FR2732340A1 - New taxoid derivs. having antitumoural and anti-leukaemic properties - Google Patents

Abstract

Taxoids of formula (I) are new. Z = H or a gp. of formula (II); R1 = benzoyl (opt. substd.), thienyl, furyl or R2OCO; R2 = 1-8C alkyl, 2-8C alkenyl, 3-8C alkynyl, 3-6C cycloalkyl, 4-6C cycloalkenyl or 7-10C bicycloalkyl (all opt. substd.) or Ph or alpha - or beta - naphthyl (all opt. substd.) or 4-6C satd. heterocycle (opt. substd. by one or more 1-4C alkyl); R3 = 1-8C alkyl, 2-8C alkenyl, 2-8C alkynyl, 3-6C cycloalkyl, Ph or alpha - or beta - naphthyl (opt. substd.) or 5-membered aromatic heterocycle (contg. 1 or more of N, O or S and opt. substd.); provided that alkyl=1-4C alkenyl and alkynyl=2-8C and aryl=Ph or alpha - or beta -naphthyl in the definitions of phenyl, alpha - or beta - naphthyl and heteroaryl; R4 = 1-6C alkoxy, 3-6C alkenyloxy, 3-6C alkynyloxy, 3-6C cycloalkyloxy or 4-6C cycloalkenyloxy (all opt. substd.); R5 = 1-6C alkoxy (opt. substd. by 1-4C alkoxy), 3-6C alkenyloxy, 3-6C alkynyloxy, 3-6C cycloalkyloxy, 3-6C cycloalkenyloxy (all opt. substd.). 3 Cpds. (I) are specifically claimed e.g.: (2R,3S)-4 alpha -acetoxy-2 alpha -benzoyloxy-5 beta ,20-epoxy- 1 beta -hydroxy-7 beta ,10 beta -dimethoxy-9-oxo-13 alpha -taxene- 11-yl 3-tert.-butoxycarbonylamino 2-hydroxy 3-phenyl propionate.

Description

dans laquelle
Z représente un atome d'hydrogène ou un radical de formule générale:

dans laquelle:
R1 représente un radical benzoyle éventuellement substitué par un ou plusieurs atomes ou radicaux, identiques ou différents, choisis parmi les atomes d'halogène et les radicaux alcoyles contenant 1 à 4 atomes de carbone, alcoxy contenant 1 à 4 atomes de carbone ou trifluorométhyle, thénoyle ou furoyle ou un radical R2-O-CO- dans lequel R2 représente:: - un radical alcoyle contenant 1 à 8 atomes de carbone, alcényle contenant 2 à 8 atomes de carbone, alcynyle contenant 3 à 8 atomes de carbone, cycloalcoyle contenant 3 à 6 atomes de carbone, cycloalcényle contenant 4 à 6 atomes de carbone, bicycloalcoyle contenant 7 à 10 atomes de carbone, ces radicaux étant éventuellement substitués par un ou plusieurs substituants choisis parmi les atomes d'halogène et les radicaux hydroxy, alcoxy contenant 1 à 4 atomes de carbone, dialcoylamino dont chaque partie alcoyle contient 1 à 4 atomes de carbone, pipéridino, morpholino, pipérazinyl-l (éventuellement substitué en -4 par un radical alcoyle contenant 1 à 4 atomes de carbone ou par un radical phénylalcoyle dont la partie alcoyle contient 1 à 4 atomes de carbone), cycloalcoyle contenant 3 à 6 atomes de carbone, cycloalcényle contenant 4 à 6 atomes de carbone, phényle (éventuellement substitué par un ou plusieurs atomes ou radicaux choisis parmi les atomes d'halogène et les radieux alcoyles contenant 1 à 4 atomes de carbone ou alcoxy contenant 1 à 4 atomes de carbone), cyano, carboxy ou alcoxycarbonyle dont la partie alcoyle contient 1 à 4 atomes de carbone, - un radical phényle ou a- ou Snaphtyle éventuellement substitué par un ou plusieurs atomes ou radicaux choisis parmi les atomes d'halogène et les radicaux alcoyles contenant 1 à 4 atomes de carbone ou alcoxy contenant 1 à 4 atomes de carbone ou un radical hétérocyclique aromatique à 5 chaînons choisi de préférence parmi les radieux furyle et thiényle, - ou un radical hétérocyclyle saturé contenant 4 à 6 atomes de carbone éventuellement substitué par un ou plusieurs radicaux alcoyles contenant 1 à 4 atomes de carbone,
R3 représente un radical alcoyle droit ou ramifié contenant 1 à 8 atomes de carbone, alcényle droit ou ramifié contenant 2 à 8 atomes de carbone, alcynyle droit ou ramifié contenant 2 à 8 atomes de carbone, cycloalcoyle contenant 3 à 6 atomes de carbone, phényle ou a- ou Fnaphtyle éventuellement substitué par un ou plusieurs atomes ou radicaux choisis parmi les atomes d'halogène et les radicaux alcoyles, alcényles, alcynyles, aryles, aralcoyles, alcoxy, alcoylthio, aryloxy, arylthio, hydroxy, hydroxyalcoyle, mercapto, formyle, acyle, acylamino, aroylamino, alcoxycarbonylamino, amino, alcoylamino, dialcoylamino, carboxy, alcoxycarbonyle, carbamoyle, alcoylcarbamoyle, dialcoylcarbamoyle, cyano, nitro et trifluorométhyle, ou un hétérocycle aromatique ayant 5 chaînons et contenant un ou plusieurs hétéroatomes, identiques ou différents, choisis parmi les atomes d'azote, d'oxygène ou de soufre et éventuellement substitué par un ou plusieurs substituants, identiques ou différents, choisis parmi les atomes d'halogène et les radicaux alcoyles, aryles, amino, alcoylamino, dialcoylamino, alcoxycarbonylamino, acyle, arylcarbonyle, cyano, carboxy, carbamoyle, alcoylcarbamoyle, dialcoylcarbamoyle ou alcoxycarbonyle, étant entendu que, dans les substituants des radicaux phényle, a- ou frnaphtyle et hétérocyclyles aromatiques, les radicaux alcoyles et les portions alcoyles des autres radicaux contiennent 1 à 4 atomes de carbone et que les radicaux alcényles et alcynyles contiennent 2 à 8 atomes de carbone et que les radicaux aryles sont des radieux phényles ou a- ou Snaphtyles,
R4 représente un atome d'hydrogène ou un radical hydroxy ou un radical alcoxy contenant 1 à 6 atomes de carbone en chaîne droite ou ramifiée, alcényloxy contenant 3 à 6 atomes de carbone en chaîne droite ou ramifiée, alcynyloxy contenant 3 à 6 atomes de carbone en chaîne droite ou ramifiée, cycloalcoyloxy contenant 3 à 6 atomes de carbone, cycloalcényloxy contenant 3 à 6 atomes de carbone, alcanoyloxy dont la partie alcanoyle contient 1 à 6 atomes de carbone en chaîne droite ou ramifiée, alcénoyloxy dont la partie alcénoyle contient 3 à 6 atomes de carbone en chaîne droite ou ramifiée, alcynoyloxy dont la partie alcynoyle contient 3 à 6 atomes de carbone en chaîne droite ou ramifiée, alcoxyacétyle dont la partie alcoyle contient 1 à 6 atomes de carbone en chaîne droite ou ramifiée, alcoylthioacétyle dont la partie alcoyle contient 1 à 6 atomes de carbone en chaîne droite ou ramifiée, alcoyloxycarbonyloxy dont la partie alcoyle contient 1 à 6 atomes de carbone en chaîne droite ou ramifiée, ces radicaux étant éventuellement substitués par un ou plusieurs atomes d'halogène ou par un radical alcoxy contenant 1 à 4 atomes de carbone, alcoylthio contenant 1 à 4 atomes de carbone, ou un radical carboxy, alcoyloxycarbonyle dont la partie alcoyle contient 1 à 4 atomes de carbone, cyano, carbamoyle, N-alcoylcarbamoyle ou
N,N-dialcoylcarbamoyle dont chaque partie alcoyle contient 1 à 4 atomes de carbone ou forme avec l'atome d'azote auquel elle est liée un radical hétérocyclique saturé contenant 5 ou 6 chaînons et éventuellement un second hétéroatome choisi parmi les atomes d'oxygène, de soufre ou d'azote éventuellement substitué par un radical alcoyle contenant 1 à 4 atomes de carbone ou un radical phényle ou un radical phénylalcoyle dont la partie alcoyle contient 1 à 4 atomes de carbone, ou bien R4 représente un radical benzoyloxy ou hétérocyclylcarbonyloxy dans lequel la partie hétérocyclique représente un hétérocycle aromatique 5 ou 6 chaînons contenant un ou plusieurs hétéroatomes choisis parmi les atomes d'oxygène, de soufre ou d'azote,
R5 représente un radical alcoxy contenant 1 à 6 atomes ce carbone en chine droite ou ramifiée éventuellement substitué par un radical alcoxy contenant 1 à 4 atomes de carbone, alcényloxy contenant 3 à 6 atomes de carbone, alcynyloxy contenant 3 à 6 atomes de carbone, cycloalcoyloxy contenant 3 à 6 atomes de carbone, cycloalcényloxy contenant 3 à 6 atomes de carbone, ces radicaux étant éventuellement substitués par un ou plusieurs atomes d'halogène ou par un radical alcoxy contenant 1 à 4 atomes de carbone, alcoylthio contenant 1 à 4 atomes de carbone, ou un radical carboxy, alcoyloxycarbonyle dont la partie alcoyle contient 1 à 4 atomes de carbone, cyano, carbamoyle, N-alcoylcarbamoyle ou N,N-dialcoylcarbamoyle dont chaque partie alcoyle contient 1 à 4 atomes de carbone ou forme avec l'atome d'azote auquel elle est liée un radical hétérocyclique saturé contenant 5 ou 6 chaînons et éventuellement un second hétéroatome choisi parmi les atomes d'oxygène, de soufre ou d'azote éventuellement substitué par un radical alcoyle contenant 1 à 4 atomes de carbone ou un radical phényle ou un radical phénylalcoyle dont la partie alcoyle contient 1 à 4 atomes de carbone. NEW TAXOIDS. THEIR PREPARATION AND COMPOSITIONS
PHARMACEUTIOUES YES CONTAIN THEM
The present invention relates to new taxoides of general formula:

in which
Z represents a hydrogen atom or a radical of general formula:

in which:
R1 represents a benzoyl radical optionally substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, alkoxy containing 1 to 4 carbon atoms or trifluoromethyl, thenoyl or furoyl or an R2-O-CO- radical in which R2 represents: - an alkyl radical containing 1 to 8 carbon atoms, alkenyl containing 2 to 8 carbon atoms, alkynyl containing 3 to 8 carbon atoms, cycloalkyl containing 3 with 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, bicycloalkyl containing 7 to 10 carbon atoms, these radicals being optionally substituted by one or more substituents chosen from halogen atoms and hydroxy radicals, alkoxy containing 1 to 4 carbon atoms, dialkoylamino, each alkyl part of which contains 1 to 4 carbon atoms, piperidino, morpholino, piperazinyl-1 (optionally substituted at -4 by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical in which the alkyl part contains 1 to 4 carbon atoms), cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, phenyl (optionally substituted by one or more atoms or radicals chosen from halogen atoms and radiant alkyls containing 1 to 4 carbon atoms or alkoxy containing 1 to 4 carbon atoms), cyano, carboxy or alkoxycarbonyl the alkyl part of which contains 1 to 4 carbon atoms, - a phenyl or a- or Snaphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy containing 1 to 4 carbon atoms or a 5-membered aromatic heterocyclic radical preferably chosen from the furyl and thienyl radicals, or a saturated heterocyclyl radical containing 4 to 6 carb atoms one optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms,
R3 represents a straight or branched alkyl radical containing 1 to 8 carbon atoms, straight or branched alkenyl containing 2 to 8 carbon atoms, straight or branched alkynyl containing 2 to 8 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, phenyl or a- or Fnaphthyle optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, formyl, radicals acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkoylamino, dialcoylamino, carboxy, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialcoylcarbamoyl, cyano, nitro and trifluoromethyl, or one or more hetero rings or hetero rings, having one or more different, or one or more hetero rings, or having one or more hetero rings, or having one or more hetero rings, nitrogen, oxygen or sulfur atoms and optionally substituted by one or more substituents, identical or different, chosen from halogen atoms and alkyl, aryl, amino, alkyllamino, dialkoylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxy, carbamoyl, alkylcarbamoyl, dialkoylcarbamoyl or alkoxycarbonyl radicals, it being understood that in the radicals phenoxy , a- or frnaphthyl and aromatic heterocyclyl, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms and that the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms and that the aryl radicals are phenyl or a- or Snaphtyles,
R4 represents a hydrogen atom or a hydroxy radical or an alkoxy radical containing 1 to 6 carbon atoms in a straight or branched chain, alkenyloxy containing 3 to 6 carbon atoms in a straight or branched chain, alkynyloxy containing 3 to 6 carbon atoms straight or branched chain, cycloalkoyloxy containing 3 to 6 carbon atoms, cycloalkenyloxy containing 3 to 6 carbon atoms, alkanoyloxy in which the alkanoyl part contains 1 to 6 carbon atoms in straight or branched chain, alkenoyloxy in which the alkenoyl part contains 6 carbon atoms in a straight or branched chain, alkynoyloxy of which the alkynoyl part contains 3 to 6 carbon atoms in a straight or branched chain, alkoxyacetyl of which the alkyl part contains 1 to 6 carbon atoms in a straight or branched chain, alkylthioacetyl of which alkyl contains 1 to 6 carbon atoms in straight or branched chain, alkyloxycarbonyloxy of which the alkyl part contains 1 to 6 atoms of carbon in a straight or branched chain, these radicals being optionally substituted by one or more halogen atoms or by an alkoxy radical containing 1 to 4 carbon atoms, alkylthio containing 1 to 4 carbon atoms, or a carboxy, alkyloxycarbonyl radical the alkyl part contains 1 to 4 carbon atoms, cyano, carbamoyl, N-alkylcarbamoyl or
N, N-dialkoylcarbamoyl each alkyl part of which contains 1 to 4 carbon atoms or forms, with the nitrogen atom to which it is linked, a saturated heterocyclic radical containing 5 or 6 members and optionally a second heteroatom chosen from oxygen atoms , sulfur or nitrogen optionally substituted by an alkyl radical containing 1 to 4 carbon atoms or a phenyl radical or a phenylalkyl radical in which the alkyl part contains 1 to 4 carbon atoms, or else R4 represents a benzoyloxy or heterocyclylcarbonyloxy radical in in which the heterocyclic part represents a 5 or 6-membered aromatic heterocycle containing one or more heteroatoms chosen from oxygen, sulfur or nitrogen atoms,
R5 represents an alkoxy radical containing 1 to 6 atoms of this carbon in straight or branched china optionally substituted by an alkoxy radical containing 1 to 4 carbon atoms, alkenyloxy containing 3 to 6 carbon atoms, alkynyloxy containing 3 to 6 carbon atoms, cycloalkyloxy containing 3 to 6 carbon atoms, cycloalkenyloxy containing 3 to 6 carbon atoms, these radicals being optionally substituted by one or more halogen atoms or by an alkoxy radical containing 1 to 4 carbon atoms, alkylthio containing 1 to 4 atoms carbon, or a carboxy radical, an alkyloxycarbonyl in which the alkyl part contains 1 to 4 carbon atoms, cyano, carbamoyl, N-alkylcarbamoyl or N, N-dialcoylcarbamoyl in which each alkyl part contains 1 to 4 carbon atoms or forms with the atom of nitrogen to which it is linked a saturated heterocyclic radical containing 5 or 6 members and optionally a second heteroatom chosen from oxygen, so ufre or nitrogen optionally substituted by an alkyl radical containing 1 to 4 carbon atoms or a phenyl radical or a phenylalkyl radical in which the alkyl part contains 1 to 4 carbon atoms.

 Preferably, the aryl radicals which can be represented R3 are phenyl or a- or snaphthyl radicals optionally substituted by one or more atoms or radicals chosen from halogen atoms (fluorine, chlorine, bromine, iodine) and alkyl, alkenyl radicals, alkynyls, aryls, arylalkyls, alkoxy, alkylthio, aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkoylamino, carboxy, alkoxycarbonyl carbamoyl, carboxycarbonyl, carboxycarbonyl, carboxycarbyl methyl, it being understood that the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, that the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms and that the aryl radicals are phenyl or a- or frnaphthyl radicals .

 Preferably, the heterocyclic radicals which can be represented by R3 are aromatic heterocyclic radicals having 5 members and containing one or more atoms, identical or different, chosen from nitrogen, oxygen or sulfur atoms, optionally substituted by one or more substituents, identical or different, chosen from halogen atoms (fluorine, chlorine, bromine, iodine) and alkyl radicals containing 1 to 4 carbon atoms, aryls containing 6 to 10 carbon atoms, alkoxy containing 1 to 4 carbon atoms carbon, aryloxy containing 6 to 10 carbon atoms, amino, alkylamino containing 1 to 4 carbon atoms, dialkoylamino in which each alkyl part contains 1 to 4 carbon atoms, acylamino in which the acyl part contains 1 to 4 carbon atoms, alkoxycarbonylamino containing 1 to 4 carbon atoms, acyl containing 1 to 4 carbon atoms, arylcarbonyl the aryl part of which contains 6 to 10 carbon atoms, cyano, carboxy, carbamoyl, alkylcarbamoyl in which the alkyl part contains 1 to 4 carbon atoms, dialkoylcarbamoyl in which each alkyl part contains 1 to 4 carbon atoms or alkoxycarbonyl in which the alkoxy part contains 1 to 4 carbon atoms.

Preferably the radicals R4 and Rg, identical or different, represent straight or branched alkoxy radicals containing 1 to 6 carbon atoms optionally substituted by a methoxy, ethoxy, methyltio, ethylthio, carboxy, methoxycarbonyl, ethoxycarbonyl, cyano, carbamoyl radical, N -methylcarbamoyl, N-ethylcarbamoyl, N, N-dimethylcarbamoyl, N, NZiethylcarbamoyle,
N-pyrrolidinocarbonyl or N-piperidinocarbonyl.

 More particularly, the present invention relates to the products of general formula (I) in which Z represents a hydrogen atom or a radical of general formula (II) in which R1 represents a benzoyl radical or an R2-O-CO radical in which R2 represents a tert-butyl radical and R3 represents an alkyl radical containing 1 to 6 carbon atoms, alkenyl containing 2 to 6 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, phenyl optionally substituted by one or more atoms or radicals, identical or different chosen from halogen atoms (fluorine, chlorine) and alkyl radicals (methyl), alkoxy (methoxy), dialcoylamino (dimethylamino), acylamino (acetylamino), alkoxycarbonylamino (tertbutoxycarbonylamino) or trifluoromethyl or a furyl-2 radical or -3, 2-thienyl or -3 or 2-thiazolyl, -4 or -5 and R4 and Rg, identical or different, represent a straight or branched alkyloxy radical containing 1 to 6 atom es of carbon.

More particularly still, the present invention relates to the products of general formula (I) in which Z represents a hydrogen atom or a radical of general formula (II) in which R1 represents a benzoyl radical or a radical
R2-O-CO- in which R2 represents a tert-butyl radical and R3 represents an isobutyl, isobutenyl, butenyl, cyclohexyl, phenyl, furyl-2, furyl-3, thienyl-2, thienyl-2, thiazolyl-radical, thiazolyle-4 or thiazolyle-5, R4 and R5 each represent a methoxy radical.

 The products of general formula (I) in which Z represents a radical of general formula (II) have remarkable antitumor and antileukemic properties.

dans laquelle R4 et R5 sont définis comme précédemment, au moyen d'un acide de formule générale:

dans laquelle R1 et R3 sont définis comme précédemment, ou bien R6 représente un atome d'hydrogène et R7 représente un groupement protecteur de la fonction hydroxy, et ou bien R6 et R7 forment ensemble un hétérocycle saturé à 5 ou 6 chaînons, ou d'un dérivé de cet acide pour obtenir un ester de formule générale:

dans laquelle R1, R3, R4, Rg, R6 et R7 sont définis comme précédemment, suivi du remplacement des groupements protecteurs représentés par R7 et/ou R6 et R7 par des atomes d'hydrogène.According to the present invention, the new products of general formula (I) in which Z represents a radical of general formula (II) can be obtained by esterification of a product of general formula:

in which R4 and R5 are defined as above, by means of an acid of general formula:

in which R1 and R3 are defined as above, or else R6 represents a hydrogen atom and R7 represents a protective group for the hydroxy function, and either R6 and R7 together form a 5 or 6-membered saturated heterocycle, or a derivative of this acid to obtain an ester of general formula:

in which R1, R3, R4, Rg, R6 and R7 are defined as above, followed by the replacement of the protective groups represented by R7 and / or R6 and R7 by hydrogen atoms.

 Esterification using an acid of general formula (IV) can be carried out in the presence of a condensing agent (carbodiimide, reactive carbonate) and an activating agent (aminopyridines) in an organic solvent (ether, ester, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between -10 and 90 "C.

 Esterification can also be carried out using the acid of general formula (IV) in the form of a symmetrical anhydride, operating in the presence of an activating agent (aminopyridines) in an organic solvent (ethers, esters, ketones, nitriles , aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between 0 and 90 C.

 The esterification can also be carried out using the acid of general formula (IV) in the form of halide or in the form of mixed anhydride with an aliphatic or aromatic acid, optionally prepared in situ, in the presence of a base (amine tertiary aliphatic) by operating in an organic solvent (ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between 0 and 80 "C.

 Preferably, R6 represents a hydrogen atom and R7 represents a group protecting the hydroxy function or else R6 and R7 together form a saturated heterocycle with 5 or 6 members.

 When R6 represents a hydrogen atom, R7 preferably represents a methoxymethyl, 1-ethoxy-ethyl, benzyloxymethyl, trimethylsilyl, triethylsilyl, sstrimethylsilylethoxymethyl, benzyloxycarbonyl or tetrahydropyrannyl radical.

 When R6 and R7 together form a heterocycle, the latter is preferably an oxazolidine ring optionally mono-substituted or gem-disubstituted in position -2.

dans laquelle R1 est défini comme précédemment, R8 et Rg, identiques ou différents, représentent un atome d'hydrogène ou un radical alcoyle contenant 1 à 4 atomes de carbone, ou un radical aralcoyle dont la partie alcoyle contient 1 à 4 atomes de carbone et la partie aryle représente, de préférence, un radical phényle éventuellement substitué par un ou plusieurs radicaux alcoxy contenant 1 à 4 atomes de carbone, ou un radical aryle représentant, de préférence un radical phényle éventuellement substitué par un ou plusieurs radicaux alcoxy contenant 1 à 4 atomes de carbone, ou bien R8 représente un radical alcoxy contenant 1 à 4 atomes de carbone ou un radical trihalométhyle tel que trichlorométhyle ou un radical phényle substitué par un radical trihalométhyle tel que trichlorométhyle et Rg représente un atome d'hydrogène, ou bien R8 et Rg forment ensemble avec l'atome de carbone auquel ils sont liés un cycle ayant 4 à 7 chaînons, le remplacement du groupement protecteur formé par R6 et R7 par des atomes d'hydrogène peut être effectué, selon les significations de R1, R8 et Rg, de la manière suivante::
a) lorsque R1 représente un radical tert-butoxycarbonyle, R8 et Rg, identiques ou différents, représentent un radical alcoyle ou un radical aralcoyle (benzyle) ou aryle (phényle), ou bien R8 représente un radical trihalométhyle ou un radical phényle substitué par un radical trihalométhyle, et Rg représente un atome d'hydrogène, ou bien R8 et Rg forment ensemble un cycle ayant de 4 à 7 chaînons, le traitement de l'ester de formule générale (V) par un acide minéral ou organique éventuellement dans un solvant organique tel qu'un alcool conduit au produit de formule générale::

dans laquelle R3, R4 et R5 sont définis comme précédemment, qui est acylé au moyen de chlorure de benzoyle dans lequel le noyau phényle est éventuellemnt substitué, de chlorure de thénoyle, de chlorure de furoyle ou d'un produit de formule générale:
R2-O-CO-X (VIII) dans laquelle R2 est défini comme précédemment et X représente un atome d'halogène (fluor, chlorure) ou un reste -O-R2 ou -O-CO-O-R2, pour obtenir un produit de formule générale (I) dans laquelle Z représente un radical de formule générale (in). The replacement of the protective groups R7 and / or R6 and R7 with hydrogen atoms can be carried out, depending on their nature, as follows: 1) when R6 represents a hydrogen atom and R7 represents a protective group for the hydroxy function , the replacement of the protective groups by hydrogen atoms is carried out by means of a mineral acid (hydrochloric acid, sulfuric acid, hydrofluoric acid) or organic acid (acetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p.toluenesulfonic acid) used alone or as a mixture, operating in an organic solvent chosen from alcohols, ethers, esters, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons or nitriles at a temperature between -10 and 60 "C, 2) when R6 and R7 together form a 5 or 6-membered saturated heterocycle and more particularly an oxazolidine ring of general formula e:

in which R1 is defined as above, R8 and Rg, identical or different, represent a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms, or an aralkyl radical in which the alkyl part contains 1 to 4 carbon atoms and the aryl part preferably represents a phenyl radical optionally substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms, or an aryl radical representing, preferably a phenyl radical optionally substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms, or else R8 represents an alkoxy radical containing 1 to 4 carbon atoms or a trihalomethyl radical such as trichloromethyl or a phenyl radical substituted by a trihalomethyl radical such as trichloromethyl and Rg represents a hydrogen atom, or else R8 and Rg together with the carbon atom to which they are linked form a cycle having 4 to 7 links, replacing the gro highly protective formed by R6 and R7 by hydrogen atoms can be carried out, according to the meanings of R1, R8 and Rg, as follows:
a) when R1 represents a tert-butoxycarbonyl radical, R8 and Rg, which may be identical or different, represent an alkyl radical or an aralkyl (benzyl) or aryl (phenyl) radical, or else R8 represents a trihalomethyl radical or a phenyl radical substituted by a trihalomethyl radical, and Rg represents a hydrogen atom, or else R8 and Rg together form a ring having 4 to 7 members, the treatment of the ester of general formula (V) with a mineral or organic acid optionally in a solvent organic such as an alcohol leads to the product of general formula:

in which R3, R4 and R5 are defined as above, which is acylated by means of benzoyl chloride in which the phenyl nucleus is optionally substituted, of thenoyl chloride, of furoyl chloride or of a product of general formula:
R2-O-CO-X (VIII) in which R2 is defined as above and X represents a halogen atom (fluorine, chloride) or a residue -O-R2 or -O-CO-O-R2, to obtain a product of general formula (I) in which Z represents a radical of general formula (in).

 Preferably, the product of general formula (V) is treated with formic acid at a temperature in the region of 20 "C to provide the product of general formula (VII).

 Preferably, the acylation of the product of general formula (VII) by means of a benzoyl chloride in which the phenyl radical is optionally substituted, of thenoyl chloride or of furoyl chloride or of a product of general formula (VIII ) is carried out in an inert organic solvent chosen from esters such as ethyl acetate, isopropyl acetate or n.butyl acetate and halogenated aliphatic hydrocarbons such as dichloromethane or 1-dichloro, 2 ethane in the presence of a mineral base such as sodium bicarbonate or organic such as triethylamine. The reaction is carried out at a temperature between 0 and 50 "C., preferably close to 20" C.

 b) when R1 represents an optionally substituted benzoyl radical, thenoyl or furoyl or an R2O-CO- radical in which R2 is defined as above, R8 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or a radical phenyl substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms and Rg represents a hydrogen atom, the replacement of the protective group formed by R6 and R7 by hydrogen atoms is carried out in the presence of a mineral acid (hydrochloric acid, sulfuric acid) or organic (acetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p.toluenesulfonic acid) used alone or as a mixture in stoichiometric or catalytic amount, operating in an organic solvent chosen from alcohols, ethers, esters, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons and aromatic hydrocarbons at a temperature between e between -10 and 60 "C, preferably between 15 and 300C.

According to the invention, the products of general formula (III), that is to say the products of general formula (I) in which Z represents a hydrogen atom,
R4 is defined as above but cannot represent a hydrogen atom or a hydroxy radical and R5 is defined as above, can be obtained from 10-deacetyl-baccatin III of formula:

dans laquelle R' est défini comme précédemment, puis action d'un produit de formule générale::
R'4-X1 (XII) dans laquelle R'4 représente un radical alcoyle, alcényle,alcynyle, cycloalcoyle, cycloalcényle, alcanoyle, alcénoyle, alcynoyle, alcoxyacétyle, alcoylthioacétyle ou alcoyloxycarbonyle éventuellement substitué, ou un radical benzoyle ou hétérocyclylcarbonyle, ces différents radicaux et substituants ayant une définition identique à celle donnée dans la définition de R4 et X1 représente un reste d'ester réactif ou un atome d'halogène pour obtenir un produit de formule générale:

dans laquelle R' et R4 sont définis comme précédemment dont les groupements protecteurs silylés sont remplacés par des atomes d'hydrogène pour obtenir un produit de formule générale:

dans laquelle R4 est défini comme précédemment, qui est éthérifié sélectivement en position 7 par action d'un produit de formule générale::
R'5-X2 (XV) dans laquelle R'5 représente un radical alcoyle, alcényle, alcynyle, cycloalcoyle, cycloalcényle éventuellement substitué, ces différents radicaux et substituants ayant une définition identique à celle donnée dans la définition de R5 et X2 représente atome d'halogène ou un reste d'ester réactif tel qu'un reste d'ester sulfurique ou sulfonique pour donner le produit de formule générale (fui). It may be particularly advantageous to selectively protect the hydroxy functions in positions 7 and 13, for example in the form of a silylated diether which can be obtained by the action of a silyl halide of general formula:
(R ') 3-Si-Hal (X) in which the symbols R', identical or different, represent an alkyl radical containing 1 to 4 carbon atoms optionally substituted by a phenyl radical, or a phenyl radical, on the 10- deacetyl-baccatin III to obtain a product of general formula:

in which R 'is defined as above, then action of a product of general formula:
R'4-X1 (XII) in which R'4 represents an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkanoyl, alkenoyl, alkynoyl, alkoxyacetyl, optionally substituted alkylthioacetyl or alkoyloxycarbonyl, or a benzoylcarbonyl radical, and substituents having a definition identical to that given in the definition of R4 and X1 represents a reactive ester residue or a halogen atom to obtain a product of general formula:

in which R 'and R4 are defined as above, the silylated protective groups of which are replaced by hydrogen atoms to obtain a product of general formula:

in which R4 is defined as above, which is selectively etherified in position 7 by the action of a product of general formula:
R'5-X2 (XV) in which R'5 represents an alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl radical optionally substituted, these different radicals and substituents having a definition identical to that given in the definition of R5 and X2 represents atom d halogen or a reactive ester residue such as a sulfuric or sulfonic ester residue to give the product of general formula (leak).

 Generally, the action of a silylated derivative of general formula (X) on lO-deaetylbaccatin III is carried out in pyridine or triethylamine optionally in the presence of an organic solvent such as an aromatic hydrocarbon such as benzene, toluene or xylenes at a temperature between 00C and the reflux temperature of the reaction mixture.

 Generally, the action of a product of general formula (XII) on a product of general formula (XI) is carried out, after metallation of the hydroxy function in position 10 by means of an alkali metal hydride such as sodium hydride, an alkali metal amide such as lithium amide or an alkali metal alkyl such as butyllithium, operating in an organic solvent such as dimethylformamide or tetrahydrofuran at a temperature between 0 and 50 "VS.

 Generally the replacement of the silylated protecting groups of the product of general formula (XIII) by hydrogen atoms is carried out by means of an acid such as hydrofluoric acid or trifluoroacetic acid in the presence of a base such as triethylamine or pyridine optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, optionally combined with an inert organic solvent such as a nitrile such as acetonitrile or a halogenated aliphatic hydrocarbon such as dichloromethane at a temperature between 0 and 80 "VS.

 Generally the action of a product of general formula (XV) on a product of general formula (XIV) takes place under the conditions indicated above for the action of a product of general formula (XII) on a product of formula general (XI).

 The products of general formula (hui) in which R4 represents a hydrogen atom or a hydroxy radical and R5 is defined as above, can be obtained by the action of a product of general formula (XV) on a product of general formula ( XIV) in which R4 represents a hydrogen atom or a hydroxy radical under the conditions described above for the action of a product of general formula (XII) on a product of general formula (XI).

 The products of general formula (XIV) in which R4 represents a hydrogen atom can be obtained under the conditions described in international applications PCT WO 94/11547 and PCT WO 93/06093.

dans laquelle R1, R3, R6 et R7 sont définis comme précédemment par silylation en position 7 au moyen d'un produit de formule générale (X) pour obtenir un produit de formule générale:

dans laquelle R', R1, R3, R6 et R7 sont définis comme précédemment, qui est fonctionnalisé en position 10 au moyen d'un produit de formule générale (XII) pour donner un produit de formule générale::

dans laquelle R', R1, R3, R4, R6 et R7 sont définis comme précédemment dont le groupement protecteur silylé est remplacé par un atome d'hydrogène pour donner un produit de formule générale:

qui, par action d'un produit de formule générale (XV) conduit au produit de formule générale (V) dont les groupements protecteurs sont remplacés par des atomes d'hydrogène pour donner un produit de formule générale (I) dans laquelle Z représente un radical de formule générale (II).According to the invention, the products of general formula (I) in which Z represents a radical of general formula (II), R4 is defined as above but cannot represent a hydrogen atom or a hydroxy radical and R5 is defined as previously, can be obtained from a product of general formula:

in which R1, R3, R6 and R7 are defined as above by silylation in position 7 using a product of general formula (X) to obtain a product of general formula:

in which R ', R1, R3, R6 and R7 are defined as above, which is functionalized in position 10 by means of a product of general formula (XII) to give a product of general formula:

in which R ', R1, R3, R4, R6 and R7 are defined as above, the silylated protective group of which is replaced by a hydrogen atom to give a product of general formula:

which, by the action of a product of general formula (XV) leads to the product of general formula (V) whose protective groups are replaced by hydrogen atoms to give a product of general formula (I) in which Z represents a radical of general formula (II).

 The silylation, functionalization and replacement of the protective groups with hydrogen atoms are carried out under conditions analogous to those described above.

dans laquelle R1 et R3 sont définis comme précédemment selon les méthodes connues de protection de la fonction hydroxy de la chaîne latérale sans toucher au reste de la molécule.The products of general formula (XVI) can be obtained under the conditions described in European patent EP 0336 841 and international PCT applications WO 92/09589 and WO 94/07878 or from the products of general formula:

in which R1 and R3 are defined as above according to known methods for protecting the hydroxy function of the side chain without affecting the rest of the molecule.

According to the invention, the products of general formula (I) in which Z represents a radical of general formula (II), R4 represents a hydrogen atom or a hydroxy radical and R5 is defined as above, can be obtained by action d 'a product of general formula (XV) on a product of general formula (XIX) in which R4 represents a hydrogen atom or a hydroxy radical, R1,
R3, R6 and R7 are defined as above by operating under the conditions
described above for the action of a product of general formula (XII) on a
product of general formula (XI) to give the product of general formula (XIII),
followed by the replacement of the protective groups by hydrogen atoms.

The products of general formula (XIX) in which R4 represents a
hydrogen atom can be obtained under the conditions decreed in the
PCT international applications WO 94/11547 and WO 93/06093.

The new products of general formula (I) obtained by the implementation
The processes of the invention can be purified according to known methods such as crystallization or chromatography.

The products of general formula (I) in which Z represents a radical of
general formula (II) have remarkable biological properties.

 In vitro, the measurement of the biological activity is carried out on the tubulin extracted from pig brain by the method of M.L. Shelanski et al., Proc. Natl.

Acad. Sci. USA, 70, 765-768 (1973). The study of the depolymerization of
microtubules in tubulin is carried out according to the method of G. Chauvière et al.,
CR Acad. Sci., 293, Series II, 501-503 (1981). In this study, the products of general formula (I) in which Z represents a radical of general formula (II) is
are shown to be at least as active as taxol and Taxotere.

In vivo, the products of general formula (I) in which Z represents a radical of general formula (II) have been shown to be active in mice grafted with
B16 melanoma at doses between 1 and 10 mg / kg intraperitoneally,
as well as other liquid or solid tumors.

 The new products have anti-tumor properties and more particularly an activity on tumors which are resistant to Taxon) or to Taxotere. Such tumors include colon tumors which have high expression of the mdr 1 gene (multi-drug resistance gene). Multi-drug resistance is a common term referring to the resistance of a tumor to different products with different structures and mechanisms of action. Taxoids are generally known to be highly recognized by experimental tumors such as P388 / DOX, a cell line selected for its resistance to doxorubicin (DOX) which expresses mdr 1.

 The following examples illustrate the present invention.

EXAMPLE 1
To a suspension containing 217.8 mg of acetoxy-4a benzoyloxy-2a epoxy5ss, 20 dihydroxy-lss, 13a dimethoxy-7ss, 10ss oxo-9 taxene-li, 200 mg of tert-butoxycarbonyl-3 (4-methoxyphenyl) acid -2 phenyl4 oxazolidine-1,3 carboxylic-5 (2R, 4S, 5R) and 50 mg of molecular sieve 4 in powder in 2 cm3 of ethyl acetate, successively added, at a temperature in the region of 200C, 126 mg of dicyclohexylcarbodiimide, then 14 mg of N, N'-dimethylamino-4 pyridine. The suspension obtained is stirred at a temperature in the region of 20 "C, under an argon atmosphere, for 16 hours then concentrated to dryness under reduced pressure (0, 27 kPa) at a temperature close to 40 "C. The residue obtained is purified by chromatography at atmospheric pressure on 50 g of silica (0.063-0.2 mm) contained in a column 2 cm in diameter (elution gradient: ethyl acetate-dichloromethane from 10-90 to 40 -60 by volume) by collecting 10 cm 3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 "C for 2 hours. This gives 271.8 mg of tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl4 oxazolidine-1,3 carboxylate-5 (2R, 4S, 5R) acetoxy-4a benzoyloxy-2a epoxy-5,20 hydroxy-1 dimethoxy-7ss, 10ss oxo-9 taxene-1 1 yl-13a in the form of '' a white solid with the following characteristics: - 1 H NMR spectrum (400 MHz; CDC13 with a few drops of CD30D d4 chemical shifts 6 in ppm; coupling constants J in Hz): 1.02 (s, 9H
C (CH3) 3); 1.10 (s, 3H: CH3); 1.17 (s, 3H: CH3); 1.63 (s, 3H: CH3); from 1.65 to 1.85 and 2.60 (2 mts, 1H each: CH2 in 6); 1.78 (mf, 3H: CH3); 2.02 and 2.15 (2 dd, J = 14 and 9.1 H each: CH2 at 14); 2.14 (s, 3H: CH3); 3.22 and 3.35 (2 sec, 3H each: OCH3); 3.64 (d, J = 7.1H: Hen3) 3.73 (mt, 1H: H in; 3.76 (s, 3H:
ArOCH3); 4.06 and 4.16 (2 d, J = 8.5, 1H each: CH2 in 20); 4.53 (d, J = 5.1H: H in 2 '); 4.67 (s, 1H: H at 10); 4.85 (broad d, J = 10, 1H: H at 5); 5.36 (mt, 1H: H 3 '); 5.52 (d, J = 7.1H: H 2); 6.07 (mt, 1H: H at 13); 6.33 (mf, 1H: H in 5 '); 6.88 (d, J = 8.2H: aromatic H in ortho of OCH3); from 7.25 to 7.40 (mt, 7H: aromatic H in 3 'and aromatic H in meta of OCH3); 7.43 (t, J = 7.5, 2H
OCOC6H5 H in meta); 7.58 (t, J = 7.5, 1H: OCOC6H5H in para); 7.96 (d, J = 7.5, 2H: OCOC6H5 H in ortho).

 A solution of 446.3 mg of tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl4 oxazolidine-1,3 carboxylate-5 (2R, 4S, 5R) of acetoxy-4a benzoyloxy-2a epoxy-5ss, 20 hydroxy-1 dimethoxy-7ss, 10ss oxo-9 taxene-11 yle-13a in 11.6 em3 of a 0.1N solution of hydrochloric methanol is stirred at a temperature close to 0 C for 16 hours under an argon atmosphere . The reaction mixture is then diluted with 40 cm3 of dichloromethane and 5 cm3 of distilled water.

After decantation, the aqueous phase is extracted with 5cm3 of dichloromethane. The organic phases are combined, dried over magnesium sulphate, filtered through sintered glass and then concentrated to dryness under reduced pressure (0.27 kPa) at a temperature in the region of 40 C. This gives 424.2 mg of a pale yellow solid which are purified by preparative thin layer chromatography [12 Merck preparative plates,
Kieselgel 60F254, thickness 1 mm, deposit in solution in a methanoldichloromethane mixture (5-95 by volume), eluting with a methanoldichloromethane mixture (5-95 by volume). After elution of the zone corresponding to the main product by a methanol mixture -dichloromethane (15-85 by volume), filtration through sintered glass, then evaporation of the solvents under reduced pressure (0.27 kPa) at a temperature in the region of 40 C, 126 mg of tert-3-carboxy-3-amino-2-phenyl-3 is obtained acetoxy4a benzoyloxy-2a epoxy-5ss, 20 hydroxy- 113 dimethoxy-7ss, 10ss oxo-9 taxene-ll yl- 13a propionate- (2R, 3 S) in the form of an ivory-colored meringue, the characteristics of which are as follows : - rotary power [a] D20 = -32.9 (c = 0.5; methanol) - 1 H NMR spectrum (400 MHz; CDC13; chemical shifts 6 in ppm coupling constant J in Hz) 1.23 (s , 3H: CH3); 1.25 (s, 3H: CH3); 1.39 (s, 9H: C (CH3) 3); 1.70 (s, 1H: OH in 1); 1.75 (s, 3H: CH3); 1.82 and 2.72 (2 mts, 1H each: CH2 in 6); 1.91 (s, 3H: CH3); 2.31 (AB limit, 2H: CH2 at 14); 2.39 (s, 3H: COCH3); 3.33 and 3.48 (2 sec, 3H each: OCH3); 3.48 (mt, 1H: OH in 2 '); 3.85 (d, J = 7.1H: H 3); 3.88 (dd, J = 11 and 7, 1H: H 7); 4.20 and 4.33 (2 d, J = 8.5, 1H each: CH2 at 20); 4.65 (mt, 1H: H in 2 '); 4.83 (s, 1H: H at 10); 5.00 (broad d, J = 10, 1H: Hen 5); 5.30 (broad d, J = 10.1H: H in 3 '); 5.47 (d, J = 10.1H:
CONH); 5.66 (d, J = 7.1H: H 2); 6.24 (broad t, J = 9.1H: H at 13); 6.33 (mt, 1H: H in 5 '); from 7.30 to 7.50 (mt, 5H: aromatic H in 3 '); 7.52 (t, J = 7.5, 2H:
OCOC6H5 H in meta); 7.63 (t, J = 7.5, 1H: OCOC6H5H in para); 8.12 (d, J = 7.5, 2H: OCOC6H5 H ortho).

Acetoxy-4a benzoyloxy-2a epoxy-5ss, 20 dihydroxy-113,13a dimethoxy7ss, 10ss oxo-9 taxene-ll (or 713,1 0 (methoxy-713, 1013 1 O-deacetoxy-baccatin III) can be prepared as follows:
To a solution of 500 mg of acetoxy-4a benzoyloxy-2a epoxy-5ss, trihydroxy-113,713,13a methoxy-10ss oxo-9 taxene-ll in 5 cm3 of iodomethane and 0.5 cm3 of dimethylformamide, kept under atmosphere of argon, at a temperature in the region of 0 ° C., 86 mg of sodium hydride at 50% by weight in petrolatum oil are added in portions. After 45 minutes at a temperature close to OOC, the reaction mixture is diluted with 50 cm3 of ethyl acetate and 8 cm3 of distilled water.

After decantation, the organic phase is washed with twice 8 cm3 of distilled water, then 8 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered through sintered glass, and concentrated to dryness under reduced pressure (0.27 kPa) at a temperature close to 40 "C. This gives 570 mg of a pale yellow solid which is purified by chromatography at atmospheric pressure on 50 g of silica (0.063-0.2 mm) contained in a column 2.5 cm in diameter, eluting with a methanol-dichloromethane mixture (2-98 by volume), collecting 10 cm 3 fractions. The fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 "C for 2 hours. This gives 380 mg of acetoxy-4a benzoyloxy-2a epoxy-5 (3.20 dihydroxy-113,13a dimethoxy-713,1013 oxo-9 taxene-li in the form of a pale yellow solid, the characteristics of which are as follows: - 1 H NMR spectrum (400 MHz CDCl3 with a few drops of CD30D d4; chemical shifts 6 in ppm; coupling constants J in Hz): 1.03 (s, 3H
CH3); 1.11 (s, 3H: CH3); 1.65 (s, 3H: CH3); 1.72 and 2.67 (2 mts, 1H each
CH2 in 6); 2.05 (s, 3H: CH3); 2.21 (AB limit, J = 14 and 9, 2H: CH2 at 14); 2.25 (s, 3H: COCH3); 3.26 and 3.40 (2 sec, 3H each: OCH3); 3.85 (d, J = 7.1H: H at 3); 3.89 (dd, J = 11 and 6.5, 1H: H at 7); 4.12 and 4.25 (2 d, J = 8.5, 1H each: CH2 in 20); 4.78 (tlarge, J = 9, 1H: Henl3); 4.83 (s, 1H: H in 10); 4.98 (dlarge, J = 10, 1H: HenS) 5.53 (d, J = 7.1, 1H: Hen2); 7.43 (t, J = 7.5, 2H: OCOC6H5 Hen meta); 7.56 (t, J = 7.5, 1H: OCOC6H5H in para); 8.05 (d, J = 7.5, 2H
OCOC6H5 H ortho).

Acetoxy-4a benzoyloxy-2a epoxy-5ss, trihydroxy- 113,713.1 3a methoxy 1013 oxo-9 taxene-11 (or 10ss-methoxy 10-deacetoxy-baccatin III) can be prepared as follows:
To a solution of 3.62 g of acetoxy-4a benzoyloxy-2a epoxy-513.20 hydroxy 1 (3 methoxy-10 (3 oxo-9 bistriethylsilyloxy-713,13a taxene-11 in 30 cm3 of dichloromethane), maintained under Argon atmosphere, at a temperature close to OOC, 50 cm3 of hydrogen fluoride-pyridine complex (3HF.Et3N) are slowly added.

After 48 hours at a temperature in the region of 20 "C, the reaction mixture is poured onto a suspension of 100 cm 3 of an aqueous solution supersaturated with sodium hydrogencarbonate maintained at a temperature in the region of 0 C. After decantation, the aqueous phase is reextracted with three times 80 cm3 of dichloromethane, then twice 80 cm3 of ethyl acetate The organic phases are combined, dried over magnesium sulfate, filtered over magnesium sulfate and concentrated to dryness under reduced pressure (0.27 kPa) at a temperature close to 40 "C.

3.45 g of a yellow meringue are thus obtained which are purified by chromatography at atmospheric pressure on 150 g of silica (0.063-0.2 mm) contained in a column 3.5 cm in diameter, eluting with a methanol-dichloromethane mixture (5-95 by volume), collecting 35 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 "C for 2 hours. This gives 1.97 g of acetoxy-4a benzoyloxy-2a epoxy 5 (3 , 20 trihydroxy-113,713,13a methoxy-10 oxo-9 taxene-11 in the form of a white solid whose characteristics are as follows: - 1 H NMR spectrum (400 MHz; CDC13, chemical shifts 6 in ppm coupling constant J in Hz) 1.10 (s, 3H: CH3); 1.19 (s, 3H: CH3); 1.48 (d,
J = 8.5, 1H: OH at 13); 1.70 (s, 3H: CH3); 1.81 and 2.61 (2 mts, 1H each: CH2 in 6); 2.09 (d, J = 5.1H: OH at 7); 2.11 (s, 3H: CH3); 2.30 (s, 3H: COCH3) 2.32 (d, J = 9.2H: CH2 at 14); 3.48 (s, 3H: OCH3); 3.97 (d, J = 7.1H: H at 3); 4.18 and 4.33 (2 d, J = 8.5, 1H each: CH2 at 20); 4.31 (mt, 1H: H at 7); 4.93 (mt, 1H: H at 13); 4.99 (s, 1H: H in 10); 5.01 (broad d, J = 10, 1H: H at 5); 5.66 (d, J = 7.1H: H 2); 7.49 (t, J = 7.5, 2H: OCOC HH in meta); 7.63 (t, J = 7.5, 1H: OCOC6H5 Hen para); 8.12 (d, J = 7.5, 211: OCOC6H5 H ortho).

Acetoxy-4a benzoyloxy-2a epoxy-5 (3.20 hydroxy-113 methoxy-1013 oxo-9 bistriethylsilyloxy-713.13a taxene-1 1 (or 10ss-methoxy 10-deacetoxy 7,13-bistriethylsilyl-baccatin III) can be prepared as follows:
To a solution of 5 g of acetoxy-4a benzoyloxy-2a epoxy-5ss, 20 dihydroxy 1C3,10 (3 oxo-9 bistriethylsilyloxy-7 (3,13a taxene-11 in 25 cm3 of iodomethane, maintained under an atmosphere of argon, at a temperature in the region of 0 ° C., 375 mg of sodium hydride at 50 GB by weight in petroleum jelly is added in portions. The solution is stirred for 45 minutes at a temperature in the region of 0 ° C. then for 5 hours 30 minutes at a temperature in the region of 20 "C. The reaction mixture is again cooled to a temperature in the region of at 0 C., and 125 mg of sodium hydride at 50 No by weight are added in portions in petroleum jelly. After 1 hour at 200C, then 18 hours at 5 "C, the reaction mixture is diluted by adding 50 cm3 of dichloromethane, poured onto 50 cm3 of a saturated aqueous solution of ammonium chloride and decanted. The aqueous phase is extracted with 2 times 30 cm3 of dichloromethane, then the organic phases are combined es, washed with
10 cm3 of distilled water, dried over magnesium sulfate, filtered through sintered glass, and concentrated to dryness under reduced pressure (0.27 kPa) at a temperature in the region of 40 C.

5.15 g of a yellow meringue are thus obtained which are purified by chromatography at atmospheric pressure on 300 g of silica (0.063-0.2 mm) contained in a column 5 cm in diameter (elution gradient: ethyl acetate-dichloromethane from 0-100 to 10-90 by volume), collecting 30 cm 3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 "C for 2 hours. This gives 3.62 g of acetoxy4a benzoyloxy-2a epoxy- 513.20 hydroxy - 113 methoxy-10 oxo-9 bistriethylsilyloxy 713,13a taxene-li in the form of a pale yellow meringue the characteristics of which are as follows: - 1 H NMR spectrum (600 MHz; CDCl3; chemical shifts 6 in ppm constant of coupling J in Hz): 0.58 and 0.69 (2 mts, 6H each: CH2 ethyl); 0.97 and 1.04 (2 t, J = 7.5, 9H each: CH3 ethyl); 1.15 ( s, 3H: CH3); 1.18 (s, 3H
CH3); 1.58 (s, 1H: OH in 1); 1.68 (s, 3H: CH3); 1.89 and 2.48 (2 mts, 1H each: CH2en6); 2.04 (s, 3H: CH3); 2.15 and 2.23 (2 dd, J = 16 and 9, 1H each: CH2 at 14); 2.29 (s, 3H: COCH3); 3.40 (s, 3H: OCH3); 3.83 (d, J = 7.1H: H at 3); 4.15 and 4.30 (2 d, J = 8.5, 1H each: CH2 in 20); 4.43 (dd, J = 11 and 7, 1H: H at 7); 4.91 (s, 1H: H at 10); 4.96 (broad d, J = 10, 1H: H at 5); 5.01 (wide t, J = 9.1H
H in 13); 5.62 (d, J = 7.1H: H 2); 7.46 (t, J = 7.5, 2H: OCOC6H5 H in meta); 7.60 (t, J = 7.5, 1H: OCOC6H5H in para); 8.09 (d, J = 7.5, 2H: OCOC6H5 H ortho).

Acetoxy-4a benzoyloxy-2a epoxy-5 13,20 dihydroxy- 113,1013 oxo-9 bistsiethylsilyloxy-713,13a taxene-1 1 (or 10-deacetyl 7,13-bistriethylsilyl-baccatine
III) can be prepared as follows:
To a solution of 14 g of acetoxy-4a benzoyloxy-2a epoxy-513.20 tetrahydroxy-ss1ss, 7ss, 10ss, 13 α oxo-9 taxene-1 1 (10-deacetyl-baccatin m) in 50 cm3 of anhydrous pyridine, maintained under an argon atmosphere, at a temperature in the region of 20 C, 10.8 cm3 of triethylsilyl chloride are added. hours at a temperature in the region of 20 C, the reaction mixture is brought to a temperature in the region of 115 C, then 10.8 cm 3 of triethylsilyl chloride are added. After 3 hours 15 minutes at a temperature in the region of 115 C, the reaction mixture is brought to a temperature in the region of 20 C, diluted with 30 cm3 of ethyl acetate and 100 cm3 of distilled water. After decantation, the aqueous phase is extracted with 2 times 50 cm3 of ethyl acetate. The organic phases are combined, washed with 50 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered through glass. sintered and then concentrated to dryness under reduced pressure (0.27 kPa) at a temperature in the region of 40 "C. This gives 63.1 g of a brown oil which is purified by chromatography at atmospheric pressure on 800 g of silica (0.063-0.2 mm) contained in a column 7 cm in diameter (elution gradient: ethyl acetate-dichloromethane from 0-100 to 5-95 by volume), collecting 60 cm3 fractions. containing only the desired product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 "C for 2 hours. This gives 9.77 g of acetoxy-4a benzoyloxy-2a epoxy-5ss, 20 dihydroxy 1 (3.10P oxo-9 bistriethylsilyloxy-7 (3.13a taxene-li in the form of a cream meringue of which l The characteristics are as follows: - 1 H NMR spectrum (400 MHz; CDC13. chemical shifts 6 in ppm constant coupling J in Hz): 0.55 and 0.68 (2 mts, 6H each: ethyl CH2); 0.94 and 1.03 (2 t, J = 7.5, 9H each: ethyl CH3); 1.08 (s, 3H: CH3); 1.17 (s, 3H
CH3); 1.58 (s, 1H: OH in 1); 1.73 (s, 3H: CH3); 1.91 and 2.57 (2 mts, 1H each.

CH2 in 6); 2.04 (s, 3H: CH3); 2.12 and 2.23 (2 dd, J = 16 and 9, 1H each: CH2 at 14); 2.30 (s, 3H: COCH3); 3.88 (d, J = 7.1H: H at 3); 4.16 and 4.32 (2 d, J = 8.5, 1H each: CH2en20) 4.27 (d, J = 1, 1H: OH in 10) 4.40 (dd, J = 11 and 7, 1H:
Hen7); 4.95 (dlarge, J = 10, 1H: HenS) 4.95 (mt, 1H: Hen13); 5.16 (d, J = 1.1H: Hen 10); 5.60 (d, J = 7.1H: Hen2); 7.46 (t, J = 7.5, 2H: OCOC6H5 Hen meta); 7.60 (t, J = 7.5, 1H: OCOC6H5H in para); 8.09 (d, J = 7.5, 2H
OCOC6H5 H ortho).

 The new products of general formula (I) in which Z represents a radical of general formula (II) manifest a significant inhibitory activity of abnormal cell proliferation and have therapeutic properties allowing the treatment of patients with pathological conditions associated with cell proliferation abnormal. Pathological conditions include abnormal cell proliferation of malignant or non-malignant cells of various tissues and / or organs, including, but not limited to, muscle, bone or connective tissue, skin, brain, lungs, sexual organs, the lymphatic or renal systems, the mammary or blood cells, the liver, the digestive system, the pancreas and the thyroid or adrenal glands. These pathological conditions may also include psoriasis, solid tumors, ovarian, breast, brain, prostate, colon, stomach, kidney or testicular cancer, Kaposi's sarcoma, cholangiocarcinoma, choriocarcinoma, neuroblastoma, Wilms tumor, Hodgkin's disease, melanomas, multiple myelomas, chronic lymphocytic leukemias, acute or chronic granulocytic lymphomas. The new products according to the invention are particularly useful for the treatment of ovarian cancer. The products according to the invention can be used to prevent or delay the onset or recurrence of pathological conditions or to treat these pathological conditions.

 The products according to the invention can be administered to a patient in different forms adapted to the chosen route of administration which, preferably, is the parenteral route. Parenteral administration includes intravenous, intraperitoneal, intramuscular or subcutaneous administration. More particularly preferred is intraperitoneal or intravenous administration.

 The present invention also includes pharmaceutical compositions which contain at least one product of general formula (I) in a sufficient amount suitable for use in human or veterinary therapy. The compositions can be prepared according to the usual methods using one or more pharmaceutically acceptable adjuvants, carriers or excipients. Suitable carriers include diluents, sterile aqueous media and various non-toxic solvents. Preferably the compositions are in the form of aqueous solutions or suspensions, injectable solutions which may contain emulsifying agents, dyes, preservatives or stabilizers. However, the compositions can also be in the form of tablets, pills, powders or granules which can be administered orally.

 The choice of adjuvants or excipients can be determined by the solubility and chemical properties of the product, the particular mode of administration and good pharmaceutical practices.

 For parenteral administration, aqueous or non-aqueous sterile solutions or suspensions are used. For the preparation of non-aqueous solutions or suspensions can be used natural vegetable oils such as olive oil, sesame oil or paraffin oil or injectable organic esters such as ethyl oleate . The sterile aqueous solutions can consist of a solution of a pharmaceutically acceptable salt dissolved in water. The aqueous solutions are suitable for intravenous administration as long as the pH is suitably adjusted and the isotonicity is achieved, for example, by a sufficient amount of sodium chloride or glucose. Sterilization can be carried out by heating or by any other means which does not alter the composition.

 It is understood that all the products entering into the compositions according to the invention must be pure and non-toxic for the quantities used.

 The compositions can contain at least 0.01 TB of therapeutically active product. The amount of active ingredient in a composition is such that a suitable dosage can be prescribed. Preferably, the compositions are prepared in such a way that a unit dose contains from 0.01 to 1000 mg approximately of active product for parenteral administration.

 Therapeutic treatment can be carried out concurrently with other therapeutic treatments including antineoplastic drugs, monoclonal antibodies, immunological therapies or radiotherapies or modifiers of biological responses. Response modifiers include, but are not limited to, lymphokines and cytokines such as interleukins, interferons (a, t3 or b) and TNF. Other chemotherapeutic agents useful in the treatment of disorders caused by abnormal proliferation cells include, without limitation, alkylating agents such as nitrogen mustards such as mechioretamine, cyclophosphamide, melphalan and chlorambucil, alkyl sulfonates such as busulfan, nitrosoureas such as carmustine, lomustine , semustin and streptozocin, triazenes such as dacarbazine, antimetabolites such as folic acid analogs such as methotrexate, pyrimidine analogs such as fluorouracil and cytarabine, purine analogs such as mercaptopurine and thioguanine, natural products such as vinca alkaloids such as vinblastine, vincristine and vendesine, epipodophyllotoxins co even etoposide and teniposide, antibiotics like dactinomycin, daunorubicin, doxorubicin, bleomycin, plicamycin and mitomycin, enzymes like L-asparaginase, various agents like platinum coordination complexes like cisplatin, substituted ureas such as hydroxyurea, methylhydrazine derivatives such as procarbazine, adrenocotic suppressants such as mitotane and aminoglutethymide, hormones and antagonists such as adrenocorticosteroids such as prednisone, progestins such as hydroxyprogesterone caproate , methoxyprogesterone acetate and megestrol acetate, estrogens like diethylstilbestrol and ethynylestradiol, antioestrogens like tamoxifen, androgens like testosterone propionate and fluoxymesterone.

 The doses used to implement the methods according to the invention are those which allow a prophylactic treatment or a maximum therapeutic response. The doses vary according to the form of administration, the particular product selected and the specific characteristics of the subject to be treated. In general, the doses are those which are therapeutically effective for the treatment of disorders due to abnormal cell proliferation. The products according to the invention can be administered as often as necessary to obtain the desired therapeutic effect.

Some patients may respond quickly to relatively large or low doses and may require low or no maintenance doses. Generally, low doses will be used at the start of treatment and, if necessary, increasing doses will be administered until an optimum effect is obtained. For other patients it may be necessary to administer maintenance doses 1 to 8 times a day, preferably 1 to 4 times, depending on the physiological needs of the patient concerned. lt is also possible that for some patients it is necessary to use only one or two daily administrations.

 In humans, the doses are generally between 0.01 and 200 mg / kg. Intraperitoneally, the doses will generally be between 0.1 and 100 mg / kg and, preferably between 0.5 and 50 mg / kg and, even more specifically between 1 and 10 mg / kg. Intravenously, the doses are generally between 0.1 and 50 mg / kg and, preferably between 0.1 and 5 mg / kg and, even more specifically between 1 and 2 mg / kg. It is understood that, in order to choose the most appropriate dosage, the route of administration, the patient's weight, his general state of health, his age and all the factors which may influence the effectiveness of treatment must be taken into account .

 The following example illustrates a composition according to the invention.

EXAMPLE
40 mg of the product obtained in Example 1 are dissolved in 1 cm 3 of Emulphor
EL 620 and 1 cm3 of ethanol then the solution is diluted by adding 18 cm3 of physiological saline.

 The composition is administered by infusion for 1 hour by introduction into physiological saline.

Claims (13)

1 - New taxoides of general formula:

 in which  Z represents a hydrogen atom or a radical of general formula:

 in which:  R1 represents a benzoyl radical optionally substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, alkoxy containing 1 to 4 carbon atoms or trifluoromethyl, thenoyl or furoyl or an R2-O-CO- radical in which R2 represents: - an alkyl radical containing 1 to 8 carbon atoms, alkenyl containing 2 to 8 carbon atoms, alkynyl containing 3 to 8 carbon atoms, cycloalkyl containing 3 with 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, bicycloalkyl containing 7 to 10 carbon atoms, these radicals being optionally substituted by one or more substituents chosen from halogen atoms and hydroxy radicals, alkoxy containing 1 to 4 carbon atoms, dialkoylamino, each alkyl part of which contains 1 to 4 carbon atoms, piperidino, morpholino, piperazinyl-1 (optionally substituted at -4 by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical in which the alkyl part contains 1 to 4 carbon atoms), cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, phenyl (optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy containing 1 to 4 carbon atoms), cyano, carboxy or alkoxycarbonyl in which the alkyl part contains 1 to 4 carbon atoms, - a phenyl or a- or ssnaphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy containing 1 to 4 carbon atoms or a 5-membered aromatic heterocyclic radical preferably chosen from the furyl and thienyl radicals, - or a saturated heterocyclyl radical containing 4 to 6 carbon atoms arbone optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms,  R3 represents a straight or branched alkyl radical containing 1 to 8 carbon atoms, straight or branched alkenyl containing 2 to 8 carbon atoms, straight or branched alkynyl containing 2 to 8 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, phenyl or a- or ssnaphthyl optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, fonnyl radicals, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkyl ino, dialcoylamino, carboxy, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialcoylcarbamoyl, cyano, nitro and trifluoromethyl, or a different aromatic heterocycle or having 5 or more hetero rings, chosen from several aromatic groups or hetero rings, having 5 or more hetero rings, from nitrogen, oxygen or sulfur atoms and optionally substituted by one or more, identical substituents or different, chosen from halogen atoms and alkyl, aryl, amino, alkyllamino, dialkoylamino, alkoxycarbonylarnino, acyl, arylcarbonyl, cyano, carboxy, carbamoyl, alkylcarbamoyl, dialkoylcarbamoyl or alkoxycarbonyl radicals, it being understood that in radicals, in radicals, phenyl, a- or fnaphthyl and aromatic heterocyclyl, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms and that the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms and that the aryl radicals are phenyl radiant or a- or frnaphtyles,  R4 represents a hydrogen atom or a hydroxy radical or an alkoxy radical containing 1 to 6 carbon atoms in a straight or branched chain, alkenyloxy containing 3 to 6 carbon atoms in a straight or branched chain, alkynyloxy containing 3 to 6 carbon atoms straight or branched chain, cycloalkoyloxy containing 3 to 6 carbon atoms, cycloalkenyloxy containing 3 to 6 carbon atoms, alkanoyloxy in which the alkanoyl part contains 1 to 6 carbon atoms in straight or branched chain, alkenoyloxy in which the alkenoyl part contains 6 carbon atoms in a straight or branched chain, alkynoyloxy of which the alkynoyl part contains 3 to 6 carbon atoms in a straight or branched chain, alkoxyacetyl of which the alkyl part contains 1 to 6 carbon atoms in a straight or branched chain, alkylthioacetyl of which alkyl contains 1 to 6 carbon atoms in straight or branched chain, alkyloxycarbonyloxy of which the alkyl part contains 1 to 6 carbon atoms e straight or branched chain carbon, these radicals being optionally substituted by one or more halogen atoms or by an alkoxy radical containing 1 to 4 carbon atoms, alkylthio containing 1 to 4 carbon atoms, or a carboxy, alkyloxycarbonyl radical of which the alkyl part contains 1 to 4 carbon atoms, cyano, carbamoyl, N-alkylcarbamoyl or N, N-dialkoylcarbamoyl each alkyl part of which contains 1 to 4 carbon atoms or forms, with the nitrogen atom to which it is linked, a saturated heterocyclic radical containing 5 or 6 members and optionally a second heteroatom chosen from oxygen atoms , sulfur or nitrogen optionally substituted by an alkyl radical containing 1 to 4 carbon atoms or a phenyl radical or a phenylalkyl radical in which the alkyl part contains 1 to 4 carbon atoms, or else R4 represents a benzoyloxy or heterocyclylcarbonyloxy radical in in which the heterocyclic part represents a 5 or 6-membered aromatic heterocycle containing one or more heteroatoms chosen from oxygen, sulfur or nitrogen atoms,  R5 represents an alkoxy radical containing 1 to 6 atoms of this carbon in a straight or branched chain optionally substituted by an alkoxy radical containing 1 to 4 carbon atoms, alkenyloxy containing 3 to 6 carbon atoms, alkynyloxy containing 3 to 6 carbon atoms, cycloalkoyloxy containing 3 to 6 carbon atoms, cycloalkenyloxy containing 3 to 6 carbon atoms, these radicals being optionally substituted by one or more halogen atoms or by an alkoxy radical containing 1 to 4 carbon atoms, alkylthio containing 1 to 4 atoms carbon, or a carboxy, alkyloxycarbonyl radical in which the alkyl part contains 1 to 4 carbon atoms, cyano, carbamoyl, N-alkylcarbamoyl or N, N-dialcoylcarbamoyl in which each alkyl part contains 1 to 4 carbon atoms or forms with the atom of nitrogen to which it is linked a saturated heterocyclic radical containing 5 or 6 members and optionally a second heteroatom chosen from oxygen atoms, sulfur or nitrogen optionally substituted by an alkyl radical containing 1 to 4 carbon atoms or a phenyl radical or a phenylalkyl radical in which the alkyl part contains 1 to 4 carbon atoms.  2 - New taxoldes according to claim for which Z represents a hydrogen atom or a radical of general formula (II) in which R1 represents a benzoyl radical or a radical R2-O-CO- in which R2 represents a tert-butyl radical and R3 represents an alkyl radical containing 1 to 6 carbon atoms, alkenyl containing 2 to 6 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, phenyl optionally substituted by one or more atoms or radicals, identical or different chosen from atoms halogen and the alkyl, alkoxy, dialkoylamino, acylamino, alkoxycarbonylamino or trifluoromethyl radicals or a furyl-2 or -3, thienyl-2 or -3 or thiazolyl-2, -4 or -5 and R4 and Rg radical, identical or different, represent a straight or branched alkoxy radical containing 1 to 6 carbon atoms.  3 - New taxoides according to claim 1 for which Z represents a hydrogen atom or a radical of general formula (II) in which R1 represents a benzoyl radical or an R2-O-CO- radical in which R2 represents a tert-butyl radical and R3 represents an isobutyl, isobutenyl, butenyl, cyclohexyl, phenyl, furyl-2, furyl-3, thienyl-2, thienyl-3, thiazolyl-2, thiazolyl-4 or thiazolyl-5 radical, each of which represents a methoxy radical.  4 - Process for the preparation of taxoids according to one of claims 1, 2 or 3 for which Z represents a radical of general formula (II) characterized in that a product of general formula is esterified:

 in which R4 and R5 are defined as in one of claims 1, 2 or 3, by means of an acid of general formula:

  in which R1 and R3 are defined as above, or else R6 represents a hydrogen atom and R7 represents a protective group for the hydroxy function, and either R6 and R7 together form a 5 or 6-membered saturated heterocycle, or a derivative of this acid to obtain an ester of general formula:

 in which R1, R3, R4, Rg, R6 and R7 are defined as above, in which the protective groups represented by R7 and / or R6 and R7 are replaced by hydrogen atoms.  5 - Process according to claim 4 characterized in that the esterification is carried out by means of an acid of general formula (IV) in the presence of a condensing agent and an activating agent in an organic solvent at a temperature between -10 and 90 "C.  6 - Process according to claim 4 characterized in that the esterification is carried out using an acid of general formula (IV) in the form of symmetrical anhydride by operating in the presence of an activating agent in an organic solvent to a temperature between 0 and 90 "C.  7 - Process according to claim 4 characterized in that the esterification is carried out using the acid of general formula (IV) in the form of halide or in the form of mixed anhydride with an aliphatic or aromatic acid, optionally prepared in situ , in the presence of a base, operating in an organic solvent at a temperature between 0 and sOOC.  8 - Process according to claim 4 characterized in that the protective groups R7 and / or R6 and R7 are replaced by hydrogen atoms, operating, according to their nature, as follows: 1) when R6 represents a d atom hydrogen and R7 represents a protecting group for the hydroxy function, the protecting groups are replaced by hydrogen atoms by means of a mineral or organic acid used alone or as a mixture, operating in an organic solvent chosen from alcohols, ethers, esters, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons or nitriles at a temperature between -10 and 60 "C, 2) when R6 and R7 together form a 5 or 6-membered saturated heterocycle of formula general ::

 in which R1 is defined as above, R8 and Rg, identical or different, represent a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms, or an aralkyl radical in which the alkyl part contains 1 to 4 carbon atoms and the aryl part preferably represents a phenyl radical optionally substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms, or an aryl radical representing, preferably a phenyl radical optionally substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms, or else R8 represents an alkoxy radical containing 1 to 4 carbon atoms or a trihalomethyl radical such as trichloromethyl or a phenyl radical substituted by a trihalomethyl radical such as trichloromethyl and Rg represents a hydrogen atom, or else R8 and Rg together with the carbon atom to which they are linked form a ring having 4 to 7 links, we replace the group protective entity formed by R6 and R7 by hydrogen atoms, operating, according to the meanings of R1, R8 and Rg, as follows:  a) when R1 represents a tert-butoxycarbonyl radical, R8 and Rg, which are identical or different, represent an alkyl radical or an aralkyl or aryl radical, or else R8 represents a trihalomethyl radical or a phenyl radical substituted by a trihalomethyl radical, and Rg represents a hydrogen atom, or else R8 and Rg together form a ring having from 4 to 7 members, the ester of general formula (V) is treated with a mineral or organic acid optionally in an organic solvent such as an alcohol to obtain the product of general formula:

 in which R3, R4 and R5 are defined as above, which is acylated by means of benzoyl chloride in which the phenyl ring is optionally substituted, of thenoyl chloride, of furoyl chloride or of a product of general formula: :  R2-O-CO-X (VIII) in which R2 is defined as above and X represents a halogen atom or a residue -O-R2 or -OC OO-R2, to obtain a product of general formula (I) in which Z represents a radical of general formula (II), b) when R1 represents an optionally substituted benzoyl radical, thenoyl or furoyl or an R2O-CO- radical in which R2 is defined as above, R8 represents a hydrogen atom or a alkoxy radical containing 1 to 4 carbon atoms or a phenyl radical substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms and Rg represents a hydrogen atom, the protective group formed by R6 and R7 is replaced by d atoms hydrogen is carried out in the presence of a mineral or organic acid used alone or as a mixture in a stoichiometric or catalytic amount, operating in an organic solvent chosen from alcohols, ethers, esters, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons and aromatic hydrocarbons at a temperature between -10 and 60 "C, preferably between 15 and 300C.  R'5-X2 (XV) in which R'5 represents an alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl radical optionally substituted, these different radicals and substituents having a definition identical to that given in the definition of R5 in one of the Claims 1, 2 or 3 and X2 represents a reactive ester residue or a halogen atom to give the product of general formula (I) in which Z represents a hydrogen atom.  in which R4 is defined as above, which is selectively etherified in position 7 by the action of a product of general formula:

  in which R 'and R4 are defined as above, the silylated protective groups of which are replaced by hydrogen atoms to obtain a product of general formula:

 R'4-X1 (XII) in which R'4 represents an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkanoyl, alkenoyl, alkynoyl, alkoxyacetyl, optionally substituted alkylthioacetyl or alkyoyloxycarbonyl or benzylcarbonyl radical or a benzylcarbonyl radical or a benzoyl radical substituents having a definition identical to that given in the definition of R4 in claims 1, 2 or 3 and X1 represents a halogen atom or a reactive ester residue such as a sulfuric or sulfonic ester residue to obtain a product of general formula:  in which R 'is defined as above, which is treated with a product of general formula:

 (R ') 3-Si-Hal (X) in which the symbols R', identical or different, represent an alcolyl radical containing 1 to 4 carbon atoms optionally substituted by a phenyl radical, or a phenyl radical to obtain a product of general formula:  with a silyl halide of general formula:

 9 - Process for the preparation of a new taxoid according to one of claims 1, 2 or 3 for which Z represents a hydrogen atom, R4 is defined as in one of claims 1, 2 or 3 but cannot represent a hydrogen atom or a hydroxy radical and R5 is defined as in one of claims 1, 2 or 3 characterized in that lton treats 1 0-deacetyl-baccatin III of formula:  10 - Process for the preparation of a new taxoid according to claim 1 for which Z represents a hydrogen atom, R4 represents a hydrogen atom or a hydroxy radical and R5 is defined as in one of claims 1, 2 or 3 characterized in that a product of general formula is reacted:  R'5-X2 (XV) on a product of general formula:

  in which R4 represents a hydrogen atom or a hydroxy radical, after metallation of the hydroxy function in position 7, operating in an organic solvent at a temperature between 0 and 500C.  11 - Process for preparing a product according to one of claims 1, 2 or 3 for which Z represents a radical of general formula (in), R4 is defined as in one of claims 1,2 or 3 but does not may not represent a hydrogen atom or a hydroxy radical and R5 is defined as in one of claims 1, 2 or 3 characterized in that a product of general formula is treated:

 in which R1, R3, R6 and R7 are defined as in one of claims 1, 2, 3 or 4 by means of a product of general formula:  (R ') 3Si-Hal (X) in which the symbols R', identical or different, represent an alkyl radical containing 1 to 4 carbon atoms, optionally substituted by a phenyl radical, or a phenyl radical to obtain a product of formula general:

 in which R ', R1, R3, R6 and R7 are defined as above, which is functionalized in position 10 by means of a product of general formula:  R'4-X1 (XII) in which R4 is defined as in claim 9 and X1 represents a halogen atom or a residue of reactive ester to give a product of general formula:

 in which R ', R1, R3, R4, R6 and R7 are defined as above, the silylated protective group of which is replaced by a hydrogen atom to give a product of general formula:

 which, by the action of a product of general formula (XV) leads to the product of general formula (V) whose protective groups are replaced by hydrogen atoms to give a product of general formula (I) in which Z represents a radical of general formula (II).  12 - Process for the preparation of a product according to claims 1 for which Z represents a radical of general formula (I), R4 represents a hydrogen atom or a hydroxy radical and R5 is defined as in one of claims 1, 2 or 3 characterized in that a product of general formula is reacted:  R'5-X2 (XV) in which R5 is defined as in claim 9 and X2 represents a halogen atom or a reactive ester residue, on a product of general formula:

  in which R4 represents a hydrogen atom or a hydroxy radical, R1, R3 are defined as in one of claims 1, 2 or 3, R6 and R7 are defined as in claim 4 operating in an organic solvent at a temperature between 0 and 500C, followed by the replacement of the protective groups by hydrogen atoms to obtain a product of general formula (I) in which Z represents a radical of general formula (II) and R4 represents a hydrogen atom or a hydroxy radical.  13 - Pharmaceutical composition characterized in that it contains at least one product according to one of claims 1, 2 or 3 for which Z represents a radical of general formula (II) in association with one or more diluents or pharmaceutically acceptable adjuvants and optionally one or more compatible and pharmacologically active compounds.