Hexahydronaphthalene ester derivatives, their preparation and their therapeutic uses

A compound of formula (I):

• ##STR18## wherein R.sup.1 represents a group of formula (II):
• ##STR19## R.sup.2 represents a hydrogen atom or a group of formula --OR.sup.3 ;
• R.sup.3, R.sup.3a and R.sup.3b are independently selected from the group consisting of hydrogen atoms, hydroxy-protecting groups, alkyl groups having from 1 to 6 carbon atoms, alkanesulfonyl groups having from 1 to 6 carbon atoms, halogenated alkanesulfonyl groups having from 1 to 6 carbon atoms and arylsulfonyl groups, in which the aryl part is an aromatic hydrocarbon ring which has from 6 to 14 ring carbon atoms and is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents .alpha., defined below;
• R.sup.4 represents a hydrogen atom or a carboxy-protecting group;
• R.sup.5 represents an aryl group having from 6 to 14 ring carbon atoms;
• an aryl group having from 6 to 14 ring carbon atoms and substituted by at least one substituent selected from the group consisting of substituents .alpha., defined below;
• an aralkyl group in which the or each aryl portion has from 6 to 14 ring carbon atoms, and the alkyl portion has from 1 to 6 carbon atoms;
• or an aralkyl group, in which the or each aryl portion has from 6 to 14 ring carbon atoms, and the alkyl portion has from 1 to 6 carbon atoms, substituted on the ring by at least one substituent selected from the group consisting of substituents .alpha., defined below;
• and
• W represents an alkylene group having from 1 to 6 carbon atoms, or an alkylene group having from 1 to 6 carbon atoms and substituted by at least one substituent selected from the group consisting of substituents .beta., defined below;
• said substituents .alpha. are selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms;
• said substituents .beta. are selected from the group consisting of alkyl groups having from 1 to 6 carbon atoms;
• wherein said hydroxy protecting group is selected from the group consisting of:
• methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, t-butoxymethyl, 2-methoxyethoxymethyl, 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl, 1-isopropoxyethyl, 2,2,2-trichloroethyl, 2-(phenylselenyl)ethyl, acetoxymethyl, dimethylaminoacetoxy methyl, propionyloxymethyl, butyryloxymethyl, isobutyryloxymethyl, pivaloyloxymethyl, 1-pivaloyloxyethyl, 1-acetoxyethyl, 1-isobutyryloxyethyl, 1-pivaloyloxypropyl, 2-methyl-1-pivaloyloxypropyl, 2-pivaloyloxypropyl, 1-isobutyryloxyethyl, 1-isobutyryloxypropyl, 1-acetoxypropyl, 1-acetoxy-2-methylpropyl, 1-propionyloxyethyl, 1-propionyloxypropyl, 2-acetoxypropyl, 1-butyryloxyethyl, 1-(alkoxycarbonyloxy)ethyl, methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl, propoxycarbonyloxymethyl, isopropoxycarbonyloxymethyl, butoxycarbonyloxymethyl, isobutoxycarbonyloxy methyl, 1-methoxycarbonyloxyethyl, 1-ethoxy carbonyloxyethyl, 1-propoxycarbonyloxyethyl, 1-isopropoxycarbonyloxyethyl, 1-butoxycarbonyloxyethyl, 1-isobutoxycarbonyloxyethyl, 1-sec-butoxycarbonyloxyethyl, 1-t-butoxycarbonyloxyethyl, 1-(1-ethylpropoxycarbonyloxy)ethyl, 1-(1,1-dipropylbutoxycarbonyloxy)ethyl, 2-methyl-1-(isopropoxycarbonyloxy) propyl, 2-(isopropoxycarbonyloxy)propyl, isopropoxycarbonyloxymethyl, t-butoxycarbonyloxymethyl, methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl, cyclohexyloxycarbonyloxymethyl, 1-methylcyclohexylcarbonyloxymethyl, 1-methylcyclohexyloxycarbonyloxymethyl, cyclopentyloxycarbonyloxymethyl, cyclopentylcarbonyloxymethyl, 1-cyclohexyloxycarbonyloxyethyl, 1-cyclohexylcarbonyloxyethyl, 1-cyclopentyloxycarbonyloxyethyl, 1-cyclopentylcarbonyloxyethyl, 1-cycloheptyloxycarbonyloxyethyl, 1-cycloheptylcarbonyloxyethyl, 1-methylcyclopentylcarbonyloxymethyl, 1-methylcyclopentyloxycarbonyloxymethyl, 2-methyl-1-(1-methylcyclohexylcarbonyloxy)propyl, 1-(1-methylcyclohexylcarbonylony)propyl, 2-(1-methylcyclohexylcarbonyloxy)propyl, 1-(cyclohexylcarbonyloxy)propyl, 2-(cyclohexylcarbonyloxy)propyl, 2-methyl-1-(1-methylcyclopentylcarbonyloxy)propyl, 1-(1-methylcyclopentylcarbonyloxy)propyl, 2-(1-methylcyclopentylcarbonyloxy)propyl, 1-(cyclopentylcarbonyloxy)propyl, 2-(cyclopentylcarbonyloxy)propyl, 1-(1-methylcyclopentylcarbonyloxy)ethyl, 1-(1-methylcyclopentylcarbonyloxy)propyl, adamantyloxycarbonyloxymethyl, adamantylcarbonyloxymethyl, 1-adamantyloxycarbonyloxyethyl, 1-adamantylcarbonyloxyethyl, cyclohexyloxycarbonyloxy(cyclohexyl)methyl, (cyclohexyl-acetoxy)methyl, 1-(cyclohexylacetoxy)ethyl, 1-(cyclohexylacetoxy)propyl, 2-methyl-1-(cyclohexylacetoxy)propyl, (cyclopentylacetoxy)methyl, 1-(cyclopentylacetoxy)ethyl, 1-(cyclopentylacetoxy)propyl, 2-methyl-1-(cyclopentylacetoxy)propyl, cyclopropylmethoxycarbonyloxymethyl, cyclobutylmethoxycarbonyloxymethyl, cyclopentylmethoxycarbonyloxymethyl, cyclohexylmethoxycarbonyloxymethyl, 1-(cyclopropylmethoxycarbonyloxy)ethyl, 1-(cyclobutylmethoxycarbonyloxy)ethyl, 1-(cyclopentylmethoxycarbonyloxy)ethyl, 1-(cyclohexylmethoxycarbonyloxy)ethyl, 1-(menthyloxycarbonyloxy)ethyl, 1-(menthylcarbonyloxy)ethyl, menthyloxycarbonyloxymethyl, menthylcarbonyloxymethyl, 1-(3-pinanyloxycarbonyloxy)ethyl, 1-(3-pinanylcarbonyloxy)ethyl, 3-pinanyloxycarbonyloxymethyl, 3-pinanylcarbonyloxymethyl, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl, (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methyl, (5-isopropyl-2-oxo-1,3-dioxolen-4-yl)methyl, (5-t-butyl-2-oxo-1,3-dioxolen-4-yl)methyl, 1-(5-methyl-2-oxo-1,3-dioxolen-4-yl)ethyl, phthalidyl, dimethylphthalidyl, dimethoxyphthalidyl, carboxymethyl and phenylalanine;
• said carboxy-protecting groups are groups which can be cleaved by chemical means or in vivo by biological means and wherein
• said carboxy-protecting groups which can be cleaved by chemical means are selected from the group consisting of
• alkyl groups having from 1 to 20 carbon atoms;
• halogenated alkyl groups having from 1 to 6 carbon atoms, and wherein the halogen atom is chlorine, fluorine, bromine or iodine;
• cycloalkyl groups having from 3 to 7 carbon atoms,
• aralkyl groups, in which the alkyl part has from 1 to 3 carbon atoms and the or each aryl part is a carbocyclic aromatic group having from 6 to 14 carbon atoms, which may be substituted or unsubstituted and, if substituted, has at least one of substituents .alpha., defined above;
• aryl groups having 6 to 14 carbon atoms and being optionally substituted by one or more substituents .alpha., defined above,
• phenacyl groups optionally substituted by one or more substituents .alpha., defined above;
• terpenyl groups, selected from the group consisting of geranyl, neryl, linalyl, phytyl, menthyl, thujyl, caryl, pinanyl, bornyl, norcaryl, norpinanyl, norbornyl, menthenyl, camphenyl and norbornenyl groups;
• and
• said carboxy-protecting group which can be cleaved in vivo by biological means is selected from the group consisting of
• alkoxyalkyl groups, in which the alkoxy and alkyl parts each have from 1 to 5 carbon atoms;
• halogenated ethyl groups;
• and arylselenyl-substituted ethyl groups, in which the aryl part is as defined above,
• aliphatic acyloxyalkyl groups, in which the acyl group is an alkanoyl group having from 2 to 6 carbon atoms, and the alkyl part has from 1 to 6 carbon atoms;
• alkoxycarbonyloxyalkyl groups wherein the alkoxy part has from 1 to 10 carbon atoms, and the alkyl part has from 1 to 6 carbon atoms;
• cycloalkylcarbonyloxyalkyl and cycloalkyloxycarboxyloxyalkyl groups, in which the cycloalkyl group has from 3 to 10, carbon atoms, is mono- or poly-cyclic and is optionally substituted by alkyl having from 1 to 4 carbon atoms and the alkyl part has from 1 to 6 carbon atoms;
• cycloalkyl-substituted aliphatic acyloxyalkyl groups, in which the acyl group is an alkanoyl group having from 2 to 6 carbon atoms, the cycloalkyl substituent has from 3 to 7 carbon atoms, and the alkyl part has from 1 to 6 carbon atoms;
• cycloalkylalkoxycarbonyloxyalkyl groups selected from the group consisting of cyclopropylmethoxycarbonyloxymethyl, cyclobutylmethoxycarbonyloxymethyl, cyclopentylmethoxycarbonyloxymethyl, cyclohexylmethoxycarbonyloxymethyl, 1-(cyclopropylmethoxycarbonyloxy)ethyl, 1-(cyclobutylmethoxycarbonyloxy)et hyl, 1-(cyclopentylmethoxycarbonyloxy)ethyl and 1-(cyclohexylmethoxycarbonyloxy)ethyl groups;
• terpenylcarbonyloxy(2-oxo-1,3-dioxolen-4-yl)alkyl groups in which each alkyl group, which may be the same or different has from 1 to 6 carbon atoms, and
• the phthalidyl group, which may be unsubstituted or may be substituted by at least one substituent selected from the group consisting of substituents .alpha. defined above;
• or a pharmaceutically acceptable salt or ester thereof.