Claims for Patent: 6,331,635

Summary for Patent: 6,331,635

Title:	Taxoids, their preparation and pharmaceutical compositions containing them
Abstract:	New taxoids of general formula (I): ##STR1## their preparation and pharmaceutical compositions containing them. The new products of general formula (I) in which Z represents a radical of general formula (II): ##STR2## display noteworthy antitumour and antileukaemic properties.
Inventor(s):	Bouchard; Herve (Ivry-sur-Seine, FR), Bourzat; Jean-Dominique (Vincennes, FR), Commer.cedilla.on; Alain (Vitry-sur-Seine, FR)
Assignee:	Aventis Pharma S.A. (Antony, FR)
Application Number:	09/066,929
Patent Claims:	1. A taxoid of the formula (I): ##STR23## in which Z represents a hydrogen atom or a radical of formula (II): ##STR24## in which: R.sub.1 represents a benzoyl radical optionally substituted with one or more identical or different atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms, and trifluoromethyl radicals, a thenoyl radical, a furoyl radical, or a radical R.sub.2 --O--CO-- in which R.sub.2 represents: an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted with one or more substituents selected from halogen atoms; hydroxyl radicals; alkoxy radicals containing 1 to 4 carbon atoms; dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms; piperidino radicals; morpholino radicals; 1-piperazinyl radicals optionally substituted at position 4 with an alkyl radical containing 1 to 4 carbon atoms or with a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms; cycloalkyl radicals containing 3 to 6 carbon atoms; cycloalkenyl radicals containing 4 to 6 carbon atoms; phenyl radicals optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing 1 to 4 carbon atoms; cyano radicals; carboxyl radicals; and alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms; alkyl radicals containing 1 to 4 carbon atoms; and alkoxy radicals containing 1 to 4 carbon atoms, a 5-membered aromatic heterocyclic radical, or a saturated heterocyclic radical containing 4 to 6 carbon atoms, optionally substituted with one or more alkyl radicals containing 1 to 4 carbon atoms, R.sub.3 represents an unbranched or branched alkyl radical containing 1 to 8 carbon atoms, an unbranched or branched alkenyl radical containing 2 to 8 carbon atoms, an unbranched or branched alkynyl radical containing 2 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a phenyl on .alpha.- or .beta.-naphthyl radical optionally substituted with one or more identical or different atoms or radicals selected from halogen atoms, alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocyclic containing one or more identical or different hetero atoms selected from nitrogen, oxygen and sulphur atoms and optionally substituted with one or more identical or different substituents selected from halogen atoms, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, with the proviso that, in the substituents of the phenyl, .alpha.- or .beta.-naphthyl and aromatic heterocyclic radicals in the definitions of R.sub.2 and R.sub.3, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and the aryl radicals are phenyl or .alpha.- or .beta.-naphthyl radicals, R.sub.4 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain, and R.sub.5 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain. 2. A taxoid according to claim 1, wherein Z represents a hydrogen atom or a radical of formula (II) in which R.sub.1 represents a benzoyl radical or a radical R.sub.2 --O--CO-- in which R.sub.2 represents a tert-butyl radical, and R.sub.3 represents an alkyl radical containing 1 to 6 carbon atoms, an alkenyl radical containing 2 to 6 carbon atoms; a cycloalkyl radical containing 3 to 6 carbon atoms; a phenyl radical optionally substituted with one or more identical or different atoms or radical selected from halogen atoms, alkyl, alkoxy, dialkylamino, acylamino, alkoxycarbonylamino and trifluoromethyl radicals, or a 2-furyl, 3- furyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl radical. 3. A taxoid according to claim 1, wherein Z represents a hydrogen atom or a radical of formula (II) in which R.sub.1 represents a benzoyl radical or a radical R.sub.2 --O--CO-- in which R.sub.2 represents a tert-butyl radical, R.sub.3 represents an isobutyl, isobutenyl, butenyl, cyclohexyl, phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl or 5-thiazolyl radical, and R.sub.4 and R.sub.5, which may be identical or different, each represents a methoxy, ethoxy or propoxy radical. 4. A taxoid according to claim 1, wherein when R.sub.2 represents a 5-membered aromatic heterocyclic radical, said radical is a furyl or thienyl radical. 5. 4.alpha.-acetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-10.beta.-ethoxy-1.be ta. -hydroxy-7.beta.-methoxy-9-oxo-11-taxen-13.alpha.-yl(2R,3S)-3-tert-butoxyc arbonylamino-2-hydroxy-3-phenylpropionate. 6. 4.alpha.-acetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-10.beta.-(1-propyl)o xy-1.beta.-hydroxy-7.beta.-methoxy-9-oxo-11-taxen-13.alpha.-yl(2R,3S)-3-ter t-butoxycarbonylamino-2-hydroxy-3-phenyl-propionate. 7. A pharmaceutical composition comprising at least one product according to claim 1 wherein Z represents a radical formula (II), in combination with one or more pharmaceutically acceptable diluents or adjuvants and optionally one or more compatible and pharmacologically active compounds. 8. A pharmaceutical composition comprising at least the product according to claim 5 in combination with one or more pharmaceutically acceptable diluents or adjuvants and optionally one or more compatible and pharmacologically active compounds. 9. A pharmaceutical composition comprising at least the product according to claim 6 in combination with one or more pharmaceutically acceptable diluents or adjuvants and optionally one or more compatible and pharmacologically active compounds. 10. An ester of the formula (V): ##STR25## wherein R.sub.1 represents a benzoyl radical optionally substituted with one or more identical or different atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms, and trifluoromethyl radicals, a thenoyl radical, a furoyl radical, or a radical R.sub.2 --O--CO-- in which R.sub.2 represents; an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted with one or more substituents selected from halogen atoms; hydroxyl radicals; alkoxy radicals containing 1 to 4 carbon atoms; dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms; piperidino radicals; morpholino radicals; 1-piperazinyl radicals optionally substituted at position 4 with an alkyl radical containing 1 to 4 carbon atoms or with a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms; cycloalkyl radicals containing 3 to 6 carbon atoms; cycloalkenyl radicals containing 4 to 6 carbon atoms; phenyl radicals optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing 1 to 4 carbon atoms; cyano radicals; carboxyl radicals; and alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms; alkyl radicals containing 1 to 4 carbon atoms; and alkoxy radicals containing 1 to 4 carbon atoms, a 5-membered aromatic heterocyclic radical, or a saturated heterocyclic radical containing 4 to 6 carbon atoms, optionally substituted with one or more alkyl radicals containing 1 to 4 carbon atoms, R.sub.3 represents an unbranched or branched alkyl radical containing 1 to 8 carbon atoms, an unbranched or branched alkenyl radical containing 2 to 8 carbon atoms, an unbranched or branched alkynyl radical containing 2 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or or 5-membered aromatic heterocyclic containing one or more identical or different hetero atoms selected from nitrogen, oxygen and sulphur atoms and optionally substituted with one or more identical or different substituents selected from halogen atoms, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, with the proviso that, in the substituents of the phenyl, .alpha.- or .beta.-naphthyl and aromatic heterocyclic radicals in the definitions of R.sub.2 and R.sub.3, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and the aryl radicals are phenyl or .alpha.- or .beta.-naphthyl radicals. R.sub.4 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain, R.sub.5 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain, and either R.sub.6 represents a hydrogen atom and R.sub.7 represents a group protecting the hydroxyl function, or R.sub.6 and R.sub.7 together form a saturated 5- or 6-membered heterocycle. 11. An ester of formula (VII): ##STR26## wherein R.sub.3 represents an unbranched or branched alkyl radical containing 1 to 8 carbon atoms, an unbranched or branched alkenyl radical containing 2 to 8 carbon atoms, an unbranched or branched alkynyl radical containing 2 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocycle containing one or more identical or different hetero atoms selected from nitrogen, oxygen and sulfur atoms and optionally substituted with one or more identical or different substituents selected from halogen atoms, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, with the provision that, in the substituents of the phenyl, .alpha.- or .beta.-naphthyl and aromatic heterocyclic radicals in the definitions of R.sub.2 and R.sub.3, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and the aryl radicals are phenyl or .alpha.- or .beta.-naphthyl radicals, R.sub.4 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain, and R.sub.5 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain. 12. 4.alpha.-Acetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1.beta.-hydroxy-7.be ta. ,10.beta.-bis(methylthiomethoxy)-9-oxo-11-taxen-13.alpha.-yl(2R,4S,5R)-3-t ert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxyla te. 13. A taxoid of the formula (I): ##STR27## in which: Z represents a hydrogen atom or a radical of formula (II): ##STR28## in which: R.sub.1 represents a benzoyl radical optionally substituted with one or more identical or different atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms, and trifluoromethyl radicals, a thenoyl radical, a furoyl radical, or a radical R.sub.2 --O--CO-- in which R.sub.2 represents: an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted with or more substituents selected from halogen atoms; hydroxyl radicals; alkoxy radicals containing 1 to 4 carbon atoms; dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms; piperidino radicals; morpholino radicals; 1-piperazinyl radicals optionally substituted at position 4 with an alkyl radical containing 1 to 4 carbon atoms or with a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms; cycloalkyl radicals containing 3 to 6 carbon atoms; cycloalkenyl radicals containing 4 to 6 carbon atoms; phenyl radicals optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing 1 to 4 carbon atoms; cyano radicals; carboxyl radicals; and alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms. a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms; alkyl radicals containing 1 to 4 carbon atoms; and alkoxy radicals containing 1 to 4 carbon atoms, a 5-membered aromatic heterocyclic radical, or a saturated heterocyclic radical containing 4 to 6 carbon atoms, optionally substituted with one or more alkyl radicals containing 1 to 4 carbon atoms, R.sub.3 represents an unbranched or branched alkyl radical containing 1 to 8 carbon atoms, an unbranched or branched alkenyl radical containing 2 to 8 carbon atoms, an unbranched or branched alkynyl radical containing 2 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more identical or different atoms or radicals selected from halogen atoms, alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocycle containing one or more identical or different hereto atoms selected from nitrogen, oxygen and sulphur atoms and optionally substituted with one or more identical or different substituents selected from halogen atoms, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, with the proviso that, in the substituents of the phenyl, .alpha.- or .beta.-naphthyl and aromatic heterocyclic radicals in the definitions of R.sub.2 and R.sub.3, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and the aryl radicals are phenyl or .alpha.- or .beta.-naphthyl radicals, R.sub.4 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain substituted with at least one substituent selected from an alkylthio radical containing 1 to 4 carbon atoms, and R.sub.5 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain substituted with at least one substituent selected from an alkylthio radical containing 1 to 4 carbon atoms. 14. An ester of the formula (V): ##STR29## wherein R.sub.1 represents a benzoyl radical optionally substituted with one or more identical or different atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms, and trifluoromethyl radicals, a thenoyl radical, a furoyl radical, or a radical R.sub.2 --O--CO-- in which R.sub.2 represents; an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted with one or more substituents selected from halogen atoms; hydroxyl radicals; alkoxy radicals containing 1 to 4 carbon atoms; dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms; piperidino radicals; morpholino radicals; 1-piperazinyl radicals optionally substituted at position 4 with an alkyl radical containing 1 to 4 carbon atoms or with a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms; cycloalkyl radicals containing 3 to 6 carbon atoms; cycloalkenyl radicals containing 4 to 6 carbon atoms; phenyl radicals optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing 1 to 4 carbon atoms; cyano radicals; carboxyl radicals; and alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms; alkyl radicals containing 1 to 4 carbon atoms; and alkoxy radicals containing 1 to 4 carbon atoms, a 5-membered aromatic heterocyclic radical, or a saturated heterocyclic radical containing 4 to 6 carbon atoms, optionally substituted with one or more alkyl radicals containing 1 to 4 carbon atoms, R.sub.3 represents an unbranched or branched alkyl radical containing 1 to 8 carbon atoms, an unbranched or branched alkenyl radical containing 2 to 8 carbon atoms, an unbranched or branched alkynyl radical containing 2 to 8 carbon atoms, cycloalkyl radical containing 3 to 6 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocycle containing one or more identical or different hetero atoms selected from nitrogen, oxygen and sulphur atoms and optionally substituted with one or more identical or different substituents selected from halogen atoms, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, with the proviso that, in the substituents of the phenyl, .alpha.- or .beta.-naphthyl and aromatic heterocyclic radicals in the definitions of R.sub.2 and R.sub.3, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and the aryl radicals are phenyl of .alpha.- or .beta.-naphthyl radicals, R.sub.4 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain substituted with at least one substituent selected from an alkylthio radical containing 1 to 4 carbon atoms, R.sub.5 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain substituted with at least one substituent selected from an alkylthio radical containing 1 to 4 carbon atoms, and either R.sub.6 represents a hydrogen atom and R.sub.7 represents a group protecting the hydroxy function, or R.sub.5 and R.sub.7 together form a saturated 5- or 6-membered heterocycle. 15. An ester of formula (VII): ##STR30## wherein R.sub.3 represents an unbranched or branched alkyl radical containing 1 to 8 carbon atoms, an unbranched or branched alkenyl radical containing 2 to 8 carbon atoms, an unbranched or branched alkynyl radical containing 2 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercaptor, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocyclic containing one or more identical or different hetero atoms selected from nitrogen, oxygen and sulphur atoms and optionally substituted with one or more identical or different substituents selected from halogen atoms, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, with the proviso that, in the substituents of the phenyl, .alpha.- or .beta.-naphthyl and aromatic heterocyclic radicals in the definitions of R.sub.2 and R.sub.3, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and the aryl radicals are phenyl or .alpha.- or .beta.-naphthyl radicals R.sub.4 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain substituted with at least one substituent selected from an alkylthio radical containing 1 to 4 carbon atoms, and R.sub.5 represents an alkoxy containing 1 to 6 carbon atoms in an unbranched or branched chain substituted with at least one substituent selected from an alkylthio radical containing 1 to 4 carbon atoms. 16. A pharmaceutical composition according to claim 7, wherein said on or more compatible and pharmacologically active compounds is present and is cisplatin. 17. A pharmaceutical composition according to claim 16, wherein Z represents a radical of formula (II) in which R.sub.1 represents a benzoyl radical or a radical R.sub.2 --O--CO-- in which R.sub.2 represents a tert-butyl radical, and R.sub.3 represents an alkyl radical containing 1 to 6 carbon atoms; an alkenyl radical containing 2 to 6 carbon atoms; a cycloalkyl radical containing 3 to 6 carbon atoms; a phenyl radical optionally substituted with one or more identical or different atoms or radicals selected from halogen atoms, alkyl, alkoxy, dialkylamino, acylamino, alkoxycarbonylamino and trifluoromethyl radicals; or a 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl radical. 18. A pharmaceutical composition according to claim 17, wherein Z represents a radical of formula (II) in which R.sub.1 represents a benzoyl radical or a radical R.sub.2 --O--CO-- in which R.sub.2 represents tert-butyl radical, R.sub.3 represents an isobutyl, isobutenyl, butenyl, cyclohexyl, phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl or 5-thiazolyl radical, and R.sub.4 and R.sub.5, which may be identical or different, each represent a methoxy, ethoxy or propoxy radical. 19. A pharmaceutical composition according to claim 16, wherein when R.sub.2 represents a 5-membered aromatic heterocyclic radical, said radical is a furyl or thienyl radical. 20. A pharmaceutical composition comprising 4.alpha.-acetoxy-2.alpha.-benzoyloxy-1.beta.-hydroxy-5.beta.,20-epoxy-7.be ta. ,10.beta.-dimethoxy-9-oxo-11-taxen-13.alpha.-yl(2R,3S)-3-tert-butoxycarbon ylamino-2-hydroxy-3-phenylpropionate and cisplatin. 21. A pharmaceutical composition comprising 4.alpha.-acetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-10.beta.-ethoxy-1.be ta. -hydroxy-7.beta.-methoxy-9-oxo-11-taxen-13.alpha.-yl(2R,3S)-3-phenylpropio nate and cisplatin. 22. A pharmaceutical composition comprising 4.alpha.-acetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-10.beta.-(1-propyl)o xy-1.beta.-hydroxy-7.beta.-methoxy-9-oxo-11-taxen-13.alpha.-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenyl-propionate and cisplatin. 23. A pharmaceutical composition comprising 4.alpha.-acetoxy-2.alpha.-benzoyloxy-1.beta.-hydroxy-5.beta.,20-epoxy-7.be ta. ,10.beta.-dimethoxy-9-oxo-11-taxen-13.alpha.-yl(2R,3S)-3-tert-butoxycarbon ylamino-2-hydroxy-3-phenylpropionate in combination with one or more pharmaceutically acceptable diluents or adjuvants and one or more compatible and pharmacologically active compounds. 24. A pharmaceutical composition comprising an ester of the formula (V): ##STR31## wherein R.sub.1 represents a benzoyl radical optionally substituted with one or more identical or different atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms, and trifluoromethyl radicals, a thenoyl radical, a furoyl radical, or a radical R.sub.2 --O--CO-- in which R.sub.2 represents an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted with one or more substituents selected from halogen atoms; hydroxyl radicals; alkoxy radicals containing 1 to 4 carbon atoms; dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms; piperidino radicals; morpholino radicals; 1-piperazinyl radicals optionally substituted at position 4 with an alkyl radical containing 1 to 4 carbon atoms or with a phenylalkyl radicals in which the alkyl portion contains 1 to 4 carbon atoms; cycloalkyl radicals containing 3 to 6 carbon atoms; cycloalkenyl radicals containing 4 to 6 carbon atoms; phenyl radicals optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing to 4 carbon atoms; cyano radicals; carboxyl radicals; and alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms; alkyl radicals containing 1 to 4 carbon atoms; and alkoxy radicals containing 1 to 4 carbon atoms, a 5-membered aromatic heterocyclic radical, or a saturated heterocyclic radical containing 4 to 6 carbon atoms, optionally substituted with one or more alkyl radicals containing 1 to 4 carbon atoms, R.sub.3 represents an unbranched or branched alkyl radical containing 1 to 8 carbon atoms, an unbranched or branched alkenyl radical containing 2 to 8 carbon atoms, an unbranched or branched alkynyl radical containing 2 to 8 carbon atoms, cycloalkyl radical containing 3 to 6 carbon atoms, a phenyl or .alpha.- or .beta.-naphthyl radical optionally substituted with one or more atoms or radicals selected from halogen atoms, alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxy hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocycle containing one or more identical or different hetero atoms selected from nitrogen, oxygen and sulphur atoms and optionally substituted with one or more identical or different substituents selected from halogen atoms, alkyl, aryl, amino, alkylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, with the proviso that, in the substituents of the phenyl, .alpha.- or .beta.-naphthyl and aromatic heterocyclic radicals in the definitions of R.sub.2 and R.sub.3, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and the aryl radicals are phenyl or .alpha.- or .beta.-naphthyl radicals, R.sub.4 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain, R.sub.5 represents an alkoxy radical containing 1 to 6 carbon atoms in an unbranched or branched chain, and R.sub.6 and R.sub.7 each represents a hydrogen atom in combination with one or more pharmaceutically acceptable diluents or adjuvants and one or more compatible and pharmacologically active compounds. 25. A pharmaceutical composition according to claim 24, wherein said one or more compatible and pharmacologically active compounds is cisplatin.