UA61882C2 - Taxoids, methods for preparation thereof and a pharmaceutical composition containing them - Google Patents

Abstract

Novel taxoids of general formula (I), the preparation thereof and pharmaceutical compositions containing them are described, wherein Z is a hydrogen atom or a radical of general formula (II), wherein R1 is an optionally substituted benzoyl radical or a radical R2-O-CO-where R2 is an optionally substituted phenyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, or heterocyclyl radical, R3 is an aromatic heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, phenyl or naphthyl radical, R4 is a substituted alkanoyloxy, alkenoyloxy, alkynoyloxy or cycloalkanoyloxy radical and R5 is an optionally substituted alkoxy radical or a cycloalkyloxy or cycloalkenyloxy radical. The novel products of general formula (I), where Z is a radical of general formula (II), have remarkable anti-tumour and anti-leukemia properties.

Description

Description of the invention

The invention relates to new taxoids of the general formula (1): and E o (F id

U - Fe not

But in ososn, osSOsn a 5 in which 7 means a hydrogen atom or a radical of the general formula (II)

К, ХН о ОН (II) ra an in which

Ku means a benzoyl radical, possibly substituted by one or more, the same or different atoms with or radicals selected from halogen atoms and alkyl radicals with 1-4 carbon atoms, (39 alkyl radicals with 1-4 carbon atoms or a trifluoromethyl radical; thenoyl or furoyl radical or radical co-0o-CO.-, where K" means c - an alkyl radical with 1-8 carbon atoms, an alkenyl radical with 2-8 carbon atoms, an alkynyl radical with 3-8 carbon atoms, a cycloalkyl radical with 3-6 carbon atoms, a cycloalkenyl radical with 4-6 carbon atoms, a bicycloalkyl radical with 7-10 carbon atoms, and these radicals can be substituted with one or more substituents chosen from among halogen atoms and a hydroxyl radical, an alkyl radical with 1-4 carbon atoms, a dialkylamino radical, each alkyl part of which contains 1-4 atoms

From carbon, a piperidine radical, a morpholino radical, a piperazin-1-yl radical (perhaps substituted in position 4 by an alkyl radical with 1-4 carbon atoms or a phenylalkyl radical, the alkyl part of which contains 1-4 carbon atoms), a cycloalkyl radical with 3-6 carbon atoms, a cycloalkenyl radical with 4-6 carbon atoms, a phenyl radical (possibly substituted by one or more atoms or radicals selected from halogen atoms and alkyl radicals with 1-4 carbon atoms or from alkyl radicals with 1 -4 carbon atoms), cyano-radical, carboxyl or alkoxycarbonyl, the alkyl part of which contains 1-4 carbon atoms; z" - phenyl or 9- or В-naphthyl radical, possibly substituted by one or more atoms or radicals, which are selected from among halogen atoms and alkyl radicals with 1-4 carbon atoms or alkyl radicals with 1-4 79 carbon atoms;

Ф - heterocyclic aromatic five-membered radical, which is chosen from among furyl and thienyl radicals; - a heterocyclic saturated radical with 4-6 carbon atoms, possibly substituted by one or more alkyl radicals with 1-4 carbon atoms; (about 50 Kz means a linear or branched alkyl radical with 1-8 carbon atoms; a linear or branched alkenyl radical with 2-8 carbon atoms; a linear or branched alkynyl radical with 2-8 carbon atoms; a cycloalkyl radical with 3-6 carbon atoms ; phenyl or u- or B-naphthyl radical, possibly substituted by one or more atoms or radicals selected from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkyl, alkylthio-, aryloxy-, arylthio-, 59 hydroxyl, hydroxyalkyl, mercapto-, formyl, acyl, acylamino-, aroylamino-,

HF) alkoxycarbonylamino-, amino-, alkylamino-, dialkylamino-, carboxyl, alkoxycarbonyl, 7-carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano-, nitro-, and trifluoromethyl radicals; or a heterocyclic aromatic five-membered radical containing one or more identical or different heteroatoms selected from nitrogen, oxygen or sulfur atoms and possibly substituted by one or more, for the same or different, substituents selected from halogen atoms and alkyl, aryl , amino-, alkylamino-, dialkylamino-, alkoxycarbonylamino-, acyl, arylcarbonyl, cyano-, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, or alkoxycarbonyl radicals, provided that the substituents of phenyl, u- or β-naphthyl and aromatic heterocyclic radicals, alkyl radicals and alkyl parts of other radicals contain 1-4 carbon atoms, and alkenyl and alkynyl radicals contain 2-8 carbon atoms, and aryl radicals are phenyl or β- or β-naphthyl radicals.

Ku means - alkyl radical, the alkyl part of which contains 2-6 carbon atoms in a linear or branched chain, with the exception of the acetyl radical, alkenyloxy- radical, the alkenyl part of which contains 3-6 carbon atoms in a linear or branched chain, alkynyloxy- radical, alkynyl part of which contains 3-6 carbon atoms in a linear or branched chain, and these radicals can be replaced by one or more halogen atoms or an 1-4 carbon alkyl radical, an 1-4 carbon alkylthio radical, a carboxyl radical, an alkyloxycarbonyl radical , the alkyl part of which contains 1-44 carbon atoms, a cyano group, a carbamoyl radical, an M-alkylcarbamoyl radical, or a 70 M,M-dialkylcarbamoyl, each alkyl part of which contains 1-4 carbon atoms, or together with the nitrogen atom to which it is connected bound, forms a saturated five- or six-membered heterocyclic radical, possibly containing a second heteroatom, chosen from atoms k nitrogen, sulfur or nitrogen, possibly substituted by an alkyl radical with 1-4 carbon atoms or a phenyl radical or a phenylalkyl radical, the alkyl part of which contains 1-4 carbon atoms; - a cycloalkyl radical, the cycloalkyl part of which contains 4-8 carbon atoms; or a cycloalkenyloxy radical, the cycloalkenyl part of which contains 4-8 carbon atoms; - benzoyloxy-radical or heterocyclyl-carbonyloxy-radical, the heterocyclic part of which is an aromatic five- or six-membered heterocycle containing one or more heteroatoms selected from oxygen, sulfur or nitrogen atoms;

K5 means - an alkyl radical with 1-6 carbon atoms in a linear or branched chain (possibly substituted by an alkyl radical with 1-4 carbon atoms), an alkenyloxy radical with 3-6 carbon atoms, an alkynyloxy radical with 3-6 carbon atoms, cycloalkyloxy -radical with 3-6 carbon atoms, cycloalkenyloxy-radical with 3-6 carbon atoms, and these radicals can be substituted by one or several halogen atoms or an alkyl radical with 1-4 carbon atoms, an alkylthio radical with 1-4 atoms carbon, carboxyl radical, alkyloxycarbonyl radical, the alkyl part of which contains i) 1-44 carbon atoms, cyano group, carbamoyl radical, M-alkylcarbamoyl radical or

M,M-dialkylcarbamoyl radical, each alkyl part of which contains 1-4 carbon atoms, or together with the nitrogen atom to which it is connected, forms a saturated five- or six-membered heterocyclic radical, which may contain a second heteroatom, which is chosen from oxygen, sulfur or nitrogen atoms, possibly substituted by an alkyl radical with 1-4 carbon atoms or a phenyl radical or a phenylalkyl radical, the alkyl part of which contains 1-4 carbon atoms. co

Preferably, the aryl radicals represented by C are phenyl or 9- or B-naphthyl radicals, possibly substituted by one or more atoms or radicals selected from halogen atoms (77 (fluorine, chlorine, bromine, iodine) and alkyl , alkenyl, alkynyl, aryl, arylalkyl, alkyl, He) alkylthio-. aryloxy-, arylthio-, hydroxyl, hydroxyalkyl, mercapto-, formyl, acyl, acylamino-, aroylamino-, alkoxycarbonylamino-, amino-, alkylamino-, dialkylamino-, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano-, nitro- and trifluoromethyl radicals, provided that alkyl radicals and alkyl parts of other radicals contain 1-4 carbon atoms, alkenyl and alkynyl radicals contain 2-8 carbon atoms, and aryl radicals are phenyl or u- or naphthyl radicals. Preferably, the heterocyclic radicals designated as Kz are aromatic heterocyclic five-membered "» radicals containing one or more, the same or different, heteroatoms selected from oxygen, sulfur, or nitrogen atoms, possibly substituted by one or more of the same or by various substituents chosen from among halogen atoms (fluorine, chlorine, bromine, iodine) and alkyl radicals with 1-4 carbon atoms, aryl

Ge) radicals with 6-10 carbon atoms, alkyl radicals with 1-4 carbon atoms, aryloxy radicals with 6-10 -3 carbon atoms, amino groups, alkylamino radicals with 1-4 carbon atoms, dialkylamino radicals, each alkyl part which contain 1-4 carbon atoms, acylamino radicals, the alkyl part of which contains 1-4 carbon atoms (oo), alkoxycarbonylamino radicals with 1-4 carbon atoms, acyl radicals with 1-4 carbon atoms, arylcarbonyl radicals, the aryl part of which contains 6-10 carbon atoms, cyano-, carboxyl, co-carbamoyl, alkylcarbamoyl radicals, the alkyl part of which contains 1-4 carbon atoms,

Kz dialkylcarbamoyl radicals, each alkyl part of which contains 1-4 carbon atoms, or alkoxycarbonyl radicals, the alkyl part of which contains 1-4 carbon atoms.

Preferably Ku) means an alkyloxyacetoxy radical, the alkyl part of which contains 1-4 carbon atoms, a cycloalkyl radical, the cycloalkyl part of which contains 4-8 carbon atoms, a cycloalkenyloxy radical, the cycloalkenyl part of which contains 4-8 carbon atoms, a benzoyloxy radical, or ) heterocyclyl-carbonyloxy-radical, the heterocyclic part of which is an aromatic five- or six-membered i.e.) heterocycle containing one or more heteroatoms selected from oxygen, sulfur or nitrogen atoms; and

K5 represents an alkyl radical with 1-6 carbon atoms in a linear or branched chain, possibly substituted by methoxy-, ethoxy-, methylthio-, ethylthio-, carboxy-, methoxycarbonyl, ethoxycarbonyl, cyano-, carbamoyl, M-methylcarbamoyl, M-ethylcarbamoyl , M,M-dimethylcarbamoyl,

M,M-diethylcarbamoyl, M-pyrrolidinecarbonyl or M-piperidinocarbonyl radical.

More specifically, the present invention relates to products of the general formula (I), where 7 means a hydrogen atom or a radical of the general formula (II), in which K 4 means a benzoyl radical or a radical K»-0O-CO-, where Co 65 means tert. -butyl radical, and Kz means an alkyl radical with 1-6 carbon atoms, an alkenyl radical with 2-6 carbon atoms, a cycloalkyl radical with 3-6 carbon atoms, a phenyl radical, possibly substituted by one or more, the same or different atoms or radicals, which are chosen from among halogen atoms (fluorine, chlorine) and alkyl (methyl), alkoxy (methoxy-), dialkylamino- (dimethylamino-), acylamino- (acetylamino-), alkoxycarbonylamino- (tert.-butoxycarbonylamino-) or trifluoromethyl radicals, or 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl or 5-thiazolyl radical; and Ku means an alkyloxy-acetoxy radical, the alkyl part of which contains 1-4 carbon atoms, a cycloalkyl radical, the cycloalkyl part of which contains 4-6 carbon atoms, a pyridylcarbonyloxy radical; and K;5 means a linear or branched alkyl radical with 1-6 carbon atoms. 70 More specifically, the present invention relates to products of the general formula (I), where 7 means a hydrogen atom or a radical of the general formula (II), in which Ku means a benzoyl radical or a radical of K»-O-CO-, where Ko means tert.- butyl radical, and Kz means isobutyl, isobutenyl, butenyl, cyclohexyl, phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl or 5-thiazolyl radical; and Ku. means methoxy-acetoxy-, cyclopentylcarbonyloxy-, pyridyl-2-carbonyloxy- or 7/5 Pyridyl-3-carbonyloxy- radical; and K5 is a methoxy radical.

Products of the general formula (I), in which 7 represents the radical of the general formula (I)/ exhibit valuable antitumor and antileukemic properties.

According to the invention, new products of the general formula (I), where 7 means the radical of the general formula (II), can be obtained by esterification of the product of the general formula (III):

Kk, o B (1) 5 no ia, Ge same (0) o

N:-

M. ososn, osos, Nn, sch

What , . in which Ku and K5 have the above values, under the influence of an acid of the general formula (IM): (2.0)

Iv E. (M) t 6 o so - Zh iy z5 K, pon te)

O-V. in which Ku and Kz have the above values, and or Ko means a hydrogen atom, and K; means a protective group for the hydroxyl function, or Ke and K7 together form a saturated five- or six-membered heterocycle, or a derivative of this acid to obtain a complex ester of the general formula (M): -

Sov ku in What "of them C 6. Mo h viniere in:

KG. would you? I o r o

O-V. ra no: 7 t no ososn,

Go) i so osOs,N.

Kz in which Ku, Kz, Ku, Kv, Ko and K7 have the above meaning, with subsequent replacement of the protective groups K7 or Ke and K7 with hydrogen atoms.

Esterification using a product of the general formula (XII), in which X/ means a hydroxyl radical,

It can be performed in the presence of a condensation agent (carbodiimide, reactive carbonate) and an activation agent (aminopyridines) in an organic solvent (simple and complex ethers, ketones, nitriles, aliphatic (F) hydrocarbons, aliphatic halogenated hydrocarbons, aromatic hydrocarbons) at a temperature from -107C to 9076.

GI Esterification can also be carried out using a product of the general formula (XII!), in which X 4 represents the radical K)-O-, working in the presence of an activating agent (aminopyridine) in an organic solvent (simple and complex ethers, ketones, nitriles, aliphatic hydrocarbons, aliphatic halogenated hydrocarbons, aromatic hydrocarbons) at a temperature from ОС to 9070.

Etherification can also be carried out using a product of the general formula (XII), in which X 4 represents a halogen atom, in the presence of a base (tertiary aliphatic amine), working in an organic solvent (simple and complex ethers, ketones, nitriles, aliphatic hydrocarbons, aliphatic halogenated 65 hydrocarbons, aromatic hydrocarbons) at a temperature from 0"C to 807C.

Preferably, Co represents a hydrogen atom and K7 represents a hydroxyl protecting group, or Kv and K7 together form a saturated five- or six-membered heterocycle.

When Ke means a hydrogen atom, K; is mainly a methoxymethyl radical, 1-ethoxyethyl, benzyloxymethyl, trimethylsilyl, triethylsilyl, B-trimethylsilylethoxy-methyl, benzyloxycarbonyl or tetrahydropyranyl radical.

When Ke; and K7 together form a heterocycle, then it is preferably an oxazolidine ring, possibly monosubstituted or heme-disubstituted in position 2.

Replacement of protective groups K7 and/or Ko and K7 with hydrogen atoms can be carried out, depending on their nature, in the following way: 70 1) when Ko means a hydrogen atom, and K; means the protective group of the hydroxyl function, the replacement of protective groups with hydrogen atoms is carried out with the help of inorganic acid (hydrochloric acid, sulfuric acid, hydrofluoric acid) or organic acid (acetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid), using it individually or in mixtures, working in an organic solvent chosen from among alcohols, simple and complex ethers, aliphatic hydrocarbons, aliphatic /5-hapogenated hydrocarbons, aromatic hydrocarbons or nitriles, at a temperature from -107C to 60"7C. 2) When Ke and K together form a saturated five- or six-membered heterocycle, preferably an oxazolidine ring, of the general formula (MI): 7 u

In B, c where Ku has the above value; Ka and Ko, the same or different, mean a hydrogen atom or an alkyl radical o with 1-4 carbon atoms, or an aralkyl radical, the alkyl part of which contains 1-4 carbon atoms, and the aryl part mainly means a phenyl radical, possibly substituted by one or more alkyl radicals with 1-4 carbon atoms, or an aryl radical, preferably a phenyl radical, possibly substituted by one or more alkyl radicals with 1-4 carbon atoms; or with

Ka represents an 1-4 carbon alkyl radical or a trihalomethyl radical such as trichloromethyl, or a phenyl radical substituted with a trihalomethyl radical such as trichloromethyl, and

Ko means a hydrogen atom; or Kae and Ko together with the carbon atom to which they are connected form a 4-7-ene ee) cycle; replacement of Ke formed by radicals; and K7 of the protective group with hydrogen atoms can be carried out, depending on the values of Ku, Pv and Ko, in the following way: - a) when Ki means a tert.-butoxycarbonyl radical, Ka and Ko, the same or different, mean an alkyl "o radical or an aralkyl a radical (benzyl) or an aryl radical (phenyl), or Ka means a trihalomethyl radical or a phenyl radical substituted with a trihalomethyl radical, and Ko means a hydrogen atom, or Ka; and Co together form a 4-7-ene cycle, treat the complex ester of the general formula (M) with an inorganic or organic acid, if necessary in an organic solvent, such as alcohol, and obtain a product of the general formula (MI): - c I at; In (MI) ts 5 a nm o honor o On No t NO ososn,

Ho c) : bo 20 osos,n, in which Kz, Ka and K5 have the above values, which is adilated with the help of benzoyl chloride, in which the phenyl nucleus is possibly substituted, thenoyl chloride, furoyl chloride, or the product of the general formula (MI):

K»-0-SO-X (MI),

Where K" has the above value, and X means a halogen atom (fluorine, chlorine) or a group -0-K" or -0-СО-О-К», 29 3 by obtaining a product of the general formula (I), where 7 means a radical of the general formulas (II).

GF) Preferably, the product of the general formula (M) is treated with formic acid at a temperature of about 207 to obtain the product of the general formula (MI). where Preferably, the acylation of the product of the general formula (MII) with benzoyl chloride, in which the phenyl radical is possibly substituted, thenoyl chloride or furoyl chloride or the product of the general formula (MII) 60 is carried out in an inert organic solvent, which is selected from esters such as ethyl acetate , isopropyl acetate or n-butyl acetate, and aliphatic halogenated hydrocarbons such as dichloromethane or 1,2-dichloroethane in the presence of an inorganic base such as sodium bicarbonate or an organic base such as triethylamine. The reaction is carried out at a temperature from 0"C to 50"C, preferably around 20"; b) when Ku means a possibly substituted benzoyl radical, thenoyl radical, or furoyl radical, or the radical K»O-CO-, in which Ko has the above value, Ka means a hydrogen atom or an alkyl radical with 1-4 carbon atoms or a phenyl radical substituted by one or more alkyl radicals with 1-4 carbon atoms, and Ko means a hydrogen atom, the replacement of the formed Ko and K; the protective group with hydrogen atoms is carried out in the presence of an inorganic acid (hydrochloric acid, sulfuric acid) or an organic acid (acetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid), using It individually or in a mixture, in a stoichiometric or catalytic amount, working in an organic solvent that is chosen among alcohols, simple and complex esters, aliphatic hydrocarbons, aliphatic halogenated hydrocarbons, aromatic hydrocarbons or nitriles, at a temperature of -1 07C to 60C, mostly at 15-307C. 70 According to the invention, products of the general formula (II), i.e. products of the general formula (I), in which 7 represents a hydrogen atom, K and Ko have the above-mentioned values, can also be obtained starting from 10-desacetyl-baccatin-III of the formula (IX) : (x) but o

NO on 10 ;

But no. 13 o

Н - more ОсосН, осос,Н,

It is especially important to selectively protect the hydroxyl functions in positions 7 and 13, for example, in the form of a simple silylated diester, which can be obtained by a halogenation reaction, under the influence of a silyl halide of the general formula (X): (Kyuz-5i-Na! (X) in which

E, the same or different, mean an alkyl radical with 1-4 carbon atoms, possibly substituted by a phenyl EM radical, or a phenyl radical, on 10-desacetyl-baccatin-iiII, and obtaining a product of the general formula (XI): со

But, oh,

PO 9-5), co "-

And! (Se) (K), 5-0 p.e

And : And)

Н - но ососн, " - - зо осос,н, с "" in which K has the above-mentioned value, which is then processed by the product of the general formula (XII): " In a-Hu (XII) in which Kz means such a radical that K '/-O- is identical to the radical K/, which has the above-mentioned meaning, but cannot represent a hydrogen atom or a hydroxyl radical, and X. represents a halogen atom, to obtain

Me. of the product of the general formula (XII): - o , (XII)

Kk, 100 0-5), and (ee) x I x AC (ee) y ; . I I to (83.50: che t /E z o

N. ososn no: 3 o osos,n, in which K and K. have the above-mentioned values, then the silylated protective groups of the obtained compound are replaced by hydrogen atoms and a product of the general formula (CHEM): 60 b5 is obtained

CHEM) o (

V, 7" ON no pe.

And with Fr

NN-: but ososn,

And оСсОос НН 65 in which K. has the above-mentioned value, which is selectively esterified in position 7, acting as a product of the general formula (ХМ): 5 V'ueyeXx; (ХМ) in which K'5 means such a radical that K'5-O- is identical to the radical Kb, which has the above-mentioned meaning, and X0 represents a halogen atom or a residue of a complex ester of sulfuric or sulfonic acid, to obtain a product of the general formula ( PP).

Usually, the treatment with a silylated derivative of the general formula (X) of 10-desacetyl-baccatin-P is carried out in pyridine or triethylamine, possibly in the presence of an organic solvent, such as an aromatic hydrocarbon, for example, benzene, toluene, and xylenes, at a temperature from 07C to the boiling point reaction mixture.

Typically, treatment with a compound of general formula (XII) of a compound of general formula (XI) is carried out after the formation of a metal salt with a hydroxyl function in position 10 with an alkali metal hydride such as sodium hydride, an alkali metal amide such as lithium amide, or an alkali metal alkyl derivative , such as c butyllithium, working in an organic solvent such as dimethylformamide or tetrahydrofuran at a temperature of 0"C to 5070.

Usually, the replacement of the silylated protective groups of the product of the general formula (XIII) with hydrogen atoms is carried out using an acid, such as hydrofluoric acid or trifluoroacetic acid, in the presence of a base, such as triethylamine or pyridine, possibly substituted by one or more alkyl radicals with 1-4 carbon atoms , if necessary, in combination with inert organic solvents, such as a nitrile, for example, with acetonitrile, or an aliphatic halogenated hydrocarbon, for example, dichloromethane, at a temperature from 0"C to vogs.

Usually, the interaction of the product of the general formula (XM) with the product of the general formula (XIM) is carried out under conditions identical to those mentioned above, in order to treat the compound of the general formula with the compound of the general formula (XII)

Zo (X)).

According to the invention, the products of the general formula (I), where 7 means the radical of the general formula (I), Ku; and K5 have the above values, can be obtained based on the product of the general formula (ХМИ1): no o (ХМ) « 4 |х on их -

M o

АГ и и : о Й Ф -

O-E. no: oh '

F no osOsn, - osoOs,n.

Go! in which Ki, Kz, Kv and Ku have the above-mentioned values, by silylation in position 7 with the help of 5p bpoluk of the general formula (X), to obtain a compound of the general formula (HMIII): then 0-5, m o what di -toa M

Kk, (8) / i t, Ii "U o O-v. /ri yu no Uh ososn, zo osos,H, in which K, Kl, Kz, Kv and K7 have the aforementioned values, which is functionalized in position 10 with the help of a compound of the general formula (XII), to obtain a compound of the general formula (XM): b5

And about 4 more O-55K)

K,x Ah, k!

Mo and AD

KE, - (0) 1 " y - t, E d)

O-E. No:

NO M ososn, 70 I osos, n. (KhMI) in which K, K., Kz, Ky, Kv and K7 have the above-mentioned values, the silylated protective group of which is replaced by a hydrogen atom, obtaining a compound of the general formula (XIX): 15 o XIX p. in KE, ono 0 xy m o ra "y I i yu Ku too! r o) o-K. ni no ososH, z osos,H, cm which after interaction with a compound of the general formula (XM) leads to the formation of a compound of the general formula (o) (M) , the protective groups of which are replaced by hydrogen atoms, obtaining a product of the general formula (I), in which 7 means a radical of the general formula (II).

The reaction of silylation, functionalization and replacement of protective groups on hydrogen atoms is carried out under the conditions that sch 30 are similar to those mentioned above.

Products of the general formula (XMI) can be obtained under the conditions described in the European patent EP 0 336 00 841 and in international applications PCT UUO 92/09589 and MO 94/07878 or based on the products of the general formula со (ХХ): но о ОН ( XX) - 35 KE, MN (Se)

Mo ra f" '

Kk; : oh! I " : o o 40 on N - - s NO M ososi, ;" OoSOsS.N. in which Ku and Kz have the aforementioned values, according to known methods of protecting the hydroxyl function in the side 45 chain, without affecting the rest of the molecule.

Me. According to the invention, products of the general formula (I), where 7 means a hydrogen atom or a radical of the general formula - (I), can be obtained by reacting activated Raney nickel in the presence of an aliphatic alcohol with 1-3 carbon atoms on a compound of the general formula (XXI): со (XX) o 50 , o) coffin

Kk ray

K, o o V

F) 7 sh- 2-0 PI A bo ho o; нН- no ososn, osos,n, 65 in which K. has the above-mentioned value, and K' and KK", the same or different, represent a hydrogen atom or an alkyl radical with 1-6 carbon atoms, an alkenyl radical with 2-6 atoms carbon, a cycloalkyl radical with 3-6 carbon atoms or a cycloalkyl radical with 3-6 carbon atoms, or K' and K" together with the carbon atom to which they are connected form a cycloalkyl radical with 3-6 carbon atoms, and 74 represents a hydrogen atom or a radical of the general formula (XXII) (XXII)

Kuhn, -K

I M o o : Y t ov. in which Ku and Kz have the above-mentioned values, and either Co represents a hydrogen atom and K7 represents a hydroxyl protecting group, or Co and K7 together form a five- or six-membered saturated heterocycle, and Ku has the above-mentioned meaning, to give a compound of the general formula (XX):

E (0) (XXI) 4

Kih "KE, Kk, cho

And you about Ku F

And And oh

O-E. nn: i no ososn, osos,n. cm and further, if 7 4 represents a radical of the general formula (XXII), that is, when the compound of the general formula (XXIII) is identical to the compound of the general formula (M), the replacement of the protective groups designated as Ke and/or Ko and K7 by hydrogen atoms under the above conditions.

Of course, treatment with activated Raney nickel is carried out in the presence of aliphatic alcohol at a temperature from -107C to 60"C.

According to the invention, the compound of the general formula (XXI), in which 74 and K. have the above-mentioned values, can (ee) be obtained by reacting dialkylsulfoxide of the general formula (XXIM): со в в (XXIM)' ; є " 1 E "

K "50 Kk (Ce) in which K' and K" have the above-mentioned values, with the compound of the general formula (XIX).

Usually, the reaction of the sulfoxide of the general formula (XXIM), preferably dimethyl sulfoxide, with the product of the general formula (XIX) is carried out in the presence of a mixture of acetic acid with acetic anhydride or a derivative of acetic acid, such as haloacetic acid, at a temperature from 07C to 50C, preferably around 2570. t s According to the invention, products of the general formula (I), where 7 means a radical of the general formula (I), can be obtained by acting with a compound of the general formula (XII) on a compound of the general formula (XXM): "о (XXUM)

But. 9th century

Kh | 5

F M o - AH narrow (o) x m. 6) be 0 O.K, H - no hm ososn,

Ko) ri osos,H, in which Kl, Kz, K5, Ko and K7 have the above-mentioned values, under the above-mentioned conditions by exposure to the compound 5o of the general formula (XI) and the compound of the general formula (XI), with subsequent replacement of the protective groups K7 or BC

F! and K7 on hydrogen atoms under the aforementioned conditions.

The product of the general formula (XXU) can be obtained by acting with a zinc halide, for example, zinc iodide, or with hydrazine on a compound of the general formula (XXMI1): 60 b5 snyusNnCoo, o (XXM))

K, z, KE, x E, an vu. In ;

OK. yani: o yu NO M ososn, osos,n, in which Ku, Kz, Ko, Kv and K7 have the above-mentioned values.

Usually, the reaction is carried out in an aliphatic alcohol with 1-4 carbon atoms, such as methanol or ethanol, at a temperature from 0"C to 5070.

Products of the general formula (XXMI) can be obtained by reacting with activated Raney nickel in the presence of an aliphatic alcohol with 1-3 carbon atoms on a compound of the general formula (XXMII): ' (XXMII)

Kk

And I thre

E snOsnoo. 000

With t (6) in"

K, - shchi KE, se

Mo; - ra o

K; And 0 (o) b.

О.К. I), based on the compound of the general formula (XXI). "o

Products of the general formula (XXMII) can be obtained by reacting with a sulfoxide of the general formula (XXIM) a compound of the general formula (XXMIP): snoOsn,soo oo) « m o on

K.V. 2

M o x s to with you" GO) 1n- is,

K rud y o i ok /n; o BUT hmm ososn. - osos, n. co in which Ku, Kz, Ko and K7 have the aforementioned values, under the aforementioned conditions for the sulfoxide reaction of the general

Ge | 20 of the formula (XX/IM) with a compound of the general formula (XIX). che Products of the general formula (XXMIII) can be obtained starting from the compound of the general formula (XXIX): (XXIX) sn.osSNn.soo shi 9 0-5tsv

Kk -K, 7 ts 4

M o vovttitot o-V, no-o 60

BUT M OsOsN, osos,n. in which Ku, Kz, Ko and K7 have the above-mentioned values, under the above-mentioned conditions for replacing the silylated groups of the compound of the general formula (XIII) with hydrogen atoms.

Compounds of the general formula (XXIX) can be obtained under the conditions described in the international PCT application UMO 95/11241.

New products of the general formula (I), obtained by carrying out the method according to this invention, can be purified by known methods, such as crystallization or chromatography.

Products of the general formula (I), in which 7 means the radical of the general formula (II), have valuable biological properties.

The biological activity of migo was measured on tubulin extracted from the brain of a pig, according to the method of M. YIM. ZpeiapeKi and others, Rhos. May Asai. All together. OBA, 70, 765-768 (1973). The study of depolymerization of 70 tubulin microtubules was carried out according to the method of S. Spatsimiege et al. S. K. Asai. 5si., 293, series II, 501-503 (1981). In these experiments, the products of general formula (I) in which 7 represents the radical of general formula (I) proved to be at least as active as taxol and taxotere.

In i.p. mimo studies, products of general formula (I) in which 7 is a radical of general formula (I) have been shown to be active in mice transplanted with B16b melanoma at doses of 1 to 1 ug/ml by 7/5 intraperitoneal administration, and also on other liquid and solid tumors.

The new products have antitumor activity, more specifically, activity against tumors that are resistant to taxol or taxotere?F. Such tumors include colon tumors that have increased expression of the gene and (multidrug resistance gene). Multidrug resistance is a common term that means resistance of a tumor to medicinal products of different structures and different mechanisms of action. Taxoids are generally known to be highly recognized by experimental tumors, such as RZ88/0OX, a doxorubicin (OX)-resistant cell line characterized by gene overexpression and 1.

The following examples illustrate the present invention.

Example 1 ch 25 243mMg of 4o-acetoxy-2o-benzoyloxy-5f,20-epoxy-1p-hydroxy-7D-methoxy-9-oxo-10p-(pyrid-3-yl-carbonyl)oxy-tax- 11-en-1Zo-yl-(2K,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate is dissolved in 4.5 ml of 0.1N solution of hydrogen chloride in ethanol. The solution obtained in this way is stirred at a temperature of about 207C for 3 hours, then 25 cm3 of dichloromethane is added to it. The organic phase with 30 is separated by decantation and washed at least 2 times with a saturated aqueous solution of sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40°C. 290 mg of a light white mass are obtained , which is purified by thin-layer co-chromatography on silica gel | mm gel layer on 20x20 cm plates, eluent: a mixture of dichloromethane and methanol in a water/r volume ratio of 95:5 | fractions of 8 Ω (4 plates). After localization using 3o UV irradiation - by the rays of the adsorption zone of the target product, the silica gel is scraped and washed through a fritted glass, ee, 10 cm? of ethyl acetate. The filtrates are combined, concentrated to dryness under reduced pressure (2.7 KPa) at 20"С. A precipitate is obtained in the form of a light white mass, which is purified by chromatography (2 plates: 20x20 cm x!mm, eluent: a mixture of dichloromethane and methanol in a volume ratio of 95:5). Thus, 297 mg of -o-4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p-hydroxy-7D-methoxy-9-oxo-10p-(pyrid-3-yl-carbonyl)coxy -tax-11-ene-13 y-yl-(2K,35)-3-tert.-butoxycarbonylamino-2-hydroxy-3-phenyl-propionate in the form of a light mass of white color, which has the following characteristics: - rotational ability : Fo - -34"(c - 0.5; methanol); 45 TN-NMR spectrum (30 OMHCs; deuterochloroform; chemical shifts 5 ppm (ppm); binding constants

Ф У in Hz): 1.30 (s, ЗН: -СНз in position 16 or 17), 1.35 | (c, 12Н: -СН»z in position 16 or 17 and -С(СНУ3)з1 | 1-75 (с, - ЗН: -СНУ), 1.82 and 2.77 (mts, 1Н each: -СНо-in position 6 ), 1.97 (s, ЗН: -СН»з), 2.35 (d, У - 9, 2Н: -СНо- in position 14), 2.39 (s, ЗН: -СОСН»), 3.38 (d, у) - 5, 1H: -OH- in position 2), 3.42 (s, ЗН: -ОСН»), 3.88 (d, У - bo 7.5, 1Н: -Н in position 3), 3.96 (dd, у - 11 and 7.5 , 1Н: -Н in position 7), 4.18 and 4.32 (2d, 9 - 8.5, 1Н each: (ос) 20 -СНо- in position 20), 4.64 (mt, 1ТН: -Н in position 2), 4.98 ( ush.d, 9) - 10, 1H: -H in position 5), 5.28 (ush.d, y) - 10, 1H: -H in position 3), 5.39 (d, 9 - 10, 1H: -СОМН -), 5.70 (d, 9) - 7.5, 1H: -H in position 2), with 6.22 (ush.t, U 2 9, 1H: -H in position 13), 6.69 (s, 1H: -H in position 10), 7.25-7.45 (mt, 5H: -SeN in position

З), 7.44 |dd, У - 8.5 and 6, 1Н: -ОСОСБ5НАМ (-Н in position 5)), 7.50 |д, У -7.5, 2Н: -ОСОС»Н5 (-Н in position З and -Н in position 5), 7.62 |t, У - 7.5, 1ТН: -ОСОС»Н5 (-Н in position 4)), 8.12 |d, У - 7.5, 2Н: -0ОСОС»Нь (-Н in position 2 and -Н in position 6)), 8.35 |dt, U - 8.5 and 1, 1TN: -ОСОСБН,М (-Н in position 4))|, 8.82 |dd, U - 6 and

ГФ) 1, T/N: -ОССОСБН,М (-Н in position b)), 9.32 |d, У - 1, IN: - ВБОСОСБНАМ (-Н in position 2)). 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p-hydroxy-7p-methoxy-9-oxo(pyrid-3-yl-carbonyl)-10p-oxy-tax-11-ene-13 y, vo -yl-(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate can be obtained as follows:

To a solution of 4 mg of Z-pyridine-carboxylic acid in 25 cm? of anhydrous ethyl acetate in an argon atmosphere, with stirring, at a temperature of about 2076, add 290 mg of 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p,10p-dihydroxy-7p-methoxy-9-oxo-tax-11-ene- 13 g of sulf-(2K45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate, 18.5 mg of 4-methylaminopyridine, O, 5 g of molecular sieve 4 A and 112 mg of M,M'-bicyclohexylcarbodiimide. The reaction mixture is stirred for 16 hours at a temperature of about 207C, then 4 mg of 2-pyridine-carboxylic acid, 18.5 mg of 4-dimethylaminopyridine, 0.5 g of molecular sieve 4 A and 112 mg of M,M'-bicyclohexylcarbodiimide are added and stirred again for 24 hours; the cycle is repeated 2 more times. The reaction mixture is filtered through

Fritted glass containing cylite. Fritted glass is washed 2 times in 5Osm? of ethyl acetate, the filtrates are combined, washed at least 2 times in 10 cm? of a saturated aqueous solution of sodium bicarbonate and b times in 20 cm? of distilled water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 407s. In this way, 298 mg of 4o-acetoxy-2o-benzoyloxy-5p3,20-epoxy-1p-hydroxy-7D-methoxy-9-oxo(pyrid-3-yl-carbonyl)-10 Dd 70. -oxy-tax- 11-ene-139, -yl-(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in the form of a light mass of white color 4o-acetoxy-2o-benzoyloxy-5f,20-epoxy-1rf,10p-dihydroxy-7D-methoxy-9-oxo-tax-11-en-13o; -yl-(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate can be obtained as follows:

To the solution 150 mg of 4o-acetoxy-2o-benzoyloxy-5f8,20-epoxy-1p-hydroxy-7D-methoxy-10p-methoxyacetoxy-9-oxo-tax-11-ene-13o; -yl-(2kK,45.5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in 4 cm3 of anhydrous ethanol in an argon atmosphere, stirring, at at a temperature of about 20" add 0.263 cm³ of hydrazine monohydrate dropwise. The reaction mixture is stirred for 1 hour at a temperature of about 202C, then poured into a mixture of 100 cm³ of ethyl acetate and 50 cm³ of distilled water. The organic phase is separated by decantation and the aqueous phase is extracted twice with 5 cm³ of ethyl acetate. the phases are combined, washed 4 times in Bosm? distilled water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7kKPa) at 40"C. 18Omg of a light white mass is obtained, which is purified by thin-layer chromatography on silica gel (mm gel layer on 20x20cm plates, eluant: a mixture of dichloromethane and methanol in a volume ratio of 90:10) in fractions of 9Omg (2 plates). After localization in the UV rays of the adsorption zone of the target product, the silica gel is scraped and washed on fritted glass 10 times for 10cm? ethyl acetate. The filtrates are combined and concentrated to dryness under reduced pressure (2.7 KPa) at 40"C. In this way, 113 mg of 4o-acetoxy-2o-benzoyloxy-5rf3,20-epoxy-1B, 10rD-dihydroxy-7p are obtained -methoxy-9-oxo-tax-11-ene-13 o, -yl-(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3- oxazolidine-5-carboxylate in the form of a light mass of white color. 11-Jan-13 about

Zo-yl-(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate can be obtained in the following way:

To a solution of 1.041 g of 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p-hydroxy-10p-methoxyacetoxy-7 dD-methylthiomethoxy-9-oxo-tax-11-e" du n-1Zo-yl- (2k,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in 100 cm3 of anhydrous ethanol in an argon atmosphere, stirring, at a temperature at about 20C, add 100 cm3 of a suspension of Raney-activated nickel in ethanol (obtained from 8Osm? 50965 commercial aqueous suspension by washing 15 times in 100 cm C of distilled water and 4 times in 150 cm? of ethanol to a pH value of about 7).

The reaction mixture is stirred for 7 days at a temperature of about 20°C, then filtered on fritted glass. The fritted glass is washed three times with 100 ml of ethanol, the filtrates are combined and concentrated to dryness under (22) reduced pressure (2.7 kPa) at 40 WITH. 821 mg of a light white mass is obtained, which is purified by chromatography on 75 g of silicon dioxide (0.063-0.2 mm), which is in a column with a diameter of 2.5 cm (eluent: a mixture of dichloromethane and ethyl acetate in a volume ratio of 90:10), collecting fractions of 5 cm?. Fractions containing only the target product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 402C. bo 020 In this way, 228 mg of 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p-hydroxy-7D-methoxy-10p-methoxyacetoxy-9-oxo-tax-11-ene-13o, iz -yl -(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in the form of a light mass of white color. 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1 pD-hydroxy-10D-methoxyacetoxy-7 VD 59 -methylthiomethoxy-9-oxo-tax-11-ene-13 o, (F)-yl-(2kK ,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate can d) be obtained as follows:

To a solution of 5g of 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p, 7D-dihydroxy-10dD-methoxyacetoxy-9-oxo-tax-11-ene-13o; -yl-(2kK,45.5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in 165 cm3 of anhydrous dimethyl sulfoxide in an argon atmosphere, stirring, at at a temperature of about 207"C, add 3.3 BcmO of acetic acid and 11.5 cm? of acetic anhydride. The reaction mixture is stirred for 3 days at a temperature of about 202C, then poured into 500 cm? of dichloromethane. While stirring well, add 65 100 cm of a saturated aqueous solution of potassium carbonate to pH value about 7. After 10 minutes of stirring, the organic phase is separated by decantation and the aqueous phase is extracted twice with 250 ml of dichloromethane. The organic phases are combined, washed three times with 100 ml of distilled water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 407"С. 9.5 mg of a pale yellow oily substance is obtained, which is purified by chromatography on 250 g of silicon dioxide (0.063-0.4 mm) in a column with a diameter of 3 cm (eluent: a mixture of dichloromethane and methanol in a volume ratio of 99:1), collecting fractions of 5Osm?. Fractions containing only the target product are combined and concentrated to dryness under reduced pressure (2.7kPa) at 407s. In this way, 3.01 g of 4o-acetoxy-2o-benzoyloxy-5p3,20-epoxy-1r-hydroxy-10rD-methoxyacetoxy-7D-methylthiomethoxy-9-oxo-tax-11-ene-13o, 70 are obtained. yl-(28,45,58)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in the form of a light mass of white color. 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p, 7D-dihydroxy-10dD-methoxyacetoxy-9-oxo-tax-11-ene-13o; -yl-(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate can be obtained as follows:

To a solution of 20 g of 4o-acetoxy-2o-benzoyloxy-5f8,20-epoxy-7D-triethylsilyloxy-1p-hydroxy-10dD-methoxyacetoxy-9-oxo-tax-11-en-1Zo-yl-(2K,45 ,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in 200 cm? of anhydrous dichloromethane in an argon atmosphere, with stirring, at a temperature of about 07C, add 220 cm3 of the complex triethylamine-hydrofluoric acid in a molar ratio of 3:1. The reaction mixture is heated to a temperature of about 20"C, after three hours of incubation at this temperature, the mixture is poured into 4 liters of a saturated aqueous solution of sodium bicarbonate. In this way, the pH value of the medium is brought to about 7. After stirring for 10 minutes, the organic phase is separated by decantation, and then the aqueous phase is extracted twice with 100 cm? of dichloromethane. The organic phases are combined, washed with 100 cm? of distilled water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 407 s. In this way, 17 4 g and) 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p,7o-dihydroxy-10p-methoxyacetoxy-9-oxo-tax-11-ene-13o,-yl-(2kK,45,5K)-3 -tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in the form of a light mass of white color. c 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-7 p-triethylsilyloxy-1 p-hydroxy-1oD co-methoxyacetoxy-9-oxo-tax-11-en-13 9, -yl-(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4- methoxyphenyl)-4 -phenyl-1,3-oxazolidine-5-carboxylate can be prepared under the conditions described in the international PCT application UUO 95/11241. "-

Example 2

According to the methodology of example 1, but based on Kk! 210 mg is), da-acetoxy-2o-benzoyloxy-5820-epoxy-1 p-hydroxy-7 p-methoxy-9-oxo-10B-(pyrid-2-yl-carbonyl)oxy-tax-11-e n- 1Zo-yl-(2k,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate, 145 mg of di 4o-acetoxy-2o -benzoyloxy-5p,20-VPOKOP-1B-hydroxy-7B-methoxy-9-OXO-10B-(pyrid-2-yl-carbonyl)oxy-tax- z 11-en-1Zo-yl-(2K,35) -3-tert.-Otoxycarbonylamino-2-hydroxy-3-phenyl-propionate in the form of a light mass of white c color, which has the following characteristics: -» - rotatability: хо - -52"(c - 0.5; methanol);

TN-NMR spectrum (400MHz; deuterochloroform; chemical shifts 5 ppm); binding constants.) in Hz): 1.31 (s, ЗН: -СНу3 in position 16 or 17), 1.37 Ks, 12Н: -СНуз in position 16 or 17 and -С(СН3з)з1, 1-74 (s , 1H: -OH in

Me position 1), 1.78 (s, ZN: -CH»3) / 1.82 and 2.78 (2mts, 1H each: -CH»o- in position 6), 1.97 (s, ZN: -CH»z), 2.35 (d, - У 9, 2Н: -СНо- in position 14), 2.40 (s, ЗН: -СОСН»), 3.40 (d, У - 4.5, 1Н: -ОН- in position 2), 3.43 (s ,

ЗН: -ОСНЗз), 3.92 (d, 9У - 7.5, 1Н: -Н in position 3), 3.98 dd, 9) - 11 and 7, 1Н: -Н in position 7), 4.20 and

Со 4.32 (2d, 9 - 8.5, 1ТН each: -СНо- in position 20), 4.64 (mt, 1Н: -Н in position 2, 5.00 (ush.d, у) - 10, 1Н: at 20 -Н in position 5), 5.28 (ush.d, 9 - 10, 1H: -H in position 3), 5.43 (d, 9) - 10, 1H: -СОМН-), 5.73 (d, 9 - 7.5, 1H: - Н in position 2), 6.22 (ush.t, U - 9, 1Н: -Н in position 13), 6.67 (s, 1Н: -Н in position 10), with 7.25-71.45 (mt, 5Н: -СбН in position 3), 7.51 |mt, ЗН: -ОСОСНЙ (-Н in position З and -Н in position 5) and -ОСОСБНАИМ (-Н in position 5)), 7.61 (t, У - 7.5, 1ТН: -ОСОСНЙ5 ( -H in position 4)), 7.88 (t, - 81 1, 1H: -OSOSBNAM (H in position 4), 8.12 |d, U - 7.5, 2H: -OSOS»H5 (-H in position 2 and -H in position 6)|, 8.20 29 (Ush.d, U - 8, 1H: -OSOSBNA,M (-H in position 3)|, 8.82 (Ush.dd, U) - 5 and 1, 1H: -OSOSBNAM ( -H in position 6).

GF) According to the methodology of example 1, but based on Kk! ZOOmg t 4o-acetoxy-2o-benzoyloxy-5p,20-epoxy-1p,10p-dihydroxy-7p-methoxy-9-oxo-tax-11-ene-13o,-yl-(2kK,45.5K )-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate, 230 mg of 4o-acetoxy-2o-benzoyloxy-58,20-epoxy-1B- hydroxy-7B-methoxy-9-OXO-108-(pyrid-2-yl-carbonyl)oxy-tax-11-en-1Zo-yl-(2K,45,5K)-3-tert.-butoxycarbonyl-2- (4-Methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate in the form of a light mass of white color.

Example C 65 According to the methodology of example 1, but based on Kk! ZOOmg 4o-acetoxy-2A-benzoyloxy-108-cyclopentylcarbonyloxy-58,20-epoxy-1B-hydroxy-7B-methoxy-9-OXO-Tax-1

1-ene-13A-yl-(2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate, 9bmg of 4u-acetoxy -2o-benzoyloxy-108-cyclopentylcarbonyloxy-58,20-epoxy-1B-hydroxy-7B-methoxy-9-oxo-oxy-so 8500060-11-en-13A-yl-(2K,35)-3-tert. -butoxycarbonylamino-2-hydroxy-3-phenyl-propionate. In the form of a light mass of white color, which has the following characteristics: - rotational capacity: Fo - -667 (s - 0.5; methanol);

TN-NMR spectrum (400 MHz; deuterochloroform; chemical shifts 5 ppm); binding constants. in Hz): 1.25 70 (s, 6Н: -СНу in positions 16 and 17), 1.39 (Кс, 9Н: -С(СНУ)з) 1-55 - 1.80 and 1.90 - 2.10 (2mts, 4Н each: -CH»- cyclopentyl), 1.71 (s, ТН: -OH in position 1), 1.75 (s, ЗН: -СН3z), 1.82 and 2.75 (2mts, 1Н each: -СНо- in position 6), 1.93 (s . 3.38 (c, ЗН: -ОСН3), 3.40 (d, 9) - 5, 1Н: -ОН- in position 2), 3.88 (d, У - 7.5, 1Н: -Н in position 3), 3.91 (dd, y) - 11 and 7.5, 1Н: -Н in position 7), 4.19 and 4.32 (2d, У - 8.5, 1Н each: -СНо- in 75 position 20), 4.65 (mt, 1Н: -Н in position 2) . -СОМН-), 5.68 (d, 9У - 7.5, 1Н: -Н in position 2), 6.21 (ush.t, у) 2 9, 1Н: -Н in position 13), 6.45 (s, 1Н: -Н in position 10), 7.25-7.45 (mt, 5Н: -СеН in position 3), 7.51 (g, У 2 7.5, 2Н: -ОСОСН5 (-Н in position З and -Н in position 5)), 7.63 |t , U - 7.5, 1Н: -ОСОСН5 (-Н in half 4)|, 8.12 Id, in 2 7.5, 2H: -POSOS»Nb (-H in position 2 and -H in position 6)).

According to the methodology of example 1, but based on Kk! ZOOmg 4o-acetoxy-2o-benzoyloxy-5f8,20-epoxy-1D,10B-dihydroxy-7B-methoxy-9-oxo-tax-11-ene-13o,-yl-(2kK,45,5K)- 3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate, obtain a410 mg of 4o-acetoxy-2o-benzoyloxy-10p-cyclopentylcarbonyloxy-5p,20-epoxy -1o-hydroxy-7u-methoxy-9-oxo-tax-11-e with 285 H-1Zo-yl-(2Kk,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)- 4-phenyl-1,3-oxazolidine-5-carboxylate, in the form of a light mass of white color. at

Example 4

According to the methodology of example 1, but based on Kk! ZOOmg 4o-acetoxy-2o-benzoyloxy-10D-cyclopropylcarbonyloxy-5p,20-epoxy-1p-hydroxy-7p-methoxy-9-oxo-tax-11-ene-139, so -yl-( 2kK,45,5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate, get 130 mg of 4y-acetoxy-2A-benzoyloxy-10B-cyclopropylcarbonyloxy -5B,20-epoxy-1B-hydroxy-7B-methoxy-9-OXO-OXY-tT - ax-11-en-1Zo-yl-(2kK,35)-3-tert.-butoxycarbonylamino-2-hydroxy- 3-phenyl-propionate in the form of a light mass of white color, which has the following characteristics: i-oi - rotational capacity: (93295 - -712 (c - 0.5; methanol);

TN-NMR spectrum (400 MHz; deuterochloroform; chemical shifts 5 ppm); binding constants. in Hz): 1.00 and 1.19 (2mts, 2H each: -СНо cyclopropyl), 1.25 (s, ЗН: -СН3 in position 16 or 17), 1.27 (s, ЗН: -СН3 in « position 16 or 17), 1.39 | (c, 9Н: -С(СН»)z) 1.71 (c, 1Н: -OH in position 1), 1.75 (c, ЗН:-СН3), 1.70-1.90 (mt, shu с 1Н: -CH-cyclopropyl), 1.82 and 2.75 (2mts, 1H each: -CH»o- in position 6), 1.93 (c, ЗН: -CH3z), 2.33 (d, U - 9, . 2H: -СН»о- in position 14), 2.40 (s, ЗН: -СОСН»У), 3.35 (s, ЗН: -ОСН»), 3.40 (d, 9 - 5, 1Н: -ОН- in position 2) , and? 3.88 (d, 9 - 7.5, 1H: -H in position 3), 3.89 (dd, 9) - 11 and 7.5, 1H: -H in position 7), 4.19 and 4.32 (2d, 5 - 8.5, 1H each: -СНо- in position 20), 4.65 (mt, 1Н: -Н in position 23, 5.00 (уш.д, у) - 10, 1Н: -Н in position 5), 5.28 (уш.д, ) - 10, 1H: -H in position 3), 5.42 (d, U - 10, 1H: -СОМН-), 5.68 (d, 9U - 7.5, 1H:

He» -H in position 2), 6.21 (ush.t, U 2 9, 1H: -H in position 13), 6.48 (s, 1H: -H in position 10), 7.25-7.45 (mt, 5H: - SeNe in position 3), 7.52 |t, y - 7.5, 2Н: -ОСОС»НБ5 (-Н in position З and -Н in position 5)), 7.64 (t, У - 7.5, 1Н: - -ОСОС NB ( -H in position 4)), 8.12 |d, U 2 7.5, 2H: - OSOS»H5 3-H in position 2 and -H in position 6).

Go! According to the methodology of example 1, but based on Kk! ZOOmg 4o-acetoxy-2A-benzoyloxy-58,20-epoxy-18,10 p-dihydroxy-7 dD-methoxy-9-oxo-tax-11-ene-1Z o; so -yl-(2kK,45.5K)-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate is obtained

Kz 435 Mmg 4o-acetoxy-2o-benzoyloxy-10p-cyclopropylcarbonyloxy-58,20-epoxy-1B-hydroxy-7B-methoxy-9-oxo-tax-11-e n-1Zo-yl-(2k,45,5K )-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate, in the form of a light mass of white color.

Gee! Example 5

According to the methodology of example 1, but based on Kk! A4ZomMg where d4a-acetoxy-2A-benzoyloxy-58,20-epoxy-1B-hydroxy-7B-methoxy-10B-methoxyacetoxy-9-oxo-tax-11-ene-13 9, -yl-(2kK,45.5K )-3-tert.-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate, obtain 60 164 mg of 4o-acetoxy-2o-benzoyloxy-58,20-epoxy-1B- hydroxy-7B-methoxy-10B-methoxyacetoxy-9-OXO-tax-11-ene-13 o, -yl-(2kK,35)-3-tert.-butoxycarbonylamino-2-hydroxy-3-phenyl-propionate in the form light mass of white color, which has the following characteristics: 65 - rotational capacity: хо - -487 (с - 0.5; methanol);

TN-NMR spectrum (ZOOMHz; deuterochloroform; chemical shifts 5 ppm); binding constants .) in Hz): 1.17

(с, ЗН: -СНУз),, 1.22 (с, ЗН: -СН»з), 1.35 (с, 9Н: -С(СНЗ)з)| 1-75 (s, ЗН: -СНУ), 1.82 and 2.75 (2mts, 1Н each: -СНо- in position 6), 1.90 (s, ЗН: -СН»), 2.30 (d, У - 9, 2Н: -СНо- in position 14), 2.37 (s, ЗН: -СОСН»), 3.35 and 3.55 (2s, ЗН each: -ОСН»з), 3.40 (d, У - 5, 1Н: -ОН- in position 2 ), 3.85 (d, 9U - 7, 1H: -H in position 3), 3.88 (dd, y - 11 and 7, 1H: -H in position 7), 4.17 and 4.32 (2d, 3 - 8.5, 1H each : -СНо- in position 20), 4.19 and 4.27 (2d, 9) - 15, 1Н each: -"ОСОСНООСН") , 4.65 (mt, 1Н: -Н in position 2), 4.97 (ush.d, U - 10, 1H: -H in position 5), 5.25 (ush.d, 9) - 10, 1H: -H in position 3), 5.42 (d, 9) - 10, 1H: -СОМН-), 5.66 (d . mt, 5H: -SeNe in position 3), 7.51 (t, y - 7.5, 2H: -ОСОС»НЬ5 (-Н in position З and -Н in position 5)), 7.63 (t, У - 7.5, 1Н: 7/0. OSOSc Hv (-H in position 4)), 8.12 |d, y - 7.5, 2H: -OSOS»Nv (-H in position 2 and -H in position 6)).

New products of the general formula (I), in which 7 represents a radical of the general formula (II), exhibit significant inhibitory activity in relation to abnormal cell proliferation and have therapeutic properties that allow the treatment of diseases with pathological conditions that are associated with abnormal cell proliferation .

Pathological conditions are abnormal proliferation of malignant or non-malignant cells of various tissues and/or organs, which include, among others, muscle, bone or connective tissue, skin, brain, lungs, genitals, lymphatic or renal systems, mammary cells glands or blood cells, liver, digestive organs, pancreas and thyroid gland or adrenal glands. These conditions may also include psoriasis, solid tumors, ovarian, breast, brain, prostate, colon, stomach, kidney, or testicular cancers, Kaposi's sarcoma, cholangiocarcinoma, choriocarcinoma, neuroblastoma, Wilms' tumor, Hodgkin's disease, melanoma, multiple myeloma, lymphocytic chronic leukemia, granulocytic acute or chronic lymphomas. The new products according to the invention are particularly suitable for the treatment of ovarian cancer. Products according to the invention can be used to prevent or slow down the occurrence or recurrence of pathological conditions or to treat these pathological conditions.

The products according to the invention can be administered to the patient in various forms that are suitable for the chosen route of administration, the best of which is the parenteral route. The parenteral route of administration includes intravenous, intraperitoneal, intramuscular or subcutaneous administration. The best are i) intraperitoneal and intravenous routes of administration.

The present invention also relates to pharmaceutical compositions containing at least one product of the general formula (I), in which 7 is a radical of the general formula (II), in an effective amount suitable for use in human or animal therapy. The compositions are prepared by conventional methods, using one or more additives, seeds or excipients that are fPharmaceutically acceptable. Suitable carriers include co-diluents, sterile aqueous media, and a variety of non-toxic solvents. The best forms for co-compositions are aqueous media or suspensions, solutions for injections, which may contain emulsifiers, dyes, preservatives or stabilizers. --

The choice of additives or excipients depends on the solubility and chemical properties of the product, the specific method of administration and established pharmaceutical practice.

Sterile aqueous or non-aqueous solutions or suspensions are used for parenteral administration. Natural vegetable oils such as olive oil, sesame oil or paraffin oil or complex organic esters for injection such as ethyl oleate can be used to make non-aqueous solutions or suspensions. "

Sterile aqueous solutions can be a solution of a pharmaceutically acceptable salt in water. Aqueous solutions with c are suitable for intravenous administration, provided that the necessary pH value is established and its isotonicity is ensured, for example, with the help of sodium chloride or glucose. Sterilization can be performed by: heating or any other method that does not impair the properties of the composition.

Of course, all products included in the composition according to the invention must be pure and non-toxic in the quantities used.

Ф The compositions may contain at least 0.0195 therapeutically active product. The amount of active product in the composition is such that the required dosage can be prescribed. In the best case, the compositions are obtained in such a way that a single dose contains about 0.01-4000 mg of the active product for parenteral administration.

Therapeutic treatment can be carried out simultaneously with other therapeutic treatment, which includes the use of cytostatic drugs, monoclonal antibodies, immunological therapy or

X-ray therapy or biological response modifiers. Response modifiers include, but are not limited to, lymphokines and cytokines, such as interleukins, interferons (A, B, or γ), and tumor necrosis factor. Other chemotherapeutic agents suitable for treating disorders resulting from abnormal cell proliferation include, but are not limited to, alkylating agents such as mustard gases, such as mechlorethamine, cyclophosphamide, melphalan, and chlorambucil; alkyl sulfonates such as bisulfan; nitrosoureas such as iF) carmustine, lomustine, semustine and streptozocin; triazenes such as dacarbazine; antimetabolites, such as analogs of folic acid, for example, methotrexate; pyrimidine analogs such as fluorouracil and cytarabine; purine analogs such as mercaptopurine and thioguanine; natural products such as mips alkaloids such as vinblastine, vincristine and vindesine; epipodophyllotoxins such as etoposide and teniposide; antibiotics such as dactinomycin, daunorubicin, doxorubicin, bleomycin, plicamycin and mitomycin; enzymes such as

I -asparaginase; various agents, such as coordination complexes of platinum, for example, as cisplatin; urea derivatives such as hydroxyurea; methylhydrazine derivatives such as prosarbazine; adrenocorticoid suppressors such as adrenocorticosteroids such as prednisone; progestins such as 65 hydroxyprogesterone caproate, methoxyprogesterone acetate and megestrol acetate; estrogens such as diethylstrilbestrol and ethinylestradiol; anti-estrogens such as tamoxifen; androgens such as testosterone propionate and fluoxymesterone.

The doses used for treatment according to the invention are those that allow prevention or maximum therapeutic response. Doses vary depending on the form of administration, the specific product chosen and the characteristics of the subject being treated. In general, doses are those that are therapeutically effective for the treatment of disorders resulting from abnormal cell proliferation. Products according to the invention can be administered as often as necessary to achieve the desired therapeutic effect. Some patients may quickly develop a reaction-feedback to relatively strong or weak doses, after which weak maintenance doses are required or their administration can be abandoned. Usually, weak doses are used at the beginning of treatment and, if necessary, higher and higher doses are introduced until the optimal effect is achieved. In other cases, it may be necessary to administer maintenance doses 1-8 times a day, preferably 1-4 times, depending on the physiological needs of a particular patient. Also, for some patients, it is possible to administer the medicine only twice a day.

For humans, doses are usually 0.01-200 mg/kg. For intraperitoneal administration, doses are usually 0.1-100 mg/kg, preferably 0.5-50 mg/kg, and best 1-10 mg/kg. For intravenous administration, doses are usually 0.1-5mg/kg, better - 0.1-5mg/kg, and best - 1-2mg/kg. It is clear that in order to choose the most suitable dosage, it is necessary to take into account the route of administration, the weight of the patient, his general state of health, his age and all factors that can affect the effectiveness of the treatment. The following example illustrates the composition according to the invention.

Example 40 mg of the product obtained in example 1 is dissolved in a tablespoon of Emulfor EI 620 and a tablespoon of ethanol, then the solution is diluted by adding 18 cm3 of physiological serum.

The composition is administered by perfusion for 1 hour with saline solution. with o

Claims (14)

The formula of the invention 1. Taxoids of the general formula (1): si KE. With co Е. со в и оба ОТ (о (се) Н: НО с: ОоСсОсСН. ососен" " in which с т0 7 means a hydrogen atom or a radical of the general formula (I): 8 and in А р 45 С in which - Ку means benzoyl radical, possibly substituted by one or more, the same or different O atoms or radicals selected from among halogen atoms and alkyl radicals with 1-4 carbon atoms, 5-alkyl radicals with 1-4 carbon atoms or a trifluoromethyl radical; thenoyl or furoyl co radical or Kz radical K.-O-00-, where K" means - alkyl radical with 1-8 carbon atoms, alkenyl radical with 2-8 carbon atoms, alkynyl radical with 3-8 carbon atoms, cycloalkyl radical with 3-6 carbon atoms, a cycloalkenyl radical with 4-6 carbon atoms, a bicycloalkyl radical with 7-10 carbon atoms, and these radicals can be substituted i) by one or more substituents chosen from among halogen atoms and a hydroxyl radical, i) an alkyl radical with 1- 4 carbon atoms, dialkylamino radicals, each alkyl part of which contains 1-4 carbon atoms, a piperidine radical, a morpholino radical, a piperazin-1-yl radical (perhaps because it is substituted in position 4 by an alkyl radical with 1-4 carbon atoms or a phenylalkyl radical, the alkyl part of which contains 1-4 carbon atoms), cycloalkyl radical with 3-6 carbon atoms, cycloalkenyl radical with 4-6 carbon atoms, phenyl radical (possibly substituted by one or more atoms or radicals selected from halogen atoms and alkyl radicals with 1-4 carbon atoms or alkyl radicals with 1-4 carbon atoms), cyano-radical, carboxyl or alkoxycarbonyl, the alkyl 65 part of which contains 1-4 carbon atoms; - phenyl or 27 or io-naphthyl radical, possibly substituted by one or more atoms or radicals selected from among halogen atoms and alkyl radicals with 1-4 carbon atoms or alkyl radicals with 1-4 carbon atoms; - a heterocyclic aromatic five-membered radical, which is chosen among furyl and thienyl radicals; - heterocyclic saturated radical with 4-6 carbon atoms, possibly substituted by one or more alkyl radicals with 1-4 carbon atoms; Kz means a linear or branched alkyl radical with 1-8 carbon atoms; linear or branched 70 alkenyl radical with 2-8 carbon atoms; linear or branched alkynyl radical with 2-8 carbon atoms; cycloalkyl radical with 3-6 carbon atoms; phenyl or 27 or - naphthyl radical, possibly substituted by one or more atoms or radicals selected from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkyl, alkylthio-, aryloxy-, arylthio-, hydroxyl, hydroxyalkyl, mercapto-, formyl, acyl, acylamino-, aroylamino-, t-alkoxycarbonylamino-, amino-, alkylamino-, dialkylamino-, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano-, nitro- and trifluoromethyl radicals; or a heterocyclic aromatic five-membered radical containing one or more identical or different heteroatoms selected from nitrogen, oxygen or sulfur atoms and optionally substituted with one or more identical or different substituents selected from halogen atoms and alkyl, aryl , amino-, alkylamino-, dialkylamino-, alkoxycarbonylamino-. acyl, arylcarbonyl, cyano-, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl or alkoxycarbonyl radicals, provided that the substituents of phenyl, 2 7 or - naphthyl and aromatic heterocyclic radicals, alkyl radicals and alkyl parts of other radicals contain 1-4 carbon atoms , and that alkenyl and alkynyl radicals Ha contain 2-8 carbon atoms, and aryl radicals are phenyl or there are 7 or 4 - naphthyl radicals; o Ku means - alkanoyloxyl radical, the alkanoyl part of which contains 2-6 carbon atoms in a linear or branched chain, with the exception of the acetyl radical, alkenoyloxy radical, the alkenoyl part of which contains 3-6 carbon atoms in a linear or branched chain, alkinoyloxy radical, the alkynyl part of which contains 3-6 carbon atoms in a linear or branched chain, and these radicals can be co-substituted by one or more halogen atoms or an alkyl radical with 1-4 carbon atoms, an alkylthio radical with 1-4 carbon atoms, a carboxyl radical , an alkyloxycarbonyl radical, the alkyl part of which contains 1-4 carbon atoms, a cyano group, a carbamoyl radical, "- M-alkylcarbamoyl radical or M,M-dialkylcarbamoyl, each alkyl part of which contains 1-4 carbon atoms, or together with a nitrogen atom , with which it is connected, forms a saturated five- or six-membered ise) heterocyclic radical, possibly containing a second heteroatom, selected from oxygen, sulfur or nitrogen atoms, possibly substituted by an alkyl radical with 1-4 carbon atoms or a phenyl radical or a phenylalkyl radical, the alkyl part of which contains 1-4 carbon atoms; « - cycloalkanoyloxyl radical, the cycloalkanoyl part of which contains 4-8 carbon atoms; or a cycloalkenoyloxy radical, the cycloalkenoyl part of which contains 4-8 carbon atoms; C is a benzoyloxy radical or a heterocyclylcarbonyloxy radical, the heterocyclic part of which is an aromatic "» five- or six-membered heterocycle containing one or more heteroatoms, which are selected from the atoms of "oxygen, sulfur, or nitrogen; K5 means - an alkyl radical with 1-6 carbon atoms in a linear or branched chain (possibly substituted Me. alkyl radical with 1-4 carbon atoms), alkenyloxy radical with 3-6 carbon atoms, - alkynyloxy radical with 3-6 carbon atoms, cycloalkoxy radical with 3-6 carbon atoms, cycloalkenyloxy radical with 3-6 carbon atoms , and these radicals can be substituted by one or more halogen atoms or an alkyl radical with 1-4 carbon atoms, an alkylthio radical with 1-4 to 20 carbon atoms, a carboxyl radical, an alkyloxycarbonyl radical, the alkyl part of which contains 1-44 carbon atoms , a cyano group, a carbamoyl radical, an M-alkylcarbamoyl radical or a r» M,M-dialkylcarbamoyl radical, each alkyl part of which contains 1-4 carbon atoms, or together with the nitrogen atom to which it is connected, forms a saturated five - or a six-membered heterocyclic radical optionally containing a second heteroatom selected from oxygen, sulfur or nitrogen atoms, optionally substituted by a 22 alkyl radical of 1-4 carbon atoms or a phenyl radical or a phenylalkyl radical kalom, GF) whose alkyl part contains 1-4 carbon atoms. 2. Taxoids according to claim 1, where 7 means a hydrogen atom or a radical of the general formula (II), in which K/ means a benzoyl radical or a K»-0O-CO- radical, where Ko means a tert-butyl radical and Kz means an alkyl radical with 1-6 carbon atoms, an alkenyl radical with 2-6 carbon atoms, a cycloalkyl radical with 3-6 60 carbon atoms, a phenyl radical, possibly substituted by one or more, the same or different atoms or radicals selected from halogen atoms and alkyl , alkyl, dialkylamino, acylamino, alkoxycarbonylamino, or trifluoromethyl radicals, or a 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl radical; and Ku; means the alkyloxyacetoxy radical, the alkyl part of which contains 1-4 carbon atoms, the cycloalkanoyloxyl radical, because the cycloalkanoyl part of which contains 4-8 carbon atoms, the pyridylcarbonyloxyl radical; and K5 means a linear or branched alkyl radical having 1-6 carbon atoms. C. Taxoids according to claim 1, where 7 means a hydrogen atom or a radical of the general formula (II), in which K 4 means a benzoyl radical or a radical Co»-0O-CO-, where Co means a tert-butyl radical, and Kz means isobutyl, an isobutenyl, butenyl, cyclohexyl, phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl or 5-thiazolyl radical; K,; means a methoxyacetoxy-, cyclopropylcarbonyloxy-, cyclopentylcarbonyloxy-, pyridyl-2-carbonyloxy- or pyridyl-3-carbonyloxy radical; Yes; is a methoxy radical. 4. The method of obtaining taxoids described in any of claims 1, 2 or 3, where 7 means a radical of the general 7/0 formula (II), which differs in that it esterifies the product of the general formula (II): Е, о 4 ВЕ . non Ц т шеше: " Not NO: OSOSN. Oososn. in which K; and K5 have the values indicated in any of claims 1, 2 or З, acting with an acid of the general formula (IM): E Cr. Го г» Vi to SON o О-Е in which K/u Kz have the above values, and either K 5 means a hydrogen atom, and K7 means a protective group for the hydroxyl function, or Ke and K7 together form a saturated five- or six-membered heterocycle, or with a derivative of this acid to obtain a complex ether of the general formula (M): in not BUT: OSOSN» osOosen. " in which K., Kz, Ku, Kv, Ko and K7 have the above values, with subsequent replacement of protective groups K7 and/or Ke with c and K7 hydrogen atoms. 5. The method according to claim 4, which differs in that esterification is carried out with the help of common acid. NO - . and formulas (IM) in the presence of a condensation agent and an activation agent in an organic solvent at a temperature from -107C to 9076. 6. The method according to claim 4, which differs in that the esterification is carried out with the help of an acid of the general formula (IM) in the form of a symmetrical anhydride, working in the presence of an activating agent in an organic solvent at a temperature from 0"C to 9070. - 7. The method according to claim 4, which is distinguished by the fact that esterification is carried out with the help of common acid Ho! of the formula (IM) in the form of a halide anhydride or in the form of a mixed anhydride with an aliphatic or aromatic acid, possibly obtained by ipsi, in the presence of a base, working in an organic solvent at a temperature from 0"C to 80". Ge 8. The method according to claim 4, which differs in that the replacement of protective groups K; and/or Co.; and K, hydrogen atoms are carried out, depending on their nature, as follows: 1) when Ke means a hydrogen atom and K7 means a protective group for the hydroxyl function, the replacement of protective groups OV with hydrogen atoms is carried out with the help of an inorganic or organic acid, using it individually or in the form of a mixture, working in an organic solvent chosen from among alcohols, simple and complex F) ethers, aliphatic hydrocarbons, aliphatic halogenated hydrocarbons, aromatic hydrocarbons or nitriles, at a temperature from -107C to 60"C; 2) when Kb and K7 together form a saturated five- or six-membered heterocycle of the general formula (MI): 60 - to SL) 65 | шо | Y where Ku has the above value, Ka and Ko, the same or different, denote a hydrogen atom or an alkyl radical from 1 -4 carbon atoms, or an aralkyl radical, the alkyl part of which contains 1-4 carbon atoms, and the aryl part mainly means a phenyl radical, possibly substituted by one or more alkyl radicals with 1- 4 carbon atoms, or an aryl radical, which means a phenyl radical, possibly substituted by one or more alkyl radicals with 1-4 carbon atoms; or Ka represents an 1-4 carbon alkyl radical or a trihalomethyl radical such as trichloromethyl or a phenyl radical substituted with a trihalomethyl radical such as trichloromethyl and Co represents a hydrogen atom, or Ka and Co together with a carbon atom with which they are connected, form a 4-7-ene cycle, a protective group formed by radicals K" and K7, replaced by hydrogen atoms, depending on the values of K., Pv, and Ko, in the following way: 70 a) when K; represents a tert-butoxycarbonyl radical, Ka and Co, whether the same or different, represent an alkyl radical or an aralkyl radical or an aryl radical, or Ka represents a trihalomethyl radical or a phenyl radical substituted with a trihalomethyl radical, and Co represents a hydrogen atom, or Ka and Co together form 4 -7--len cycle, complex ester of the general formula (M) is treated with an inorganic or organic acid, if necessary in an organic solvent, such as alcohol, to obtain a product of the general 7/5 formula (MII): Kk, o in nm o 5 and that F Schell 7 bn : 9 no ves Ososn, 5 I s de Kz, Ku and K5 have the above values, which are acylated with the help of benzoyl chloride, in which the phenyl nucleus is possibly substituted, i) thenoyl chloride, furoyl chloride or a product of the general formula (MIP): k.-0-СО0-х , Сли) where Ko has the above value, and X means a halogen atom or a group -О-Ко or -0-СО-О-К», with obtaining a product of the general formula (I), where 2 means the radical of the general formula (I); co b) when Ku means a possibly substituted benzoyl radical, thenoyl radical or furoyl radical, or the radical K»O-CO-, in which Ko has the above meaning, Ka means a hydrogen atom or an alkyl radical co with 1-4 carbon atoms or phenyl radical substituted by one or more alkoxyl radicals with 1-4 -/ where carbon atoms, and Ko means a hydrogen atom, the replacement of the formed Ko and K7 protective group with hydrogen atoms is carried out in the presence of an inorganic or organic acid, using it individually or in a mixture, in ise) of a stoichiometric or catalytic amount, working in an organic solvent chosen from among alcohols, simple and complex esters, aliphatic hydrocarbons, aliphatic halogenated hydrocarbons and aromatic hydrocarbons, at a temperature from -107C to 60"7C. " 9. The method of obtaining the taxoid described in any of claims 1, 2 or 3, in which 7 means a hydrogen atom, K 4 is defined in any of claims 1, 2 or 3, and K»5 is defined in any which of claims 1, 2 or C, which differs in that 10-desacetyl-baccatin-IIII formula (IX): z» no o on (o) NaOee-e / СО - 13 pu I in; so NO: osOsn, because o OoSsOosen. Ge is treated with a silyl halide of the general formula (X): (Vdy-ya-Nai СО in which K, the same or different, means an alkyl radical with 1-4 carbon atoms, possibly substituted by 29 phenyl radical, a cycloalkyl radical with 3-6 carbon atoms or phenyl radical, and obtain HF) a product of the general formula (XII): in which K has the above-mentioned value, which is then treated with the product of the general formula (XII): 1, 2 or C values, and X/ represents a halogen atom, to obtain the product of the general formula (XII): Kk 9 O-VKV). other No BUT: OSOSN, OSOSUn. no in which KE and Ku have the above-mentioned values, followed by replacement of the silylated protective groups of the obtained compound with hydrogen atoms, obtaining a product of the general formula (CHM): EK, o Z On non) | that's me. (9) "NOT сч в на: ОСсОСсН" about ОосОосен, in which K. has the above-mentioned value, which is selectively esterified in position 7, acting as a product of the general formula (ХМ): сч в.-Х. 7 (in which Kye means such a radical that K'5-O- is identical to the radical Ko having the value mentioned in any of claims 1, 09 2 or C, and Xo represents a halogen atom or a reactive residue of a complex ether, and (ee) obtain a compound of the general formula (I), where 7 is a hydrogen atom. - 10. The method of obtaining a compound according to any of claims 1, 2 or 3, in which 7 means a radical of the general formula (II), Ka is defined in any of paragraphs. I, 2 or 3, and K5 is defined in any of claims 1, 2 or C, which differs (Ce) in that the compound of the general formula (HMI): Tone. | i s EZ I I s h I » S- No: p - ono : 7 ososN, 15 OosOos,n. Me in which Cl, Kz, Ko and K; have the values mentioned in any of claims 1, 2, C or 4, are treated with a compound of the general formula (X): (Коз3-51-Най, (Х) со in which K, the same or different, denote an alkyl radical from 1 -4 carbon atoms, possibly substituted by a phenyl radical, or a cycloalkyl radical with 3-6 carbon atoms, or a phenyl radical, and a product of the general formula (CHMII) is obtained: - ra and Y P) o Kz efe t O-E. nn: NO: osOsn, 60 ososeNe in which K, Cl, Kz, Kv and Ku have the above-mentioned values, which is functionalized in position 10 with the help of a compound of the general formula (XII): vyh 0.00 65 in which K'4 means a radical such that K'/-O- is identical to the radical Ku having the meaning mentioned in any of claims 1, 2 or C, and Xy represents a halogen atom or a reactive residue of a complex ether, to obtain a product of the general formula (XMII): Е ВЕ. o O-SHYUz ra I z (their il) Kz ee O-E. nn: to no: Oososn. autumn in which K, K., Kz, Kl, Kv and K7 have the aforementioned values, the silylated protective group of which is replaced by a hydrogen atom, obtaining a compound of the general formula (XIX): : And there are 7 O-v. NO NO: осОоснУ ОосОосн- which, after interaction with a compound of the general formula (ХМ), ensures the formation of a compound of the general formula (М), whose protective groups are replaced by hydrogen atoms, obtaining a product of the general formula (I), in which 7 means a radical of the general formula ( II). and) 11. The method of obtaining a compound according to any of claims 1, 2 or C, which is characterized by the effect of activated Raney nickel in the presence of an aliphatic alcohol with 1-3 carbon atoms or a simple ether on a compound of the general formula (XXI): Does she have them? and KE 4 o S E" or (Se) don Fe oo OZ o N chryu NO: OsOosn. - s osOos,n. and in which K. has the value mentioned in any of claims 1, 2 or C, K ' and K", the same or different, represent "" a hydrogen atom or an alkyl radical with 1-6 carbon atoms, an alkenyl radical with 2-6 carbon atoms, an alkynyl radical with 3-6 carbon atoms, a cycloalkyl radical with 2-6 carbon atoms or, as necessary, a substituted cycloalkenyl radical with 3-6 carbon atoms, or K' and K" together with the carbon atom to which they are (o) bonded form a cycloalkenyl radical with 3-6 carbon atoms or a cycloalkenyl radical with 4-6 atoms - carbon, and 74 is a hydrogen atom or a radical of the general formula (XXII): со Ко bo " thing ! кт) ) Кз О-Е, in which К/ and Кз have the values mentioned in claims 1-3, and Кб and K; have the values mentioned in claim 4, with a compound of the general formula (ХХХ): (Ф) КЕ, (about E. name) in the bottom that "ХХХ is : ; ГОВ НН: no : ОосОосН, ososn. b5. and further, if 75 is a radical of the general formula (XXII), by replacing the protecting groups designated as Kv and/or K; and K7, on hydrogen atoms under the conditions described in claim 8. 12. The method of preparation according to claim 11, which differs in that the reaction is carried out at a temperature from -107C to 13. A pharmaceutical composition, characterized in that it contains at least one compound according to any one of claims 1, 2 or 3, where 7 represents a radical of the general formula (II), in combination with one or more pharmaceutically acceptable diluents or additives. 14. Pharmaceutical composition according to claim 13, which is characterized in that it additionally contains one or more compatible pharmaceutically active compounds. 0. и и и 0. Official Bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated microcircuits", 2003, M 12, 15.12.2003. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine. s schi 6) s (ee) (ee) «- (Se) - with . and? (o) - (ee) ge» SHY Ko) ime) 60 b5