Steroids, the method of regulation of meiosis

 

(57) Abstract:

The invention relates to steroids Sterol number of General formula I, where R1and R2independently selected from the group comprising hydrogen and unbranched or branched C1-C6-alkyl; R3selected from the group including hydrogen, methylene, hydroxy, oxo, =NOR26where R26represents hydrogen and hydroxy and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton, or R3together with R9or R14designate an additional bond between the carbon atoms that are associated with R3and R9or R14; R4selected from the group comprising hydrogen and oxo, or R4together with R13designate an additional bond between the carbon atoms that are associated with R4and R13; R5selected from the group comprising hydrogen and hydroxy, or R5together with R6designate an additional bond between the carbon atoms that are associated with R5and R6; R6represents hydrogen or R6together with R5designate an additional bond between the carbon atoms that are associated with R6and R5or R14; R9is vodorode bound R9and R3or R10; R10represents hydrogen or R10together with R9designate an additional bond between the carbon atoms that are associated with R10and R9; R11selected from the group comprising hydroxy, acyloxy, oxo, = NOR28where R28represents hydrogen, halogen, or R11together with R12designate an additional bond between the carbon atoms that are associated with R11and R12; R12represents hydrogen or R12together with R11designate an additional bond between the carbon atoms that are associated with R12and R11; R13represents hydrogen or R13together with R4or R14designate an additional bond between the carbon atoms that are associated with R13and R4or R14; R14represents hydrogen or R14together with R3, R6or R13designates an additional bond between the carbon atoms that are associated with R14and R3or R6or R13; R15is hydrogen; R16selected from the group comprising hydrogen, hydroxy, oxo or16together with R17designate an additional bond between the carbon atoms that are associated with R16another link between carbon atoms, associated with R17and R16; R18and R19represent hydrogen; R25selected from the group including hydrogen, and C1-C4-alkyl; a represents a carbon atom or a nitrogen atom; when a represents a carbon atom, R7selected from the group including hydrogen, hydroxy and fluorine, and8selected from the group including hydrogen, C1-C4-alkyl, methylene, and halogen, or R7together with R8designate an additional bond between the carbon atoms that are associated with R7and R8; R20is1-C4-alkyl; R21selected from the group including1-C4-alkyl, C1-C4-hydroxyalkyl,1-C4-halogenated containing up to three halogen atoms; when a represents a nitrogen atom, R7denotes a lone pair of electrons, and R8selected from the group comprising hydrogen and oxo; R20and R21are1-C4-alkyl with the proviso that the compound of General formula (I) does not have any cumulated double bonds and with the additional condition that the connection is not one of the known cholestenone compounds. The compounds I are suitable for use in the regulation of meiosis in the tsya the invention

The present invention relates to pharmacologically active compounds and their use as medicines. In particular, it was found that derivatives of sterols of the invention can be used for regulation of meiosis.

Background of the invention

Meiosis is a special and major case division of sex cells, which is the basis for sexual reproduction. Meiosis involves two meiotic division. During the first division exchange takes place between maternal and paternal genes before a pair of chromosomes divides into two daughter cells. They contain only half the number (1n) chromosomes and DNA 2C. The second meiotic division takes place without DNA synthesis. This division, therefore, leads to the formation of haploid gametes only with 1C DNA.

Magaznie cases are the same in male and female germ cells, but the schedule time and the differentiation processes that lead to the egg and the sperm are completely different. All female gametes come into profeso first masnago division in the early period of life, often before birth, but later as all the oocytes remain in prophase (status dictyate) prior to ovulation after sexual streuner, until stock is depleted. Meiosis in females does not end before the subsequent fertilization and gives sexual cell, only one egg and two abortive polar bodies. In contrast, only some of the male germ cells enter meiosis after puberty and leave the ancestral population of germ cells throughout life. Once started, the meiosis in the male cage continues without significant delay and forms 4 sperm.

We know only a little about the mechanisms that regulate the initiation of meiosis in males and females. New research shows that in the oocyte during meiotic delay should be responsible follicular purines, gipoksantin or adenosine (Downs, S. M. et al., Dev. Biol. , 82 (1985) 454-458; Eppig, J. J. et al., Dev. Biol., 119 (1986) 313-321; and Downs, S. M. , Mol. Reprod. Dev., 35 (1933) 82-94). The presence of diffusing meiosis regulating substance was first described Byskov, A. G. et al., Dev. Biol., 52 (1976) 193-200 system for culture of fetal mouse gonads. Activating meiosis substance (MAS) was secreted fetal mouse ovary, in which meiosis continued, and prevents meiosis substance (MPS) was allocated from the morphologically differentyou is entrale MAS and MPS regulated the beginning, the stop and the resumption of meiosis in male and female germ cells (Byskov, A. G. et al.. The discrimination of Reproduction (eds. Knobil, E. and Neill, J. D., Raven Press, New York (1994)). Obviously, if you can regulate meiosis, it is possible to control reproduction. In a recent article (Byskov, A. G. et al., Nature, 374 (1995) 559-562) describes the secretion from bovine testes and from human follicular fluid of some sterols, which can activate the oocyte meiosis. Unfortunately, these sterols is very labile, and the use of interesting discoveries could therefore greatly facilitated if they were available stable compounds that activate meiosis.

Summary of the invention

The aim of the present invention is to provide compounds and methods useful for the liberation of infertility in females and males gender, particularly mammals, more particularly humans.

Another objective of the present invention is to provide compounds and methods useful as contraceptives for females and males gender, particularly mammals, more particularly humans.

In accordance with the present invention presents a new, stable compounds with interesting the tah and in male germ cells.

In its broadest aspect the present invention relates to compounds of General formula (I).

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where R1and R2independently selected from the group comprising hydrogen and unbranched or branched C1-C6-alkyl which may be substituted with halogen, hydroxy or cyano, or R1and R2together represent methylene, or together with the carbon atom to which they are bound, form cyclopropane ring, cyclopentane ring or cyclohexane ring; R3selected from the group including hydrogen, methylene, hydroxy, methoxy, acetoxy, oxo, =NOR26where R26represents hydrogen or C1-C3-alkyl, halogen and hydroxy, and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton, or R3together with R9or R14designate an additional bond between the carbon atoms that are associated with R3and R9or R14; R4selected from the group including hydrogen, methylene, hydroxy, methoxy, acetoxy, oxo, = NOR27where R27represents hydrogen or C1-C3-alkyl, halogen and hydroxy and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton, or vasani R4and R13or R15; R5selected from the group including hydrogen, C1-C4-alkyl, methylene, hydroxy, methoxy, oxo, =NOR22where R22represents hydrogen or C1-C3-alkyl, or R5together with R6designate an additional bond between the carbon atoms that are associated with R5and R6; R6represents hydrogen or R6together with R5designate an additional bond between the carbon atoms that are associated with R5and R6; R9represents hydrogen or R9together with R3or R10designate an additional bond between the carbon atoms that are associated with R9and R3or R10; R10represents hydrogen or R10together with R9designate an additional bond between the carbon atoms that are associated with R10and R9; R11selected from the group comprising hydroxy, alkoxy, substituted alkoxy, acyloxy, sulfonyloxy, phosphoryloxy, oxo, =NOR28where R28represents hydrogen or C1-C3-alkyl, halogen and hydroxy, and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton, or R11together with R12indicate additional sweatered, C1-C3-alkyl, vinyl, C1-C3-alkoxy and halogen, or R12together with R11designate an additional bond between the carbon atoms that are associated with R12and R11; R13represents hydrogen or R13together with R4or R14designate an additional bond between the carbon atoms that are associated with R13and R4or R14; R14represents hydrogen or R14together with R3, R6or R13designate an additional bond between the carbon atoms that are associated with R14and R3or R6or R13; R15selected from the group including hydrogen, C1-C4-alkyl, methylene, hydroxy, methoxy, acetoxy, oxo, =NOR23where R23represents hydrogen or C1-C3-alkyl, or R15together with R4designate an additional bond between the carbon atoms that are associated with R15and R4; R16selected from the group including hydrogen, C1-C3-alkyl, methylene, hydroxy, methoxy, oxo, =NOR24where R24represents hydrogen or C1-C3-alkyl, or R16together with R17designate an additional bond between the carbon atoms that are associated with R16< between carbon atoms, associated with R17and R16; R18and R19independently represent hydrogen or fluorine; R25selected from the group including1-C4-alkyl, methylene, hydroxy and oxo; a is a carbon atom or a nitrogen atom; when a represents a carbon atom, R7selected from the group including hydrogen, hydroxy and fluorine, and8selected from the group including hydrogen, C1-C4-alkyl, methylene, and halogen, or R7together with R8designate an additional bond between the carbon atoms that are associated with R7and R8; R20selected from the group including C1-C4-alkyl, trifluoromethyl and C3-C6-cycloalkyl, and R21selected from the group including C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-halogenated containing up to three halogen atoms, methoxymethyl, acetoxymethyl and C3-C6-cycloalkyl, or R20and R21together with the carbon atom to which they are bound, form a3-C6-cycloalkyl ring; and when a represents a nitrogen atom, R7denotes a lone pair of electrons, and R8selected from the group including hydrogen, C1-C4-alkyl and oxo; R20the compound of General formula (I) do not have any cumulated double bonds and with the additional condition that, that connection is not one of the following connections:

The cholesterol-7-EN-3-ol;

4-Metalholic-7-EN-3-l;

4-Atilhan-7-EN-3-ol;

4,4-Dimethylpent-7-EN-3-ol;

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4,4-Diestelhorst-7-EN-3-ol;

4-Profilelist-7-EN-3-ol;

4-Bootyholes-7-EN-3-ol;

4-Isobutyryl-7-EN-3-ol;

4,4-Tetramethylene-7-EN-3-ol;

4,4-Pentamethylene-7-EN-3-ol;

The cholesterol-8-EN-3-ol;

4-Metalholic-8-EN-3-ol;

4-Atilhan-8-EN-3-ol;

4,4-Dimethylpent-8-EN-3-ol;

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4,4-Diestelhorst-8-EN-3-ol;

4-Profilelist-8-EN-3-ol;

4-Bootyholes-8-EN-3-ol;

4-Isobutyryl-8-EN-3-ol;

4,4-Tetramethylene-8-EN-3-ol;

4,4-Pentamethylene-8-EN-3-ol;

The cholesterol-8(14)-EN-3-ol;

4-Metalholic-8(14)-EN-3-ol;

4-Atilhan-8(14)-EN-3-ol;

4,4-Dimethylpent-8(14)-EN-3-ol;

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4,4-Diestelhorst-8(14)-EN-3-ol;

4-Profilelist-8(14)-enol;

4-Bootyholes-8(14)-EN-3-ol;

4-Isobutyryl-8(14)-EN-3-ol;

4,4-Tetramethylene-8(14)-EN-3-ol;

4,4-Pentamethylene-8(14)-EN-3-ol;

Cholesta-8,14-Dien-3-ol;

4-Methylfolate-8,14-Dien-3-ol;

4-Atelierista-8,14-Dien-3-ol;

4,4-Dimethylpent-8,14-Dien-3-ol;

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4,4-Diestelhorst-8,14-Dien-3-ol;

4-Profilelist-8,14-Dien-3-ol;

4,4-Pentamethylenebis-8,14-Dien-3-ol;

Cholesta-8,24-Dien-3-ol;

4-Methylfolate-8,24-Dien-3-ol;

4-Atelierista-8,24-Dien-3-ol;

4,4-Dimethylpent-8,24-Dien-3-ol;

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4,4-Diestelhorst-8,24-Dien-3-ol;

4-Propylgallate-8,24-Dien-3-ol;

4-Butyrolactam-8,24-Dien-3-ol;

4-Isobutyrate-8,24-Dien-3-ol;

4,4-Tetramethylaniline-8,24-Dien-3-ol;

4,4-Pentamethylenebis-8,24-Dien-3-ol;

Cholesta-8,14,24-triene-3-3-ol;

4-Methylfolate-8,14,24-triene-3-ol;

4-Atelierista-8,14,24-triene-3-ol;

4,4-Dimethylpent-8,14,24-triene-3-ol;

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4,4-Diestelhorst-8,14,24-triene-3-ol;

4-Propylgallate-8,14,24-triene-3-ol;

4-Butyrolactam-8,14,24-triene-3-ol;

4-Isobutyrate-8,14,24-triene-3-ol;

4,4-Tetramethylaniline-8,14,24-triene-3-ol;

4,4-Pentamethylenebis-8,14,24-trienol;

and their esters and ethers, and even with the additional condition that the compound of General formula (I) is a compound of General formula (II)

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where R1*and R2*independently selected from the group including hydrogen, unbranched or branched C1-C6-alkyl which may be substituted with halogen or hydroxy, or R1*and R2*together with the carbon atom to which they swapanala the relationship between carbon atoms, with which they are associated, in this case, R3*represents hydrogen, and R6*and R5*or are hydrogen or together they designate an additional bond between the carbon atoms to which they are linked; or R3*and R14*together denote an additional bond between the carbon atoms to which they are linked, in this case, R13*is hydrogen and R6*and R5*or are hydrogen or together they designate an additional bond between the carbon atoms to which they are linked; or R6*and R14*together denote an additional bond between the carbon atoms to which they are linked, in this case, R13*, R3*and R5*everything is hydrogen; R8*and R7*represents hydrogen or together they designate an additional bond between the carbon atoms to which they are linked; and*represents either hydrogen or acyl, including sulfonyloxy group or postonline group, or a group which together with the rest of the molecule forms a simple ether.

In a preferred implementation of the invention, the compound of the above formula (I) is a compound where R1and R2both represent hydrogen.

BEM, where one of R1and R2represent hydrogen while the other represents methyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R1and R2both represent methyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R1represents an unbranched or branched C1-C6-alkyl, optionally substituted with halogen, hydroxy or cyano.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R2represents an unbranched or branched C1-C6-alkyl, optionally substituted with halogen, hydroxy or cyano.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R1and R2together represent methylene.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R1and R2together with the carbon atom to which they are connected, form cyclopropenone to what is the connection, where R1and R2together with the carbon atom to which they are attached, form a cyclopentane ring.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R1and R2together with the carbon atom to which they are bound form a cyclohexane ring.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3represents methylene.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3represents methoxy or acetoxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3represents halogen.

In another preferred assests CLASS="ptx2">

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3is =NOH.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3is =NOR26where R26represents C1-C3-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3represents hydroxy and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton,

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3together with R9designate an additional bond between the carbon atoms that are associated with R3and R9.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R3together with R14designate an additional bond between the carbon atoms that are associated with R3and R14.

In another preferred implementation of the invention, the compound of the above FD is the implementation of the invention, the compound of the above formula (I) is a compound, where R4represents methylene.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R4represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R4represents methoxy or acetoxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R4is oxo.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R4is =NOH.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R4is =NOR27where R27represents C1-C3-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R4represents hydroxy and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton,

In another preferred implementation invented the additional bond between the carbon atoms, associated with R4and R13.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R4together with R15designate an additional bond between the carbon atoms that are associated with R4and R15.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R5represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R5is1-C4-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R5represents methylene.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R5represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R5represents methoxy.

In another preferred implementation of the invention, the connection specified sushestvennee of the invention, the compound of the above formula (I) is a compound, where R5is =PONT.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R5is =NOR22where R22represents C1-C3-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R5together with R6designate an additional bond between the carbon atoms that are associated with R5and R6.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R6represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R6together with R14designate an additional bond between the carbon atoms that are associated with R6and R14.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R9represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R<>and R10.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R10represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11represents alkoxy, aralkylated, alkoxyalkane or alkanoyloxy, and each group contains a total of up to 10 carbon atoms, preferably up to 8 carbon atoms.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is1-C4-alkoxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11represents methoxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is ethoxy.

In another preferred ASU is CH3OCH2O-.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is pivaloyloxymethyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is alloctype derived from acids having from 1 to 20 carbon atoms.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is alloctype selected from the group including acetoxy, benzoyloxy, pivaloyloxy, butyryloxy, nicotinuric, isonicotinoyl, hemisuccinate, hemiglutarate, butylcarbamoyl, phenylcarbamoyloxy, butoxycarbonylamino, tert-butoxycarbonylamino, ethoxycarbonyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is sulfonyloxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is phosphoryloxy.

the Institute of economy and management, where R11is oxo.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is =NOH.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11is =NOR28where R28represents C1-C3-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11represents halogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11represents hydroxy and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R11together with R12designate an additional bond between the carbon atoms that are associated with R11and R12.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R1212represents C1-C3-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R12represents C1-C3-alkoxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R12represents halogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R13represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R13together with R14designate an additional bond between the carbon atoms that are associated with R13and R14.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R14represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R15represents hydrogen.

In another preferred implementation of the invention tx2">

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R15represents methylene.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R15represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R15represents methoxy or acetoxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R15is oxo.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R15is =NOH.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R15is =NOR23where R23represents C1-C3-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R16represents hydrogen.

In another PR>6
represents C1-C3-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R16represents methylene.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R16represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R16represents methoxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R16is oxo.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R16is =NOH.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R16is =NOR24where R24represents C1-C3-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R16together CLASS="ptx2">

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R17represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R17represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R18and R19both represent hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R18and R19both represent fluorine.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where one of R18and R19is fluorine and the other is hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R25represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R25represents C1-C4is a compound where R25represents methylene.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R25represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where R25is oxo.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R7represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R7represents hydroxy.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R7is fluoride.

In another preferred implementation of the invention, the compound of the above formula (I) is with the remote control carbon atoms, associated with R7and R8.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R8represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R8represents C1-C4-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R8represents methylene.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R8represents halogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R20represents C1-C4-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R20pre is Oh in the above formula (I) is a compound, where a represents a carbon atom, and R20is3-C6-cycloalkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R21represents C1-C4-alkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R21represents C1-C4-hydroxyalkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R21represents C1-C4-halogenated containing up to three halogen atoms.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R21is acetoxymethyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R21is methoxymethyl.

In another predpochtitel carbon atom and R21is3-C6-cycloalkyl.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a carbon atom, and R20and R21together with the carbon atom to which they are bound, form a3-C6-cycloalkyl ring, preferably cyclopropyl ring, cyclopentene ring or tsiklogeksilnogo ring.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a nitrogen atom and R7denotes a lone pair of electrons.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a nitrogen atom, R7denotes a lone pair of electrons and R8represents hydrogen.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a nitrogen atom, R7denotes a lone pair of electrons and R8represents C1-C4-alkyl.

In another preferred implementation of the invention soedineniya pair of electrons and R8is oxo.

In another preferred implementation of the invention, the compound of the above formula (I) is a compound where a represents a nitrogen atom, R7denotes a lone pair of electrons and R20and R21independently selected from the group including C1-C4-alkyl, cyclopropyl, cyclopentyl and cyclohexyl.

In the following preferred aspect the present invention relates to the use of compounds of the above formula (I) as a medicine, particularly as a drug for use in the regulation of meiosis. The connection can be used in undiluted form or in the form of liquid or solid composition containing auxiliary ingredients commonly used in this field.

In the present context the expression "regulating meiosis" is used to indicate that some compounds of the invention can be used for stimulation of meiosis in vitro, in vivo or ex vivo. Thus, compounds that may be agonists meet in the nature of a substance that activates meiosis, can be used in the treatment of infertility, which is caused by inadequate stimulation masatami meet in the nature of the substance, activating meiosis, can be used for regulation of meiosis, preferably in vivo, in a way which makes them suitable as a contraceptive. In this case, the "regulation" means a partial or complete inhibition.

In another further preferred aspect the present invention relates to the use of compounds of the above formula (I) for the regulation of oocyte meiosis, especially oocyte mammal, more particularly of the human oocyte.

In another further preferred aspect the present invention relates to the use of compounds of the above formula (I) for stimulation of oocyte meiosis, especially oocyte mammal, more particularly of the human oocyte.

In another further preferred aspect the present invention relates to the use of compounds of the above formula (I) for inhibition of oocyte meiosis, especially oocyte mammal, more particularly of the human oocyte.

In another further preferred aspect the present invention relates to the use of compounds of the above formula (I) for the regulation of meiosis male reproductive cells, particularly of the male reproductive cells mlekopitayushchie the present invention relates to the use of compounds of the above formula (I) to stimulate meiosis male reproductive cells, especially the male reproductive cells of a mammal, more particularly of the male reproductive cells of a human.

In another further preferred aspect the present invention relates to the use of compounds of the above formula (I) for inhibition of meiosis male reproductive cells, particularly of the male reproductive cells of a mammal, more particularly of the male reproductive cells of a human.

In another further preferred aspect the present invention relates to a method for regulation of meiosis in sexual cell of a mammal, which consists of introducing an effective amount of the compound of the above formula (I) sexual intercourse by a cell in need of such treatment.

In another further preferred aspect the present invention relates to a method for regulation of meiosis in sexual cell of the mammal, where the compound of the above formula (I) is administered in the reproductive cell by introducing this compound to the mammal, which is the owner of this cell.

In another further aspect the present invention relates to a method, where sex cell, meiosis which you want to adjust using the compounds of the above formula (I) is the I of meiosis in the oocyte, where the compound of the above formula (I) is injected into the oocyte ex vivo.

In another further aspect the present invention relates to a method for regulation of meiosis male reproductive cells by introducing the compound of the above formula (I) into the cell.

In another further aspect the present invention relates to a method by which a Mature gametes are formed by the introduction in vitro of the compounds of the above formula (I) in testicular tissue containing immature cells.

Detailed description of the invention

Used in the present description and the claims the expression C1-C3-alkyl denotes an alkyl group having from one to three carbon atoms; preferred examples are methyl, ethyl and propyl, more preferred methyl and ethyl. Similarly, the expression C1-C4-alkyl denotes an alkyl group having from one to four carbon atoms; preferred examples are methyl, ethyl, propyl, isopropyl and butyl, more preferred methyl and ethyl. The expression C1-C6-alkyl denotes an alkyl group having from one to six carbon atoms, preferred examples are methyl, who drank, butyl and tert-butyl, even more preferred methyl and ethyl.

Used in the present description and the claims the expression C1-C3-alkoxy denotes alkoxygroup having from one to three carbon atoms; preferred examples are methoxy, ethoxy and propoxy preferably methoxy, ethoxy.

Used in the present description and the claims the expression halogen preferably represents fluorine and chlorine, more preferably fluorine.

Connection on p. 1 have a number of chiral centers in the molecule and therefore exist in several isomeric forms. All of these isomeric forms and their mixtures are within the scope of this invention.

Compounds of the present invention will affect meiosis in oocytes and male germ cells.

For some time aware of the existence in nature of inducing meiosis substances. Until recently, however, the nature of the inducing meiosis substance or substances was unknown.

There are several prospects to be able to affect meiosis. In accordance with a preferred embodiment of the present invention, connecting the present invention compounds on p. 1 used for stimulation of meiosis in humans. Thus, connection on p. 1 promising as a new regulatory fertility agents without the usual side effects on somatic cells, which have used up to this time of hormonal contraceptives, which are based on the estrogen and/or progestogen.

For use as contraceptives for females inducing meiosis substance you can enter to prematurely induce the continuation of meiosis in the oocyte, while they are still in the growing follicle before ovulation how is the peak of gonadotropins. In women, the continuation of meiosis can be induced, a week after the termination of the preceding menstruation. Then most likely produced during ovulation aged oocytes are not fertilized. It is unlikely that a normal menstrual cycle changes. In this regard, it is important to note that the biosynthesis of progesterone in cultured grainy human cells (somatic cells of the follicle) is not affected by the presence of the inducing meiosis substances, whereas the estrogen and the progestogen used in applied up to the present time hormonal contraceptives, really eye inventions inducing meiosis connection on p. 1 can be used in the treatment of some cases of infertility in individuals female, including women, the introduction of its individuals female who, due to lack of own production meiosis activating substance is not able to play Mature oocytes. In addition, when fertilization is done in vitro, the best results are achieved when the connection on p. 1 add in an environment in which retain the oocyte.

When infertility in male individuals, including men, is called lack of own produced meiosis activating substance and, thus, the absence of Mature spermatozoa, the introduction of a connection on p. 1 can ease this problem.

Alternatively, the above-described method of contraception in females can be achieved by introducing the compound under item 1, which inhibits meiosis, so that did not play Mature oocytes. Similarly contraception in male individuals can be achieved by introducing the compound under item 1, which inhibits meiosis, so that never played ripe sperm.

By introducing the compositions containing the compound under item 1, may be any route, which effectively transports the active compound to the site of its action.

Thus, when the compounds of this isoteric at least one connection on p. 1 in combination with a pharmaceutically acceptable carrier. For oral administration, such compositions are preferably in the form of capsules or tablets.

From the above it should be clear that the required scheme is the introduction will depend on the conditions in which treatment. Thus, when the connection is used in the treatment of infertility, the introduction can be performed only once or for a limited period, for example to achieve pregnancy. When used as a contraceptive connection on p. 1 should be introduced continuously or intermittently. When used as a contraceptive by females and introduction is not carried out in a continuous way, it is important the timing of the introduction regarding ovulation.

Pharmaceutical compositions containing the compound under item 1, may further comprise carriers, diluents, tools that enhance the absorption, preservatives, buffers, agents to establish osmotic pressure, agents, dezintegriruetsja tablets, and other ingredients that are usually used in this field. Examples of solid carriers are magnesium carbonate, magnesium stearate, dextrin, lactose, sugar, talc, gelatin, pectin, tragakant, methylcellulose, nitrocarburization. Such liquid compositions may be suitable for injection or for use in connection with fertilization ex vivo or in vitro. Liquid compositions can contain other ingredients commonly used in this field, some of them are mentioned in the list above.

In addition, the composition for percutaneous introduction of the compounds according to this invention can be presented in the form of plaster and composition for nasal injection may be presented in the form of nasal spray in liquid or powder form.

The dose used compounds according to the invention will be determined by the physician and will depend, among other things, on the specific compound, the route of administration and purpose.

Connection on p. 1 can be synthesized by known methods.

The present invention is additionally illustrated by the following examples which, however, should not be construed as limiting the scope of protection. The features described in the foregoing description and the following examples, can be in any combination of material for carrying out the invention in its various forms.

EXAMPLES

Example 1

Getting 7-oxo-inicom in a mixture of 30 ml of ethanol and 20 ml of 1 M aqueous sodium hydroxide for 1 hour. After cooling to room temperature, add 23 ml of 1 M hydrochloric acid and 100 ml of water. After cooling in a water bath the precipitate was separated by filtration, washed with water and dried, obtaining 0,435 g of crude compound, which was purified by chromatography on silica gel (methylene chloride/methanol 40:1 (wt./wt.)) and crystallized from methanol/water, getting 0,198 g specified in the connection header.

Melting point: 115-117oC.

1H NMR spectrum (CDCl3, ) showed characteristic signals at: 0,59 (s, 3H); 1.18 to (s, 3H); to 3.64 (m, 1H).

13The NMR spectrum (CDCl3, 100,6 MHz) showed characteristic signals at: 69,5; 132,8; 164,8; 198,6.

Example 2

Getting 7-oxo-5-cholesterol-8,14-Dien-3-ol

This connection receive, as described in Fieser, L. F. et al. (J. Am. Chem. Soc. , (1953) 4719), it shows the following characteristic physical constants:

Melting point: 140-142oC.

1H NMR spectrum (CDCl3, ): of 0.79 (s, 3H); 1.14 in (s, 3H); 3,66 (m, 1H), 6,45 (s, 1H).

13The NMR spectrum (CDCl3, 100,6 MHz): 69,4; 126,1; 126,6; 140,8; 164,9; 197,2.

Example 3

Obtain 7-methyl-5-cholesterol-8-ene-3,7-diol

0.50 g of 3-acetoxy-7-oxo-5-cholesterol-8-ene (Fieser, L. F., J. Am. Chem. Soc., (1953) 4395) dissolved in 10 ml tetrades stirred at room temperature for 1 hour, cooled to 0oAnd dropwise within 5 minutes add 50 ml of 1 M solution of ammonium chloride. The mixture is extracted with twice 50 ml of ethyl acetate. The combined organic phases are washed with water and brine and evaporated, getting 474 mg of crude product which is recrystallized from a mixture of ethyl acetate/heptane, getting 168 mg specified in the connection header.

Melting point: 92-94oWITH

1H NMR spectrum (CDCl3, ) showed characteristic signals at: 0,69 (s, 3H); of 1.03 (s, 3H); to 1.37 (s, 3H), 3,62 (m, 1H).

13The NMR spectrum (CDCl3and 50.3 MHz) showed characteristic signals at: 70,7; 73,8; 132,9; 139,2.

From the mother liquor was separated and the other portion (107 mg) specified in the connection header.

Example 4

Getting 11-oxo-5-cholesterol-8-EN-3--ol

This connection receive, as described Parish, E. S. et al., (Steroids 48 (1986) 407), it shows the physical constants described in the literature.

Example 5

Obtain 3-hydroxy-5-cholesterol-8-EN-7-oxime

0.25 g of 7-oxo-5-cholesterol-8-EN-3-ol (see Example 1) dissolved in 10 ml of dry pyridine. Type of 0.43 g of hydroxylamine hydrochloride and the mixture is stirred at 70oC for 3 hours. After evaporation to dryness the residue grow the unity.

Melting point: 218-223oWITH

1H NMR spectrum (CDCl3, ) showed characteristic signals at: 0,62 (s, 3H); of 1.03 (s, 3H); 3,0 (DD, 1H), 3,62 (m, 1H); 7,52 (Shir.s, 1H).

13The NMR spectrum (CDCl3, 100,6 MHz) showed characteristic signals at: 69,9; 126,7; 149,8; 157,7.

Example 6

Obtain 3-acetoxy-7-oxo-5-cholesterol-8-ene

This connection receive, as described in Fieser, L. F. et al.(J. Am. Chem. Soc. , (1953) 4395, it showed the physical constants, as described in the literature.

Example 7

Obtain 3-acetoxy-7-oxo-5-cholesterol-8,14-Dien

This connection receive, as described in Fieser, L. F. et al.(J. Am. Chem. Soc., (1953) 4719), it showed the physical constants, as described in the literature.

Example 8

Getting 7-oxo-5-cholesterol-8-EN-3-eventout

This connection receive, as described Parish, E. J. et al., Steroids 48 (1986) 407, it showed the physical constants, as described in the literature.

Example 9

Getting 7-methylene-5-cholesterol-9-EN-3-ol

of 0.54 g of sodium hydride (60%) dissolved in 10 ml of dimethyl sulfoxide at 70oC. After 15 minutes, add a solution of 5.24 g of bromide methyltriphenylphosphonium in 33 ml of dimethylformamide and then a solution of 3-acetoxy-7-oxo-5-cholesterol-8-ene (cf. Example 6) in 28 ml of benzene. The mixture was stirred at 60o

Melting point: 44-50oC.

1H NMR spectrum (CDCl3, ) showed characteristic signals at: 0,65(s, 3H); 1.06 a(s, 3H); 2,62(d, 1H); to 3.58(m, 1H); and 4.68(d, 2H); at 5.27(d, 1H).

13The NMR spectrum (CDCl3, 100,6 MHz) showed characteristic signals at: 70,5; 105,2; 115,7; 146,1; 150,5.

Example 10

Obtain 7-methyl-5-cholesta-6,8-Dien-3-ol

of 0.90 g of 7-methyl-5-cholesterol-8-ene-3,7-diol (see Example 3) was suspended in 55 ml of formic acid and stirred overnight at room temperature. The mixture was poured on ice water and the precipitated compound is separated by filtration, washed with water and dried. The residue (0.84 g) is refluxed in a mixture of 50 ml ethanol and 25 is chloride and water. The organic phase is evaporated to dryness and crystallized from a mixture of ethanol/water, getting 395 mg specified in the connection header.

Melting point: 112-113oWITH

1H NMR spectrum (CDCl3, ) showed characteristic signals at: 0,58(s, 3H); from 0.88(s, 3H); to 1.83(s, 3H); to 3.58(m, 1H); lower than the 5.37(d, 1H).

13The NMR spectrum (CDCl3, 100,6 MHz) showed characteristic signals at: 70,9; 116,6; 129,0; 129,6; 145,3.

Example 11

Getting 11-oxo-5-cholesterol-8-EN-3-eventout

This connection receive, as described Parish, E. J. et al., Steroids 48 (1986), 407, it showed the physical constants, as described in the literature.

Example 12

Getting cholesta-8,14-Dien-5-N-3-it

This connection receive in accordance with Dolle J. Org. hm., 51 (1986), 4047-4053. The product showed the following physical characteristics:

1H NMR: H: 5,78 (d, 1H, SN), 5,16 (1H, m, SN).

Elemental analysis:

Calculated: From 84.7; N 11,1; 4,18.

Found: From 84.7; H 11,4.

Example 13

Obtaining 3-Feroleto-8,14-Dien

Cholesta-8,14-Dien-3-ol (1,17 g, 3 mmol) dissolved in 10 ml of methylene chloride and cooled to -78oC. for 10 min at -78oTo add a solution of the TRIFLUORIDE diethylaminoethyl (1.4 g, 8,7 mmol) in 10 ml of methylene chloride. The mixture paramesh and with continued stirring 15 ml of water. The organic phase is separated and washed with 30 ml of 5% NaHCO3and then water. The organic phase is dried gSO4and evaporated to dryness. The residue is purified column chromatography using heptane to obtain a first fraction and a mixture of heptane/acetone, 95:5 (wt./wt.) to obtain a second fraction containing 3-Feroleto-8,14-Dien, 0.14 g (12%).

Melting point: 98,6oC.

Elemental analysis:

Calculated: 83,88; N 11,21; F 4,91

Found: 83,92; N 11,75.

19F NMR: 181,0 and 181,2 (JHCF=45,2 Hz, C3-F).

Example 14

Getting cholesta-2,8,14-triens

Specified in the title compound is obtained using the method similar to the method described in J. Chemical Research (miniprint) (1979), 4714-4755.

Cholesta-8,14-Dien-3-ol (1,17 g, 3 mmol) dissolved in 10 ml of methylene chloride and cooled to -78oC. for 10 min at -78oTo add a solution of the TRIFLUORIDE diethylaminoethyl (1.4 g, 8,7 mmol) in 10 ml of methylene chloride. The mixture is stirred and then slowly warmed to room temperature. To the reaction mixture with continued stirring 15 ml of water. The organic phase is separated and washed with 30 ml of 5% Panso3and then water. The organic phase is dried gSO4evaporate dash what I cholesta-2,8,14-triene, 0,23 g

Melting point: 104,7oC.

Elemental analysis:

Calculated: 88,45; N 11,55.

Found: 88,58; N 11,89.

NMR: H: 5,64(m, 2H; C2-N; C3-N), to 5.35(s, 1H, 15 NM).

C: 125,95(C3), 125,67(C2).

Example 15

Getting cholesta-8,14-Dien-5(H)-3-(E),(Z)-oxime

Cholesta-8,14-Dien-3-one (1.0 g, 2,61 mmol) dissolved in 15 ml of pyridine and to the solution add hydroxylamine Hcl (0.29 grams, to 4.23 mmol). The reaction mixture is heated at 70-72oC for 1.5 hours under stirring. The reaction mixture is cooled and evaporated to dryness. Add 30 ml of 50% solution of acetic acid/water and the formed crystals are separated by filtration. The crystals are dissolved in heptane and washed with water. The organic phase is separated and evaporated to dryness. The crystals recrystallized from ethanol, receiving of 0.91 g of 5-cholesta-8,14-Dien-3-(E) and (Z)-oxime.

Elemental analysis:

Calculated: 81,55; N 10,90; N 3,52; Was 4.02.

Found: 81,65; N 11,30; N 3,43.

13With NMR: 159,66 and 159,51(3-C).

Example 16

N, N-Dimethylamide 3-hydroxy-4,4-dimethyl-5-hole-8,14-Dien-24-OIC acid.

3-tert-butyldimethylsilyloxy-4,4-dimethyl-5-hole-8,14-Dien-24-OIC acid (0,30 g) dissolved in 10 ml of anhydrous dichlo is stirred at -15oC for 20 minutes, then add 1,74 ml of a 2.0 M solution of N,N-dimethylamine in THF. The mixture is stirred overnight and the temperature is slowly increased to room. After treatment with water and crystallized from methanol to obtain N, N-dimethylamide 3-tert-butyldimethylsilyloxy-4,4-dimethyl-5-hole-8,14-Dien-24-OIC acid (0,231 g). So pl. 143-145oS.1H-NMR (CDCl3, 400 MHz): = to 5.35(1H, s); 3,20(1H, m); 3,03(3H, s); 2,95(3H, s); 0,90(N, C); 0,05(6N, m).

N, N-dimethylamide 3-tert-butyldimethylsilyloxy-4,4-dimethyl-5-hole-8,14-Dien-24-OIC acid (0.10 g) was dissolved in 5 ml of ethanol, add 0.2 ml of 6N. hydrogen chloride and the mixture is stirred over the weekend. The product precipitated with 10 ml water, filtered and recrystallized from ethanol/heptane to obtain specified in the title compound (59 mg). So pl. 192-195 (in Russian)oC.1H-NMR1H-NMR (CDCl3, 400 MHz): = are 5.36(1H, s); 3,24(1H, m); to 3.02(3H, s); to 2.94(3H, s); Molecular weight: Calculated: 427,7. Found (mass-spectrometry): 427,4.

Example 17

4,4-Dimethyl-24-dimethylamino-5-hole-8,14-Dien-3-ol.

This compound is synthesized by recovery in THF N,N-dimethylamide 3-hydroxy-4,4-dimethyl-5-hole-8,14-Dien-24-OIC acid using sociallyengaged.1H-NMR1H-NMR (CDCl3, 400 Mga

Stage 1. A mixture of (25R)-cholesterol-5-ene-3,26-diol (6,24 g of 15.4 mmol), imidazole (4,21 g, 61 mmol) and tert-butyldimethylsilyl (2,34 g of 15.4 mmol) and dimethylformamide heated to 60oC for 1.5 hours, then poured into water (300 ml) and extracted with diethyl ether (5100 ml). In the flash-chromatography receive (25R)-26-(tert-butyldimethylsilyloxy)cholesterol-5-EN-3-ol (5,09 g).

Melting point: 93,5oC. Range1H-NMR (CDCl3showed characteristic signals at: 0,01(C, 6N), was 0.63(s, 3H), of 0.90(s, N), 3,4(m, 3H, H-26 and H-3), 5,32(d, 1H, H-6). Range 13C-NMR (CDCl3, ) showed characteristic signals at: 50,1(C-9), Or 56.1(C-14), of 56.7(C-17), and 68.5(C-26), Of 71.7(C-3), To 121.6(C-6), 140,7(C-5). The mass spectrum showed characteristic peaks at: 516, 5 (M+).

Stage 2. A mixture of (25R)-26(tert-butyldimethylsilyloxy)cholesterol-5-EN-3-ol (7,4 g of 14.3 mmol) and 1-methylpiperidine (55 ml) in toluene (550 ml) was heated to boiling point under reflux with 100 ml of toluene drove away. Then within 10 minutes was added in portions triisopropoxide aluminum (15 g, 137 mmol) and the resulting mixture was boiled under reflux for 4 hours. After cooling, was added water (300 ml) and the aqueous layer was extracted with diethyl ether (5100 ml). United argory was purified by using pleskrestore with the receipt of 6.26 g (25R)-26-(tertBUTYLPEROXY)of cholesterol-4-EN-3-one (6,26 g).

Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,01(C, 6N), to 0.66(s, 3H), 0,89(s,N), to 3.35(m, 2H, H-26), 5,67(s, 1H, H-4). Range13C-NMR (CDCl3, ) showed characteristic signals at: 53,7(C-9) And 55.8(C-14), 56,0(C-17), And 68.5(C-26), 123,7(C-4), 171,6(C-5), 199,8(C-3). The mass spectrum showed characteristic peaks at: 515,4 (M+).

Stage 3. To a stirred suspension of KOtBu (13,17 g, 117 mmol) in tBuOH (300 ml) at a temperature of 45oWith added (25R)-26-(tert-butyldimethylsilyloxy)of cholesterol-4-EN-3-one (12 g, 23.5 mmol) and the resulting mixture was stirred for 10 minutes. Added logmean (18 ml) and the reaction mixture was stirred for 0.5 hours, concentrated to one-third of the original volume of the mixture was poured into 500 ml of ice water. In the extraction with diethyl ether, drying over magnesium sulfate and concentration of the mixture was obtained residue, which was purified flash chromatography to obtain 4,4-dimethyl-(25R)-26-(tert-butyldimethylsilyloxy)of cholesterol-4-EN-3-one (8,88 g).

Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,02(C, 6N), of 0.65(s, 3H), 0,89(s,N), to 3.35(m, 2H, H-26), 5,52(m, 1H, H-6). Range13C-NMR (CDCl3, ) showed characteristic signals at: 49,0(C-9), Of 56.2(C-14), With 56.8(C-17), Only 68.6(C-26), To 120.0(C-6), 149,8(C-5), 216,8(C-3). M is em-butyldimethylsilyloxy) of cholesterol-4-EN-3-one (86 mg, 0,17 mmol) and tetrabutylammonium (140 mg, of 0.53 mmol) in THF (2 ml) was stirred for 2 hours at room temperature. After removal of the solvent under reduced pressure, the obtained residue, which was purified flash chromatography to obtain 4,4-dimethyl-(25R)-26-hydroxyoleic-5-ene-3-one (47 mg).

Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,65 (s, 3H), 0,72(s, 3H), 0.88 to(s, 3H), of 0.91(s, 3H), of 2.50(m, 2H, H-2), of 3.42(m, 2H, H-26), 5,52(m, 1H, H-6). Range13C-NMR (CDCl3, ) showed characteristic signals at: 49,3(C-9), Of 56.5(C-14), To 57.1(C-17), 68,8 C-26), To 120.3(C-6), To 150.1(C-5), 217,1(C-3). The mass spectrum showed characteristic peaks at: 428,34 (M+).

Example 19

4,4-Dimethyl-(25R)-cholesterol-5-ene-3,26-diol

Stage 1. To a suspension of sociallyengaged (0,76 g, 20 mmol) in THF (60 ml) at a temperature of an ice bath was added 4,4-dimethyl-(25R)-26-(tert-butyldimethylsilyloxy)of cholesterol-4-EN-3-one (8,58 g, 15 mmol) in THF (50 ml). After 1.5 hours the reaction extinguished with water and the resulting material was filtered through a layer of Celite. Concentration under reduced pressure gave a residue that was dissolved in dichloromethane, dried over magnesium sulfate and purified flash chromatography to obtain 3-hydroxy-4,4-dimethyl-(25R)-26-(tert-butyldimethylsilyloxy)cholesterol-5-eichische signals: 0,02(s, 6N), was 0.63(s, 3H), of 0.90(s, N), 3,3(m, 3H, H-26 and H-3), 5,52(m, 1H, H-6). Range 13C-NMR (CDCl3, ) showed characteristic signals at: 50,7(C-9), Of 55.9(C-14), To 57.1(C-17) And 68.4(C-26), To 77.4(C-3), To 120.0(C-6), 149,6(C-5). The mass spectrum showed characteristic peaks at: 544,4 (M+).

Stage 2. Removing the protective silyl group in 3-hydroxy-4,4-dimethyl-(25R)-26-(tert-butyldimethylsilyloxy)cholesterol-5-ene (60 mg, 0.11 mmol) using tetrabutylammonium and recrystallization from methanol was obtained 4,4-dimethyl-(25R)-cholesterol-5-ene-3,26-diol (30 mg).

Melting point 174-175oC. Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,65(s, 3H), of 0.90(s, N), to 0.92(s, 3H), of 1.03(s, 3H), of 1.05(s, 3H), 1.14 in(s, 3H), of 1.23(s, 3H), UP 3.22 (1H, s, H-3), of 3.45(m, 2H, H-26), of 5.53(m, 1H, H-6). The mass spectrum showed characteristic peaks at: 430,4 (M+).

Example 20

4,4-Dimethyl-(25R)-cholesterol-5,7-Dien-3,26-diol

Stage 1. A mixture of 3-hydroxy-4,4-dimethyl-(25R)-26-(tert-butyldimethylsilyloxy)

the cholesterol-5-ene (7.2 mg, 13,2 mmol), tert-butyldimethylsilyloxy (3,99 g, 26 mmol) and imidazole (4,49 g, 66 mmol) in THF (250 ml) was heated for 16 hours at 60oC, poured into water (300 ml) and was extracted with diethyl ether. In the concentration under reduced calltemplate melting 97,0oC. Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,02(s, N), was 0.63(s, 3H), of 0.90(s, N) and 3.15(m, 1H, H-3), 3,39(m, 2H, H-26), 5,52(m, 1H, H-6). Range13C-NMR (CDCl3, ) showed characteristic signals at: 50,8(C-9), Of 55.9(C-14), To 57.1(C-17), To 68.3 (C-26), With 77.7(C-3), 119,5(C-6), To 150.1 (C-5). The mass spectrum showed characteristic peaks at: 658,5 (M+).

Stage 2. A mixture of 3-(25S)-26-bis(tert-butyldimethylsilyl-hydroxy)-4,4-dimethylpent-5-ene (4,2 g, 6,37 mmol) and 1,3-dibromo-5,5-dimethylhydantoin (1.63 g, 5,73 mmol) in benzene (150 ml) and hexane (60 ml) was heated at the boiling point under reflux for 0.5 hours. After cooling, the solid was removed by filtration and the organic phase was concentrated under reduced pressure. Added giraldin (9 ml) and o-xylene (250 ml) and the resulting mixture was heated at 140oC for 0.5 hour. In the concentration of the reaction mixture and chromatography was obtained 3-(25S)-26-bis(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5,7-diene (4.4 g).

Range1H-NMR (CDCl3, ) showed characteristic signals; 0,02(s, N), and 0.6(s, 3H), of 0.90(s, N), to 3.35(m, 3H, H-26 and H-3), 5,52(m, 1H, H-6), by 5.87(d, 1H, H-7).

Range13C-NMR (CDCl3, ) showed characteristic signals at: 47,0(C-9), 54, is key when: 656,6 (M+).

Stage 3. Hydrogen fluoride (4 ml, 40% in/in water) and 3-(25S)-26-bis(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5,7-diene (30 mg, 0.05 mmol) in acetonitrile (3 ml) was stirred for 16 hours at room temperature. The reaction extinguished saturated ammonium carbonate (50 ml) and product was extracted with dichloromethane, and purified flash chromatography and recrystallized from methanol to obtain 4,4-dimethyl-(25R)-cholesterol-5,7-Dien-3,26-diol (17 mg).

Melting point 168,5-169oC. Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,58(s, 3H), of 0.90(s, 3H), of 0.92(s, 3H), were 0.94(s, 3H), and 0.98(s, 3H), 1,10(s, 3H), of 1.18(s, 3H), of 3.45(m, 3H, H-26 and H-3), of 5.53(m, 1H, H-6), 5,90(d, 1H, H-7). The mass spectrum showed characteristic peaks at: 428,3 (M+).

Example 21

(25R)-4,4-Dimethyl-5-cholesta-8,14-Dien-3,26-diol

A mixture of 3-(25R)-26-bis(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5,7-diene (450 mg, 0.83 mmol), concentrated model HC1 (6 ml), benzene (6 ml) and ethanol (25 ml) was heated to boiling point under reflux for 5 hours. After cooling, the reaction mixture was concentrated to half volume and added water (35 ml). The resulting crystalline precipitate was collected by filtration, dried in vacuum, paracrystalline 180-182oC. Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,80(s, 3H), of 0.82(s, 3H), of 0.90(s, 3H), of 0.93(s, 3H), of 0.95(s, 3H), of 1.02(s, 3H), of 1.05(s, 3H), up 3.22(DD, 1H, H-3), of 3.43(m, 2H, H-26), 5,33(m, 1H, H-15). Range13C-NMR (CDCl3, ) showed characteristic signals at: 68,4 (C-26), To 78.7(C-3), 117,4(C-15), 122,8(C-14), 141,8 (C-9), 151,1(C-8). The mass spectrum showed characteristic peaks at: 428,4 (M+).

Example 22

(25R)-26-Chloro-4,4-dimethyl-5-cholesta-8,14-Dien-3-ol

Stage 1. A solution of (25R)-3-(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5,7-Dien-26-ol (0.5 g, to 0.92 mmol) and p-toluensulfonate (0.55 g, 2.8 mmol) in pyridine (10 ml) was stirred for 0.5 hour in an ice bath and for 4 hours at room temperature. Concentration of the reaction mixture and flash chromatography gave (25R)-3-(tert-butyldimethylsilyloxy) -4,4-dimethylpent-5,7-Dien-26-tosylate (0,57 g).

Melting point 68oC. Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,02(d, N), of 0.52(s, 3H), of 0.90(s, N), is 2.40(s, 3H, Agsn3), 3,30(m, 1H, H-3), of 3.80(m, 2H, H-26), 5,52(m, 1H, H-6), to 5.58(d, 1H, H-7), 7,30(d, 2H, aryl), 7,74(d, 2H, aryl). Range13C-NMR (CDCl3, ) showed characteristic signals at: 47,5(C-9), 54,7(C14), 56,0(C-17), To 75.6 (C-26), 78,0(C-3), To 118.0(C-6), 119,2(C-7), 128,3(C-ortho), is 130.2(C-met is">

Stage 2. A solution of (25R)-3-(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5,7-Dien-26-toluensulfonate (0,57 g, 0.82 mmol) and lithium chloride (300 g, 7 mmol) in dimethylformamide was heated at 50oC for 2 hours. By adding water (30 ml), extraction with ether and chromatography was received (25R)-3-(tert-butyldimethylsilyloxy)-4,4-dimethyl-26-chloro-cholesterol-5,7-diene (424 mg).

Melting point 114-116oC. Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,02(d, N), of 0.52(s, 3H), of 0.90(s, N), was 1.04(s, 3H), of 1.08(s, 3H), at 3.35(m, 3H, H-3 and H-26), of 5.50(m, 1H, H-6), of 5.83(d, 1H, H-7). Range13C-NMR (CDCl3, ) showed characteristic signals at: 77,4(C-3), To 117.7(C-6), 118,9(C-7), 141,1 (C-8), 150,8(C-5). The mass spectrum showed characteristic peaks at: 560,4 (M+).

Stadia.A mixture of(25R)-3-(tert-butyldimethylsilyloxy)-4,4-dimethyl-26-chloroplast-5,7-diene (380 mg, 0.67 mmol), concentrated Hcl (5 ml), benzene (6 ml) and ethanol (25 ml) was heated at the boiling point under reflux for 5 hours. The reaction mixture was concentrated to half volume and added water (30 ml). As a result of extraction with dichloromethane, drying over magnesium sulfate and removal of solvent under reduced pressure, the obtained residue that crystal is and melting 145-145,5oC. Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,80(s, 3H), of 0.82(s, 3H), of 0.92(s, 3H), were 0.94(s, 3H), 0,99(s, 3H), 1,01(s, 3H), of 1.03(s, 3H), 3,24(m, 1H, H-3 ), of 3.42(m, 2H, H-26), 5,33(m, 1H, H-15). Range13C-NMR (CDCl3, ) showed characteristic signals at: 57,6(C-26), 79,4(C-3), To 117.7(C-15), Of 123.2(C-14), To 142.1 (C-9), 151,4(C-8). The mass spectrum showed characteristic peaks at: 446,3 (M+).

Elemental analysis:

Calculated: From The Sideways Range Between 77.90; H 10,59; C1 To 7.93.

Found: 77,85; N 11,07; C1 8,05.

Example 23

(25R)-26-Iodine-4,4-dimethyl-5-cholesta-8,14-Dien-3-ol

A mixture of (25R)-26-chloro-4,4-dimethyl-5-cholesta-8,14-Dien-3-ol (50 mg, 0.1 mmol) and sodium iodide (0.8 g) in acetone (3 ml) was heated at 55oC and the reaction vessel was tightly closed for 3 days. By adding water, extraction with diethyl ether and koncentrirali under reduced pressure, the obtained residue, which was led 3 times from hexane to obtain specified in the title compound (37 mg).

Melting point 148oC.

Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,80(s, 3H), of 0.82(s, 3H), 1,01(s, 3H), of 1.02(s, 3H), 3,20(m, 3H, H-26 and H-3), 5,33(m, 1H, H-15).

The mass spectrum showed characteristic peaks at: 538,3 (M+).

Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,82(s, 3H), or 0.83(s, 3H), 0,86(s, 3H), of 0.97 (d, 3H), of 1.03(s, 3H), 3,50(m, 1H, H-3), to 5.35(m, 1H, H-6). Range 13C-NMR (CDCl3, ) showed characteristic signals at: 72,0(C-3), 121,4(C-6), 141,4(C-5), 218,0(C-16). The mass spectrum showed characteristic peaks at: 400,4 (M+).

Example 25

Cholestan-3,16-diol

The cholesterol-5-ene-3,16-diol (600 mg, 1.4 mmol) in ethyl acetate (15 ml) was first made over 5% palladium on coal for 3 days under conditions of atmospheric pressure. After removal of catalyst by filtration through Celite and purification of the residue flash-chromatography has been specified in the title compound (190 mg).

Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,81(s, 3H), 0 is s when: 71,7(C-3), to 72.9(C-8). The mass spectrum showed characteristic peaks at: 404,4 (M+).

Example 26

4,4-Dimethylpent-5-ene-16-ol-3-one

Stage 1.

To a solution of cholesterol-5-ene-3,16-diol-3-benzoate (6,1 g, 12 mmol) (obtained as described in Bioorg. Med. Chem. Lett. 1995, 3, 367-374) in dichloromethane (50 ml) at a temperature of an ice bath was added tert-butyldimethylsilyl (20 mmol) and the solution was stirred for 0.5 hour. Added water and the aqueous phase was extracted with dichloromethane. After removal of the solvent under reduced pressure and purification of the residue by crystallization from methanol received 16-(tert-butyldimethylsilyloxy)cholesterol-5-EN-3-yl benzoate (8.1 g).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,01(s, 3H), of 0.02(s, 3H), 4,25(m, 1H, H-16), and 4.75(m, H-3), 5,42(d, 1H,H-6), and 7.4(m, 3H, aryl), and 8.2(m, 2H, aryl).

The mass spectrum showed characteristic peaks at: 621,6 (M+).

Stage 2. To a suspension of sociallyengaged (4.5 g, 120 mmol) in diethyl ether (700 ml) was added dropwise 16-(tert-butyldimethylsilyloxy)cholesterol-5-EN-3-yl benzoate (8.1 g, 12 mmol) in diethyl ether (50 ml). After stirring at room temperature for 15 minutes and at 40oC for 0.5 hour was added to the water. Neorganicheskiye flash chromatography to obtain 16-(tert-butyldimethylsilyloxy)cholesterol-5-EN-3-ol (6.7 g).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,01(s, 3H), of 0.02(s, 3H), 3,49(m, H-3), 4,25(m, 1H, H-16), 5,32(s, 1H, H-6).

Stage 3. A mixture of 16-(tert-butyldimethylsilyloxy)cholesterol-5-EN-3-ol (6.7 g, 12 mmol) and 1-methylpiperidine (25 ml) in toluene (500 ml) was heated to boiling point under reflux with 50 ml toluene drove away. Then was added dropwise triisopropoxide aluminum (9,8 g, 48 mmol) in toluene (50 ml) and the resulting mixture was heated at the boiling point under reflux for 4 hours. After cooling, was added water (200 ml) and the aqueous layer was separated and was extracted with diethyl ether. The combined organic layers were washed with water (100 ml), dried over magnesium sulfate and concentrated to obtain residue, which was purified by crystallization from methanol to obtain 16-(tert-butyldimethylsilyloxy)of cholesterol-4-EN-3-one (5.4 g).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,01(s, 3H), of 0.02(s, 3H), 4.26 deaths(m, 1H, H-16), of 5.68(m, 1H, H-16). Range13C-NMR (CDCl3, ), showed characteristic signals at: 72,1(C-16), 123,8(C-4), which is 171,5(C-5), 199,6(C-3). The mass spectrum showed characteristic peaks at: 515,5 (M+).

Stage 4. To a stirred suspension of KotBu (5,6 is (15 ml) and the resulting mixture was stirred for 20 minutes. Added logmean (6.2 ml) and the reaction mixture was stirred for another 0.5 hours, concentrated to half the original volume and poured into 200 ml of ice water. In the extraction with ethyl acetate, drying over magnesium sulfate and concentration was obtained residue, which was purified by recrystallization from methanol to obtain 4,4-dimethyl-16-(tert-butyldimethylsilyloxy)of cholesterol-4-EN-3-one (4.0 g).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,01(s, 3H), of 0.02(s, 3H), of 2.50(m, 2H, H-2), 4,30 (m, 1H, H-16), 5,54(m, 1H, H-6). Range13C-NMR (CDCl3, ), showed characteristic signals at: 72,3(C-16), 119,7(C-6), 150,0(C-5), 216,0(C-3). The mass spectrum showed characteristic peaks at: 543.5 nm (M+).

Stage 5. A mixture of 4,4-dimethyl(tert-butyldimethylsilyl-hydroxy)cholesterol-5-ene-3-one (40 mg, 0.07 mmol), concentrated Hcl (0.2 ml) and ethanol (5 ml) was heated at the boiling point under reflux for 20 hours. After removal of the solvent under reduced pressure and recrystallization from methanol (two times) was obtained 4,4-dimethylpent-5-ene-16-ol-3-one (20 mg).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,87(s, 3H), 0.88 to(s, 3H), of 0.91(s, 3H), 0,99(d, 3H), of 1.20(s, 3H), 1,21(s, 3H), 4,4 is -5), 216,7(C-3). The mass spectrum showed characteristic peaks at: 428,4 (M+).

Example 27

The cholesterol-5-ene-4,4-dimethyl-3,16-diol

Stage 1. To a suspension of sociallyengaged (570 mg, 15 mmol) in diethyl ether (200 ml) was added 4,4-dimethyl-16-(tert-butyldimethylsilyloxy)of cholesterol-4-EN-3-one (2.8 g, 15 mmol) in 20 ml of ether and the resulting mixture was stirred for 1.5 hours. Added water and the solution was filtered through a layer of Celite. In the extraction with ether and concentration under reduced pressure, the obtained residue, which was purified by crystallization from methanol to obtain 3-hydroxy-4,4-dimethyl-16-(tert-butyldimethylsilyloxy)of cholesterol-4-ene (400 mg).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,01(s, 3H), of 0.02(s, 3H), of 1.07(d, 3H), of 1.08(s, 3H), of 1.16(s, 3H), 3,21(m, 1H, H-3), 4,25(m, 1H, H-16), the 5.51(m, 1H, H-6). Range13C-NMR (CDCl3, ), showed characteristic signals at: 72,8(C-16), Up 77.9(C-3), To 120.3(C-6), Of 150.4(C-5). The mass spectrum showed characteristic peaks at: 545,5 (M+).

Stage 2. A mixture of 3-hydroxy-4,4-dimethyl-16-(tert-butyldimethylsilyloxy)of cholesterol-4-ene (1.1 g, 2 mmol), concentrated Hcl (2.5 ml) and ethanol (25 ml) was heated at the boiling point under reflux for 2 days. The mixture is i.i.d. organic phase was washed with sodium bicarbonate and water. In the concentration under reduced pressure, the obtained residue, which was purified flash chromatography to obtain cholesterol-5-ene-4, 4-dimethyl-3,16-diol (225 mg).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,86(s, 3H), of 0.87(s, 3H), of 0.95(d, 3H), of 1.07(d, 3H), of 1.08(s, 3H), of 1.16(s, 3H), 3,21(m, 1H, H-3), or 4.31(m, 1H, H-16), the 5.51(m, 1H, H-6). Range13C-NMR (CDCl3, ), showed characteristic signals at: 77,0(C-3), 119,4(C-6), 149,4(C-5). The mass spectrum showed characteristic peaks at: 430,4 (M+).

Example 28

4,4-dimethylpent-5,7-diene-3,16-diol

Stage 1. A mixture of 3-hydroxy-4,4-dimethyl-16-(tert-butyldimethylsilyloxy)of cholesterol-4-ene (4.0 g, 7,3 mmol), tert-butyldimethylsilyloxy (5.5 g, 35 mmol) and imidazole (10.0 g, 146 mmol) in DMF (250 ml) was heated for 7 hours at a temperature of 70oC, poured into water (250 ml) and was extracted with diethyl ether. In the concentration under reduced pressure and crystallization from methanol received 3,16-bis(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5-ene (4.3 g).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,02(m, N), or 0.83(s, 3H), 3,20(m, 1H, H-3), 4,32(m, 1H, H-16), 5,52(m, 1H, H-6). Range13C-NMR (CDCl3, ), showed CLASS="ptx2">

Stage 2. A mixture of 3.16-bis(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5-ene (500 mg, 0.75 mmol) and 1,3-dibromo-5,5-dimethylhydantoin (140 mg, 0.5 mmol) in benzene (15 ml) and hexane (35 ml) was heated at the boiling point under reflux for 1 hour. After cooling, the solid was removed by filtration and the organic phase was concentrated under reduced pressure. Added giraldin (1 ml) and o-xylene (25 ml) and the resulting mixture was heated at a temperature of 140oC for 1 hour, the concentration of the reaction mixture and chromatography got 3,16-bis(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5,7-diene (310 mg).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,02(m, N), or 0.83(s, 3H), of 1.05(d, 3H), of 1.07(s, 3H), 3,30(m, 1H, H-3), 4,35(m, 1H, H-16), of 5.50(m, 1H, H-6), of 5.85(m, H-7). Range13C-NMR (CDCl3, ), showed characteristic signals at: 72,7(C-16), With 77.7(C-3), 114,0(C-6), To 117.9(C-7), 140,9(C-8), To 154.2(C-5). The mass spectrum showed characteristic peaks at: 656,5 (M+).

Stage 3. A mixture of 3.16-bis(tert-butyldimethylsilyloxy)-4,4-dimethylpent-5,7-diene (110 mg, 0.2 mmol) and DIBAL (8 ml 1.0 M in hexane) was heated to boiling point under reflux for 3 days. Added water and water shall eat the residue, which was purified flash chromatography to obtain 4,4-dimethylpent-5,7-diene-3,16-diol (33 mg).

Melting point: 171-173oC. Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,80(s, 3H), 0,84(s, 3H), of 0.87(s, 3H), 3,24(m, 1H, H-3), of 3.42(m, 2H, H-26), of 4.45(m, 1H, H-16), 5,52(m, 1H, H-6), 5,95(d, 1H, H-7).

Range13C-NMR (CDCl3, ), showed characteristic signals at: 72,2(C-16), 117,3(C-8), Of 118.8(C-7), 139,9(C-6), To 150.1(C-5). The mass spectrum showed characteristic peaks at: 428,3 (M+).

Example 29

4,4-Dimethyl-5-cholesta-8,14-diene-3,16-diol

A mixture of 4,4-dimethylpent-5,7-diene-3,16-diol (65 mg, 0.15 mmol), concentrated Hcl (0.35 ml), benzene (0.35 ml) and ethanol (4 ml) was heated to boiling point under reflux for 4 hours. The result of concentrating the mixture under reduced pressure and crystallization of the residue from methanol has been specified in the title compound (5 mg).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 3,42(m, 1H, H-3), 5,95(d, 1H, H-15).

Example 30

4,4-Dimethylpent-5-ene-3,16-dione

To a mixture of cholesterol-5-ene-4,4-dimethyl-3,16-diol (43 mg, 0.1 mmol), sodium acetate (340 mg, 2.5 mmol) and glacial acetic acid (4 ml) was added chromium trioxide (33 ml) and the reaction mixture was concentrated under reduced pressure. Added water and the aqueous phase was extracted with dichloromethane. In the drying over magnesium sulfate, concentration and purification flash chromatography got mentioned in the title compound (40 mg).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,80(s, 3H), 0,84(s, 3H), of 0.92(d, 3H), 5.56mm(m, 1H, H-6). Range13C-NMR (CDCl3, ), showed characteristic signals at: 119,7(C-6), 150,5(C-5), 216,8(C-3), 218,9(C-16). The mass spectrum showed characteristic peaks at: to 426.2 (M+).

Example 31

Cholesta-5,16-Dien-3-one

To a stirred suspension of KOtBu (900 mg, 8.2 mmol) in tBuOH (25 ml) at 45oWith added cholesta-4,16-Dien-3-one (620 mg, 1.6 mmol) in THF (5 ml) and the resulting mixture was stirred for 20 minutes. Added logmean (1 ml) and the reaction mixture was stirred for 12 hours, concentrated to half the original volume and poured into 20 ml of ice water. In the extraction with ethyl acetate, drying over magnesium sulfate and concentration was obtained residue, which was purified on a flash chromatography with obtaining specified in the title compound (220 mg).

Range1H-NMR (CDCl3, ), showed characteristic signals at: 0,81(s, 3H), of 0.85(s, 3H), of 0.87(s, 3H), 0,89(s, 3H), 0,95(dealuminated (80 mg, 2 mmol) in diethyl ether (15 ml) was added 4,4-dimethylpent-5,16-Dien-3-one (220 mg, 0.5 mmol) in 10 ml of ether and the resulting mixture was stirred for 1.5 hours. Added water and the solution was filtered through a layer of Celite. The aqueous phase was extracted with ether, washed with 4n. HCl, saturated salt solution, dried over magnesium sulfate and concentrated under reduced pressure to obtain 3-hydroxy-4,4-dimethylpent-5,16-diene (220 mg)

Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,79(s, 3H), or 0.83(s, 3H), of 0.85(s, 3H), of 0.95(d, 3H), of 1.03(s, 3H), of 1.07(s, 3H), of 1.12(s, 3H), 3,20(m, 1H, H-3), and 5.30(s, H-16), to 5.57(m, 1H, H-6).

Example 33

4,4-Dimethylpent-5-ene-3,17-diol

Stage 1. To a solution of 3-hydroxy-4,4-dimethylpent-5,16-diene (220 mg, 0.5 mmol) in pyridine (1.5 ml) at the temperature of an ice bath was added benzoyl chloride (0.1 ml) and the resulting mixture was stirred for 1.5 hours. In the concentration under reduced pressure and purification of the residue flash chromatography was obtained 3-benzoyloxy-4,4-dimethylpent-5,16-diene (300 mg).

Range1H-NMR (CDCl3, ) showed characteristic signals at: 4,74(m, 1H, H-3), and 5.30(s, H-16), 5,61(m, 1H, H-6), to 7.50(m, 3H, aryl), 8,07(d, 2H, aryl).

Stage 2. To a solution of 3-benzoyloxy-4,4-Dimethylol the resulting mixture was stirred for 3 hours. Added 2n. NaOH (5 ml) and the aqueous phase was extracted with dichloromethane. In the concentration under reduced pressure, the obtained residue, which was triturated with methanol and purified flash chromatography with 3-benzoyloxy-4,4-dimethyl-16-epoxycholesterol-5-ene (50 mg).

Range1H-NMR (CDCl3, ) showed characteristic signals at: 3,24 (s, 1H, H-16), 4,71(m, 1H, H-3), the ceiling of 5.60(m, H-6), to 7.50(m, 3H, aryl), 8,07(d, 2H, aryl).

Stage 3. 3-benzoyloxy-4,4-dimethyl-16-epoxycholesterol-5-ene (40 mg, of 0.075 mmol) in THF (1 ml) was added to a suspension of sociallyengaged (50 mg, 1.3 mmol) in THF (3 ml) and the resulting mixture was heated to boiling point under reflux for 6 hours. Added diethyl ether (50 ml) and 4n. NaOH (0.2 ml) and the precipitate was collected by filtration and washed with ether. After treatment, the flash-chromatography has been specified in the title compound 4,4-dimethyl-cholesterol-5-ene-3-17-diol (12 mg).

Range1H-NMR (CDCl3, ) showed characteristic signals at: 0,78(s, 3H), of 0.85(s, 3H), of 0.87(s, 3H), of 0.90(s, 3H), of 1.05(s, 3H), of 1.07(s, 3H), of 1.12(s, 3H), 3,23(m, 1H, H-3), 5.56mm(m, 1H, H-6). Range13C-NMR (CDCl3, ) showed characteristic signals at: 86,8(C-17), Of 120.5(C-6), Of 149.0(C-5). The mass spectrum showed the characteristic PI-he

(25R)-Cholesterol-5-ene-3,26-diol

Received in accordance with the procedure described in Arunachalam et al., J. Org. Chem., 1981, 46, 2966-2968.

Examples 37 and 38

The cholesterol-5-ene-3,16-diol

The cholesterol-5-ene-3,16-diol 3 benzoate

These two compounds were obtained as described Kim in Bioorg. Med. Chem. 1995, 3, 367-374.

Example 39

4,4-Dimethylpent-8-ene-3,15-diol

Received likewise the General method described Dolle et al. in J. Chem. Soc. Chem. Comm. 1988, 19.

Example 40

4,4-dimethyl-5-cholesta-8,14,24-triene-3-one

Stage 1. A suspension of 4,4-dimethyl-5-hole-8,14-Dien-3,24-diol (500 mg, 1,29 mmol), N-methylmorpholin-N-oxide (600 mg, 5.2 mmol), TRR (45 mg, 0.13 mmol) and crushed molecular sieves (2 g) in dichloromethane (5 ml) was stirred for 30 minutes at room temperature. By adding ether (15 ml) and filtration through kieselguhr received a dark brown solution, which was concentrated under reduced pressure and purified via chromatography (eluent: 3 hexane: 1 ethyl acetate) to obtain 3-oxo-4,4-dimethyl-5-hole-8,14-Dien-24-aldehyde (345 mg, 70%) as a white solid with a melting point of 96.5-97oC.

1H-NMR (CDCl3, 300 MHz) of 5.40(1H, s, H-5), 1,10) and 1.04(3H each, s, CH34A and 18), of 0.93(3H, d J=Hz, CH3-20), 0,82(6N, s, CH3-4b and 19 1.4 M solution in hexane, 0.26 mmol) to a suspension of isopropyltriphenylphosphonium (98 mg, 0.26 mmol) in THF (2 ml) at the temperature of the ice bath. Accordingly, the resulting solution of phosphorane dark red color was stirred for another 0.5 hour and then was added dropwise via syringe to a solution of 3-oxo-4,4-dimethyl-5-hole-8,14-Dien-24-aldehyde (71 mg, 0.18 mmol) in THF (2 ml) at a temperature of -78oC and was stirred for 2 hours and then slowly heated to room temperature and was stirred overnight. Was added a saturated solution of ammonium chloride (3 ml) and the aqueous phase was extracted using diethyl ether and the organic phase was dried over anhydrous sodium sulfate. In the flash-chromatography (eluent: 6 hexane: 1 ethyl acetate) has been specified in the title compound (38 mg, 50%).

1H-NMR (CDCl3, 300 MHz) of 5.40(1H, s, H-15), 5,10 (1H, t, J=6H, H-24), 1,67 and 1.60 (3H each, s, CH3-26 and 27), of 0.95(3H, d J=Hz, CH3-20), or 0.83(6N, s, CH3-4b and 19), 2,6-0,8(m, remaining H).

FiI: 4475/ANS/03 NE 18-40

Analysis of oocytes using naked oocytes, the determination of the relative percentage of GVB

Culture of mouse oocytes

Analysis of in vitro culture, by definition, the resumption of meiosis in mouse oocytes is performed with the use of ooltewah under controlled conditions of illumination and temperature. Mice injected with intraperitoneal injection of 0.2 ml of gonadotropins (e.g., Gonal-F, Serono) containing 20 IU FSH, and after 48 hours the animals killed by the collapse of the neck. At autopsy, remove the ovaries and oocytes isolated in NC medium (see below) under a stereo microscope by rupture of follicles manually using a pair of needle size 27. Select spherical naked oocytes (NO) or enclosed in a shell accumulations of oocytes (CEO) with intact nuclei of oocytes (GV), and placed in the minimum basic medium (-MEM containing no ribonucleosides, Gibco BRL, Cat. No. 22561), supplemented with 3 mm gipoksantina (Sigma Cat. No. H-9377), 8 mg/ml albumin human serum (HAS, State Serum Institute, Denmark), 0.23 mm pyruvate (Sigma, Cat. No. S-8636), 2 mm glutamate (Flow Cat. No. 16-801), 100 IU/ml penicillin and 100 g/ml streptomycin (Flow Cat. No. 16-700). This Wednesday is designated as NC-Wednesday.

Oocytes from two to three times washed in NC environment and uniform in size oocytes divided into groups of CEOS and NO. NO cultured in 4-hole plates (Nunclon, Denmark) in which each well contains 0.4 ml NC-environment and 30-45 oocytes. One control well (i.e., 30-45 oocytes cultured in the same medium without addition of test compound) always cultivated simultaneously to the wells containing escaut from the original solution, containing 1-4 mg/ml of the compounds dissolved in methanol. Adding ethanol (3,8 l/ml) for controls does not affect the indications for the control sample. Oocytes were cultured in humidified atmosphere with 5% content of CO2in the air for 19-24 hours at 37oC.

By the end of the cultivation period, the number of oocytes with nuclei of oocytes (GV), the destruction of the nuclei of oocytes (GVB) and polar bodies (PB), respectively counted using a stereomicroscope (Wild, Leica MZ 12). % GVB, defined as the percentage of oocytes undergoing GVB, of the total number of oocytes in the hole, calculated as %GVB=(GVB + number PB/total number of oocytes)100.

% GVB count for control, FF-MAS and test the connection.

The relative effect GVB calculated as 100(%GVBuse-%Vcounter.)/(%GVBFF-MAS-%GVBcounter.).

Each compound was tested at least 2 times and presented as the average values of the relative impacts of GVB.

The examples in table 1, showing high values of relative GVB (i.e., compounds that show similar or better than that of FF-MAS properties to stimulate meiosis), are particularly useful to the TV by initiating maturation of the oocyte prior to ovulation, thus, there will be ovulation aged oocytes (i.e. there will be no fertilization).

The examples in table 2, showing low values of the relative GVB, especially useful as contraceptives.

1. Steroids of General formula (I)

< / BR>
where R1and R2independently selected from the group comprising hydrogen and unbranched or branched C1-C6-alkyl;

R3selected from the group including hydrogen, methylene, hydroxy, oxo, = NOR26where R26represents hydrogen and hydroxy and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton, or R3together with R9or R14designate an additional bond between the carbon atoms that are associated with R3and R9or R14;

R4selected from the group comprising hydrogen and oxo, or R4together with R13designate an additional bond between the carbon atoms that are associated with R4and R13;

R5selected from the group comprising hydrogen and hydroxy, or R5together with R6designate an additional bond between the carbon atoms that are associated with R5and R6;

R6PR is which bound R6and R5;

R9represents hydrogen or R9together with R3or R10designate an additional bond between the carbon atoms that are associated with R9and R3or R10;

R10represents hydrogen or R10together with R9designate an additional bond between the carbon atoms that are associated with R10and R9;

R11selected from the group comprising hydroxy, acyloxy, oxo, = NOR28where R28represents hydrogen, halogen, or R11together with R12designate an additional bond between the carbon atoms that are associated with R11and R12;

R12represents hydrogen or R12together with R11designate an additional bond between the carbon atoms that are associated with R12and R11;

R13represents hydrogen or R13together with R4or R14designate an additional bond between the carbon atoms that are associated with R13and R4or R14;

R14represents hydrogen or R14together with R3, R6or R13designates an additional bond between the carbon atoms that are associated with R14and R3or R6or R13;

R/SUP> together with R17designate an additional bond between the carbon atoms that are associated with R16and R17;

R17represents hydrogen or hydroxy, or R17together with R16designate an additional bond between the carbon atoms that are associated with R17and R16;

R18and R19represent hydrogen;

R25selected from the group including hydrogen, and C1-C4-alkyl;

A represents a carbon atom or a nitrogen atom; when a represents a carbon atom, R7selected from the group including hydrogen, hydroxy and fluorine, and8selected from the group including hydrogen, C1-C4-alkyl, methylene, and halogen, or R7together with R8designate an additional bond between the carbon atoms that are associated with R7and R8;

R20is1-C4-alkyl;

R21selected from the group including1-C4-alkyl, C1-C4-hydroxyalkyl,1-C4-halogenated containing up to three halogen atoms; and when a represents a nitrogen atom, R7denotes a lone pair of electrons, and R8selected from the group comprising hydrogen and oxo; R20and R21prestanic relations and with the additional condition that, that connection is not one of the following connections:

The cholesterol-7-EN-3-ol;

4-Metalholic-7-EN-3-ol;

4-Atilhan-7-EN-3-ol;

4,4-Dimethylpent-7-EN-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-7-EN-3-ol;

4-Profilelist-7-EN-3-ol;

4-Bootyholes-7-EN-3-ol;

4-Isobutyryl-7-EN-3-ol;

4,4-Tetramethylene-7-EN-3-ol;

4,4-Pentamethylene-7-EN-3-ol;

The cholesterol-8-EN-3-ol;

4-Metalholic-8-EN-3-ol;

4-Atilhan-8-EN-3-ol;

4,4-Dimethylpent-8-EN-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8-EN-3-ol;

4-Profilelist-8-EN-3-ol;

4-Bootyholes-8-EN-3-ol;

4-Isobutyryl-8-EN-3-ol;

4,4-Tetramethylene-8-EN-3-ol;

4,4-Pentamethylene-8-EN-3-ol;

The cholesterol-8(14)-EN-3-ol;

4-Metalholic-8(14)-EN-3-ol;

4-Atilhan-8(14)-EN-3-ol;

4,4-Dimethylpent-8(14)-EN-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8(14)-EN-3-ol;

4-Profilelist-8(14)-enol;

4-Bootyholes-8(14)-EN-3-ol;

4-Isobutyryl-8(14)-EN-3-ol;

4,4-Tetramethylene-8(14)-EN-3-ol;

4,4-Pentamethylene-8(14)-EN-3-ol;

Cholesta-8,14-Dien-3-ol;

4-Methylfolate-8,14-Dien-3-ol;

4-Atelierista-8,14-Dien-3-ol;

4,4-Dimethylpent-8,14-Dien-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8,14-Dien-3-ol;

4-Profilelist-8,14-Dien-3-ol;

4,4-Pentamethylenebis-8,14-Dien-3-ol;

Cholesta-8,24-Dien-3-ol;

4-Methylfolate-8,24-Dien-3-ol;

4-Atelierista-8,24-Dien-3-ol;

4,4-Dimethylpent-8,24-Dien-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8,24-Dien-3-ol;

4-Propylgallate-8,24-Dien-3-ol;

4-Butyrolactam-8,24-Dien-3-ol;

4-Isobutyrate-8,24-Dien-3-ol;

4,4-Tetramethylaniline-8,24-Dien-3-ol;

4,4-Pentamethylenebis-8,24-Dien-3-ol;

Cholesta-8,14,24-triene-3-ol;

4-Methylfolate-8,14,24-triene-3-ol;

4-Atelierista-8,14,24-triene-3-ol;

4,4-Dimethylpent-8,14,24-triene-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8,14,24-triene-3-ol;

4-Propylgallate-8,14,24-triene-3-ol;

4-Butyrolactam-8,14,24-triene-3-ol;

4-Isobutyrate-8,14,24-triene-3-ol;

4,4-Tetramethylaniline-8,14,24-triene-3-ol;

4,4-Pentamethylenebis-8,14,24-triene-3-ol;

< / BR>
7-Oxo-5-cholesterol-8-universiat;

11-Oxo-5-cholesterol-8-universiat;

3-Hydroxy-5-cholesterol-8-EN-11-he;

4,4-Dimethylpent-5-andiol;

their esters and ethers.

2. Connection on p. 1 with the proviso that it is not a compound of General formula (II)

< / BR>
where R1*and R2*independently selected from the group including hydrogen, unbranched or branched C1-WITH6Ala whom they are associated, in this case, R3*represents hydrogen, and R6*and R5*or are hydrogen or together they designate an additional bond between the carbon atoms to which they are linked; or

R3*and R14*together denote an additional bond between the carbon atoms to which they are linked, in this case, R13*is hydrogen and R6*and R5*or are hydrogen or together they designate an additional bond between the carbon atoms to which they are linked; or

R6*and R14*together denote an additional bond between the carbon atoms to which they are linked, in this case, R13*, R3*and R5*all represent hydrogen;

R8*and R7*represent hydrogen or together they designate an additional bond between the carbon atoms to which they are linked; and

IN*represents either hydrogen or acyl, or a group which together with the rest of the molecule forms a simple ether.

3. Connection under item 1 or 2, where R1and R2both represent hydrogen.

4. Connection under item 1 or 2, where one of R1and R2represents hydrogen while the other represents methyl.

5. Soedinen> represents an unbranched or branched C1-C6-alkyl.

7. Connection under item 1 or 2, where R2represents an unbranched or branched C1-C6-alkyl.

8. The compound according to any one of the preceding paragraphs, where R3represents hydrogen.

9. The compound according to any one of paragraphs. 1-7, where R3represents methylene.

10. The compound according to any one of paragraphs. 1-7, where R3represents hydroxy.

11. The compound according to any one of paragraphs. 1-7, where R3is oxo.

12. The compound according to any one of paragraphs. 1-7, where R3is = NOH.

13. The compound according to any one of paragraphs. 1-7, where R3represents hydroxy and C1-C4-alkyl, related to the same carbon atom of the Sterol skeleton.

14. The compound according to any one of paragraphs. 1-7, where R3together with R9designate an additional bond between the carbon atoms that are associated with R3and R9.

15. The compound according to any one of paragraphs. 1-7, where R3together with R14designate an additional bond between the carbon atoms that are associated with R3and R14.

16. The compound according to any one of paragraphs. 1-15, where R4represents hydrogen.

<-15, where R4together with R13designate an additional bond between the carbon atoms that are associated with R4and R13.

19. The compound according to any one of paragraphs. 1-18, where R5represents hydrogen.

20. The compound according to any one of paragraphs. 1-18, where R5represents hydroxy.

21. The compound according to any one of paragraphs. 1-18, where R5together with R6designate an additional bond between the carbon atoms that are associated with R5and R6.

22. The compound according to any one of paragraphs. 1-21, where R6represents hydrogen.

23. The compound according to any one of paragraphs. 1-21, where R6together with R14designate an additional bond between the carbon atoms that are associated with R6and R14.

24. The compound according to any one of paragraphs. 1-23, where R9represents hydrogen.

25. The compound according to any one of paragraphs. 1-20, where R9together with R10designate an additional bond between the carbon atoms that are associated with R9and R10.

26. The compound according to any one of paragraphs. 1-20, where R10represents hydrogen.

27. The compound according to any one of paragraphs. 1-21, where R11represents hydroxy.

28. The compound according to any one of paragraphs. 1-21, where R11is ALLO the e R11is alloctype selected from the group including acetoxy, benzoyloxy, pivaloyloxy, butyryloxy, nicotinuric, isonicotinoyl, hemisuccinate, hemiglutarate, butylcarbamoyl, phenylcarbamoyloxy, butoxycarbonylamino, tert-butoxycarbonylamino, ethoxycarbonyl.

30. The compound according to any one of paragraphs. 1-21, where R11is oxo.

31. The compound according to any one of paragraphs. 1-21, where R11is = NOH.

32. The compound according to any one of paragraphs. 1-21, where R11represents halogen.

33. The compound according to any one of paragraphs. 1-21, where R11together with R12designate an additional bond between the carbon atoms that are associated with R11and R12.

34. The compound according to any one of paragraphs. 1-32, where R12represents hydrogen.

35. The compound according to any one of paragraphs. 1-34, where R13represents hydrogen.

36. The compound according to any one of paragraphs. 1-34, where R13together with R14designate an additional bond between the carbon atoms that are associated with R13and R14.

37. The compound according to any one of paragraphs. 1-35, where R14represents hydrogen.

38. The compound according to any one of paragraphs. 1-37, where R16is water is E. according to any one of paragraphs. 1-37, where R16is oxo.

41. The compound according to any one of paragraphs. 1-37, where R16together with R17designate an additional bond between the carbon atoms that are associated with R16and R17.

42. The compound according to any one of paragraphs. 1-41, where R17represents hydrogen or hydroxy.

43. The compound according to any one of the preceding paragraphs, where R25represents hydrogen.

44. The compound according to any one of the preceding paragraphs, where R25is1-C4-alkyl.

45. The compound according to any one of paragraphs. 1-44, where a represents a carbon atom.

46. Connection on p. 45, where R7represents hydrogen.

47. Connection on p. 45, where R7represents hydroxy.

48. Connection on p. 45, where R7is fluoride.

49. Connection on p. 45, where R7together with R8designate an additional bond between the carbon atoms that are associated with R7and R8.

50. Connection on p. 45, where R8represents hydrogen.

51. Connection on p. 45, where R8is1-C4-alkyl.

52. Connection on p. 45, where R8represents methylene.

53. The connection on t1-C4-alkyl.

55. The compound according to any one of paragraphs. 1-53, where R21is1-C4-hydroxyalkyl.

56. The compound according to any one of paragraphs. 1-53, where R21is1-C4-halogenated containing up to three halogen atoms.

57. The compound according to any one of paragraphs. 1-44, where a represents a nitrogen atom.

58. The compound according to any one of paragraphs. 57, where R8represents hydrogen.

59. Connection on p. 57, where R8is oxo.

60. The compound according to any one of paragraphs. 1-59 for use as a medicine.

61. The compound of General formula (I) according to any one of paragraphs. 1-59 for use in the regulation of meiosis.

62. The method of regulation of meiosis in sexual mammal cells, ex vivo which includes the introduction in the sexual cell an effective amount of a steroid of General formula (I)

< / BR>
where R1and R2independently selected from the group comprising hydrogen and unbranched or branched C1-C6-alkyl;

R3selected from the group including hydrogen, methylene, hydroxy, oxo, = NOR26where R26represents hydrogen, hydroxy and C1-C4-alkyl, associated with one GU the relationship between carbon atoms, associated with R3and R9or R14;

R4selected from the group comprising hydrogen and oxo, or R4together with R13designate an additional bond between the carbon atoms that are associated with R4and R13;

R5selected from the group comprising hydrogen and hydroxy, or R5together with R6designate an additional bond between the carbon atoms that are associated with R5and R6;

R6represents hydrogen or R6together with R5designate an additional bond between the carbon atoms that are associated with R6and R5;

R9represents hydrogen or R9together with R3or R10designate an additional bond between the carbon atoms that are associated with R9and R3or R10;

R10represents hydrogen or R10together with R9designate an additional bond between the carbon atoms that are associated with R10and R9;

R11selected from the group comprising hydroxy, acyloxy, oxo, = NOR28where R28represents hydrogen, halogen, or R11together with R12designate an additional bond between the carbon atoms that are associated with R11and R1212and R11;

R13represents hydrogen or R13together with R4or R14designate an additional bond between the carbon atoms that are associated with R13and R4or R14;

R14represents hydrogen or R14together with R3, R6or R13designates an additional bond between the carbon atoms that are associated with R14and R3or R6or R13;

R15represents hydrogen;

R16selected from the group comprising hydrogen, hydroxy, oxo, or R16together with R17designate an additional bond between the carbon atoms that are associated with R16and R17;

R17represents hydrogen or hydroxy, or R17together with R16designate an additional bond between the carbon atoms that are associated with R17and R16;

R18and R19represent hydrogen;

R25selected from the group including hydrogen and C1-C4-alkyl;

A represents a carbon atom or a nitrogen atom; when a represents a carbon atom, R7selected from the group including hydrogen, hydroxy and fluorine, and 8selected from the group including hydrogen, C1-With< the carbon associated with R7and R8; R20is1-C4-alkyl; R21selected from the group including1-C4-alkyl, C1-C4-hydroxyalkyl,1-C4-halogenated containing up to three halogen atoms; when a represents a nitrogen atom, R7denotes a lone pair of electrons, and R8selected from the group comprising hydrogen and oxo; R20and R21are1-C4-alkyl, with the proviso that the compound of General formula (I) does not have any cumulated double bonds and with the additional condition that the connection is not one of the following connections:

The cholesterol-7-EN-3-ol;

4-Metalholic-7-EN-3-ol;

4-Atilhan-7-EN-3-ol;

4,4-Dimethylpent-7-EN-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-7-EN-3-ol;

4-Profilelist-7-EN-3-ol;

4-Bootyholes-7-EN-3-ol;

4-Isobutyryl-7-EN-3-ol;

4,4-Tetramethylene-7-EN-3-ol;

4,4-Pentamethylene-7-EN-3-ol;

The cholesterol-8-EN-3-ol;

4-Metalholic-8-EN-3-ol;

4-Atilhan-8-EN-3-ol;

4,4-Dimethylpent-8-EN-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8-EN-3-ol;

4-Profilelist-8-EN-3-ol;

4-Bootyholes-8-EN-3-ol;

4-Isobutyryl-8-EN-3-ol;

4,4-Tetrame is;

4-Atilhan-8(14)-EN-3-ol;

4,4-Dimethylpent-8(14)-EN-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8(14)-EN-3-ol;

4-Profilelist-8(14)-EN-3-ol;

4-Bootyholes-8(14)-EN-3-ol;

4-Isobutyryl-8(14)-EN-3-ol;

4,4-Tetramethylene-8(14)-EN-3-ol;

4,4-Pentamethylene-8(14)-EN-3-ol;

Cholesta-8,14-Dien-3-ol;

4-Methylfolate-8,14-Dien-3-ol;

4-Atelierista-8,14-Dien-3-ol;

4,4-Dimethylpent-8,14-Dien-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8,14-Dien-3-ol;

4-Propylgallate-8,14-Dien-3-ol;

4-Butyrolactam-8,14-Dien-3-ol;

4-Isobutyrate-8,14-Dien-3-ol;

4,4-Tetramethylaniline-8,14-Dien-3-ol;

4,4-Pentamethylenebis-8,14-Dien-3-ol;

Cholesta-8,24-Dien-3-ol;

4-Methylfolate-8,24-Dien-3-ol;

4-Atelierista-8,24-Dien-3-ol;

4,4-Dimethylpent-8,24-Dien-3-ol;

< / BR>
< / BR>
4,4-Diestelhorst-8,24-Dien-3-ol;

4-Propylgallate-8,24-Dien-3-ol;

4-Butyrolactam-8,24-Dien-3-ol;

4-Isobutyrate-8,24-Dien-3-ol;

4,4-Tetramethylaniline-8,24-Dien-3-ol;

4,4-Pentamethylenebis-8,24-Dien-3-ol;

Cholesta-8,14,24-triene-3-ol;

4-Methylfolate-8,14,24-triene-3-ol;

4-Atelierista-8,14,24-triene-3-ol;

4,4-Dimethylpent-8,14,24-trienol;

< / BR>
< / BR>
4,4-Diestelhorst-8,14,24-triene-3-ol;

4-Profilelist angelesca-8,14,24-triene-3-ol; and

4,4-Pentamethylenebis-8,14,24-triene-3-ol;

and their esters and ethers.

63. The method according to p. 62, where the compound is administered in the reproductive cell by assigning it to the mammal, the master of the cells.

64. The method according to p. 62 or 63, where sexual cell, meiosis which is subject to regulation, is the oocyte.

65. The method according to p. 62, where the compound is injected into the oocyte ex vivo.

66. The method according to p. 63, where sexual cell, meiosis which is subject to regulation, is the male reproductive cell.

67. The method according to p. 62, through which a Mature male sex cells are produced by introducing the compound into testicular tissue in vitro.

Priority points:

23.06.1995 - PP. 1-67;

22.12.1995 - clarification of signs on PP. 1-67.

 

Same patents:
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< / BR>
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The invention relates to the field of medicine

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FIELD: medicine, hepatology.

SUBSTANCE: at achieving alkaline phosphatase of 580 U and more one should introduce ursodesoxycholic acid at the dosage of 15-20 mg/kg and orlistate at the dosage of 90-100 mg twice or thrice daily for patients with steatohepatitis. According to normalization of clinical and biochemical values of blood analyses it is possible to conclude upon successfulness of therapy performed. The method provides clinic-laboratory remission of the disease.

EFFECT: higher efficiency of therapy.

3 ex

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