Leo Pharmaceutical Products Ltd. A/s

Leo Pharmaceutical Products Ltd. A/s (lovens Kemiske Fabrik

Poul Rodbroe Rasmussen

Welf Von Daehne

Fusidic acid derivatives which possess anti-bacterial, antimicrobial and pharmacokinetic properties. These derivatives include, for example, 3.alpha.,11.alpha.-dihydroxy-16.beta.-(2'-methlyphenyl) thiofusida-13(17),24-dien-21-oic acid and pharmaceutically acceptable, non-toxic salts or easily hydrolysable esters thereof.

Fusidic acid derivatives

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 fusidic acid derivatives having the general formula: ##STR1## in which the dotted line between C-24 and C-25 indicates that the carbon atoms in question are connected by either a double bond or a single bond, and in which Q.sub.1 represents oxygen or one of the groupings ##STR2## Z being a hydroxy group, a halogen atom, an alkylsulfonyloxy or arylsulfonyloxy group, such as methanesulfonyloxy or p-toluenesulfonyloxy, an azido or a nitro group, Q.sub.2 is oxygen or the grouping ##STR3## and R.sub.1 stands for a straight or branched alkyl radical having from 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl or the known isomers of pentyl and hexyl, a phenyl or a heterocyclyl radical having 5 to 6 ring atoms and containing nitrogen, oxygen and/or sulfur atoms, these radicals being optionally substituted with halogen, nitro, lower alkyl or lower alkoxy radicals. The present compounds show both in vitro and in vivo interesting antimicrobial and pharmacokinetic properties.

16-S-acyl derivatives of fusidic acid

The invention relates to a new series of fusidic acid derivatives, to salts and easily hydrolyzable esters thereof, to the preparation of these compounds and to pharmaceutical compositions containing the compounds, the new compounds having the general formula: ##STR1## in which Q.sub.1 and Q.sub.2 stand for the group ##STR2## or oxygen, A represents oxygen or sulphur, and R.sub.1 stands for a straight or branched alkyl radical having from 1 to 12 carbon atoms, R.sub.1 can further be an alkenyl or alkynyl radical having from 3 to 6 carbon atoms, a cycloalkyl radical having from 3 to 7 carbon atoms in the alicyclic ring, an aralkyl or aryl radical, R.sub.1 can also be a heterocyclic radical having 5 or 6 ring atoms and containing oxygen, sulphur and/or nitrogen atoms, R.sub.1 optionally being further substituted, and in which formula I the dotted line between C-24 and C-25 indicates that the carbon atoms in question are connected by either a double bond or a single bond, and the asterix at C-20 indicates that the compounds exist in two diastereomeric forms, and thus the invention comprises the pure diastereomers as well as mixtures of these. The compounds of the present invention possess antibacterial properties and show further interesting antimicrobial and pharmacokinetic properties.

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.

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Frederikssund, Denmark

Poul Rodbroe Rasmussen