US 4,060,606 A · 16-Ethers of fusidic acid derivatives

Abstract

The present invention relates to a new series of fusidic acid derivatives, to salts and easily hydrolysable esters thereof, to the preparation of these compounds, and to pharmaceutical compositions containing the compounds. The new compounds have the general formula ##STR1## in which the C.sub.24-25 bond is a single or a double bond, and in which Q.sub.1 and Q.sub.2 stand for ##STR2## or oxygen; A stands for oxygen, sulphur or a sulfinyl radical; R.sub.1 stands for a straight or branched alkyl radical having from 1 to 8 carbon atoms, an alkenyl or alkynyl radical having from 2 to 6 carbon atoms, a cycloalkyl radical having from 3 to 7 carbon atoms in the alicyclic ring, an aryl or aralkyl radical, a heterocyclic radical having 5 or 6 ring atoms, and containing oxygen, sulphur or nitrogen atoms, and pharmaceutically acceptable salts and easily hydrolysable esters thereof. The compound of the present invention show interesting antimicrobial and pharmacokinetic properties. Thereby the compounds of the invention can be used in the treatment of bacterial infections in humans and animals.

Claims46

Dependent claims

A compound of the following formula I:

##STR34## in which the C.sub.24-25 bond is a single or a double bond, and in which Q.sub.1 and Q.sub.2 stand for ##STR35## or oxygen;
A stands for oxygen, sulphur or a sulfinyl radical;
R.sub.1 stands for a straight or branched alkyl radical having from 1 to 8 carbon atoms, an alkenyl or alkynyl radical having from 2 to 6 carbon atoms, a cycloalkyl radical having from 3 to 7 carbon atoms in the alkyclic ring, an aryl, aralkyl or heterocyclylalkyl radical, or a heterocyclic radical having 5 or 6 ring atoms and containing oxygen, sulphur or nitrogen selected from the group consisting of 2- or 3-pyrrolyl, 2- or 3-furyl, 2- or 3-thienyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 2- or 3-pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl and thiadiazolyl, all R.sub.1 radicals being optionally substituted;
and non-toxic pharmaceutically acceptable salts and easily hydrolyzable esters thereof.

1 more element

A method for the preparation of a compound of formula I ##STR42## in which the C.sub.24-25 bond is a single or a double bond, and in which Q.sub.1 and Q.sub.2 stand for ##STR43## or oxygen;

A stands for oxygen, sulphur or a sulfinyl radical;
R.sub.1 stands for a straight or branched alkyl radical having from 1 to 8 carbon atoms, an alkenyl or alkynyl radical having from 2 to 6 carbon atoms, a cycloalkyl radical having from 3 to 7 carbon atoms in the alicyclic ring, an aryl, aralkyl or heterocyclylalkyl radical, or a heterocyclic radical having 5 or 6 ring atoms and containing oxygen, sulphur or nitrogen atoms, all R.sub.1 radicals being optionally substituted;
and pharmaceutically acceptable salts and easily hydrolyzable esters thereof comprising reacting a compound of formula Vb ##STR44## in which Q.sub.1 ' is Q.sub.1 or ##STR45## R.sub.2 being an alkanoyl, an aralkanoyl or an aroyl radical;
Q.sub.2 is as defined above;
Y stands for chlorine, bromine or iodine;
and R.sub.3 stands for a straight or branched alkyl radical having from 1 to 6 carbon atoms, an aralkyl radical an alkanoyl- or aroylmethyl radical, an alkanoyl- or aroyl-oxyalkyl radical, an alkyloxymethyl or a cyanomethyl radical;
with a compound of formula VII:
R.sub.1 -A-H, in which R.sub.1 is as defined above and A represents oxygen or sulphur, yielding a compound of formula VIII:
##STR46## in which Q.sub.1 ', Q.sub.2, R.sub.1 and R.sub.3 are as defined above, and A is oxygen or sulphur, which compound is thereafter subjected to a hydrolysis, if desired, and a compound of formula I, A being sulphur, optionally is oxidized to a compound of formula I, A being a sulfinyl radical;
and the free acid can be transformed into a pharmaceutically acceptable salt or an easily hydrolyzable ester thereof.

7 more elements

Dependencies are inferred from the claim text.

16-Ethers of fusidic acid derivatives

Life of this patent

16-Ethers of fusidic acid derivatives

Life of this patent

Abstract

Claims46