acceptable salts thereof.
Dependencies are inferred from the claim text.