MXPA00011133A - Meiosis regulating compounds - Google Patents

Abstract

Certain novel sterol derivatives can be used for regulating the meiosis in oocytes and in male germ cells.

Description

REGULATORY COMPOUNDS OF THE MEIOSIS FIELD OF THE INVENTION The present invention relates to certain pharmacologically active compounds, to pharmaceutical compositions containing certain compounds as an active substance and to their use as medicaments. More particularly, it has been found that the derivatives described herein can be used to regulate meiosis.

BACKGROUND OF THE INVENTION Meiosis is the only and last event of the germ cells on which sexual reproduction is based. Meiosis comprises two meiotic divisions. During the first division, the exchange between maternal and paternal genes takes place before the pairs of chromosomes separate into the two daughter cells. These contain only half the number (ln) of chromosomes and 2c DNA. The second meiotic division proceeds without a synthesis of DNA. This division, therefore, Ref: 124545 results in the formation of haploid germ cells only with lc DNA. Meiotic events are similar in male and female germ cells, but the timing and differentiation processes that lead to egg and sperm differ profoundly. All female germ cells enter the prophase of the first meiotic division in early life, often before birth, but all are arrested as oocytes later in the prophase (state of death) until ovulation after puberty. In this way, from early life, women have a reserve of oocytes that are extracted until the reserve is exhausted. Meiosis in women is not completed until after fertilization, and results in only one egg and two abortive polar bodies per germ cell. In contrast, only some of the male germ cells enter meiosis from puberty and leave a major population of major cells throughout life. Once initiated, meiosis in the male cell proceeds without significant delay and produces sperm.

Little is known about the mechanisms that control the onset of meiosis in men and women. In the oocyte, new studies indicate that follicular purines, hypoxanthine or adenosine, may be responsible for meiotic arrest (Do ns, S.M. et al Dev. Bi ol. (1985) 45 -458; Eppig, J.J. et al. Dev. Bi ol. 119 (1986) 313-321; and Downs, S.M. Mol. Reproel. Dev. 35 (1993), 82-94). The presence of a diffusible substance that regulates meiosis was first described by Byskov et al. in a fetal mouse gonad culture system (Byskov, A.G. et al., in Dev. Bi ol., 52 (1976), 193-200). A meiosis-activating substance (MAS) was secreted by the mouse fetal ovary in which meiosis was progressing, and a substance that prevents meiosis (MPS) was released from the testes morphologically differentiated with non-meiotic germ cells, at rest. It was suggested that the concentrations of MAS and MPS regulate the initiation, arrest, and resumption of meiosis in male and female germ cells (Byskov, AG et al in The Physiology of Reproducti on (eds, Knobil, E. and Neill, JD, Raven Press, New York (1994).) Clearly, if the meiosis can be regulated, reproduction can be controlled. A recent article (Byskov, A.G. et al. In Na ture 37_ (1995), 559-562) describes the isolation from bull testes and from human follicular fluid of certain sterols that activate the meiosis of oocytes. Unfortunately, these sterols are rather labile and the use of the interesting finding could thus be greatly facilitated if more stable meiosis activating compounds were available. In Aus t. J. Chem. 35 (1982), 629-640, Horn et al. compounds that have possibly biological activity (insect shedding hormones) are treated. Examples of compounds specifically mentioned herein are 5-cyano-5-β-cholest-7-en-3-one; 5-cyano-5β-cholest-7-en-3β-ol; 5-methyl-5β-cholest-7-en-3-one; 5-methyl-5β-cholest-7-en-3a-ol; and 5-methyl-5β-cholest-7-en-3ß-ol. In Bull. Soc. Chim. Fr. (1971), 2037-204.7, Levisalles et al., Cholesta-4, 8 (14) -dien-3-one is described as an intermediate. In Just. Li eb. Ann. Chem. 542 (1939), 218-224, indaus et al., Mention is made of the cholesta-4,7- dien-3-one; cholesta-4, 7-dien-3a-ol; and cholesta-4,7-dien-3ß-ol as intermediates. In Pharm. Bull. 1 (1953) 224-227, Arima mentions cholesta-, 8-dien-3-one as an intermediate. In Lipids 13 (1978), 704 et seq., Kandutsch et al. describe some cholestane derivatives that can be potent inhibitors of sterol synthesis. The compounds specifically mentioned herein are, in Figure 1, 3β, 7a-dihydroxycholest-5-ene; 3β, 7β-dihydroxycholest-5-ene; 3β-hydroxycholest-5-en-7-one; 3β, hydroxycholest-7-one; 7a-hydroxycholest-4-en-3-one; in Figure 2 (compounds 1-5), cholest-3, 6-dione; 3β-hydroxylest-6-one; 3β, 6β-dihydroxylestanol; cholest-4-en-3, 6-dione; 3β, 5α, 6β-trihydroxylestanol; in Figure 3, 3β, 5a-dihydroxycholestane; 3β, 4β-dihydroxycholest-5-ene; and in Figure 4 (compounds 1, 3, 4 and 5), cholest-2-en-6-one; cholest-4, 6-dien-3-one; cholest-4, 7-dien-3-one; cholest-3, 5-dien-7-one. The Danish patent application with publication number 130,992, has to do with compounds that possibly have progestomimetic properties. Examples of specifically mentioned compounds are 19-nor-21- methylpregna-4,9-dien-17a-hydroxy-3,20-dione; 19-nor-21-methyl-pregna-4, -dien-17a-acetoxy-3,20-dione; 19-nor-21, 21-dimethylpregna-, 9-diene-17a-hydroxy-3, 20-dione; and 17a-21, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione. In the Danish patent application with publication number 136,909, 3a-acetoxy-24-nor-colan-23-one is mentioned as intermediates; the methyl ester of 3a-hydroxy-26,27-di-nor-23-trans-5β-cholest-23-en-25-carboxylic acid; 3a-hydroxy-26,27-di-nor-5β-cholesta-25-carboxylic acid methyl ester; 3-keto-26, 27-di-nor-5β-cholesta-25-carboxylic acid methyl ester; 3-keto-4-bromo-26, 27-di-nor-5β-cholesta-25-carboxylic acid methyl ester; 3-keto-26, 27-di-nor-cholest-4-en-25-carboxylic acid methyl ester; 3β-acetoxy-26,27-di-nor-cholesta-diene-25-carboxylic acid methyl ester; 3β-hydroxy-26, 27-di-nor-cholest-5-en-25-carboxylic acid methyl ester; 3-keto-26, 27-di-nor-cholest-4,6-dien-25-carboxylic acid methyl ester; 3β-hydroxy-26,27-di-nor-cholesta-3,5,7-trien-25-carboxylic acid methyl ester; and 3-hydroxy-26,27-di-nor-cholesta-5,7-diene-25-carboxylic acid methyl ester are mentioned as intermediates.

The Danish patent application with publication number 146,390, has to do with compounds that have possibly pharmacological properties, for example, an inhibiting action of the cholesterol production in serum. Examples of the compounds specifically mentioned herein are 3β, 22-di-acetoxicolesta-5-en-25-ol; 3β, 22-diacetoxy-25-fluorocholesterol-5-ene; 22-hydroxycholesta-5-en-25-fluoro-3β-hemi succinate; 3β, 22-diacetoxy-25-dichlorocholesterol-5-ene; 3β, 22-dihydroxy-25-chlorocholesterol-5-ene; 22-hydroxy-25-chlorocholesterol-5-en-3β-hemisuccinate; 3β, 22-dihydroxy-25-bromocholesterol-5-ene; and 3β, 22-dihydroxy-25-fluorocholesterol-5-ene. In the Danish patent applications with publication numbers 156,726 and 156,644, the broader acid is mentioned as intermediates; 3β-acetoxylesta-5-en-25-de-d? methyl-24-one; 3, 24-d? Acetox? Colesta-25-de-d? Methyl-5, 23-diene; 3ß-acetoxy-cholesta-25-des-methyl-5-en-24-difluoro-25-one; and 3ß-acetoxy-24-difluorocholesterol-5, 7-d? en-25-ol. In the Danish patent application with publication number 158,790, 3β-hydroxy-cholest-5-en-24-one; 3ß-acetox? Colest-5-en-24-one; 5ß-cholest-24-one; 5β-cholestan-24a-homo-24-one; 3a, 6a- dihydroxy-5β-cholest-2 -one; 3a, 6a-diacetoxy-5β-cholest-24-one; 3a, 6a-diacetoxy-5β-cholest-24a-homo-24-one; 3a, 6a-dihydroxy-5β-cholest-24a, 24β-bis-homo-24-one; 3a-hydroxy-5β-cholest-24-one; 3a-acetoxy-5β-cholesta-24-one; 3a-benzoyl-oxy-5β-cholesta-24-one; 3a-ethyloxycarbonyloxy-5β-cholesta-24-one; 3a-hydroxy-5β-cholestan-24a-homo-24-one; 3a-hydroxy-24a, 24β-bis-homo-5β-cholestane; 3β-hydroxy-cholesta-5, 7-dien-24-one; 3ß-acetoxycholesta-5, 7-dien-24-one; la, 3ß-dihydroxicolesta-5, 7-diene-24-one; and 3β-diacetoxicolesta-5, 7-diene-24-one are mentioned as intermediates. The Danish patent application with publication number 159, 456 has to do with the compounds that are possibly useful in the treatment of bladder dyskinesia. Examples of compounds specifically mentioned herein are chenodeoxycholic acid; ursodeoxycholic acid; trimebutin salt of chenodeoxycholic acid; and the trimebutin salt of ursodeoxycholic acid. In the Danish patent application with publication number 162,648, 3β, 25-dihydroxy-cholest-5-en-24-one are mentioned as intermediates; 3ß-acetoxylest-5-en-24-one; 3ß-acetoxy-25- hydroxycholest-5-en-24-one; 3ß, 25-dihydroxycholest-5-en-24-one; 3β-hydroxycholest-5-en-24-one; 3β-hydroxy-25-hydroxycholest-5-en-24-one; 3β, 24,25-trihydroxycholest-5-ene; 3β-dihydroxy-cholest-5-en-24-one; la, 3β, 25-trihydroxicolest-5-en-24-one; la, 3ß, 24, 25-tetrahydroxy-cholest-5-en-24-one. In the Danish patent application with publication number 165,410, 3a-acetoxy-7a-bromocolest-5-ene is mentioned as intermediates; 3a-acetoxycholesta-5, 7-diene; and 3a-acetoxy-25-hydroxycholesta-5, 7-diene. In the Danish patent application with publication number 165,695 are mentioned as intermediates for the preparation of the vitamin D analogues, 3β, 25-dihydroxy-26, 27-hexafluoro-cholest-5-ene; and, 3β, 25-trihydroxy-26,27-hexafluoro-cholest-5-ene. The Danish patent application with publication number 167,220 has to do with compounds that are possibly useful for the treatment of liver disorders. An example of a compound specifically mentioned herein is 3a, 7a, 12a, 24R, 26, 27-hexahydroxycholestane. In U.S. Patent No. 4,425,274, acid is described as intermediate 3a-hydroxy-7-collane; 3a, 7a-dihydroxycholanic acid; 3a, 7β-dihydroxycalanic acid; Y 3a, 7β-lithium dihydroxycholate. In the Norwegian patent application with publication number 144,264, cholesta-1,4,6-trien-3-one is mentioned as intermediates; cholest-5-en-la, 3β-diol; la-hydroxycholesta-4,6-dien-3-one; la, 3β-di-hydroxycholest-5-ene; 25-hydroxycholesta-1,4,6-triene-3-one; and la, 3ß-25-trihydroxy-cholest-5-ene for the preparation of la-hydroxysteroids of the cholestane series. The Norwegian patent application with publication number 158,423, has to do with the compounds that have possibly useful in the treatment of biliary dyskinesia. An example of a compound specifically mentioned herein is 3a, 7β-dihydroxy-toxicolic acid. In the Norwegian patent application with publication number 162,562, mention is made as intermediates in the preparation of the ursodeoxycholic acid, the 3a, 7a-dihydroxy-toxicolic acid; 7-ketodeoxycholic acid; 3a, 7β-dihydroxy-toxicolic acid; colic acid; 7-ketocholic acid; 3a, β, 12a-cholic acid; and 12-ketocholic acid.

In the Norwegian patent application with publication number 162,665, there are mentioned as intermediates in the preparation of ursodeoxycholic acid, cholic acid; 3a-hydroxy-7-ketocholic acid; 3a, 7a-diacetoxycholic acid; 3a, 7a-diacetoxy-12-ketocholic acid; 3a, 7a-dihydroxy-toxicolic acid; 7-ketodeoxycholic acid; 3a, 7β-dihydroxy-toxicolic acid; and 3a, 7β-dihydroxy-12-ketocholic acid. In the Norwegian patent application with publication number 303,450, colic acid is mentioned as intermediates; methyl ester of cholic acid; 3-acetylcholic acid methyl ester; 3- (2-propenyl) cholic acid methyl ester; 3-methyl ester of 3- (3-hydroxypropyl) -colic acid; deoxycholic acid; 12-ketodeoxycholic acid; 3β-acetyloxy-12-keto-deoxycholic acid; 3β- (hydroxyethyloxy) cholic acid methyl ester; 3β- (hydroxypropyloxy) cholic acid methyl ester; 3β- (hydroxybutyloxy) cholic acid methyl ester; 3β- (hydroxy-phenyloxy) -cholic acid methyl ester; 3β- (hydroxyhexyloxy) cholic acid methyl ester; 3β- (hydroxydecanoyloxy) cholic acid methyl ester; 3β- (2-hydroxyethyl-oxy-oxy) -olic acid methyl ester; ester 3β- (2-hydroxypropyloxy) cholic acid methyl ester; 3β- (hydroxyethyloxy) deoxycholic acid methyl ester; 3β- (hydroxypropyloxy) deoxycholic acid methyl ester; 3β- (hydroxy-phenyloxy) -deoxycholic acid methyl ester; 3β- (hydroxydecyloxy) deoxycholic acid methyl ester; 3β- (2-hydroxyethyloxy) chenodeoxycholic acid methyl ester; 3β- (3-hydroxypropyloxy) chenodeoxycholic acid methyl ester; 3β- (5-hydroxypenthyloxy) chenodeoxycholic acid methyl ester; 3β- (1 O-hydroxydecyloxy) chenodeoxycholic acid methyl ester; 3β- (2-hydroxyethyl-oxy) lithocholic acid methyl ester; 3β- (3-hydroxypropyloxy) lithocholic acid methyl ester; 3β- (5-hydroxypentyloxy) lithocholic acid methyl ester; 3β- (10-hydroxydecayloxy) lithocholic acid methyl ester; 3β- (benzyloxyethyloxy) cholic acid methyl ester; 3-β-benzyloxyethyloxy) tert-butyl ester; 3-β- (2-hydroxyethyloxy) cholic acid tert-butyl ester; 3β- (2-hydroxyethyloxy) -7a, 12a-diacetyloxycholic acid methyl ester; and methyl 3β- (propionyloxy) -7a, 12a-diacetyloxy-24-carboxylic acid methyl ester.

In the Swedish patent application with publication number 385,905, the chenodeoxycholic acid which has utility for the treatment of cholelithiasis is mentioned and the cholic acid is mentioned as an intermediary for the preparation thereof. In the Swedish patent application with publication number 402, 62 mention is made of the sitosterol which may have medical application, for example for the prevention or reduction of cholesterol absorption in the small intestine, and campesterol is mentioned to diminish the effect of the sitosterol. In the Swedish patent application with publication number 413,247, it is mentioned that 3a-hydroxycholestane and 3β-hydroxycholestane have anti-inflammatory properties and slight side effects. The Swedish patent application with publication number 430,508 concerns compounds that have possibly pharmacological properties, for example, the inhibition of HMG-CoA reductase and inhibition of serum cholesterol formation. Examples of compounds specifically mentioned herein are 25-fluorocolest-5-en- 3β, 22-diol; 25-chlorocholest-5-en-3β, 22-diol; 22-hydroxy-25-fluorocolest-5-en-3β-hemisuccinate; 22-hydroxy-25-chlorocholest-5-en-3β-hemisuccinate; and cholesta-5-en-3β, 22.25-triol. Compounds known to stimulate meiosis and which are different from the compounds claimed in the present patent application are described in International patent applications having Nos. WO 96/00235, 96/27658 and 97/00884, (Novo). Nordisk A / S) and 98/55498. In the International patent application having the No. WO 98/52965, filed on May 11, 1998 and published on November 26, 1998, it is established that certain 20-aralkyl-5a-pregnane derivatives can be used in the preparation of a medicament for the control of fertility and some of the specific compounds mentioned herein are (3ß, 5a, 20R) -4, 4, 20-trimethyl-21-phenylpregna-8, 14-dien-3-ol ( Example 1); (3ß, 5a, 20R) -4, 4, 20-trimethyl-21- (3-methylphenyl) pregna-8, 14-dien-3-ol (Example 2A); and (3β, 5a, 20R) -4, -dimethyl-23-phenyl-24-norcola-8,14-dien-3-ol (Example 7A). The compounds described herein have advantages compared to known compounds.

BRIEF DESCRIPTION OF THE INVENTION A main purpose of this invention is to provide compounds that can be used to regulate meiosis. One purpose of the present invention is to provide compounds and methods useful for alleviating infertility in male and female individuals, particularly in mammals, more particularly in humans. In a further objective, the present invention has to do with the use of the compounds of the general formula lc (described in the claims, below) to alleviate infertility in male and female individuals, particularly in mammals, more particularly in humans. In a further objective of the present invention, the compounds of the general formula I are useful as contraceptives in male and female individuals, particularly in mammals, more particularly in humans. In still another embodiment, the invention relates to esters, salts, active metabolites and prodrugs of the compound of the general formula la.

In another preferred embodiment, the present invention relates to the compounds of the general formula Ib (set forth in the following claims) or the esters, salts, active metabolites or prodrugs thereof as a medicament. In a further preferred embodiment, this invention relates to the compounds of the general formula I (described in the following claims) or esters, salts, active metabolites or prodrugs thereof in the manufacture of a medicament for use in the regulation of meiosis In a further preferred aspect, the present invention relates to the use of a compound of the formula Ib / Ic or an ester, salt, active metabolite or prodrug thereof as a medicament, in particular as a medicament for use in the regulation of meiosis The compound can be used neat or in the form of a liquid or solid composition containing auxiliary ingredients conventionally used in the art. In the present context, the expression "regulation of meiosis" is used to indicate that certain of the compounds of the formula la, Ib or can be used to stimulate meiosis in vitro, in vi, or ex vi vo. In this way, the compounds of the formula la, Ib or le which can be agonists of a meiosis-activating substance, of natural origin, can be used in the treatment of infertility that is due to insufficient stimulation of meiosis in men. and in women. Other compounds of the formula la, Ib or le, which can be antagonists of a meiosis-activating substance of natural origin, can be used to regulate meiosis, preferably in vivo, in a manner that makes them suitable as contraceptives. In this case, "regulation" means partial or total inhibition. In a further preferred aspect, the present invention relates to the use of a compound of the formula I or an ester, salt, active metabolite or prodrug thereof in the regulation of the meiosis of an oocyte, in particular a mammalian oocyte, more particularly a human oocyte. In a further preferred aspect, the present invention relates to the use of a compound of the formula le or an ester, salt, active metabolite or prodrug thereof in the stimulation of the meiosis of an oocyte, in particular a mammalian oocyte, more particularly a human oocyte. In a further preferred aspect, the present invention relates to the use of a compound of the formula I or an ether, salt, active metabolite or prodrug thereof in the inhibition of the meiosis of an oocyte, in particular a mammalian oocyte, more particularly a human oocyte. In a further preferred aspect, the present invention relates to the use of a compound of formula I or an ester, salt, active metabolite or prodrug thereof in the regulation of meiosis of a male germ cell, in particular a male germ cell of mammal, more particularly a male germinal cell of a human. In a further preferred aspect, the present invention relates to the use of a compound of the formula le or an ester, salt, active metabolite or prodrug thereof in the stimulation of the meiosis of a male germ cell, in particular a male germ cell of mammal, more particularly a male germinal cell of a human.

In a further preferred aspect, the present invention relates to the use of a compound of the formula le or an ester, salt, active metabolite or prodrug thereof in the inhibition of the meiosis of a male germ cell, in particular a male germ cell. of mammal, more particularly a male germinal cell of a human. In a further preferred aspect, the present invention relates to a method for regulating meiosis in a mammalian germ cell, which method comprises administering an effective amount of a compound of the formula I or an ester, salt, active metabolite or prodrug from it to a germ cell in need of such treatment. In a further aspect, the present invention relates to a method of regulating meiosis in a mammalian germ cell, wherein a compound of the formula I or an ester, salt, active metabolite or prodrug thereof is administered to the cell germinal by administering the compound to a mammal harboring said cell.

In a further aspect, the present invention relates to a method wherein the germ cell, the meiosis of which is to be regulated by means of a compound of the formula I or an ester, salt, active etabolite or prodrug thereof is an oocyte In a further aspect, the present invention relates to a method for regulating meiosis in an oocyte, wherein a compound of formula c or an ester, salt, active metabolite or prodrug thereof is administered to the exo ve oocyte. In a further aspect, the present invention relates to a method for regulating meiosis of a male germ cell by administering a compound of formula I or an ester, salt, active metabolite or prodrug thereof to the cell. In a further aspect, the present invention relates to a method by which mature male germ cells are produced by in vi ve or in vi tro administration of a compound of the formula le or an ester, salt, active metabolite or prodrug from the same to testicular tissue that contains the immature cells. In a further aspect, the present invention relates to the compounds of the formula la. Ib and you have improved stability. According to the present invention, novel compounds of the formula la (described in claim 1 below) with interesting pharmacological properties are provided. The compounds described herein are useful for regulating meiosis in oocytes and in male germ cells.

DETAILED DESCRIPTION OF THIS INVENTION It has surprisingly been found that compounds having a side chain (R22) which is different from the side chains of cholesterol and lanosterol or compounds having specifically certain substituents chosen in the ring system, have superior properties. The preferred compounds of the formula la, Ib and c are such that they have a double bond. Other preferred compounds of the formula la, Ib and le are those wherein R 1 is hydrogen.

Other preferred compounds of the formula la, Ib and le are those wherein R 1 is halogen. Other preferred compounds of the formula la. Ib and are those where R1 is methyl. Other preferred compounds of the formula la. Ib and I are those where R1 is hydroxyl. Other preferred compounds of the formula la, Ib and le are those wherein R1 is oxo. Other preferred compounds of the formula la, Ib and le are those in which R2 together with R3 designates an additional bond between the carbon atoms in which R2 and R3 are placed. Other preferred compounds of the formula la, Ib and le are those wherein R2 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R2 is hydroxyl. Other preferred compounds of the formula la, Ib and le are those wherein R2 is alkyl of 1 to 3 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R2 is alkoxy of 1 to 3 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R2 is halogen.

Other preferred compounds of the formula la, Ib and le are those wherein R3 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R3 is hydroxyl. Other preferred compounds of the formula la. Ib and I are those in which R3 is alkoxy, aralkyloxy, alkoxyalkoxy or alkanoyloxyalkyl, each group comprising a total of up to 10 carbon atoms, preferably up to 8 carbon atoms. Other preferred compounds of the formula la. Ib and I are those wherein R 3 is alkoxy of 1 to 4 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R 3 is methoxy. Other preferred compounds of the formula la, Ib and le are those wherein R3 is ethoxy. Other preferred compounds of the formula la, Ib and le are those wherein R3 is CH3OCH20-. Other preferred compounds of the formula la, Ib and le are those wherein R3 is pivaloyloxymethoxy. Other preferred compounds of the formula la, Ib and le are those wherein R3 is a group acyloxy derived from an acid having from 1 to 20 carbon atoms. Other preferred compounds of the formula la, Ib and le are those in which R3 is an acyloxy group selected from the group consisting of acetoxy, benzoyloxy, pivaloyloxy, butyryloxy, nicotinoyloxy, isonicotinoyloxy, hemisuccinoyloxy, hemiglutaroyloxy, butylcarbamoyloxy, phenylcarbamoyloxy, butoxycarbonyloxy, tert-butoxycarbonyloxy and ethoxycarbonyloxy. Other preferred compounds of the formula la, Ib and le are those wherein R3 is sulfonyloxy.

Other preferred compounds of the formula la, Ib and le are those wherein R3 is phosphonyloxy. Other preferred compounds of the formula la, Ib and le are those wherein R3 together with R3 is oxo. Other preferred compounds of the formula la, Ib and le are those wherein R3 is the group = NOH. Other preferred compounds of the formula la, Ib and le are those wherein R3 is a group of the general formula = NOR38, wherein R38 is alkyl of 1 to 3 carbon atoms.

Other preferred compounds of the formula la, Ib and le are those wherein R3 is halogen. Other preferred compounds of the formula la. Ib and I are those in which R3 is hydroxyl and alkyl of 1 to 4 carbon atom bonded to the same carbon atom of the sterol backbone. Other preferred compounds of the formula la, Ib and le are those wherein R3 is perfluoro- (lower alkyl), preferably perfluoro (lower alkyl) having from 1 to 6, preferably from 1 to 3, carbon atoms in the alkyl group , more preferably trifluoromethyl.

Other preferred compounds of the formula la, Ib and le are those wherein R 4 and R '4 are both hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein each of R 4 and R '4 is hydrogen, while the other is methyl. Other preferred compounds of the formula la, Ib and le are those wherein R4 and R'4 are both methyl. Other preferred compounds of the formula la, Ib and le are those in which R 4 is linear or branched alkyl of 1 to 6 carbon atoms. optionally substituted with halogen, hydroxyl or cyano. Other preferred compounds of the formula la. Ib and I are those in which R 'is linear or branched alkyl of 1 to 6 carbon atoms, optionally substituted by halogen, hydroxyl or cyano. Other preferred compounds of the formula la, Ib and le are those in which R 4 is hydroxyl and R 4 is selected from the group comprising hydrogen and alkyl of 1 to 6 carbon atoms branched or unbranched, which may be substituted with halogen, hydroxyl or cyano. Other preferred compounds of the formula la, Ib and le are those in which R '4 is hydroxyl and R4 is selected from the group comprising hydrogen and alkyl of 1 to 6 carbon atoms branched or unbranched, which may be substituted with halogen , hydroxyl or cyano. Other preferred compounds of the formula la, Ib and le are those in which R4 and R'4 together designate methylene. Other preferred compounds of the formula la, Ib and le are those wherein R4 and R'4 together with the carbon atom to which they are attached form a cycle of cyclopropane. Other preferred compounds of the formula la. Ib and I are those in which R4 and R'4 together with the carbon atom to which they are attached form a cycle of cyclopentane. Other preferred compounds of the formula la, Ib and le are those wherein R 4 and R '4 together with the carbon atom to which they are attached, form a cyclohexane cycle. Other preferred compounds of the formula la, Ib and le are those wherein R5 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R 5 is halogen. Other preferred compounds of the formula la. Ib and I are those where R5 is hydroxyl. Other preferred compounds of the formula la, Ib and le are those in which R 5 is alkyl having 1 to 3 carbon atoms, preferably methyl, cyano or hydroxymethyl, or R 5 is, together with R 4, a methane bridge or R 5 is, together with R4, an additional link. Other preferred compounds of the formula la, Ib and le are those wherein R 5 is an amide primary or secondary derivative of a carboxylic acid. Other preferred compounds of the formula la, Ib and le are those wherein R 5 is an ester with an alcohol group of 1 to 6 carbon atoms. Other preferred compounds of the formula la. Ib and are those where R6 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R6 is halogen. Other preferred compounds of the formula la. Ib and are those where R6 is oxo. Other preferred compounds of the formula la, Ib and le are those wherein R6 is hydroxyl. Other preferred compounds of the formula la, Ib and le are those in which R6, together with R5, designates an additional bond between the carbon atoms in which R5 and R6 are placed. Other preferred compounds of the formula la. Ib and are those where R7 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R7 is methylene. Other compounds of the formula la, Ib and le are those wherein R7 is hydroxyl.

Other preferred compounds of the formula la, Ib and le are those wherein R7 is methoxy or acetoxy. Other preferred compounds of the formula la, Ib and le are those wherein R7 is halogen. Other preferred compounds of the formula la, Ib and le are those wherein R7 is oxo. Other preferred compounds of the formula la, Ib and le are those wherein R7 is the group = NOH. Other preferred compounds of the formula la, Ib and le are those wherein R7 is a group of the general formula = NOR36, wherein R36 is alkyl of 1 to 3 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R7 is simultaneously hydroxyl and alkyl of 1 to 4 carbon atoms both being attached to the same carbon atom of the sterol backbone, for example, in position 7. Other compounds preferred of the formula la. Ib and I are those in which R7, together with R9, designates an additional bond between the carbon atoms in which R7 and R6 are placed.

Other preferred compounds of the formula la, Ib and le are those wherein R7 together with Re designates an additional bond between the carbon atoms in which R7 and R8 are placed. Other preferred compounds of the formula la, Ib and le are those in which R8 together with R9 designates an additional bond between the carbon atoms in which R8 and R9 are placed. Other preferred compounds of the formula la, Ib and le are those wherein R8 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R8 is halogen. Other preferred compounds of the formula la, Ib and le are those wherein R8 is hydroxyl. Other preferred compounds of the formula la, Ib and le are those in which R9 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R9 is halogen. Other preferred compounds of the formula la, Ib and le are those wherein R9 is hydroxyl. Other preferred compounds of the formula la, Ib and le are those wherein R 11 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R 11 is methylene.

Other preferred compounds of the formula la, Ib and le are those wherein R11 is hydroxyl.

Other preferred compounds of the formula la, Ib and le are those wherein R 11 is halogen. Other preferred compounds of the formula la, Ib and le are those wherein R 11 is methoxy or acetoxy. Other preferred compounds of the formula la, Ib and le are those wherein R 11 is oxo. Other preferred compounds of the formula la, Ib and le are those wherein R 11 is the group = NOH. Other preferred compounds of the formula la, Ib and le are those in which R11 is a group of the general formula = NOR37, wherein R37 is alkyl of 1 to 3 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R 11 is simultaneously hydroxyl and alkyl of 1 to 4 carbon atoms both being attached to the same carbon atom of the sterol backbone, for example, in position 11. Other compounds preferred of the formula la, Ib and le are those where R11, together with R9, designates an additional bond between the carbon atoms in which R11 and R9 are placed. Other preferred compounds of the formula la, Ib and le are those in which R11, together with R12, designates an additional bond between the carbon atoms in which R11 and R12 are placed. Other preferred compounds of the formula la, Ib and le are those wherein R 12 is hydrogen.

Other preferred compounds of the formula la, Ib and le are those wherein R12 is halogen. Other preferred compounds of the formula la, Ib and le are those wherein R 12 is alkyl of 1 to 4 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R12 is methylene. Other preferred compounds of the formula la, Ib and le are those wherein R12 is hydroxyl. Other preferred compounds of the formula la, Ib and le are those wherein R 12 is methoxy or acetoxy. Other preferred compounds of the formula la, Ib and le are those wherein R12 is oxo. Other preferred compounds of the formula la, Ib and le are those wherein R12 is the group = NOH.

Other preferred compounds of the formula la. Ib and I are those in which R12 is a group of the general formula = NOR33, wherein R33 is alkyl of 1 to 3 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R 14 is hydrogen.

Other preferred compounds of the formula la, Ib and le are those wherein R 14 is hydroxyl.

Other preferred compounds of the formula la, Ib and le are those in which R14, together with R8, designates an additional bond between the carbon atoms in which R14 and R8 are placed. Other preferred compounds of the formula la. Ib and are those where R15 is hydrogen. Other preferred compounds of the formula la, Ib and le are those in which R15 is halogen. Other preferred compounds of the formula la, Ib and le are those wherein R 15 is alkyl of 1 to 4 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R15 is methylene. Other preferred compounds of the formula la, Ib and le are those wherein R15 is hydroxyl.

Other preferred compounds of the formula Other preferred compounds of the formula la, Ib and le are those wherein R15 is oxo. Other preferred compounds of the formula la, Ib and le are those wherein R15 is the group = NOH. Other preferred compounds of the formula la, Ib and le are those in which R15 is a group of the general formula = NOR32, wherein R32 is alkyl of 1 to 3 carbon atoms. Other preferred compounds of the formula la, Ib and le are those in which R15, together with R14, designates an additional bond between the carbon atoms in which R15 and R14 are placed. Other preferred compounds of the formula la, Ib and le are those wherein R16 is hydrogen.

Other preferred compounds of the formula la. Ib and are those where R16 is halogen. Other preferred compounds of the formula la, Ib and le are those wherein R16 is alkyl of 1 to 3 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R16 is methylene. Other preferred compounds of the formula la, Ib and le are those in which Rle is hydroxyl.

Other preferred compounds of the formula la, Ib and le are those wherein R16 is methoxy. Other preferred compounds of the formula la. Ib and are those where R16 is oxo. Other preferred compounds of the formula la, Ib and le are those wherein R16 is the group = NOH. Other preferred compounds of the formula la, Ib and le are those wherein R16 is a group of the general formula = NOR34, wherein R34 is alkyl of 1 to 3 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R 16 together with R 17, designates an additional bond between the carbon atoms in which R 16 and R 17 are placed. Other preferred compounds of the formula la, Ib and le are those wherein R17 is hydrogen.

Other preferred compounds of the formula la. Ib and are those where R17 is hydroxyl. Other preferred compounds of the formula la, Ib and le are those in which R17 is in the a position. Other preferred compounds of the formula la, Ib and le are those wherein R 20 is hydrogen.

Other preferred compounds of the formula la, Ib and le are those wherein R 20 is hydroxymethyl. Other preferred compounds of the formula la, Ib and le are those wherein R 20 is alkyl of 1 to 4 carbon atoms. Other preferred compounds of the formula la, Ib and le are those wherein R20 together with R'20 designates methylene. Other preferred compounds of the formula la, Ib and le are those in which R20 together with R'20 designates oxo. Other preferred compounds of the formula la, Ib and le are those wherein R'20 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R'20 is halogen.

Other preferred compounds of the formula la, Ib and le are those wherein R '20 is methyl. Other preferred compounds of the formula la. Ib and are those where R '20 is hydroxyl.

Other preferred compounds of the formula la, Ib and le are those in which R22 is cyclohexyl optionally substituted with one or more of the following groups, which substituents may be different or identical: hydroxyl, alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N-dialkylamino wherein the N-alkylamino or the N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or alkylthio lower; cyclohexylalkyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N - dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; alkyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-acylamino, N-alkylamino or N, N-dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; or alkenyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N-dialkylane wherein the substituent N-alkylamino or N, N- dialkylamino optionally is substituted by carboxyl, lower alkoxy or lower alkylthio; and R39 represents lower alkyl or aralkyl, for example, benzyl. Other preferred compounds of the formula la, Ib and le are those in which R22 is phenyl, cyclohexyl, benzyl, o-tolyl, m-tolyl, p-tolyl, but-3-enyl, 3-methylbut-3-enyl, -methylpropyl, 2-oxo-2-ethoxyethyl, 2-oxo-2- (N, N-dimethylamino) ethyl, carboxymethyl, 3-hydroxymethylbutyl, 2-cyanoethyl, cyclohexylmethyl, 3-chloro-3-methylbutyl, 2- (N , N-dimethylamino) -2-cyanoethyl, 2-chloroethyl, 2-iodoethyl, ethyl, 2-phenylethyl, 2-methoxyethyl, 2-benzyloxyethyl or 2-acetoxyethyl. Other preferred compounds of the formula la, Ib and le are those wherein R'22 is hydrogen. Other preferred compounds of the formula la, Ib and le are those in which the side chain at position 17 (for example -C (R20) (R'20) -CH (R22) (R'22)) is in the position H.H.

Other preferred compounds of the formula la, Ib and le are those wherein R2 together with R3 is an additional double bond and R'3 is hydrogen. Other preferred compounds of the formula la, Ib and le are those wherein R 1 is hydrogen, halogen, methyl, hydroxyl or oxo; R2 is selected from the group comprising hydrogen, hydroxyl, alkyl of 1 to 3 carbon atoms, vinyl, alkoxy of 1 to 3 carbon atoms and halogen, or R2 designates together with R3 an additional bond between the carbon atoms in which R2 and R3 are placed; R3 is selected from the group comprising hydrogen, hydroxyl, optionally substituted alkoxy, acyloxy, sulfonyloxy, phosphonyloxy, oxo, halogen, alkyl of 1 to 4 carbon atoms and a group of the general formula = NOR38 wherein R38 is hydrogen or alkyl of 1 to 3 carbon atoms, or R3 together with R2 designates an additional bond between the carbon atoms in which R2 and R3 are placed; wherein R 4 and R 4 ', which are different or identical, with the proviso that they are not both hydroxyl, are selected from the group comprising hydrogen, halogen, hydroxyl and alkyl of 1 to 6 carbon atoms branched or unbranched which may be substituted with halogen, hydroxyl or cyano, or where R4 and R4 'together designate methylene or oxo or, together with the carbon atom to which they are attached, form a cyclopropane ring, a cyclopentane ring, or a cyclohexane ring; R5 is hydrogen, halogen or hydroxyl, or R5 denotes, together with R6, an additional bond between the carbon atoms in which R5 and R6 are placed; R6 is hydrogen, hydroxyl, halogen or oxo, or R6 designates, together with R5 or R7, an additional bond between the carbon atoms in which R6 and R5 or R7 are placed; R7 is selected from the group comprising hydrogen, methylene, hydroxyl, methoxy, acetoxy, oxo, halogen, alkyl of 1 to 4 carbon atoms and a group of the general formula = NOR36 wherein R36 is hydrogen or alkyl of 1 to 3 atoms carbon, or R7 designates, together with R6 or R8, an additional bond between the carbon atoms in which R7 and R6 or R8 are placed; R8 is hydrogen, hydroxyl or halogen, or R8 denotes, together with R7, R9 or R14, an additional bond between the carbon atoms in which R8 and R7, R9 or R14 are placed; R9 is hydrogen, hydroxyl or halogen, or R9 designates, together with R8 or R11, an additional bond between the carbon atoms in which R9 and R8 or R11 are placed; R11 is selected from the group comprising hydrogen, methylene, hydroxyl. methoxy, acetoxy, oxoV-halogen, alkyl of 1 to 4 carbon atoms and a group of the general formula = NOR37 wherein R37 is hydrogen or alkyl of 1 to 3 carbon atoms, or R11 designates, together with R9 or R12, an additional bond between the carbon atoms in which R11 and R9 or R12 are placed; R12 is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 4 carbon atoms, methylene, hydroxyl, methoxy, acetoxy, oxo and a group of the general formula = NOR33 wherein R33 is hydrogen or alkyl of 1 to 3 atoms of carbon, or R12 designates, together with R11, an additional bond between the carbon atoms in which R11 and R12 are placed; R14 is hydrogen or hydroxyl, or R14 designates, together with R15, an additional bond between the carbon atoms in which R14 and R15 are placed; R15 is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 4 carbon atoms, methylene, hydroxyl, methoxy, oxo and a group of the general formula = NOR32 wherein R32 is hydrogen or alkyl of 1 to 3 carbon atoms , or R15 designates together with R14 an additional bond between the carbon atoms in which R15 and R14 are placed; R16 is selected from the group comprising hydrogen, halogen, alkyl of 1 to 3 carbon atoms, methylene, hydroxyl, methoxy, oxo and a group of the general formula = NOR34 wherein R34 is hydrogen or alkyl of 1 to 3 carbon atoms, or R16 designates, together with R17 an additional bond between the carbon atoms in which they place R16 and R17; R17 is hydrogen or hydroxyl, or R17 denotes, together with R16, an additional bond between the carbon atoms in which R17 and R16 are placed; R20 is selected from the group comprising hydrogen, alkyl of 1 to 4 carbon atoms and hydroxymethyl, or R20 and R20 'together denote methylene or oxo; R20 'is hydrogen, halogen, alkyl or hydroxyl, R22' is hydrogen, hydroxyl or oxo; R22 represents phenyl optionally substituted with one or more of the following groups, which substituents may be different or identical: hydroxyl, alkoxy, halogen (chloro, bromo or iodo), amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; benzyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen, (chloro, bromo or iodo), amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; cyclohexyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen (chlorine, bromine or iodine), amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; cyclohexylalkyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen (chloro, bromo or iodo), amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; alkyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen (chloro, bromo or iodo), amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; alkenyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen (chloro, bromo or iodo), ammo, N-alkylamino, N, N-dialkylamino, cyano, caboxyl or oxo; and esters of them. Other preferred compounds of the formula la, Ib and le are those wherein R7 R2"'7 R5 / R", R12, RU R16, R'20 and R'22 are each hydrogen, R3 is hydrogen, lower alkyl or perfluoro (lower alkyl), R'3 is hydroxyl, or R3 denotes, together with R'3, oxo, R4 is hydrogen or together with R 5 is a methane bridge or together with R an additional bond, R 5 is lower alkyl, cyano, hydroxymethyl, a carbaldehyde, an oxime derived from a carbaldehyde, a carboxylic acid, a primary or secondary amide derived from a carboxylic acid, an ester with an alcohol group of 1 to 6 carbon atoms or together with R4 a methane bridge, or together with R4 an additional bond, R7 is together with R8 an additional bond or a hydrogen atom, if R8 and R9 or R8 and R14 remain together for an additional bond, R8 is together with R7 or with R9 or with R14 a additional bond, R9 is together with Rs an additional bond or a hydrogen atom, if R7 and R8 or R8 and R14 remain together for an additional bond, R14 is, together with RB an additional bond or a hydrogen atom, if R ' and R8 or R8 and R9 remain together for an additional bond, R17 is hydrogen in the alpha position, R19 is methyl in the beta position, R20 is methyl in the alpha position, and R22 is 3-methylbutyl; and the ester, salt, active metabolite or prodrugs thereof. Other preferred compounds of the formula la, Ib and le are those wherein R 5 is an alkyl group of 1 to 3 carbon atoms, preferably a methyl group, a cyano group, a group hydroxymethyl or together with R4 a methane bridge or together with R4 an additional bond. It should be understood that the aforementioned preferred substituents can be combined in any way with each other. Examples of interesting and preferred compounds of the general formula la, Ib and le are the following: (20R) -20-methyl-21-phenyl-5a-pregna-8, 14-dien-3β-ol; (20R) -20-methyl-21- (3-methylphenyl) -5a-pregna-8, 14-dien-3β-ol; (20R) -2 O-methyl-21- (3-hydroxyphenyl) -5a-pregna-8, 14-dien-3β-ol; (20RJ-20-methyl-21- (cyclopentyl) -5a-pregna-8, 14-diene-3ß-ol; 24-nor-cholest-8, 14-diene-3ß-ol; (20R) -2 O- meti 1-21- (cyclohexyl) -5a-pregna-8, 14-dien-3ß-ol; (20RJ-20-met? l-22-phenyl-5a-pregna-8, 14-d? en-3ß- ol; 23,24-d? nor-cholest-8, 14-dien-3ß-ol; (20R) -2 O-methi 1-21 - (cyclobutyl) -5a-pregna-8, 14-diene-3ß- ol; 4, 4-dimeti1-17ß- ((IR) -methyl-3-methyl-2-butenyl) androsta-8, 14-dien-3-β-ol; (2 OR) -20-methyl-23- dimethylamino-5a-pregna-8, 14-dien-3β-ol; N, N-dimethylamide of 3β-hydroxy-5a-cyanocol-8-en-24-o-co-N, N-dimethylamide of 5ß-acid methylcol-8-en-3-on-24-oico; N, N-dimethylamide of 3β-hydroxy-4, 4-dimethyl-5a-14β-cola-8, 15-dien-24-oico; 3β-hydroxy - 5a-cyanocolest-8-en-24-one; 5β-methylcol-8-en-3, 24-dione; 3β-hydroxy-, 4-dimethyl-5a, 1β-cholesta-8,15-dien-24-one; 3-hydroxy-5a-cyanocol-8-en-24-oic acid cyclohexyl ester; 5-methyl-8-en-3-on-24-oic acid cyclohexyl ester; 3-hydroxy-4,4-dimethyl-5a, 14β-cola-8,15-dien-24-oic acid cyclohexyl ester; N- (4-methylpiperazinyl) amide of 3β-hydroxy-5a-cola-8,14-dien-24-oic acid; N- (4-methylpiperazinyl) amide of 3β-hydroxychola-5, 7-diene-24-oic acid; N- (4-methylpiperazinyl) amide of 3β-hydroxy-5a-cyanocol-8-en-24-oic acid; N- (4-methyl-piperazinyl) -amide of 5-methyl-8-en-3-on-24-oic acid; N- (4-methylpiperazinyl) amide of 3β-hydroxy-4,4-dimethyl-5a, 14β-cola-8,15-dien-24-oic acid; (20RJ-20-methyl-21-phenyl-5a-pregna-5, 7-diene-3β-ol; (20R) -20-methyl-21- (3-methylphenyl) -5a-pregna-5, 7- dien-3β-ol; (20R) -2 O-methyl 1-21- (3-hydroxy phenyl) -5a-pregna-5, 7-diene-3β-ol; (20R) -2 O-methyl-21- (cyclopentyl) -5a-pregna-5, 7-diene-3ß-ol; 24-nor-cholest-5, 7-diene-3ß-ol; (20R) -2 O -methi 1-21- (cyclohexyl) - 5a-pregna-5, 7-dien-3β-ol; (20R) -20-methyl-22-phenyl-5a-pregna-5, 7-dien-3β-ol; 23, 24-dinorcolest-5, 7- dien-3β-ol; (20R) -20-methyl-21- (cyclobutyl) -5a-pregna-5, 7-diene-3β-ol; 4, -dimethyl-17β- ((IR) -methyl-3- methyl-2-butenyl) androsta- , 7-dien-3ß-ol; (20R) -20-methyl-23-dimethylamino-5a-pregna-5, 7-dien-3β-ol; cholesta-5, 7-dien-25-chloro-3β-ol; cholesta-5, 7-dien-26-chloro-3-β-ol; cholesta-5,7-dien-26-ol; nor-24-cholesta-8, 1 l-dien-3β-ol; cholesta-4, 8-dien-3ß-ol; cholesta-4, 8-dien-3a-ol; cholesta-4, 8 (14) -dien-3ß-ol; cholesta-4, 8 (14) -dien-3a-ol; 5-cyano-5a-cholest-7-en-3a-ol; 5-cyano-5a-cholest-7-en-3β-ol; 5-cyano-5β-cholest-7-en-3a-ol; 5-cyano-5a-cholest-8-en-3a-ol; 5-cyano-5a-cholest-8-en-3β-ol; 5-cyano-5β-cholest-8-en-3a-ol; 5-cyano-5β-cholest-8-en-3β-ol; 5-cyano-5a-cholest-8 (14) -in-3a-ol; 5-cyano-5a-cholest-8 (14) -in-3β-ol; 5-cyano-5β-cholest-8 (14) -in-3a-ol; 5-cyano-5β-cholest-8 (1) -in-3β-ol; 3 ', 4a-dihydrocyclopropa [4,5] -5β-cholest-7-en-3β-ol; 3 ', 4β-dihydrocyclopropa [4, 5] -5a-cholest-7-en-3a-ol; 3 ', 4a-dihydrocyclopropa [4, 5] -5β-cholest-8-en-3β-ol; 3 ', 4β-dihydrocyclopropa [4, 5] -5a-cholest-8-en-3a-ol; 3 ', α-dihydrocyclopropa [4, 5] -5β-cholest-8 (14) -en-3β-ol; 3 ', 4β-dihydrocyclopropa [4,5] -5a-cholest-8 (14) -en-3a-ol; 5- (hydroxymethyl) -5a-cholest-7-en-3β-ol; 5- (hydroxymethyl) -5β-cholest-7-en-3a-ol; 5- (hydroxymethyl) -5a-cholest-en-3ß-ol; 5- (hydroxymethyl) -5β-cholest-8-en-3a-ol; 5- (hydroxymethyl) -5a-cholest-8 (14) -en-3ß-ol; 5- (hydroxymethyl) -5β-cholest-8 (14) -en-3a-ol; 5-methyl-5β-cholest-8-en-3-one; 5-methyl-5ß- cholest-8-en-3ß-ol; 5-methyl-5β-cholest-8-en-3a-ol; 5-methyl-5β-cholest-8 (14) -en-3-one; 5-methyl-5β-cholest-8 (14) -en-3β-ol; 5-methyl-5β-cholest-8 (14) -in-3a-ol; 3a- (trifluoromethyl) cholesta-4, 7-dien-3ß-ol; 3β- (tri fluoromethyl) cholesta-4, 7-diene-3a-ol; 3a- (trifluoromethyl) cholesta-4,8-dien-3β-ol; 3β- (trifluoromethyl) cholesta-4,8-dien-3a-ol; 3a- (trifluoromethyl) -4,8 (14) -dien-3β-ol; 3β- (trifluoromethyl) cholesta-4,8 (14) dien-3a-ol; 5-methyl-24-nor-5β-cholest-8 (14) -en-3-one; (20R) -5, 20-dimethyl-21-phenyl-5β-pregn-8 (14) -en-3-one; (20R) -21-cyclohexyl-5,20-dimethyl-5β-pregn-8 (14) -en-3-one; 5-methyl-24-nor-5β-cholesta-8 (14) -23-dien-3-one; 4,4-d? Met? L-24-benzoylamido-5a-cola-8, 14-dien-3ß-ol; 3-Hydroxy-, 4-dimethyl-5a-cola-8, 1 -d? In-24-o? Co-N-phenylaninamide; mono (3β-hydroxy-4,4-dimethyl-5a-cola-8, 14-diene) -24-succinate; ester (l-methyl-4-hydroxypiperidinyl) of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; N- (norleucin) 3-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide; N- (arginine) 3-hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide; N- (glutamic acid) 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid amide; N- (leucine) 3-hydroxy-4, 4-dimethyl-5a- acid amide cola-8, 14-dien-24-oico; 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid methyl ester; 3-hydroxy-4,4-dimethyl-5,7-dien-24-oic acid methyl ester; 3-hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid ethyl ester; 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; 3-hydroxy-, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid cyclohexyl ester; 3β-hydroxy-4,4-dimethyl-5a-cholesta-8,14-dien-24-one; 3β-hydroxy-4,4,24-trimethyl-5a-cola-8, 14-dien-24-one; 3β-hydroxy? -4,4-dimethyl-24-phenyl-5a-cola-8,14-dien-24-one; 3β-hydroxy-4, 4-dimethyl-2- (3-pentyl) -5a-cola-8,14-dien-24-one; N-phenylamide of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; 3β-hydroxy-, 4-d? methyl-5a-cola-8,1-diethylene-24-oic acid amide; 4, 4-d? Methyl-24-phenylamino-5a-cola-8, 1 -dien-3β-ol; 4, 4-dimethyl-24-amino-5a-cola-8, 14-dien-3β-ol; 4, 4-d? Met? L-5a-cola-8, 14-dien-3?, 24-diol; 3β-hydroxy-4,4-dimethyl-5α-cola-8,14-diene-24-aldehyde; 4,4-d? Methyl-17β - ((1 R) -methyl-4-methyl-3-pentenyl) -androsta-8, 14-dien-3β-ol; 4, 4-dimethyl-5a-cholesta-14,16, 24-trien-3ß-ol; 4, 4-dimethyl-17β- ((IR) -methi 1-3-methyl-2-butenyl) androsta-8,14-dien-3β-ol; (20R) -4.4, 20-t imeti 1-21- (4-methylphenyl) -5a-pregna-8, 1 -d? En-3β-ol; (20R) -4, 4, 20-tr? Methyl-21- (2-methylphenyl) - 5a-pregna-8, 14-dien-3ß-ol, (20R) -4,4-trimethyl-21- (cyclohexyl) -5a-pregna-8, 14-dien-3ß-ol; (20R) -4,4, 20-trimethyl-21- (3-hydroxy phenyl) -5a-pregna-8, 14-dien-3β-ol; (20R) -4, 4, 20-trimethy1-22- (cyclohexyl) -5a-pregna-8, 14-diene-3β-ol; 24-nor-4, 4-dimethyl-5a-cholest-8, 14-dien-3ß-ol; 27-nor-4, 4-dimethyl-5a-cholest-8,14, 25-trien-3ß-ol; (20R) -4,4-20-t-imethyl-21- (cyclobutyl) -5a-pregna-8,1-dieth-3ß-ol; (20R) -4,4, 20-trimethyl-21- (cyclopentyl) -5a-pregna-8, 14-dien-3β-ol; 25-chloro-4,4-dimethyl-5a-cholesta-8,14-dien-3β-ol; 4, 4-dimethyl-24- (N, N-dimethylamino) -24-cyano-5a-cholesta-8, 14-diene-3β-ol; 4, 4-dimethylcholest-8, 14,25-trien-3β-ol; 4, 4-dimethyl-17β- ((IR) -methyl-4-iodobutyl) androsta-8, 14-dien-3β-ol; 4, 4-dimethyl-17β- ((IR) -methylbutyl) androsta-8,14-dien-3β-ol; 4,4-dimethyl-17β - ((1 R) -methyl-4-cyanobutyl) androsta-8, 14-dien-3β-ol; 4, 4-dimethyl-17β- ((IR) -methyl 1-4-cyanobutyl) androsta-8, 14-dien-3β-ol; benzyl ester of 27-nor-3β-hydroxy-4,4-dimethyl-5a-cholesta-8,14-dien-26-oic acid; N- (methionine methyl ester) 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid amide; N- (methionine) amide of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-2 -oic acid; N- (4-methylpiperazinyl) amide of 3-hydroxy-, 4-dimethyl-5a-cola-8,14-dien-24-oic acid; N-tert-butylamide of 3β-hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid; N- (isonipecotic acid ethyl ester) 3β-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide; N- (isonipecotic acid) 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid amide; N- (3-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide of phenylalanine) amide; 3β-hydroxy-4,4-dimethyl-5,7,7-dien-24-oic acid; 3-Hydroxy-4, -dimethyl-5,7-dien-24-oic acid N-dimethylamide; 4, -dimethyl-24-acetamido-5a-cola-8, 14-dien-3β-ol; 4, 4-dimethyl-24-acetoxy-5a-cola-8, 14-dien-3β-ol; 4, 4-dimethyl-24-methoxy-5a-cola-8, 14-dien-3β-ol; 4-dimethyl-24-benzyloxy-5a-cola-8,14-dien-3β-ol; benzyl ester of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; 26,27-diethyl-3β-hydroxy-4,4-dimethyl-5a-cholesta-8, 14-diene-26,27-dioate; 3β-hydroxy-4, -dimethyl-5a-cholesta-8, 14-dien-26,27-dioic acid; and 27-nor-3β-hydroxy-4,4-dimethyl-5a-cholesta-8,14-dien-26-oic acid. The preferred compounds of the formula la, Ib and le are such that when tested by the method described below for the agonist properties (Example 71) they show a relative activity of at least 50, preferably at least 80, or when tested by the method described below for the antagonist properties (Example 72) shows an IC5o value below 10, preferably below 2. Examples of other preferred compounds are such that they are not active at the estrogen receptor, and preferably those compounds that are not active at other hormonal receptors. Additional preferred embodiments are mentioned in the appended claims. As used in the present description and in the claims, a lower alkyl group-when used alone or in combinations-can be a linear or branched alkyl group. Preferably, said alkyl group contains no more than 6 carbon atoms. Examples of preferred alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl and hexyl, more preferably methyl, ethyl, propyl, isopropyl, butyl and tert-butyl, still more preferably methyl and ethyl. In a preferred embodiment of this invention, the alkyl group contains no more than 4 carbon atoms, preferably no more than 3 carbon atoms.

As used in the present description and in the claims, alkoxy denotes a linear or branched alkoxy group, preferably containing not more than 6 carbon atoms, preferably not more than 4 carbon atoms, more preferably not more than 3 carbon atoms . Examples of preferred alkoxy groups are methoxy, ethoxy and propoxy, more preferably methoxy and ethoxy. As used in the present description and in the claims, N-alkylamino is an alkyl group connected to an amino group. Preferably, the alkyl group is a lower alkyl group as defined above. Preferred N-alkylamino groups are methylamino and ethylamino. As used in the present description and in the claims, N, N-alkylamino is two alkyl groups which are the same or different and which are connected to an amino group. Preferably, the alkyl group are lower alkyl groups as defined above. The preferred N, N-alkylamino groups are N, N-dimethylamino, N, N-diethylamino and N-methyl-N-ethylamino. As used in the present description and in the claims, the expression "alkenyl" denotes a straight or branched chain alkenyl group preferably containing not more than 6 carbon atoms, preferably not more than 3 carbon atoms. As used in the present description and in the claims, the expression "halogen" preferably designates chlorine, bromine or iodine. Another group of preferred halogens are fluorine and chlorine, preferably fluorine. As used in the present description and in the claims, the term cycloalkyl of 3 to 6 carbon atoms designates a cycloalkyl group containing from 3 to 6 carbon atoms in the ring. Preferred examples are cyclopropyl and cyclopentyl. As used in the present description and in the claims, the expression "acyloxy" designates a monovalent substituent comprising an alkyl group of 1 to 6 carbon atoms or optionally substituted phenyl, linked through a carbonyloxy group; such as for example acetoxy, propionyloxy, butyryloxy, isobutyryloxy, pivaloyloxy, valeryloxy, benzoyl and the like. Optionally said acyloxy group may contain a hydroxyl and / or carboxyl group.

As used in the present description and in the claims, a statement for example that R1 is oxo means that oxo (= 0) is present in position 1 and, consequently, there is no hydrogen atom in position 1. Analogous considerations they apply for similar situations. In other cases, two symbols together may represent oxo, for example, R3 and R '3. As used in the present description and in the claims, a statement that for example R12 is methylene, means that methylene (= CH2) is present in position 12 and, consequently, there is no hydrogen atom in this position. Analogous considerations apply for similar situations. In other cases, two symbols together can represent methylene, for example, R4 and R'4. As used in the present description and in the claims, a statement that alkoxy is optionally substituted (R3) means that the alkoxy group is substituted with a convenient substituent such as hydroxyl or carboxyl.

As used in the present description and in the claims, the terms "a primary or secondary amide derived from a carboxylic acid" used for the substituent R, is a group of the general formula -CONHR40 wherein R40 is hydrogen or lower alkyl. As used in the present description and in the claims, the terms "an ester with an alcohol group of 1 to 6 carbon atoms" used by the substituent R5 is a group of the formula -COOR41 wherein R41 is a lower alkyl group or aralkyl. As used in the present description and in the claims, the expression "aralkyl" designates alkyl substituted by an aryl group, for example benzyl. The salts of the compounds of the formula la, Ib and le are preferably pharmaceutically acceptable salts, especially the salts by the addition of acid, including the salts of organic acids and mineral acids. Examples of such salts include salts of organic acids such as formic acid, fumaric acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, acid succinic, malic acid, tartaric acid, citric acid, benzoic acid, salicylic acid and the like. Suitable inorganic acid addition salts include salts of hydrochloric, hydrobromic, sulfuric and phosphoric acids and the like. Additional examples of pharmaceutically acceptable organic or inorganic acid addition salts include the pharmaceutically acceptable salts listed in the Journal of Pharmaceuti cal Sci ence, 66 (1977), 2 ff. The esters of compounds of the formula la, Ib and le are formally derived by esterification of one or more hydroxyl groups of a compound of the formula la, Ib or le, respectively, with an acid which can be for example selected from the group of acids which they comprise succinic acid and other aliphatic dicarboxylic acids, nicotinic acid, isonicotinic acid, ethylcarbonic acid, phosphoric acid, sulfonic acid, sulfamic acid, benzoic acid, acetic acid, propionic acid and other aliphatic monocarboxylic acids. A "metabolite" of a compound of the formula la, Ib or le is an active derivative of a compound of the formula la, Ib or le which is produced when the compound of the formula la, Ib or is metabolized. The metabolites of the compounds of the formula la, Ib or can be identified either by administration of a compound of a compound of the formula la, Ib or a to a host and analysis of blood samples from the host, or by incubation of a compound of the formula la, Ib or le with hepatic cells in vitro and analysis of the incubation. A "prodrug" is a compound that is either converted to a compound of the formula la, Ib or le in vi vo or which has the same active metabolites as a compound of the formula la, Ib or le.

The compounds of the formula la, Ib or le have a number of chiral centers in the molecule and thus exist in various isomeric forms. All of these isomeric forms and mixtures thereof are within the scope of the invention. The compounds of the general formula la, Ib and le can be prepared analogously with the preparation of the known compounds. Therefore, the synthesis of the compounds of the formula la. Ib and can follow the well-established synthetic routes described in the extensive literature of sterols and steroids. The following Books can be used as a key source in the synthesis: L.F. Fieser & M. Fieser: Steroids: Reinhold Publishing Corporation, NY 1959; Rood's Chemistry of Carbon Compounds (ed. S. Coffrey): Elsevier Publishing Company, 1971; J. Fried and J.A. Edwards: Organic Reactions in Steroid Chemistry, Vol. I and II, Van Nostrand Reinhold Company, New York, 1972; and especially Diccionary of Steriods (editors: R.A. Hill; D.N. Kirk; H.L.J. Makin and G.M. Murphy): Chapman & Hall. The last contains an extensive list of citations to the original documents covering the period up to 1990. All these books, including the last mentioned citations, are incorporated by reference. Furthermore, the information in all previous publications (including the patent specifications) have to do with the preparation of similar compounds with compounds of the formula la, Ib and le which are incorporated by reference. Particularly, the compounds of the present invention can be synthesized according to the following general procedures: Co-5-8-dien-3-ol 1, which is synthesized as described in the literature [J. Lip. Res. 37, 1529, (1996)], can be oxidized in an Oppenauer reaction to give cholesta-4,8-dien-3-one 2 (Reaction Scheme 1). In this reaction, the sterol is treated with a ketone such as acetone, quinone or cyclohexanone in the presence of aluminum isopropoxide or aluminum tert-butoxide [eg, J. Chem. Soc. Perkin I 2667 (1994)]. The sterol can also be oxidized with pyridinium dichromate [see Synth. Common. 20 (1990). The same oxidation reaction can be carried out with the cholesta-5, 8 (14) -dien-3ß-ol, which is also synthesized as described in the literature [J. Lip. Res. 37 (1996), 1529] to give the cholesta-5, 8 (14) -dien-3-one. For this ketone, a laborious synthesis in the literature is described [Bul l. Soc. Chim. Fr. 2037 (1971)]. Cholesta-4, 7-dien-3-one is synthesized according to the procedures of the literature [Li ebi gs Ann. Chem. 542 (1939), 218] (in Reaction Scheme 1, the series with the double bond? B are shown as an example, with analogous reactions having to be performed in the series? 7 and? 8 (14 >;). In the following, only the synthesis in the series is described? 8. The derivatives in the series? 7 and? 8'14 'can be synthesized by a person skilled in the art from the corresponding initial materials in the same way.

Reaction Scheme 1: Enone 2 can be treated with different Grignard reagents of 1 to 6 carbon atoms to give two diatereoisomeric alcohols 3 and 4 (with R 3 = alkyl of 1 to 6 carbon atoms), which are easily separated by column chromatography [ example, J. Med. Chem. 40 (1997), 61].

The cholesta-4, 8-dien-3-one 2 can be reduced according to well-known procedures of the literature. The lithium-aluminum hydride, the Sodium borohydride and diisobutylaluminum hydride are especially useful [e.g., Li ebi gs Ann. Chem. 542 (1939), 218]. Two diastereoisomeric alcohols of formulas 3 and 4 (with R 3 = hydrogen) can be obtained and easily separated by column chromatography. For the introduction of perfluoroalkyl substituents in the 3-position, cholesta-4,8-dien-3-one 2 can be treated with perfluoroalkyltrialkylsilanes in the presence of fluoride sources such as tetrabutylammonium fluoride or cesium fluoride. The trifluoromethyl group is preferably introduced with reagents such as trimethylsilyltrifluoro ethane or triethylsilyltrifluoromethane [J. Org. Chem. 56 (1991), 984; J. Org. Chem. 54 (1989), 2873]. Again, two diastereoisomeric alcohols of formulas 3 and 4 (with R3 = perfluoroalkyl, preferably: trifluoromethyl) can be obtained and easily separated by column chromatography. Cyanoketones 5 and 6 are available starting from cholesta-4, 8-dien-3-one 2 via an addition of cyanide conjugate (Scheme Reaction 2). Different reagents such as diethylaluminum cyanide [J. Org. Chem. 59 (1994), 2766] and some alkali metal and alkaline earth metal cyanides [Tetrahedron Lett. 28 (1987), 4189; Dog. J. Chem. 59 (1981), 1641] can be used in this reaction.

Reaction Scheme 2 Easily separated cyanoketones 5 and 6 can be reduced according to the well-known procedures of the literature. Lithium aluminum hydride, sodium borohydride and diisobutyl aluminum hydride are preferably used [e.g., Aus t. J. Chem. 35 (1982), 629]. In the reduction reactions, two diastereomeric alcohols 7 and 8 (R3 = H) are obtained, respectively, 9 and 10 (R3 = H). The cyanoketones of formulas 5 and 6 can also be treated with Grignard reagents [eg, Chem. Pharm. Bul l. 9 (1961), 854] to give two diastereomeric tertiary alcohols 7 and 8 or 9 and 10 (with R3 = alkyl of 1 to 6 carbon atoms), respectively. The hydroxymethyl derivatives of the formulas 12 and 14 can be synthesized in two-step sequences from the cyanoalcohols 8 and 9, respectively (Scheme 3). First, the cyano group can be reduced with an electrophilic reducing agent such as diisobutylaluminium hydride to give the corresponding imines, which are hydrolyzed in itself to the carbaldehydes 11 and 13. In the second step, the carbaldehydes can be further reduced with well-known reducing agents such as lithium aluminum hydride, sodium borohydride or diisobutylaluminum hydride to the desired hydroxymethyl derivatives [eg, J. Med. Chem. 39 (1996), 5092].

Reaction Scheme 3 The methane derivatives of formulas 15 and 16 can be synthesized from the allylic alcohols 3 and 4, respectively (Reaction Scheme 4). Different variations of the reaction of? Immons-Smi'th can be employed. As reactants, the diiodomethane in the presence of the zinc / copper pair [for example, J. Or? . Chem. 31 (1966), 3869; J. Med.

Chem. 39 (1996), 4218] as well as chloroiodomethane in the presence of a solution of diethylzinc [J. Am. Chem. Soc. 108 (1986), 6343] can be used in this cyclopropanation reaction.

Reaction Scheme 4 5β-methylcholest-8-en-3-one 17 can be synthesized from cholesta-4,8-dien-3-one 2 via a conjugate addition reaction (Reaction Scheme 5). The methyl group is introduced with either lithium dimethyl caprate [e.g., Aust. J. Chem. 35 (1982), 629] or with the methyl-Grignard or trimethylaluminum compounds in the presence of nickel catalysts [for example Tetrahedron Let t. 35 (1994), 6075; Synthesis 3 (1995), 317].

Reaction Scheme 5 The subsequent reduction of 5-methylketone 17 is achieved with different well-known reducing agents such as lithium aluminum hydride, sodium borohydride and diisobutylaluminum hydride [e.g., Aust. J. Chem. 35 (1982), 629]. Two diastereoisomeric alcohols 18 and 19 (R3 = hydrogen) can be obtained and easily separated by column chromatography. If the 5-methyl ketone 17 is treated with Gignard reagents, two diastereomeric tertiary alcohols (18 and 19) are obtained, with R 3 = alkyl of 1 to 6 carbon atoms), which are easily separated by column chromatography. Analogs that combine a 5-cyano substituent with different spheroidal side chains can be synthesized by the following general route (see Reaction Scheme 6): starting from the licheterol, which can be synthesized as described in the literature [J. Chem. Soc. Perkin Trans. 1 (1981), 2125], an enone can be generated by an Oppenauer oxidation [for example, J. Chem. Soc. Perkin Trans. 1 (1994), 2667]. A cyano group can be introduced by addition of conjugate [J. Org. Chem. 59 (1994), 2766]. After the protection of 3-ketone as a ketal, the side chain can be cleaved by ozonolysis and the subsequent reductive work [Synthesis 3 (1990), 193]. The 22-alcohol can be transformed to the corresponding tosylate to generate the appropriate leaving group for the copper-catalyzed addition of the Grignard reagents. By this addition, different alkyl and aryl side chains can be introduced [Chem, Pharm. Bull. 28 (1980), 606]. After deprotection of the ketone, the latter can be reduced to the corresponding α- and β-alcohols by standard methods.

Reaction Scheme 6 The compounds of the present invention will influence meiosis in oocytes as well as in male germ cells. The existence of a substance that induces meiosis in nature has been known for some time. However, until recently, the identity of the substance or substances inducing meiosis was unknown. The prospects that are capable of influencing meiosis are several. According to a preferred embodiment of the present invention, a compound of the formula la, Ib or le or an ester, salt, active metabolite or prodrug thereof can be used to stimulate meiosis. According to another preferred embodiment of the present invention, a compound of the formula la, Ib or le or an ester, salt, active metabolite or prodrug thereof can be used to stimulate meiosis in humans. Thus, the compounds of the formula la, Ib or le and the ester, the salt, the active metabolite or prodrugs thereof are promising as new fertility regulating agents without the usual side effect on somatic cells which are known of hormonal contraceptives to date used, which are based on estrogens and / or gestagens. For use as a contraceptive agent in women, a meiosis-inducing substance can be administered to prematurely induce the resumption of meiosis in oocytes, while these are still in the growing follicle, before the ovulatory peak of the oocytes occurs. gonadotropins. In women, the resumption of meiosis can, for example, be induced one week after the previous menstruation has ceased. When they ovulate, it is most likely that the resulting oocyte oocytes are not fertilized. The normal menstrual cycle is probably not affected. In this context it is important to note that the biosynthesis of progesterone in cultured human granulosa cells (somatic cells of the follicle) is not affected by the presence of a meiosis-inducing substance, while the estrogens and progestins used in hormonal contraceptives used to date did have an adverse effect on the biosynthesis of progesterone.

According to yet another aspect of this invention, a meiosis-inducing substance of the formula la, Ib or le or an ester, a salt, an active metabolite or a prodrug thereof can be used in the treatment of certain cases of infertility in female subjects, including women, by administering them to female subjects who, due to insufficient self-production of meiosis-activating substance, are unable to produce mature oocytes. Also, when in vitro fertilization is carried out, better results can be achieved when a compound of the formula la, Ib or le or an ester, salt, active metabolite or prodrug thereof is added to the medium in which the compounds are grown. oocytes When infertility in male subjects, including man, is caused by insufficient self-production of the meiosis-activating substance, and thus a lack of mature sperm cells, the administration of a compound of the formula la, Ib or or an ester, salt, active metabolite or prodrug thereof may alleviate the problem.

As an alternative to the method described above, contraception in female subjects can also be achieved by the administration of a compound of the formula la, Ib or le or an ester, salt, active metabolite or prodrug thereof which inhibits meiosis, so that mature oocytes are not produced. Similarly, contraception in male subjects can be achieved by administering a compound of the formula la, Ib or le or an ester, salt, active metabolite or prodrug thereof, which inhibits meiosis, so that no cells are produced mature sperm The route of administration of the compositions containing a compound of the formula la, Ib or le or an ester, salt, active metabolite or prodrug thereof can be any route which effectively transports the active compound to its site of action. . Thus, when the compounds of this invention are to be administered to a mammal, they are conveniently provided in the form of a pharmaceutical composition comprising at least one compound of the formula la, Ib or le or an ester, salt, metabolite active or prodrug of the themselves in connection with a pharmaceutically acceptable carrier. For oral use, such compositions are preferably in the form of capsules or tablets. From the above it will be understood that the administration regime required will depend on the condition to be treated. Thus, when used in the treatment of infertility, administration can take place only once, or for a limited period, for example, until pregnancy is achieved. When used as a contraceptive, the compounds of the formula la, Ib or le or an ester, salt, active metabolite or prodrug will have to be either administered continuously or cyclically. When they are used as contraceptives by female subjects and not taken continuously, the timing of administration in relation to ovulation will be important.

Pharmaceutical Compositions Pharmaceutical compositions comprising a compound of the formula la, Ib or le or an ester, salt, active metabolite or prodrug, they may further comprise carriers, diluents, absorption enhancers, preservatives, buffers, agents for adjusting the osmotic pressure, tablet disintegrating agents and other ingredients that are conveniently used in the art. Examples of solid carriers are magnesium carbonate, magnesium stearate, dextrin, lactose, sugar, talc, gelatin, pectin, tragacanth, methylcellulose, sodium carboxymethylcellulose, low melting point waxes and cocoa butter. Liquid compositions include sterile solutions, suspensions and emulsions. Such liquid compositions may be suitable for injection or for use in connection with fertilization ex vi ve and in vi tro. The liquid compositions may contain other ingredients that are conveniently used in the art, some of which are mentioned in the above list. In addition, a composition for the transdermal administration of a compound of this invention can be provided in the form of a patch, and a composition for nasal administration can be provided in the form of a nasal spray in powder or liquid form.

The dose of a compound of the formula la, Ib or le or an ester, salt, active metabolite or prodrug to be used will be determined by a physician and will depend, among other things, on the particular compound employed, of the administration route and the purpose of the use. In general, the compositions of the invention are prepared by intimately bringing into association the active compound with liquid or solid auxiliary ingredients and then, if necessary, shaping the product into the desired formulation. Usually, no more than 1000 mg, preferably no more than 100 mg, and in some preferred cases no more than 10 mg of a compound of the formula la, Ib or have to be administered to mammals, for example, to men, for day. None of the compounds of the formula la, Ib and has been shown to be toxic when administered to man in an amount of 1000 mg per day. The compounds of the formula la, Ib or le thereof can be synthesized by methods known per se. The present invention is further illustrated by the following examples which, however, do not have to be considered as limiting the scope of protection. The features described in the foregoing description and in the following examples may, in any combination thereof, be material for releasing the invention in various forms thereof.

EXAMPLE 1 3-Hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid methyl ester The 4,4-dimethyl-3-oxocol-5-en-24-oic acid methyl ester (19.8 g) (G. Aranda et al-, Tetrahedron 43 (1987), 4147) is reduced with 9.9 g of borohydride of sodium in 1900 ml of methanol at room temperature. The solution is stirred for 20 hours. After the aqueous extraction, the 3-hydroxy-4,4-dimethylcol-5-en-24-oic acid methyl ester (19.2 g) is isolated. Melting point: 136-138 ° C. NMR * H (CDC13, 400 MHz): d = 5.55 (1H, m); 3.67 (3H, s); 3.23 (1H, m). The 3β-hydroxy-4,4-dimethylcol-5-en-24-oic acid methyl ester (19.1 g) is suspended in 390 ml of N, N-dimethylformamide (hereinafter referred to as DMF) and 39 g are added. of imidazole and 34.6 g of tert-butyldimethylsilyl chloride. The reaction mixture was stirred at 70 ° C for 20 hours. After the aqueous extraction, 23.9 g of a crude product are isolated. Crystallization from tetrahydrofuran / methanol (hereinafter tetrahydrofuran and methanol are designated THF and MeOH, respectively) yields 19.55 g of tert-butyldimethylsilyloxy-4-3ß, methyl ester ác_.do 4-dimethyl-5- al en-24-oico. Melting point: 144-146 ° C. NMR * H (CDC13, 300 MHz): d = 5.52 (1H, m); 3.66 (3H, s); 3.18 (1H, m); 0.89 (9H, s), 0.02 (6H, m). The methyl ester tert-butyldimethylsilyloxy-3ß-4,4-dimetilcol-5-en-24-oic acid (9.75 g) is dissolved in a hot mixture of 122 ml benzene and 475 ml of n-hexane are added 3.95 g of 1,3-dibromo-5,5-dimethylhydantoin and the mixture is refluxed for 15 minutes. After cooling (rapid) and evaporation to dryness under reduced pressure, 475 ml of o-xylene and 21.7 ml of quinaldine are added, and the mixture is heated to reflux for 1 hour. After the aqueous extraction and trituration with methanol, 8.22 g of the 3-methyl-tert-butyldimethylsilyloxy-4,4-dimethyl-5,7-dien-24- methyl ester are isolated. oico Melting point: 116-124 ° C. NMR: H (CDC13, 300 MHz): d = 5.88 (1H, m); 5.52 (1H, m); 3.65 (3H, s); 3.32 (1H, m); 0.89 (9H, s); 0.04 (6H, m). 1 g of 3ß-tert-butyldimethylsilyloxy-4, 4-dimetilcola-5 acid methyl ester, 7-dien-24-oic acid in a mixture of 25 ml and 3.4 ml of concentrated hydrochloric acid is suspended and heated to reflux over the night. After evaporation to dryness under reduced pressure, the residues are triturated with methanol and thereafter recrystallized with methanol / water to give 0.47 g of the title compound. Melting point: 156-157 ° C. 2 H NMR (CDCl 3, 400 MHz): d = 5.36 (1H, s); 3.67 (3H, s); 3.23 (1H, m). MS (abbreviation for mass spectroscopy): Calculated: 414.6. Found 414.3.

EXAMPLE 2 3-Hydroxy-4, 4-dimethylol-5, 7-dien-24-oic acid methyl ester 0.50 g of the 3-methyl-tert-butyldimethylsilyloxy-4,4-dimethyl-5,7-dien-24-oic acid methyl ester in 5 ml of anhydrous THF are dissolved and added 0. 4 g of tetra-butylammoniofluoride hydrate and 0.4 g of powdered molecular sieves, and the mixture is stirred for 4 days. After column chromatography and crystallization from methanol / water and methanol, 195 g of the title compound are isolated. Melting point: 124-128 ° C. 1 H NMR (CDC13, 400 MHz): d = 5.91 (1H, m); 5.53 (1H, m); 3.67 (3H, s), 3.4 (1H, m). MS: Calculated: 414.6. Found 414.3.

EXAMPLE 3 Ethyl ester of 3ß-hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oico 4. 0 g of 3-methyl-tert-butyldimethylsilyloxy-4,4-dimethylamino-5, 7-dien-24-oic acid methyl ester are suspended in a mixture of 60 ml of 96% ethanol, 10.1 ml of benzene and 10.1 ml of Concentrated hydrochloric acid and heated to reflux for 3.5 hours. After aqueous extraction and column chromatography followed by crystallization from ethanol 1.37 g of the title compound are isolated. Melting point: 122-124 ° C. NMR * H (CDCl 3, 300 MHz): d = 5.35 (1H, s); 4.13 (2H, q); 3. 25 (1H, m), 1.25 (3H, t). MS: Calculated: 428.7. Found 428.3.

EXAMPLE 4 3ß-hydroxy-, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid 1. 9 g of 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid ethyl ester are suspended in a mixture of 190 ml of 96% ethanol and 63 ml of 1 M sodium hydroxide. The mixture is stirred for 3.5 hours at room temperature. After aqueous extraction and crystallization from ethanol / water, 1.48 g of the title compound are isolated. 1 H NMR (CDC13, 400 MHz): d = 5.36 (1H, s); 3. 22 (1H, m); 1.03 (3H, s); 0.97 (3H, d); 0.83 (3H, s); 0.81 (3H, s), MS: Calculated: 400.6. Found 400. 3.

EXAMPLE 5 3-Hydroxy-4, -dimethyl-5a-cola-8, 14-dien-24-oic acid cyclohexyl ester 0. 2 g of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid are suspended in 10 ml of cyclohexanol, 0.1 ml of boron trifluoride-diethyl ether is added and the mixture is stirred at 55-60 ° C for 20 hours. After evaporation to dryness under reduced pressure, the residues are purified by column chromatography and crystallized from methanol to give 49 mg of the title compound. Melting point: 130-132 ° C. NMR aH (CDC13): d = 5.35 (1H, s); 4.75 (1H, m); 3.24 (1H, m). MS: Calculated: 482.8. Found 482.4.

EXAMPLE 6 3ß-hydroxy-4,4-dimethyl-5a-cholesta-8, 14-dien-24-one 18.2 g of 3-hydroxy-4,4-diethyl-5a-cola-8,14-dien-24-oic acid methyl ester are suspended in 400 ml of DMF and 14.8 g of imidazole and 13.0 g of sodium chloride are added. t- butyldimethylsilyl. The reaction is stirred at 65 ° C for hours. After the aqueous extraction and crystallization from ether / methanol, the 21 g of 3-methyl-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid methyl ester. Melting point: 124-125 ° C. 2 H NMR (CDC13, 400 MHz): d = 5.34 (1H, s); 3.68 (3H, s); 3.2 (1H, m); 0.9 (9H, s); 0.04 (6H, m). 12 g of the 3-methyl-tert-butyldimethylsilyloxy-4-dimethyl-5a-cola-8,14-dien-24-oic acid methyl ester are dissolved in a mixture of 500 ml of THF and 400 ml of ethanol. 60 ml of 1 M sodium hydroxide are added and the mixture is stirred for 20 hours. After the aqueous extraction and crystallization from ethanol / water, 11.26 g of the 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid are obtained. Melting point: 181-184 ° C. NMR * H (CDCl 3, 300 MKz): d = 5.34 (1H, s); 3.19 (1H, m); 0.9 (9H, s); 0.04 (6H, m). 5 g of the 3β-tert-butyldimethylsilyloxy-, 4-dimethyl-5a-cola-8,14-dien-24-oic acid are dissolved in 250 ml of anhydrous dichloromethane. After cooling to -15 ° C, 2.14 ml of N-methylmorpholine and 1.27 ml of isobutyl chloroformate are added, and the mixture is stirred at -15 ° C for 20 minutes. minutes, after which 0.98 g of N, O-dimethylhydroxy / amine hydrochloride is added, and the mixture is stirred overnight and the temperature rises slowly to room temperature. After the aqueous extraction, 5.37 g of the N-methoxy-N-methylamide of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oico are obtained. Melting point: 134-135 ° C. NMR 1E (CDC13, 300 MHz): d = 5.35 (1H, s); 3.69 (3H, s); 3.2 (1H, m); 3.18 (3H, s); 0.9 (9H, s); 0.04 (6H, m). 0.57 g of the N-methoxy-N-methylamide of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic in 10 ml of anhydrous THF are dissolved and added to a 10 mmol solution of isopropylmagnesium bromide in 10 ml of THF, after which it is cooled on an ice bath. The mixture is stirred for a few hours and left overnight at 5 ° C. After aqueous extraction, column chromatography and crystallization from methanol, 238 mg of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cholesta-8,14-dien-24-one are obtained. Melting point: 120-122 ° C. 1 H NMR (CDC13, 300 MHz): d = 5.35 (1H, s); 3.2 (1H, m); 2.61 (1H, m); 0.9 (9H, s); 0.04 (6H, m).

Dissolve 0.1 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cholesta-8,14-dien-24-one in 5 ml of ethanol, add 0.2 ml of 6 N hydrogen chloride and mix It is stirred for 2 days. After aqueous extraction, column chromatography and crystallization from ethanol / water, 64 mg of the title compound are obtained. NMR * H (CDC13, 400 MHz): d 5.35 (1H, s); 3.24 (1H, m); 2.62 (1H, m). MS: Calculated: 426.7. Found. 426.3.

EXAMPLE 7 3ß-hydroxy-4,, 24-trimethyl-5a-cola-8, 14-dien-24-one 0. 57 g of the 3-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid N-methoxy-N-methylamide are reacted with methylmagnesium bromide and hydrolyzed with ethanol HCl following the procedure described in Example 6 to give the title compound (0.20 g). Melting point: 183-185 ° C. NMR: H (CDC13, 300 MHz): d = 5.35 (1H, s); 3.24 (1H, m); 2.17 (3H, s). MS: Calculated: 398.6. Found 398.3.

EXAMPLE 8 3ß-hydroxy-4,4-dimethyl-24-phenyl-5a-cola-8, 14-dien-24-one 0.57 g of N-methoxy-N-methylamide of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic are reacted with phenylmagnesium bromide and hydrolyzed with ethanol / HCl following the procedure described in Example 6 to give 0.31 g of the title compound. Melting point: 196-199 ° C. NMR * H (CDC13.300 MHz): d = 8.0-7.4 (5H, m); 5.35 (1H, s); 3.24 (1H, m); 3.0 (2H, m). MS: Calculated: 460.7. Found 460.3.

EXAMPLE 9 3ß-hydroxy-4, 4-dimeti 1-24- (3-pentyl) -5a-cola-8, 14-dien-24-one 0. 57 g of the 3-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid N-methoxy-N-methylamide are reacted with 3-pentylmagnesium bromide and hydrolyzed with ethanol / HCl following the procedure described in Example 6 to give 13 mg of the title compound. AH NMR (CDC13, 300 MHz): d = 5.35 (1H, s); 3.23 (1H, m). MS: Calculated: 454.7. Found: 454.3.

EXAMPLE 10 3-Hydroxy-4, -dimethyl-5a-cola-8, 14-dien-24-oic acid N-phenylamide 0. 50 g of the 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid were dissolved in 15 ml of anhydrous dichloromethane. After cooling to -15 ° C, 0.188 ml of N-methylmorpholine and 0.153 ml of isobutyl chloroformate are added, and the mixture is stirred at -15 ° C for 20 minutes, after which 0.44 ml of aniline are added. The mixture is stirred overnight and the temperature rises slowly to room temperature. After aqueous extraction and crystallization from methanol, 0.431 g of the 3-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid N-phenylamide are obtained. H-NMR (CDC13, 400 MHz): d = 7.53 (2H, d); 7.34 (2H, t); 7.17 (1H, s); 7.12 (1H, t); 5.35 (1H, s); 3.21 (1H, m); 0.9 (9H, s); 0.04 (6H, m). 50 mg of the N-phenylamide of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid are dissolved in 5 ml of ethanol, 0.2 ml of hydrogen chloride are added 6 N and the mixture is stirred at room temperature overnight. After the aqueous extraction and crystallization from methanol 36 mg of the title compound are obtained. H-NMR (CDC13, 400 MHz): d = 7.53 (2H, d); 7.33 (2H, t); 7.18 (1H, s); 7.12 (1H, t); 5.36 (1H, s); 3.26 (1H, m). MS: Calculated: 475.7. Found: 475.4.

EXAMPLE 11 3-Hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide 1 g of the 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid is reacted with ammonia and hydrolysed with ethanol / HCl following the procedure described in Example 10 for give 147 mg of the title compound. Melting point: 233-235 ° C. NMR * H (CDC13, 400 MHz): d = 5.36 (1H, s); 5.45-5.2 (2H, broad d); 3.25 (1H, m). MS: Calculated: 399.6. Found: 399.3.

EXAMPLE 12 4, -dimethyl-24-phenylamino-5a-cola-8, 14-dien-3ß-ol 0. 15 g of the 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid is reacted with aniline following the procedure described in Example 10, and is reduced with 0.15 g of Lithium aluminum hydride in THF at room temperature. Aqueous extraction and crystallization from methanol gives 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-24-phenylamino-5a-cola-8,14-diene (106 mg). NMR: H (CDC1, 300 MHz): d = 7.17 2H, t); 6.69 (1H, t); 6.6 (2H, d); 5.35 (1H, s); 3.6 (1H, s); 3.2 (1H, m); 3.09 (2H, m); 0.9, s); 0.04 (6H, m). 100 mg of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-24-phenylamino-5a-cola-8,14-diene are hydrolysed with ethanol / HCl at 50 ° C. Aqueous extraction and crystallization from ethanol gives 53 mg of the title compound. Melting point: 178-180 ° C. AH NMR (CDC13, 300 MHz): d = 7.19 (2H, t); 6.7 (1H, t); 6.63 (2H, d); 65.36 (1H, s); 3.6 (1H, s); 3.26 (1H, m); 3.1 (2H, m). MS: Calculated: 461.7. Found. 461.3.

EXAMPLE 13 4, 4-dimethyl-24-amino-5a-cola-8, 14-dien-3ß-ol The compound is synthesized following the procedure described in Example 12. NMR * H (DMSO-de, D20 + HCl): d = 5.3 (1H, s); 3.03 (1H, m); 2.77 (2H, m). MS: Calculated: 385.6. Found: 385.3.

EXAMPLE 14 4, 4-dimethyl-5a-cola-8, 14-dien-3β, 24-diol 6 g of the 4,4-dimethyl-3-oxocol-5-en-24-oic acid methyl ester (G. Aranda et al., Tetrahedron 43 (1987), 4147) are reduced with 3.3 g of lithium hydride. and aluminum in 600 ml of THF. After aqueous extraction and crystallization from diethyl ether, 5.21 g of 4,4-dimethyl-5-en-3β, 24-diol are obtained. Melting point: 201-202 ° C. NMR * H (CDC13, 400 MHz): d = 5.55 (1H, m); 3.61 (2H, m); 3.23 (1H, m). MS: Calculated: 388.6. Found: 388.4.

A mixture of 57 g of 4, -dimethylcol-5-en-3β, 24-diol, 125 g of imidazole and 110.5 g of tert-butyldimethylsilyl chloride in DMF are stirred at 70 ° C for 20 hours. After the aqueous extraction and crystallization from methanol, 87.7 g of the 3β, 24-bis (tert-butyldimethylsilyloxy) -4,4-dimethylcol-5-ene are obtained. Melting point: 161-162 ° C. 1 H NMR (CDC13, 400 MHz): d = 5.53 (1H, m); 3.58 2H, m); 3.21 (1H, m); 0.9 (18H, m); 0.03 (12H, m). 44 g of 3β, 24-bis (tert-butyldimethylsilyloxy) -4,4-dimethylcol-5-ene are dissolved in a hot mixture of 2 liters of hexane and 540 ml of benzene. 15.32 g of 1,3-dibromo-5,5-d? Methylhydantoin are added and the mixture is refluxed for 20 minutes, and then cooled rapidly to room temperature, and the insoluble material is removed by filtration. The filtrate is concentrated under reduced pressure and 2 liters of o-xylene and 84 ml of quinaldine are added. The mixture is heated to reflux for 1 hour. After the aqueous extraction and trituration with methanol, 39 g of 3β, 24-bis (tert-butyldimethylsilyloxy) -4,4-diemylcolane-5,7-diene are isolated. Melting point: 98-106 ° C. NMR * H (CDC13, 400 MHz): d = 5.9 (1H, m); 5.54 (1H, m); 3.58 (2H, m); 3.35 (1H, m); 0.891 (18H, s); 0.05 (12H, m). A mixture of 18.8 g of 3β, 24-bis (tert-butyldimethylsilyloxy) -4, dimethyl-5,7-diene in 375 ml of 99.9% ethanol, 55 ml of benzene and 55 ml of concentrated hydrochloric acid are added. heat to reflux for 4 hours. After standing overnight at room temperature, the reaction mixture is concentrated under reduced pressure. Crystallization of the ethanol / water remnants gives 8.44 of the title compound. Melting point: 203-208 ° C. AH NMR (CDC13, 400 MHz): d = 5.36 (1H, s); 3.62 (2H, m); 3.23 (1H, m).

EXAMPLE 15 3ß-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-aldehyde 0. 21 g of 4,4-dimethyl-5a-cola-8, 14-dien-3β, 24-diol are dissolved in 21 ml of benzene. 1.04 g of tris (triphenylphosphino) ricketthium (II) chloride are added and the mixture is stirred at room temperature for 20 hours. Purification by column chromatography gives the title compound (129 mg). XH NMR (CDC13, 300 MHz): d = 9.79 (1H, s); 5.36 (1H, s); 1.05 (3H, s), 1.01 (3H, s); 0.95 (3H, d); 0.82 (3H, s); 0.80 (3H, s).

EXAMPLE 16 4, -dimethyl-17β- ((IR) -methi 1-4 -methi 1-3-pentenyl) androsta-8, 14-dien-3β-ol 1 H NMR (CDC13, 400 MHz): d = 5.35 (1H, s); . 18 (1H, t); 3.24 (1H, dd); 1.7 (3H, s); 1.6 (3H, s).

EXAMPLE 17 4, 4-dimethyl-5a-cholesta-14, 15, 24-trien-3ß-ol AH NMR (CDC3, 400 MHz): 6 = 5.98 (1H, m); 5.8 (1H, m); 5.12 (1H, t); 3.24 (1H, m); 1.7 (3H, s); 1.58 (3H, s).

EXAMPLE 18 4, 4-dimethyl-17β- ((IR) -methyl-3-methyl-2-butenyl) androsta-8,14-dien-3ß-ol 1 H NMR (CDC13, 400 MHz: 5.35 (1H, s); 4.93 (1H, d); 3.24 (1H, m); 1.69 (3, s); 1.65 (3H, s).

EXAMPLE 19 (20R) -4,4-trimethyl-21-phenyl-5a-pregna-8, 14-dien-3ß-ol 19A: According to St eroi ds 26 (1975), p. 339-357, 4,4-dimethylstigmasterol has been synthesized. 19B: The ozonolysis of compound 19A at -70 ° C by slow introduction of 03, and then reduction to -70 ° C by sodium bis- (2-methoxyethoxy) aluminum hydride and subsequent reduction at a temperature of about 30 ° C with lithium aluminum hydride afforded 23-nor-4,4-dimethyl-5a-cholest-5-en-3β, 22-diol, which was diacetylated in pyridine with acetic acid anhydride. (IB). 19C: Compound 19B is isomerized by heating to efflux in ethanol / 6M hydrochloric acid to give 23-nor-4,4-dimethyl-5a-cholest-8, 14-dien-32β, 22-diol. 19D: Compound 19C was selectively tosylated on carbon 22 by treatment of p-toluenesulfonyl chloride in pyridine by standing overnight at room temperature. The compound was purified by column chromatography and crystallized. NMR: H ppm: 0.78 s CH3; 0.82 s CH3; 0.98 d CH3; 1.02 s CH3; 2.46 s CH3-aromatic; 3.22 m H 3 a; 5.38 s H15; 7.33 d 2H; 7.78 d 2H. This intermediary, 19D, is used in several of the following examples. 19E: Compound 19D is reacted with phenylmagnesium bromide catalyzed by Li2CuCl4 to give the title compound (Chepi, Pharm.Bul, 28 (1980), p.606-611, Masuo Monsaki et al.). H NMR ppm: 0.82 d CH3; 0.83 s CH3; 1.02 s CH3; 1.03 s CH3; 2.55 m 1H; 2.91 dd 1H; 3.25 m 3 to H; 5.4 s 1H (15); 7.17 2H; 7.28 m 3H.

EXAMPLE 20 (20R) -4,4-trimethyl-21- (3-methylphenyl) -5a-pregna-8, 14-dien-3ß-ol According to Example 19 (Compound 19D) was reacted with 3-methylphenylmagnesium bromide and Li2CuCl to give the title compound.

NMR: H ppm: 0.80 d CH3; 0.82 2s 2CH3; 1.0 2s 2CH3; 2.33 s CH3-aromatic; 3.27 m H3 at 5.40 s 1H; 6.98 m 3H; 7.17 1H.

EXAMPLE 21 (20R) -4,4-trimethyl-21- (4-methylphenyl) -5a-pregna-8, 14-dien-3ß-ol According to Example 19 (compound 19D) was reacted with 4-methylphenylmagnesium bromide and Li2CuCl4 to give the title compound.

NMR: H ppm: 0.84 s, 2d 3 CH 3; 1.04 2s 2CH3; 2.33 s CH3-aromatic; 3.25 m H3 a; 5, .40 s 1H; 7.05 m 4H.

EXAMPLE 22 (20R) -4, 4, 20-trimet? L-21- (2-methylphenyl) -5a-pregna-8, 14-dien-3ß-ol According to Example 19 (Compound 19 D) was reacted with 2-methylphenylmagnesium bromide and Li2CuCl < to give the title compound: NMR: H ppm: 0.84 s + 2d, 3 CH3; 1.04 2s 2CH3; 2.32 s CH3-aromatic; 3.25 m H3 a; 5.40 s 1H; 7.10 m 4H.

EXAMPLE 23 (20R) -4, 4, 20-trimeti 1-21- (cyclohexyl) -5a-pregna-8, 14-dien-3ß-ol According to Example 19 (Compound 19D) was reacted with cyclohexylmagnesium bromide and LÍ2CUCI4 to give the title compound.

NMR: H: mmp: 0.81 s CH3; 0.82 s CH3; 0.90 d CH3; 1.03 s CH3; 1.04 s CH3; 3.24 s H3 a; 5.37 sH; MS: 424.4.

EXAMPLE 24 (20R) -4, 4,20-trimethyl-22- (phenyl) -5a-pregna-8, 14-dien-3ß-ol According to Example 19 (Compound 19D) it is reacted with tolylmagnesium bromide and Li2CuCl4 to give the title compound. NMR: H; ppm: 0.80 s CH3; 0.82 s CH3; 1.02 s CH3; 1.04 s CH3; 1.06 d CH3; 3.25 m H3 a; 5.35 s H; 7.18 m 3H; 7.27 m 2H.

EXAMPLE 25 (20R) -4,4-trimethyl-21- (3-hydroxy phenyl) -5a-pregna-8, 14-dien-3ß-ol According to Example 19 (Compound 19D) was reacted with 3-trimethylsilyloxyphenylmagnesium bromide and Li2CuCl4 to give the title compound.

NMR: H: ppm: 0.80 d CH3; 0.83 s CH3; 0.84 s CH3; 1.01 s CH3; 1.03 s CH3; 3.26 m H3 a; 5.40 s H; 6.66 m 2H; 6.76 m H; 7.16 m H. MS: 434.3.

EXAMPLE 26 (20R) -4, 4, 20-trimethyl-22- (cyclohexyl) -5a-pregna-8, 14-dien-3ß-ol According to Example 19 (Compound 19D) was reacted with cyclohexylmethylmagnesium bromide and CuLi2Cl4 to give the title compound. NMR: H ppm: 0.80 s CH3; 0.83 s CH3; 0.91 d CH3; 1.01 s CH3; 1.03 s CH3; 3.24 m H3 a; 5.35 s H. MS: 483.3.

EXAMPLE 27 24 -. 24 -or-, -dimethyl-5a-cholest-8, 14-dien-3ß-ol According to Example 19 (Compound 19D) was reacted with isobutylmagnesium bromide and CuLi2Cl4 to give the title compound. NMR: H; ppm: 0. 80 s CH3; 0.84 s CH3; 0.86 d CH3; 0.88 d CH3; 0.91 d CH3; 1.02 s CH3; 1.04 s CH3; 3.25 m H3 a; 5.35 s H.

EXAMPLE 28 27 -. 27 -or- 4, -dimethyl-5a-cholesta-8, 14, 25-trien-3ß-ol According to Example 19 (Compound 19D) was reacted with cyclopropylmethylmagnesium bromide and Li2CuCl4 to give the title compound. NMR: H; ppm: = 0.82 s CH3; 0.84 s CH3; 0.95 d CH3; 1.02 s CH3; 1.04 s CH3; 3.24 H3 a; 4.97 dd 2H; 5.37 s 1H; 5.82 m 1H.

EXAMPLE 29 (20R) -4,4,20-trimethyl-21- (cyclobutyl) -5a-pregna-8, 14-dien-3ß-ol In the reaction of Example 28 a compound that was identified as the title compound was further isolated. NMR: H, ppm: 0.80 s CH3; 0.84 s CH3; 0.89 d CH3; 1.01 s CH3; 1.03 s CH3; 3.25 m 3 a; 5.35 s 1H.

EXAMPLE 30 (20R) -4, 4, 20-trimeti1-21- (cyclopentyl) -5a-pregna-8, 14-dien-3ß-ol According to Example 19 (Compound 19D) was reacted with cyclopentylmagnesxo bromide and Li2CuCl4 to give the title compound. NMR: H; ppm: 0.80 s CH3; 0.82 s CH3; 0.94 d CH3, 1.01 s CH3; 1.03 s CH3; 3.25 m H3 a; 5.35 s H.

Example 31 -chloro-4, 4-dime il-5a-cholesta-8, 14-dien-3ß-ol A mixture of 3β- (tert-butyldimethylsilyloxy) -4,4-dimethylchocolate-5, 7, 25-triene (50 mg), 5 ml of benzene, 5 ml of ethanol and 2 ml of concentrated HCl was heated to reflux for 4 hours. hours. The reaction was concentrated to half the volume under reduced pressure and 5 ml of water was added. Extraction of the aqueous phase with dichloromethane and concentration under reduced pressure gave a residue, which was purified by instant chromatography. Recrystallization from ethyl acetate: hexane gave the title compound as a white solid (35 mg). Melting point: 131-133 ° C. The 1H NMR spectrum (CDC13, d) showed characteristic signals at: 0.78 (s), 0.80 (s, 3H), 0.92 (d), 0.99 (s), 1.02 (s), 1.52 (s), 1.55 (s) ), 3.22 (dd), 5.33. The mass spectrum showed characteristic peaks at: 446.3 (M *).

EXAMPLE 32 4, 4, dimethyl-24- (N, N-dimethylamino) -2-cyano-5a-cholesta-8, 14-dien-3ß-ol To a mixture of 3β-hydroxy-4,4-dimethyl-5-8, 14-diene-24-aldehyde (10 mg, 0.03 mmol), 18 mg of dimethylamine hydrochloride, 16 mg of sodium acetate and 100 mg of Molecular sieves in 2 ml of methanol were added 8 mg of sodium cyanoborohydride and the reaction was stirred for 1.5 hours. 0.2 ml of dilute hydrochloric acid was added, followed by 0.3 ml of sodium bicarbonate solution and the sieves were removed by filtration. The concentration of the solution The residue gave a residue which was purified by flash chromatography to give the title compound (5 mg). The aH NMR spectrum (CDC13, d) showed characteristic signals at: 0.80 (s, 3H), 0.82 (s, 3H), 0.95 (d), 1.01 (s, 3H), 1.02 (s, 3H), 2.30 ( s, 6H), 3.20 (dd, 1H), 3.39-3.49 (m, 1H), 5.32 (s, 1H). The 13 C NMR spectrum (CDC13, d) showed characteristic signals at: 151.3, 142.3, 123.2, 117.5, 117.4, 79.1. The mass spectrum showed characteristic peaks at: 438.4 (M +).

EXAMPLE 33 4, 4-dimetiIcolest-8, 14,25-trien-3ß-ol Step 1 A solution of (25R) -4,4-dimethyl-5a-cholesta-8,14-d? En-3β, 26-d? Ol (69 mg, 0.16 mmol), toluenesulfonyl chloride (45 mg, 2.4 mmol and 1.5 ml of pyridine was stirred for 6 hours at ice bath temperature and 3 hours at room temperature, concentration under reduced pressure and purification by flash chromatography gave the (25R) - (26-) tosyloxy) -4,4-dimethyl-5a-cholesta-8,14-dien-3β-ol (61 mg). The 1H NMR spectrum (CDC13, d) showed characteristic signals at: 0.75 (s), 0.82 (s), 0.84 (s), 0.86 (s), 1.00 (s), 1.03 (s), 1.20 (s), 2.42 (s, 3H), 3.20-3.30 (, 1H), 3.62-3.80 (m, 2H), 5.33 (s, 1H), 7.32 (d, 2H), 7.75 (d, 2H).

Step 2 (25R) - (26-tosyloxy) -4,4-dimethyl-5a-cholesta-8,14-diene-3ß-ol (61 mg), sodium iodide (150 mg) and 2 ml of dimethylformamide were heated at 60 ° C for 4 hours. Water was added and the aqueous layer was extracted with dichloromethane, concentration under reduced pressure gave (25R) -26-iodo-4,4-dimethyl-5a-cholesta-8, 14-diene-3ß-ol, which was dissolved in 5 ml of chloroform. Added 1 < 8-diazobicyclo (5.4.0) undec-7-ene and the solution was heated to reflux for 5 hours, concentrated under reduced pressure and purified by flash chromatography. Recrystallization from methanol gave 5 mg of the title compound.

The 1U NMR spectrum (CDC13, d) showed characteristic signals at: 0.80 (s), 0.82 (s), 0.93 (d), 1.00 (s), 1.02 (s), 1.51 (s), 1.71 (s), 3.20-3.30 (m, 1H), 4.62 (d, 2H), 5.33 (s, 1H).

EXAMPLE 34 4, -d? Methyl-17β- ((IR) -methyl-4-chlorobutyl) androsta-8, 14-dien-3ß-ol Step 1 A mixture of 4,4-dimethyl-5a-cola-8, 14-dien-3β-24-diol (900 mg, 23 mmol), tosyl chloride (470 mg, 24 mmol) in 20 ml of pyridine was added. The mixture was stirred for 6 hours at an ice bath temperature, poured into water and extracted with diethyl ether. Drying over magnesium sulfate, concentration under reduced pressure and purification by flash chromatography gave 1.1 g of 24-toluenesulfonyloxy-4,4-d? Methyl-5a-cola-8,14-dien-3-ol. The aH NMR spectrum (CDC13, d) showed characteristic signals at: 0.79 (s, 3H), 0.83 (s, 3H), 0.90 (d, 3H), 1.01 (s, 3H), 1.02 (s, 3H), 2.42 (s, 3H), 3.21 (dd, 1H), 3.52 (m, 2H), 4.01 (t, 2H), 5.33 (s, 1H), 7.35 (d, 2H), 7.80 (d, 2H).

Step 2 A mixture of 24-toluenesulfonyloxy-4,4-dimethyl-5a-cola-8,14-dien-3-ol (45 mg, 0.8 mmol) and lithium chloride (0.6 mmol) in 1.5 ml of dimethylformamide under the atmosphere of nitrogen, it was heated at 60 ° C for 2 hours. The reaction was then poured into water and extracted with diethyl ether. Drying over magnesium sulfate, concentration under reduced pressure and purification by flash chromatography followed by recrystallization from methanol gave 12 mg of the title compound. The 1U NMR spectrum (CDC13, d) showed characteristic signals at: 0.80 (s, 3H), 0.82 (s, 3H), 0.97 (d, 3H), 1.02 (s, 3H), 1.04 (s, 3H), 3.25 (dd, 1H), 3.52 (m, 2H), 5.36 (s, 1H). The mass spectrum showed characteristic peaks at: 404.2 (M +).

EXAMPLE 35 4.4, dimeti1-17ß- ((IR) -methyl-4-iodobutyl) androsta-8, 14-dien-3ß-ol A mixture of 24-toluenesulfonyloxy-4,4-dimethyl-5a-cola-8,14-dien-3-ol (100 mg, 0.18 mmol) and 0. 9 mmol of sodium iodide in 2 ml of dimethylformamide under nitrogen atmosphere was heated at 60 ° C for 3 hours. The reaction was then poured into water and extracted with diethyl ether. Drying over magnesium sulfate, concentration under reduced pressure and purification by flash chromatography, followed by recrystallization from methanol gave 40 ml of the title compound. The 2H NMR spectrum (CDC13, d) showed characteristic signals at: 0.80 (s, 3H), 0.82 (s, 3H), 0.95 (d, 3H), 1.1 (s, 3H), 1.02 (s, 3H), 3.10-3.31 (m, 2H), 5.35 (s, 1H). The mass spectrum showed characteristic peaks at: 496.1 (M *).

EXAMPLE 36 4, 4-dimethyl-17β- ((IR) -methylbutylandrosta-8, 14-dien-3ß-ol To a solution of 24-toluenesulfonyloxy-4,4-dimethyl-5a-cola-8,14-dien-3-ol (100 mg, 0.18 mmol) in 25 ml of diethyl ether, lithium aluminum hydride (40 mg) was added. mg, 1.1 mmol) and the reaction was stirred at 16 hours at room temperature. The The reaction was then poured into water and extracted with diethyl ether. Drying over magnesium sulfate, concentration under reduced pressure and purification by flash chromatography gave 41 mg of the title compound. The NMR * H spectrum (CDC13, d) showed characteristic signals at: 0.80 (s, 3H), 0.82 (s, 3H), 0.87 (t, 3H), 0.95 (d, 3H), 1.00 (s, 3H) , 1.02 (s, 3H), 3.20-3.31 (m, 1H), 5.35 (m, 1H). The 13 C NMR spectrum (CDC13, d) showed characteristic signals at: 79.1, 117.8 (C-15), 123.2 (C-14), 142.1 (C-9), 151.4 (C-8). The mass spectrum showed characteristic peaks at: 370.3 (M +).

EXAMPLE 37 4, 4-dimethyl-17β- ((IR) -methyl-4-cyanobutyl) androsta-8, 14-dien-3ß-ol A mixture of 24-toluenesulfonyloxy-4,4-dimethyl-5a-cola-8,14-dien-3-ol (500 mg, 0.5 mmol) and sodium cyanide (90 mg, 2 mmol) in 2 ml of sulfoxide of dimethyl under nitrogen atmosphere was heated at 140 ° C for 2.5 hours. The reaction was then poured into an ammonium chloride solution and extracted with dichloromethane. Drying over magnesium sulfate, concentration under reduced pressure and purification by flash chromatography gave 240 mg of the title compound. The 1H NMR spectrum (CDC13, d) showed characteristic signals at: 0.81 (s, 3H), 0.83 (s, 3H), 0.97 (d, 3H), 1.00 (s, 3H), 1.02 (s, 3H), 3.18 -3.31 (m, 1H), 5.35 (m, 1H). The mass spectrum showed characteristic peaks at: 395.3 (M +).

EXAMPLE 38 Benzyl Ester of 27-nor-3ß-hydroxy-4, 4-dimethyl-5a-cholesta-8, 14-dien-26-oic acid The compound was synthesized following the procedures described in Example 52 below. AH NMR (CDC13, 400 MHz) d = 7.35 (5H, m); 5.34 (1H, s); 5.11 (2H, s); 3.23 (1H, m).

EXAMPLE 39 N- (methionine methyl ester) 3-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide 18 g of the 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid methyl ester are suspended in 300 ml of DMF and 14.8 g of imidazole, and 13 g of tert. -butyldimethylsilylchloride. The reaction mixture was stirred at 70 ° C for 20 hours. After aqueous extraction and crystallization from diethyl ether / methanol, 21.0 g of 3-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid methyl ester are isolated. Melting point: 124-125 ° C. NMR * H (CDC13, 400 MHz): d = 5.34 (1H, s); 3.67 (3H, s); 3.19 (1H, m); 0.9 (9H, s); 0.03 (6H, m). 3.6 g of 3-methyl-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid methyl ester were dissolved in a mixture of 150 ml of THF, 120 ml of ethanol and 18 ml of 1 M sodium hydroxide. The mixture is stirred for 20 hours at room temperature and 2 hours at 50 ° C. After extraction and crystallization from ethanol / water, the isolated 2.48 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid. 1 H NMR (CDCl 3, 300 MHz): d = 5.33 (1H, s); 3.19 (1H, m); 0.9 (oH, s); 0.03 (6H, m). 0.5 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid are dissolved in 10 ml of anhydrous dichloromethane and 0.213 ml of N-methylmorpholine. After cooling to -15 ° C, 0.132 ml of isobutyl chloroformate are added and the mixture is stirred at -15 ° C for 20 minutes, after which 0.232 g of the methyl ester hydrochloride of L-methionine are added and The mixture is stirred overnight, and the temperature rises slowly to room temperature. After the aqueous extraction, the N- (methionine methyl ester) 3-tert-butyldimethylsilyloxy-, 4-dimethyl-5a-cola-8,14-dien-24 oic acid (0.60 g) amide is obtained. NMR * H (CDCl 3, 300 MHz): d = 6.12 (1H, d); . 34 (1H, s); 4.73 (1H, m); 3.76 83H, s); 3.2 (1H, m); 2.1 (3H, s); 9.0 (9H, s); 0.03 (6H, m). 0.20 g of the N- (methionine methyl ester) 3β-tert-butyldimethylsilyloxy-, 4-dimethyl-5a-cola-8, 14-dien- 24-Oico is suspended in 20 ml of methanol, and 0.1 ml of 6 M hydrogen chloride is added, and the mixture is stirred at 50 ° C for 1.5 hours and at room temperature for 20 hours. After crystallization by the addition of water, 165 mg of the title compound are obtained. Melting point: 138-141 ° C. AH NMR (CDC13, 300 MHz): d = 6.12 (1H, d); 5.35 (1H, s); 4.73 (1H, m); 3.76 (3H, s); 3.23 (1H, m); 2.1 (3H, s). MS: Calculated: 545.8. Found 545.3.

EXAMPLE 40 N- (methionine) 3-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide 75 mg of the N- (methionine methyl ester) 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid amide is saponified overnight in a mixture of 10 ml. methanol, 5 ml of THF, 1 ml of water, and 0.6 ml of 1 M sodium hydroxide. After aqueous extraction and crystallization from methanol, 56 mg of the title compound was obtained. 1 H NMR (CDCl 3, 300 MHz): d = 6.35 (1H, d); 5.35 (1H, s); 4.7 (1H, m); 3.25 (1H, m); 2.12 (3H, s). MS: Calculated: 531.8. Found 531.8.

EXAMPLE 41 N- (4-methylpiperazinyl) amide of 3β-hydroxy-4, -dimethyl-5a-cola-8,14-dien-24-oico 0. 40 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid was reacted with N-methylpiperazine and hydrolyzed with HCl / ethanol following the procedure described in Example 39 to give 80 mg of the title compound. Melting point: 189-191 ° C. NMR * H (CDC13, 300 MHz): d = 5.35 (1H, s); 3.63 (2H, m); 3.48 (2H, m); 3.24 (1H,); 2.31 (3H, s). MS: Calculated. 482.8. Found 482.3.

EXAMPLE 42 3-Hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid N-tert-butylamide 0. 50 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid is reacted with tert-butylamine and hydrolyzed with HCl / ethanol following the procedure described in the example 39 to give 204 mg of the title compound. Melting point: 171-176 ° C. NMR 1 (CDC13, 300 MHz): d = 5.35 (1H, s); 5.21 (1H, s); 3.24 (1H, m); 1.36 (9H, s). MS: Calculated: 455.7. Found 455.4.

EXAMPLE 43 N- (isonipecotic acid ethyl ester) 3β-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide 0. 50 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid was reacted with ethyl isonipecotate and hydrolyzed with HCl / ethanol following the procedure described in Example 39 to give 85 mg of the title compound. Melting point. 116-119"C NMR aH (CDC13, 400 MHz): d 5.35 (1H, s); 4.43 (1H, m) 4.15 (2H, q); 3.82 (1H, m); 3.25 (1H, m); 3.11 (1H, m), 2.8 (1H, m), 1.28 (3H, t), MS: Calculated: 539.8, Found 539.4.

EXAMPLE 44 N- (isonipecotic acid) 3β-hydroxy-4, -dimethyl-5a-cola-8, 14-dien-24-oic acid amide 36 mg of the N- (ethyl ester of isonipecotic acid) 3-hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide is saponified overnight in a mixture of 3 ml of ethanol and 0.2 ml of 1 M sodium hydroxide. After aqueous extraction and crystallization from ethanol / water, 10 mg of the title compound are obtained. Melting point: 228-231 ° C. NMR] H (CDCl 3, 400 MHz): d = 5.36 (1H, s); 4.45 (1H, m); 3.84 (1H,); 3.27 (1H, m); 3.16 (1H, m); 2.86 (1H, m). MS: Calculated. 497.7. Found 497.6.

EXAMPLE 45 N- (Phenylalanine methyl ester) 3-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide 0. 40 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid are reacted with phenylalanine methyl ester and hydrolyzed with HCl / methanol following the procedures described in Example 39 to give 86 mg of the title compound. Melting point: 158-160 ° C. 1 H NMR (CDC13, 400 MHz): d = 7.27 (3H, m); 7.09 (2H, m); 5.86 (1H, d); 5.35 (1H, s); 4.89 (1H, m); 3.73 (3H, s); 3.25 (1H, m); 3.13 (2H, m). MS: Calculated: 561.8. Found 561.5.

EXAMPLE 46 3ß-Hydroxy-4,4-dimethyl-5,7-dien-24-oic acid 120 mg of 3-hydroxy-4,4-dimethyl-5,7-dien-24-oic acid methyl ester are saponified in a mixture of 15 ml of methanol, 15 ml of THF and 0.7 ml of 1 M sodium hydroxide. at 50 ° C.

After aqueous extraction and crystallization from methanol, 76 mg of the title compound are isolated. Melting point. 210-213 ° C. JH NMR (CDCl 3, 400 MHz): d = 5.92 (1H, d); 5.55 (1H, m); 3.38 (1H,). MS: Calculated: 400.6. Found 400.2.

EXAMPLE 47 3-Hydroxy-4, -dimethyl-5,7-dien-24-oic acid N-dimethylamide 3. 5 g of 3-methyl-tert-butyldimethylsilyloxy-, 4-dimethyl-5,7-dien-24-oic acid methyl ester are saponified and reacted with dimethylamine following the procedure described in Example 39. The protective group tert-butyldimethylsilyl is cleaved by treatment with hydrated tetra-butylammonium fluoride, according to the procedure described in Example 2, to give the title compound. AH NMR (CDCl 3, 400 MHz): d = 5.92 (1H, d); 5.54 (1H, m); 3.4 (1H, m); 3.03 (3H, s); 2.96 (3H, s). MS: Calculated: 427.7. Found 427.4.

EXAMPLE 48 4, 4-dimethyl-24-acetamido-5a-cola-8, 14-dien-3ß-ol . 0 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid are reacted with ammonia following the procedure described in Example 39 and reduced with lithium hydride and aluminum (3.0 g) in THF at room temperature. Aqueous extraction and crystallization from methanol gives 2.6 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-2,4-amino-5a-cola-8,14-diene. AH NMR (CDC13, 300 MHz): d = 5.34 (1H, s); 3.2 (1H, m); 3.0 (2H, broad s); 2.7 (1H, m); 0.9 (9H, s); 0.03 (6H, m). MS: Calculated: 499.9. Found 499.4. 050 g of 3β-tert-butyldimethylsilyloxy-4, -dimethyl-24-amino-5a-cola-8, 14-diene are acetylated in a mixture of 20 ml of pyridine and 7 ml of acetic anhydride and hydrolyzed with HCl / ethanol . After aqueous extraction and crystallization from ethanol / water, 0.24 g of the title compound are isolated. Melting point: 219-221 ° C.

JH NMR (CDCl 3, 300 MHz): d = 5.43 (1H, s); 5.35 (1H, s); 3.23 (3H, m); 1.98 (3H, s). MS: Calculated: 427.7. Found 427.4.

EXAMPLE 49 4, 4-dimethyl-24-acetoxy-5a-cola-8, 14-dien-3ß-ol . 29 g of 3-methyl-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid methyl ester are reduced with 1.75 g of lithium-aluminum hydride in 300 ml of THF at room temperature ambient. After aqueous extraction and crystallization from ethanol / water, 4.58 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-Sa-cola-8,14-dien-24-ol are isolated. NMR * H (CDCl 3, 400 MHz): d = 5.35 (1H, s); 3.65 (2H, m); 3.2 (1H, m); 0.9 (9H, s); 0.03 (6H, m). 150 mg of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-diene-24-ol is acetylated in a mixture of 2 ml of pyridine and 1 ml of acetic anhydride. The tert-butyldimethylsilyl protecting group is divided by treatment with hydrated tetra-butylammonium fluoride, according to procedure described in Example 2. After column chromatography and crystallization from acetone / water, 36 mg of the title compound are obtained. NMR * H (CDC13, 300 MHz): d = 5.35 (1H, s); 4.05 (2H, m); 3.23 (1H, m); 2.04 (3H, s). MS: Calculated: 428.7. Found 428.3.

EXAMPLE 50 4, 4-dimethyl-24-methoxy-5a-cola-8, 14-dien-3ß-ol 100 mg of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dien-24-ol is methylated with 16 mg of 60% sodium hydride and 0.125 ml of methyl iodide in 1 ml of DMF. The tert-butyldimethylsilyl protecting group is divided by treatment with HCl / ethanol. After the aqueous extraction and crystallization from methanol / water, 5 mg of the title compound are isolated. 1 H NMR (CDC13, 300 MHz): d = * = 5.35 (1H, s); 3. 36 (2H, m); 3.32 (3H, s); 3.23 (1H, m). MS: Calculated: 400.7. Found 400.3.

EXAMPLE 51 4, 4-dimethyl-24-benzyloxy-5a-cola-8, 14-dien-3ß-ol The compound is synthesized following the procedure in Example 50. Melting point: 114-115 ° C. 1 H NMR (CDC13, 300 MHz): d 7.38-7.23 (5H, m); 5.35 (1H, s); 4.51 (2H, s); 3.45 (2H, m), 3.24 (1H, m). MS: Calculated. 476.7. Found: 476.3.

EXAMPLE 52 3-Hydroxy-4, -dimethyl-5a-cola-8, 14-dien-24-oic acid benzyl ester 100 mg of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid are suspended in 5 ml of anhydrous dimethylformamide. 811 mg of cesium carbonate and 0.29 ml of benzyl chloride are added, and the mixture is stirred at 50 ° C overnight. After aqueous extraction, column chromatography and crystallization from acetone / water 55 mg of the title compound are obtained. Melting point: 118-119 ° C. 1K NMR (CDC13, 300 MHz): d = 7.35 (5H, m); 5.35 (1H, s); 5.12 (2H, s); 3.23 (1H, m). M ?: Calculated: 490.7. Found. 490.3.

EXAMPLE 53 26, 27-diethyl-3β-hydroxy-4, 4-dimethyl-l-5a-cholesta-8, 14-dien-26,27-dioate 4. 0 g of 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cola-8,14-dα-en-24-ol is dissolved in 80 ml of anhydrous pyridine at 0 ° C. 3.04 g of p-toluenesulfonyl chloride are added and the mixture is stirred at 5 ° C for 20 hours, and at room temperature for 5 hours. After aqueous extraction and crystallization from methanol, 3.01 g of β-tert-butyldimethylsilyloxy-4,4-dimethyl-24-p-toluenesulfonyloxy-5a-cola-8,14-diene are obtained. 1 E NMR (CDCl 3, 300 MHz): d = 7.79 (2H, d), 7.34 (2H, d); 5.33 (1H, s); 4.02 (2H, m); 3.19 (1H, m); 2.43 (3H, s); 0.9 (9H, s); 0.03 (6H, m). 0.50 g of 3β-tert-butyldimethylsilyloxy-4,4-d? Methyl-24-p-toluenesulfonyloxy-5a-cola-8,14-diene was added to a mixture of 0.58 ml of diethyl malonate and 137 mg of hydride of sodium (60%) in 10 ml of anhydrous THF at -70 ° C. They were stirred at -70 ° C for 15 minutes, after which the temperature was raised and heated to reflux for 9 hours. After aqueous extraction and crystallization from ethanol / water, 0.432 g of 26,27-diethyl-3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cholesta-8,14-dα-26 is obtained. , 27-dioate. 1 T NMR (CDC13, 300 MHz): 6 = 5.33 (1H, s); 4.21 (4H, q); 3.32 (1H, t); 3.2 (1H, m), 0.9 (9H, s); 0.03 (6H, m). MS: Calculated: 643.0. Found: 642.4. 0.41 g of 26, 27-diethyl-3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5a-cholesta-8,14-diene-26,27-dα-oate are dissolved in 40 ml of ethanol and 0.5 ml of 6 M hydrogen chloride. It is stirred at room temperature for 48 hours and at 40 ° C for 1 hour. The product is crystallized by the addition of water and recrystallized from ethanol to give 141 mg of the title compound. Melting point: 105-106 ° C. NMR * H (CDC13, 300 MHz): d = 5.35 (1H, s); 4.2 (4H, q); 3.33 (1H, t); 3.25 (1H, m), 1.25 (6H, t). MS: Calculated. 528.8. Found: 528.4.

EXAMPLE 54 3ß-Hydroxy-4,4-dimethyl-5a-cholesta-8, 14-dien-26,27-dioic acid 95 mg of 26,27-diethyl-3β-hydroxy-4, -dimethyl-5a-cholesta-8,14-diene-26,27-dioate is saponified in a mixture of 5 ml of 96% ethanol, 5 ml of THF and 5 ml of 1 M sodium hydroxide at room temperature. After the aqueous extraction, 60 mg of the title compound are isolated. Melting point: 188-190 ° C. 2 H NMR (DMSO-de, 400 MHz): d = 12.63 (2H, s); 5.3 (1H, s); 4.37 (1H, s); 3.2 (1H, t); 3.03 (1H, m). M ?: Calculated: 472.7. Found. 473.2 [M + H • EXAMPLE 55 27-nor-3ß-hydroxy-4, -dimethyl-5a-cholesta-8, 14-dien-26-oic acid 535 mg of 3β-hydroxy-4,4-dimethyl-5a-cholesta-8,14-dien-26,27-dioic acid are suspended in 30 ml of o-xylene and heated to reflux overnight.

After evaporation of o-xylene, the title compound is isolated by crystallization from methanol / ether. Yield: 338 mg. NMR? (DMSO-de, 400 MHz): d = 11.95 (1H, s); 5.28 (1H, s); 4.35 (1H, m); 3.0 (1H,). MS: Calculated. 428.7. Found: 428.2.

EXAMPLE 56 Synthesis of the intermediate cholesta-4, 8-dien-3-one A solution of 2.20 g of cholesta-5,8-dien-3ß-ol in 27 ml of toluene and 6 ml of cyclohexanone was heated to reflux for 10 minutes in a Dean-Stark apparatus. 0.57 g of aluminum isopropoxide are added and the reaction mixture is heated to reflux for 30 minutes. After cooling and addition of sulfuric acid (2 N), the resulting mixture is extracted with ethyl acetate. The organic layer is separated, washed with saturated sodium bicarbonate solution and water, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, the residue is subjected to chromatography with a mixture of hexane and ethyl acetate. ethyl to give 1.53 g of cholesta-4,8-dien-3-one as a white solid. 2 H NMR (CDC13): d = 0.68 (s, 3H, H-18); 0.87 (2x d, J = 7 Hz, 6H, H-26/27); 0.94 (d, J = 7 Hz, 3H, H-21); 1.35 (s, 3H, H-19); 5.77 (s, 1H, H-4). Cholesta-4, 8 (14) -dien-3-one is synthesized from cholesta-5, 8 (14) -dien-3ß-ol in the same manner. Cholesta-4, 7-dien-3-one is synthesized according to the procedures of the literature [Just. Li ebi gs Ann. Chem. 542 (1939), 218].

EXAMPLE 57 (Reaction Scheme 1) Cholesta-4, 8-dien-3a-ol and cholesta-, 8-dien-3ß-ol To a solution of 520 mg of cholesta-4,8-dien-3-one in 45 ml of tetrahydrofuran, add 1.70 ml of a solution of 1-electride (1 N, in tetrahydrofuran) dropwise at -75 °. C. The reaction mixture is warmed to room temperature within 4 hours, poured into hydrochloric acid (1 N) and extracted with ethyl acetate. The organic layer is separated, washed with brine, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, the residue was subjected to chromatography with a mixture of hexane and ethyl acetate to give 286 mg of cholesta-4, 8-diene-3ß-ol and 20 mg of cholesta-4, 8-diene-3a-ol as white solids.

Colesta-4, 8-dien-3a-ol NMR * H (CDC13): d = 0.63 (s, 3H, H-18); 0.86 (2x d, J = 7 Hz, 6H, H-26/27); 0.92 (d, J = 7 Hz, 3H, H-21); 1.11 (s, 3H, H-19); 4.04 (m, 1H, H-3); 5.47 (d, H = 5 Hz, 1H, H-4).

Cholesta-4, 8-dien-3ß-ol NMR * H (CDCl 3): d = 0.64 (s, 3H, H-18); 0.86 (2x d, J = 7 Hz, 6H, H-26/27); 0.93 (d, J = 7 Hz, 3H, H-21); 1.23 (s, 3H, H-19); 2.47 (m, 1H); 4.19 (m, 1H, H-3); 5.32 (s, 1H, H-4). The cholesta-, 7-dien-3a-ol and the cholesta-4,7-dien-3ß-ol are synthesized according to the procedures of the literature [Just. Li ebi gs Ann. Chem. 542 (1939), 218].

EXAMPLE 58 (Reaction Scheme 2): a) 5-cyano-5β-cholest-8-en-3-one and 5-cyano-5a-cholest-8-en-3-one ml of a solution of diethylamumium cyanide (1 N, in toluene) are added to a solution of 3.82 g of cholesta-, 8-dien-3-one in 60 ml of tetrahydrofuran at 0 ° C. The reaction mixture is warmed to room temperature and stirred for 4 hours. 20 ml of a sodium hydroxide solution (1 N) are added before the mixture is extracted with diethyl ether. The organic layer is separated, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, the residue was subjected to chromatography with a mixture of hexane and ethyl acetate to give 1.46 g of 5-c-ano-5β-cholest-8-en-3-one and 1.76 g of 5- cyano-5a-cholest-8-en-3-one as pale yellow crystals. -cyano-5β-cholest-8-en-3-one: NMR * H (CDC13): d = 0.69 (s, 3H, H-18); 0.87 (32x d, J = 7 Hz, 6H, H-26/27); 0.95 (d, J = 7 Hz, 3H, H-21); 1.43 (s, 3H, H-19); 2.63 (m, 1H). -cyano-5a-cholest-8-en-3-one: NMR * H (CDCl 3): d = 0.64 (s, 3H, H-18); 0.87 (2x d, J = 7 Hz, 6H, H-26/27); 0.95 (d, J = 7 Hz, 3H, H-21); 1.37 (s, 3H, H-19); 2.52 (m, 2H).

-Cyano-5β-cholest-7-en-3-one [which is known from the literature: Aust. J. Chem. 35 (1982), 629], 5-cyano-5a-cholest-7-en-3-one, 5-cyano-5β-cholest-8 (14) -en-3-one and 5-cyano-5a-cholestyl -8 (14) -en-3-one are synthesized from the corresponding initial materials in the same manner. b) 5-cyano-5a-cholest-8-en-3ß-ol and 5-cyano-5a-colest-8-en-3a-ol 327 mg of sodium borohydride are added to a solution of 1.76 g of 5-cyano-5a-cholest-8-en-3-one in 200 ml of ethanol at room temperature. The reaction mixture was stirred for 4 hours. After the addition of the hydrochloric acid (1 N), the resulting mixture is extracted with dichloromethane. The organic layer is separated, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, the residue is subjected to chromatography with a mixture of hexane and ethyl acetate to give 0.36 mg of 5-cyano-5a-cholest-8-en-3ß-ol and 1.00 g of 5-cyano-5a-cholest-8-en-3a-ol as white solids . -cyano-5a-cholest-8-en-3ß-ol AH NMR (CDCl 3): d = 0.59 (s, 3H, H-18), 0.86 (2x d, J = 7 Hz, 6H, H-26/27); 0.92 (d, J = 7 Hz, 3H, H-21); 1.08 (s, 3H, H-19); 4.12 (broad m, 1H, H-3). -cyano-5a-colest-8-en-3a-ol NMR * H (CDCl 3): d = 0.63 (s, 3H, H-18); 0.89 (2x d, J = 7 Hz, 6H, H-26/27); 0.94 (d, J = 7 Hz, 3H, H-21); 1.06 (s, 3H, H-19); 4.11 (broad m, 1H, H-3).

-Cyano-5a-cholest-7-en-3ß-ol, 5-cyano-5a-cholest-7-en-3a-ol, 5-cyano-5-cholest-7-en-3a-ol, -cyano-5β-cholest-8-en-3ß-ol, 5-cyano-5β-cholest-8-en-3a-ol, 5-cyano-5a-cholest-8 (14) -en-3β-ol, 5-cyano-5a-cholest-8 (14) -en-3a-ol, 5-cyano-5-cholest-8 (14) -en-3ß-ol and 5-cyano-5-cholest-8 (1) -in-3a-ol are synthesized in the same way.

EXAMPLE 59 (Reaction Scheme 3): a) 3ß-hydroxy-5a-cholest-8-ene-5-carbaldehyde 4. 66 ml of a solution of diisobutylaluminum hydride (1.2 N, in toluene) are added to a solution of 230 mg of 5-cyano-5a-cholest-8-en-3ß-ol in 18 ml of toluene at -10 ° C . The reaction mixture is stirred for 3 hours before 3.6 ml of sulfuric acid (1 N) is added. After heating to reflux for one hour, the resulting mixture is cooled to room temperature, diluted with water, and extracted with dichloromethane. The organic layer is separated, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, 220 mg of 3β-hydroxy-5α-cholest-8-ene-5-carbaldehyde is obtained as a white solid. NMR * H (CDC13): d = 0.63 (s, 3H, H-.18); 0.86 (2x d, J = 7 Hz, 6H, H-26/27); 0.94 (d, J = 7 Hz, 3H, H-21); 1.17 (s, 3H, H-.19); 2.23 (m, 2H); 3.61 (m, 1H, H-3); 9.86 (s, 1H, 5-CHO). b) 5- (hydroxymethyl) -5a-colest-8-en-3ß-ol A suspension of 56 mg of lithium aluminum hydride in 5 ml of tetrahydrofuran is added to a solution of 200 mg of 3β-hydroxy-5α-cholest-8-en-5-carbaldehyde in 20 ml of tetrahydrofuran at room temperature. After heating at 50 ° C for two hours, the reaction mixture is cooled to room temperature. Subsequently, 0.06 ml of water, 0.06 ml of a sodium hydroxide solution (1 N) and 0.18 ml of water are added. The resulting suspension is stirred for 15 minutes and filtered over sodium sulfate. After evaporation of the solvent, the residue is crystallized from ethyl acetate to give 80 mg of 5- (hydroxymethyl) -5a-cholest-8-en-3β-ol as a white solid. NMR * H (CDC13): d = 0.63 (s, 3H, H-18); 0.87 (2x d, J = 7 Hz, 6H, H-26/27); 0.93 (d, J = 7 Hz, 3H, H-21); 1.16 (s, 3H, H-19); 3.58 (s, 2H, 5-CH2OH); 3.97 (m, 1H, H-3). - (hydroxymethyl) -5a-cholest-7-en-3ß-ol, 5- (hydroxymethyl) -5β-cholest-8-en-3a-ol and 5- (hydroxymethyl) -5a-cholest-8 (14) -en-3ß-ol synthesize in the same manner.

EXAMPLE 60 (Reaction Scheme 4): 3 ', 4a-dihydroxylopropa [4,5] -5β-colest-8-en-3ß-ol 300 mg of zinc powder and 0.03 ml of glacial acetic acid are added to a solution of 5.4 mg of cupric acetate in 1.2 ml of dimethoxyethane at room temperature. The mixture is stirred for 30 minutes before 0.01 ml of triethylamine is added. After 5 minutes, a solution of 100 mg of cholesta-4,8-dien-3b-ol in 0.4 ml of dimethoxyethane is added. Then 0.24 ml of diiodomethane is added at a rate such that the reaction temperature does not rise above 40 ° C. The reaction mixture is stirred for an additional 6 hours. After the addition of the saturated solution of ammonium chloride, the resulting mixture is extracted with ethyl acetate. The organic layer is separated, washed with brine, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, the residue is subjected to chromatography with a mixture of hexane and ethyl acetate to give the residue. mg of 3 ', 4a-dihydrocyclopropa [5] -5β-cholest-8-en-3β-ol as a white solid. NMR 'H (CDC13): d = 0.25 (dd, J = 9 Hz, 5 Hz, 1H, 4.5-CH2); 0.63 (s, 3H, H-18), 0.76 (dd, J = 5 Hz, 5 Hz, 1H, 4.5-CH2); 0.87 (2x d, J = 7 Hz, 6H, H-26/27); 0.94 (d, J = 7 Hz, 3H, H-21); 1.11 (s, 3H, H-.19), 4.32 (m, 1H, -3).

EXAMPLE 61 (Reaction Scheme 5): a) 5-methyl-5β-cholest-8-en-3-one 0. 85 ml of a solution of methyl lithium (1.6 N, in diethyl ether) are added to a suspension of 130 mg of cuprous iodide in diethyl ether at 0 ° C. The resulting mixture is stirred for one hour before a solution of 130 mg of cholesta-4,8-dien-3-one in 1 ml of diethyl ether is added. Before being stirred for 30 minutes, the reaction mixture is poured into a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic layer is separated, washed with brine, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, the residue is subjected to chromatography with a mixture of hexane and ethyl acetate. ethyl to give 80 mg of 5-methyl-5β-cholest-8-en-3-one as a white solid. 2 H NMR (CDC13): d = 0.63 (s, 3H, H .18); 0.86 (2x d, J = 7 Hz, 6H, H-26/27); 0.90 8s, 3H, 5-CH3); 0.93 (d, J = 7 Hz, 3H, H-21); 1.06 (s, 3H, H.19); 2.42 (m, 1H). b) 5-methyl-5β-cholest-8-en-3a-ol and 5-methyl-5β-cholest-8-en-3ß-ol 0. 31 ml of a solution of K-Selectride (1 N, in tetrahydrofuran) are added to a solution of 63 mg of 5-methyl-5β-cholest-8-en-3-one in 4.4 ml of tetrahydrofuran at -65 ° C . After stirring for 2 hours, the reaction mixture is allowed to warm to room temperature, is poured into a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic layer is separated, washed with brine, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, the residue is subjected to chromatography with a mixture of dichloromethane and acetone to give 26 mg of 5-methyl-5β-cholest-8-en-3a-ol and 21 mg of 5-methyl-5β- cholest-8-en-3ß-ol as white solids. -methyl-5β-colest-8-en-3a-ol TR NMR (CDCl 3): d = 0.59 (s, 3H, H-18); 0.85 (2x d, J = 7 Hz, 6H, H-26/27); 0.86 8s, 3H); 0.90 8s, 3H); 0.92 (d, J = 7 Hz, 3H, H-21); 3.82 (m, 1H, H-3). -methyl-5β-colest-8-en-3ß-ol AH NMR (CDCl 3): d = 0.63 (s, 3H, H-18); 0.87 (2x d, J = 7 Hz, 6H, H-26/27); 0.89 (s, 3H, 5-C3, 0.93 (d, J = 7 Hz, 3H, H-21), 0.99 (s, 3H, H-19), 3.87 (m, 1H, H-3).

The 5-methyl-5β-cholest-8 (14) -en-3-one, 5-methyl-5β-cholest-8 (14) -en-3ß-ol and 5-methyl-5β-cholest-8 (14) -in-3a-ol are synthesized in the same way.

EXAMPLE 62 (Reaction Scheme 1): 3ß- (trifluoromethyl) cholesta-4, 8-dien-3a-ol and 3a- (trifluoromethyl) cholesta-4, 8-dien-3ß-ol 0. 2 ml of triethylsilyltrifluoromethane and 328 mg of tetrabutylammonium fluoride trihydrate are add to a solution of 200 mg of cholesta-4,8-dien-3-one in 10 ml of tetrahydrofuran at room temperature. After stirring for 2 hours, the reaction mixture is diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and filtered. After evaporation of the solvent, the residue is subjected to chromatography with a mixture of hexane and ethyl acetate to give 45 mg of the 3ß- (trifluoromethyl) cholesta-4,8-dien-3a-ol as a colorless oil and 170 mg of 3a- (trifluoromethyl) cholesta-4,8-dien-3β-ol as a white solid. 3ß- (trifluoromethyl) cholesta-4, 8-dien-3a-ol: NMR * H (CDC13): d = 0.65 (s, 3H, H-18); 0.87 (2x d, J = 7 Hz, 6H, H-26/27); 0.93 (d, J = 7 Hz, 3H, H-21); 1.18 (s, 3H, H-19); 2.41 (m, 1H); 5.39 (s, 1H, H-4) 3a- (trifluoromethyl) cholesta-4,8-dien-3ß-ol: AH NMR (CDCl 3): d = 0.64 (s, 3H, H-18); 0.87 (2x d, J = 7 Hz, 6H, H-26/27); 0.93 (d, J = 7 Hz, 3H, H-21); 1.25 (s, 3H, H-19); 2.43 (m, 1H); 5.25 (s, 1H, H-4).

EXAMPLES 63 + 64 (20R) -5-Cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3ß-ol and (20R) -5-cyano-21-cyclohexyl-20-methyl-5a-pregn-8- en-3a-ol a) Ergosta-4, 8, 22-trien-3-one 1. 90 g of ergosta-5, 8, 22-trien-3ß-ol (lysterol) are treated with 0.50 g of aluminum tris-isopropylate as described in Example 56. Column chromatography gave 1.54 g of ergosta-4, 8, 22-trien-3-one as a white solid. NMR 'H (CDC13); d = 0.69 (s, 3H, H-18); 0.82-1.05 (4x d, 4x Me); 1.36 (s, 3H, H-19); 5.22 (m, 2H, H-22/23); 5.77 (s, 1H, H-4). -cyano-5a-ergosta-8,22-dien-3-one 1. 54 g of ergosta-4, 8, 22-trien-3-one was treated with 11.73 ml of diethylaluminum cyanide solution (1 N, in toledo) as described in Example 58. After aqueous extraction and chromatography 0.90 g of 5-cyano-5a-ergosta-8, 22-dien-3-one was isolated as a white solid (in addition to the corresponding 5β-cyano compound). NMR aH (CDC13): d = 0.66 (s, 3H, H-18); 0.82- 1.05 (4 x d, 4 x Me); 1.28 8s, 3H, H-19); 5.21 (, 2H, H.22 / 23). c) 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-ergosta-8,22-diene A mixture of 900 mg of 5-cyano-5a-ergosta-8, 22-dien-3-one, 0.97 ml of ethylene glycol, 25 mg of p-toluenesulfonic acid in 20 ml of toluene was heated to reflux in a dean trap. -stark for 2 hours. After cooling, the reaction mixture was poured into saturated sodium bicarbonate solution, extracted with ethyl acetate and washed with water. The combined organic extracts were dried and evaporated to give 900 mg of 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-ergosta-8,22-diene as a white solid. NMR * H (CDCl 3): d = 0.63 (s, 3H, H-18); 0.82-1.05 (4 x d, 4 x Me); 1.11 (s, 3H, H-19) 3.90-4.15 (m, 4H, 3-ketal); 5.20 (m, 2H, H-22/23). d) (20R) -5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-en-20-methanol 450 mg of 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-ergosta-8,22-diene are treated with ozone as described in Example 19b. After reductive work, 172 mg of the (20R) -5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-en-20-methanol was isolated as a white solid. RMN _. (CDC13): d = 0.65 (s, 3H, H-18); 1.06 (d, J = 7 Hz, 3H, H-21); 1.10 (s, 3H, H-19); 3.35 (m, 1H, H-22); 3.66 (m, 1H, H-22); 3.90-4.12 (m, 4H, 3-ketal). e) Sulfonate of (20R) -5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-en-20-methanol-4-methylbenzene 1. 13 g of the (20R) -5-cyano-5a-pregn-8-en-20-methanol are treated with 869 mg of p-toluenesulfonyl chloride as described in Example 19 d. After aqueous extraction and column chromatography, 1.19 g of the (20R) -5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-en-20 sulfonate was isolated. -methanol-4-methylbenzene. 1 H NMR (CDCl 3): d = 0.59 (s, 3H, H.18); 1.00 (d, J = 7 Hz, 3H, H-21); 1.10 (s, 3H, H-19); 3.70-4.12 [m, 4H (3-ketal) + 2H (H-22)]. f) (20R) -5-cyano-21-cyclohexyl-20-methyl-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-ene 258 mg of the (20R) -5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-en-20-methanol-4-methylbenzene sulfonate was treated with cyclohexylmagnesium bromide analogously to Example 19e. After column chromatography, 147 mg of (20R) -5-cyano-21-cyclohexyl-20-methyl-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8- was isolated. eno like a pale yellow solid. NMR! H (CDCl 3): d = 0.62 (s, 3H, H-18); 0.90 (d, J = 7 Hz, 3H, H-21); 1.10 8s, 3H, H-19); 3.90-4.12 (m, 4H, 3-ketal). g) (20R) -5-cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3-one A mixture of 128 mg of (20R) -5-cyano-21-cyclohexyl-20-methyl-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-ene, 31 mg of amberliste fifteen and 8 ml of acetone are stirred at room temperature for 20 hours. After filtration and evaporation of the solvent, 94 mg of the (20R) -5-cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3-one was isolated. AH NMR (CDC13): d = 0.67 (s, 3H, H-18); 0.90 (d, J = 7 Hz, 3H, H-21); 1.27 8s, 3H, H-19); 2.55 (pseudo-s, 2H). h) (20R) -5-cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3ß-ol and (20R) -5-cyano-21-cyclohexyl-20-methyl-5a-pregn 8-in-3a-ol 90 mg of the (20R) -5-cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3-one was treated with 33 mg of sodium borohydride as described in Example 58b. After column chromatography, 15 mg of (20R) -5-cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3ß-ol and 25 mg of (20R) -5-cyano were isolated -21-cycloneexi 1-20-methyl-5a-pregn-8-en-3a-ol. (20R) -5-Cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3β-ol: 2 H-NMR (CDCl 3): d = 0.63 (s, 3H, H-18); 0.93 (d, J = 7 Hz, 3H, H-21); 1.11 (s, 3H, H-19); 4.12 (broad m, 1H, H-3) (20R) -5-Cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3a-ol: 2 H-NMR (CDCl 3): d = 0.62 (s, 3H, H-18); 0.92 (d, J = 7 Hz, 3H, H-21); 1.06 (s, 3H, H-19); 4.12 (narrow m, 1H, H-3).

EXAMPLES 65 + 66 (20R) -5-cyano-21-phenyl-20-methyl-5a-pregn-8-en-3β-ol and (20R) -5-cyano-21-phenyl-20-methyl-5a-pregn-8 -in-3a-ol a) (20R) -5-cyano-21-phenyl-20-methyl-3 (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-ene 400 mg of the sulfonate of (20R) -5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-en-20-methanol-4-methylbenzene (Example 63e) were treated with phenylmagnesium bromide analogously to Example 63f. After column chromatography, 190 mg of (20R) -5-cyano-21-phenyl-20-methyl-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8- was isolated. eno like a white solid. JH NMR (CDC13): d = 0.65 (s, 3H, H-18); 0.84 (d, J = 7 Hz, 3H, H-21); 1.12 (s, 3H, H-19); 2.90 (dd, J = 12 Hz, J = 3 Hz, 1H, H-21); 3.90-4.12 (m, 4H, 3-ketal); 7.12-7.30 (m, 5H, ph). b) (20R) -5-cyano-21-phenyl-20-methyl-5a-pregn-8-en-3-one 180 mg of the (20R) -5-cyano-21-phenyl-20-methyl-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-ene were treated with amberliste 15 as described at Example 63g. After filtration and evaporation of the solvent, 164 mg of the (20R) -5-Cyano-21-phenyl-20-methyl-5a-pregn-8-en-3-one.

NMR? (CDCl 3): d = 0.68 (s, 3H, H-18); 0.84 (d, J 0 7 Hz, 3H, H-21); 1.27 (s, 3H, H-19); 2.55 (pseudo-s, 2H); 2.90 (dd, J = 12 Hz, J = 3 Hz, 1H, H.21); 7.12-7.30 (m, 5H, ph). c) (20R) -5-cyano-21-pheny1-20-methyl-5a-pregn-8-en-3β-ol and (20R) -5-cyano-21-phenyl-20-methyl-5a-pregn 8-in-3a-ol 152 mg of the (20R) -5-cyano-21-cyclohexyl-20-methyl-5a-pregn-8-en-3-one was treated with 50 mg of sodium borohydride as described in Example 58b. After column chromatography, 36 mg of (20R) -5-cyano-21-phenyl-20-methyl-5a-pregn-8-en-3ß-ol and 46 mg of (20R) -5-cyano- were isolated. 21-phenyl-20-methyl-5a-pregn-8-en-3a-ol. (20R) -5-Cyano-21-phenyl-20-methyl-5a-pregn-8-en-3β-ol: NMR? (CDC13): d = 0.67 (s, 3H, H-18); 0.85 (d, J = 7 Hz, 3H, H-21); 1.10 (s, 3H, H-19), 2.90 (dd, J = 12 Hz, J = 3 Hz, 1H, H-21); 4.15 (broad m, 1H, H-3) 7.12-7.30 (m, 5H, ph). (20R) -5-Cyano-21-phen? L-20-met? L-5a-pregn-8-en-3a-ol: aH NMR (CDCI3): d = 0.65 (s, 3H, H-18); 0.84 (d, J = 7 Hz, 3H, H-21); 1.05 (s, 3H, H.19); 2.90 (dd, J 12 Hz, J = 3 Hz, 1H, H-21); 4.12 (narrow m, 1H, H-3); 7.12-7.30 (m, 5H, ph).

EXAMPLES 67 + 68 -cyano-24-nor-5a-cholest-8-en-3ß-ol and 5-cyano-24-nor-5a-colest-8-en-3a-ol a) 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -24-nor-5a-cholest-8-ene 400 mg of the sulfonate of (20R) -5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-en-20-methanol-4-methylbenzene (Example 63e) were treated with isobutylmagnesium bromide analogously to Example 63f. After chromatography, 206 mg of 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -24-nor-5a-cholest-8-ene was isolated as a white solid. 1 H NMR (CDC13): d-0.62 (s, 3H, H-18); 0.85-0.95 (3 x d, J = 7 Hz); 1.10 (s, 3H, H-19); 3.88-4.10 (m, 4H, 3-ketal). b) 5-cyano-24-nor-5a-cholest-8-en-3-one 188 mg of 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -24-nor-5a-cholest-8-ene was treated with amberliste 15 as described in Example 63g. After filtering and evaporating the solvent, 175 mg of 5-cyano-24-nor-5a-cholest-8-en-3-one was isolated. NMR * H (CDCl 3): d = 0.65 (s, 3H, H-18); 0.85-0.95 (3 x d, J = 7 Hz); 1.27 (s, 3H, H-19); 2.55 (pseudo-s, 2H). c) 5-cyano-24-nor-5a-cholest-8-en-3ß-ol and 5-cyano-24-nor-5a-cholest-8-en-3a-ol 173 mg of 5-cyano-24-nor-5a-cholest-8-en-3-one was treated with 67 mg of sodium borohydride as described in Example 58b. After column chromatography, 35 mg of 5-cyano-24-nor-5a-cholest-8-en-3ß-ol and 64 mg of 5-cyano-24-nor-5a-cholest-8-in were isolated. -3a-ol. -cyano-24-nor-5a-cholest-8-en-3β-ol: XH NMR (CDCl 3): d = 0.60 (s, 3H, H-18); 0.85-0.95 (3 x d, J = 7 Hz); 1.10 (s, 3H, H-19); 4.13 (broad m, 1H, H-3). -cyano-24-nor-5a-cholest-8-en-3a-ol: JH NMR (CDCl 3): d = 0.62 (s, 3H, H-18); 0.85-0.95 (3 x d, J = 7 Hz); 1.05 (s, 3H, H-19); 4.10 (broad m, 1H, H-3).

EXAMPLES 69 + 70 -cyano-24-nor-5a-cholesta-8, 23-dien-3ß-ol and 5-cyano-24-nor-5a-cholesta-8,23-dien-3a-ol a) 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -24-nor-5a-cholesta-8,23-diene 400 mg of the sulfonate of (20R) -5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -5a-pregn-8-en-20-methanol-4-methylbenzene (Example 63e) were treated with the Grignard reagent from l-bromo-2-methylpropene analogously to Example 63f. After column chromatography, 206 mg of 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -24-nor-5a-cholesta-8,23-diene was isolated as a white solid. NMR 1 (CDC13): d = 0.62 (s, 3H, H-18); 0.92 (d, J = 7 Hz, 3H, H-21); 1.10 (s, 3H, H.19); 1.59, 1.70 (2 x s, 2 x 3H); 3.90-4.10 (m, 4H, 3-ketal); 5.12 (t, J = 7 Hz, 1H, H-23). b) 5-cyano-24-nor-5a-cholesta-8, 23-dien-3-one 190 mg of 5-cyano-3- (spiro-2 ', 5'-dioxa-cyclopentyl) -24-nor-5a-cholesta-8,23-diene ;ai__. treated with amberliste 15 as described in Example 63g. After filtration and evaporation of the solvent, 170 mg of 5-cyano-24-nor-5a-cholesta-8,23-dien-3-one was isolated. H-NMR (CDC13): d = 0.60 (s, 3H, H.18); 0.90 (d, J = 7 Hz, 3H, H-21); 1.10 (s, 3H, H-19); 1.61, 1.72 (2 x s, 2 x 3H); 2.55 (pseudo-s, 2H); 5.12 (t, J = 7 Hz, 1H, H-23). c) 5-cyano-24-nor-5a-cholesta-8, 23-dien-3ß-ol and 5-cyano-24-nor-5a-cholesta-8, 23-dien-3a-ol 170 mg of 5-cyano-24-nor-5a-cholesta-8,23-dien-3-one was treated with 67 mg of sodium borohydride as described in Example 58b. After column chromatography and HPLC for purification, 8 mg of 5-cyano-24-nor-5a-cholesta-8,23-diene-3ß-ol and 19 mg of 5-cyano-24-nor 5a-cholesta-8,23-dien-3a-ol. -cyano-24-nor-5a-cholesta-8,23-dien-3ß-ol: JH NMR (CDCl 3): d = 0.60 (s, 3H, H-18); 0.90 (d, J = 7 Hz, 3H, H-21) 1.10 (s, 3H, H.19); 1.59, 1.72 (2 x s, 2 x 3H); 4.13 (broad m, 1H, H-3); 5.12 (5, J = 7 Hz; 1H, H-23). -cyano-24-nor-5a-cholesta-8,23-dien-3a-ol: aH NMR (CDCl 3): d = 0.61 (s, 3H, H-18); 0.90 (d, J = 7 Hz, 3H, H-21); 1.05 (s, 3H, H-19); 1.59, 1.72 (2 x s, 2 x 3H); 4.11 (narrow m, 1H, H-3); 5.12 (t, J = 7 Hz, 1H, H-23).

EXAMPLE 71 An agonist oocyte assay can be performed as follows: Oocytes were obtained from immature female mice (C57BL / 6J x DBA / 2J Fl, Bomholtgaard, Denmark) weighing 13-16 grams, which were kept under controlled temperature (20-22 ° C). C), with light (lights from 06.00 to 18.00 hours) and relative humidity (50-70%). The mice received an intra-peritoneal injection of 0.2 ml of gonadotropins (Gonal-F, Serono) containing 20 IU of FSH and 48 hours later the animals were sacrificed by cervical dislocation. The ovaries were dissected and the oocytes were isolated in Hx medium (see below) under a stereomicroscope by manual rupture of the follicles, using a pair of 27-gauge needles. The spherical oocytes showed a intact germinal vesicle (hereinafter referred to as GV) were divided into oocytes enclosed in clusters (hereinafter referred to as CEO) and naked oocytes (hereinafter designated NO) and placed in minimal essential medium a (a-MEM without ribonucleosides , Gibco BRL, Cat. No. 22561) supplemented with 3 mg / ml of bovine serum albumin (BSA, Sigma Cat. NO.A-7030), 5 mg / ml of human serum albumin (HSA, Statens Serumininstitute, Denmark), 0.23 mM pyruvate (Sigma, Cat. No. S-8636), 2 mM glutamine (Flow Cat. No. 16-801), 100 IU / ml penicillin and 100 μg / ml streptomycin (Flow Cat. No. 16- 700). This medium was supplemented with 3 mM hypoxanthine (Sigma Cat. No. H-9377) and designated Hx medium. The oocytes were rinsed 3 times in Hx medium and the oocytes of uniform size were divided into groups of CEO and NO. The CEOs and NOs were grown in 4-well multi-discs (Nunclon, Denmark) in which each well contained 0.4 ml of Hx medium. A control well (eg 35-45 oocytes cultured in identical medium without addition of test compound) was always cultivated simultaneously with 3 test wells (35- 45 oocytes per well supplemented with the test compound). The oocytes were cultured in a humidified atmosphere of 5% C02 in air for 24 hours at 37 ° C. By the end of the culture period, the number of germinal vesicle oocytes (hereinafter referred to as GV), the germinal vesicle rupture (hereinafter referred to as GVB) and the polar bodies (hereinafter referred to as PB) , respectively, were counted using a stereomicroscope (Wildt, Leica MZ 12). The percentage of GVB defined as the percentage of oocytes that undergo GVB by total number of oocytes in that well, was calculated as:% GVB = (number of GVB + number of PB / total number of oocytes) X 100. The percentage of PB was defined as the percentage of oocytes that show a polar body extruded by total number of oocytes in that well. The effect of the tested compounds has been compared against the control level and 4,4-dimethyl-5a-cholesta-8, 14, 24-trien-3ß-ol (hereinafter referred to as FF-MA?) Where the controls and FF-MAS are compared for an effect of 0 and 100, respectively. The relative effect of the tested compound is calculated as follows: Relative effect = ((% of test GVB -% of control GVB) / (FF-MA?% GVB -% of control GVB)) x 100.

Results Table 1. The average percentage of GVB, the percentage of PB and the relative Relative Effect of the compounds after the culture of the naked oocytes (NO) in vitro for 24 hours.

EXAMPLE 72 An antagonist oocyte assay can be performed as follows: Animals The oocytes were obtained from immature female mice (hybrids C57BI / 6J x DBA / 2J F-l, Bomholtgaard, Denmark) weighing 13-16 grams, which were kept under controlled temperature and illumination. Mice received an intraperitoneal injection of 0.2 ml of gonadotropins (Gonal F, Serono, Solna, Sweden, containing 20 IU of FSH, alternatively, Puregon, Organon, Swords, Ireland, containing 20 IU of FSH) and 48 hours later the animals were sacrificed by cervical dislocation.

Test of meiosis inhibiting substances in the oocyte test.

The ovaries were dissected and the oocytes were isolated in Hx medium (see below) under a stereomicroscope by manual rupture of the follicles using a pair of 27 gauge needles. Bare spherical oocytes (NO) showing an intact germ cell vesicle (GV) were placed in minimal essential medium a (a-MEM without ribonucleosides, Gibco BRL, Cat. No. 22561) supplemented with 3 mM hypoxanthine (Sigma Cat. No. H-9377), 8 mg / ml human serum albumin (HSA, Statens Seruminstitut, Denmark) 0.23 mM pyruvate (Sigma, Cat. No. S-8636), 2 mM glutamine (Flow Cat. No. 16-801), 100 IU / ml penicillin and 100 μg / ml streptomycin (Flow Cat. No. 16-700). This medium was designated Hx medium. Naked oocytes (NO) were rinsed 3 times in Hx medium. The 4, 4-dimethyl-5a-cholesta-8, 14, 2 -trien-3ß-ol (FF-MAS) has previously shown that it induces meiosis in NO in vitro (Byskov, AG and collaborators Na t ure 374 (1995), 559-562). The NO were cultured in Hx medium supplemented with 5 μM FF-MAS in co-culture with the test compounds in different concentrations of 4-well multidisc (Nunclon, Denmark) in which each well contained 0.4 ml of the medium and 35-45 oocytes. A positive control (for example 35-45 oocytes cultured in Hx medium containing FF-MAS without addition of the test compound) was always run simultaneously with the test cultures, which were supplemented with different concentrations of the compounds that are going to be tested. In addition, a negative control (35-45 oocytes cultured in Hx medium alone) was run simultaneously with the positive control.

Oocyte examination By the end of the culture period, the number of oocytes with the germinal vesicle (GV) or rupture of the germinal vesicle (GVB) and those with the polar body (PB) were counted using a stereomicroscope or an inverted microscope with contrast equipment of differential interference. The percentage of oocytes with GVB + PB per total number of oocytes was calculated in the test cultures and in the control culture groups (positive and negative). The relative inhibition of the test compound was calculated by the following formula: Inhibition of the test compound (in percent) = In the case of a dose-response curve, an IC50 (dose leading to a 50% inhibition) was calculated.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.

Claims (30)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. The novel compounds of the general formula I: characterized in that R1 is hydrogen, halogen, methyl, hydroxyl, or oxo; R2 is selected from the group consisting of hydrogen, hydroxyl, alkyl of 1 to 3 carbon atoms, vinyl, alkoxy of 1 to 3 carbon atoms and halogen, or R designates together with R, an additional bond between the carbon atoms in which R2 and R3 are placed; R3 is selected from the group consisting of hydrogen, optionally substituted alkoxy, acyloxy, sulfonyloxy, phosphonyloxy, halogen, lower alkyl or a perfluoro (lower alkyl) group; or R3 designates together with R2 an additional bond between the two carbon atoms in which R2 and R3 are placed; or R3 designates, together with R'3, oxo or a group of the general formula = NOR38 wherein R38 is hydrogen or lower alkyl; R '3 designates hydrogen or hydroxyl, with the proviso that R3 and R' 3 are not simultaneously hydrogen; R4 and R'4, which are different or identical with the proviso that they are not both hydroxyl, are selected from the group comprising hydrogen, halogen, hydroxyl and alkyl of 1 to 6 carbon atoms which may be substituted with halogen , hydroxyl or cyano, or wherein R4 and R 'together designate methylene or oxo or, together with the carbon atom to which they are attached, form a cyclopropane ring, a cyclopentane ring, a cyclohexane ring; or R4 designates, together with R '4 and R5, a methane bridge between the carbon atoms in the 4 and 5 position or an additional bond between the carbon atoms in the 4 and 5 position; R5 is hydrogen, halogen, hydroxyl, lower alkyl, cyano, hydroxymethyl, a carbaldehyde, an oxime derived from a carbaldehyde, a carboxylic acid, a primary or secondary amide derived from a carboxylic acid, an ester with an alcohol group from 1 to 6 carbon atoms; or R5 designates together with R6, an additional bond between the carbon atoms in which R5 and R6 are placed; R6 is hydrogen, hydroxyl, halogen or oxo, or R6 designates, together with R5 or R7, an additional bond between the carbon atoms in which R6 and R5 or R7 are placed; R7 is selected from the group comprising hydrogen, hydroxyl, lower alkoxy, acyloxy, halogen and lower alkyl; or R7 designates, together with R6 or R8, an additional bond between the carbon atoms in which R7 and R6 or R8 are placed; R'7 is hydrogen, or, if R7 is lower alkyl, R '7 is hydrogen or hydroxyl; or R7 designates together with R'7, methylene, oxo or a group of the general formula = NOR36, wherein R36 is hydrogen or lower alkyl; R8 is hydrogen, hydroxyl or halogen, or R8 designates together with R7, R9 or R14, an additional bond between the carbon atoms in which R8 and R R9 O R14 are placed; R9 is hydrogen, hydroxyl or halogen, or R9 designates together with R8 or R11, an additional bond between the carbon atoms in which R9 and R8 or R11 are placed; R11 is selected from the group comprising hydrogen, hydroxyl, lower alkoxy, acyloxy, halogen and lower alkyl, or R11 designates, together with R9 or R12, an additional bond between the carbon atoms in which R11 and R9 or R12 are placed; R'11 is hydrogen, or, if R11 is lower alkyl, R'11 is hydrogen or hydroxyl, or R11 designates, together with R'U methylene, oxo or a group of the general formula = NOR37, wherein R37 is hydrogen or lower alkyl; R12 is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 4 carbon atoms, methylene, hydroxyl, lower alkoxy, acyloxy, oxo and a group of the general formula = NOR33 wherein R33 is hydrogen or alkyl of 1 to 3 atoms of carbon, or R12 designates, together with R, an additional bond between the carbon atoms in which R11 and R12 are placed; R14 is hydrogen or hydroxyl, or R14 designates together with R15, an additional bond between the carbon atoms, in which R14 and R15 are placed; R15 is selected from the group consisting of hydrogen, halogen, lower alkyl, methylene, hydroxyl, lower alkoxy, oxo and a group of the general formula = NOR32 wherein R32 is hydrogen or alkyl of 1 to 3 carbon atoms, or R15 designates, together with R14 an additional bond between the carbon atoms in which R15 and R14 are placed; Rld is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 3 carbon atoms, methylene, hydroxyl, lower alkoxy, oxo and a group of the general formula = NOR34 wherein R34 is hydrogen or lower alkyl, or R16 designates together with R17, an additional bond between the carbon atoms in which R16 and R17 are placed; R17 is hydrogen or hydroxyl, or R17 designates, together with R16, an additional bond between the carbon atoms (__1 which are placed R17 and R16; R20 is selected from the group consisting of hydrogen, lower alkyl and hydroxymethyl, or R20 and R'20 together designate methylene or oxo; R'20 is hydrogen, halogen, lower alkyl or hydroxyl; R'22 is hydrogen, hydroxyl or oxo; R22 represents phenyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, N-alkylamino or N, N - dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; benzyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N - dialkylamino wherein the N-alkylamino or N, -dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; cyclohexyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N- dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; cyclohexylalkyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N - dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; alkyl optionally substituted with one or more of the following groups, which substituents may be different or identical: hydroxyl, alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-acylamino, N-alkylamino or N, N-dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; or alkenyl optionally substituted with one or more of the following groups, which substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N , N-dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; and R39 represents lower alkyl or aralkyl, and further, when R1, R2, R4, R5, RU R12, RU R16, R'20 and R'22 are each hydrogen, R3 is hydrogen, lower alkyl or perfluoro (alkyl) lower), R'3 is hydroxyl, or R3 designates, together with R'3, oxo, R4 is hydrogen or together with R5 is a methane bridge or together with R5 is an additional bond, R5 is lower alkyl, cyano, hydroxymethyl, carbaldehyde, an oxime derived from a carbaldehyde, a carboxylic acid, a primary or secondary amide derived from a carboxylic acid, an ester with an alcohol group of 1 to 6 carbon atoms or together with R4 a methane bridge, or together with R4 an additional bond, R7 is together with R8 an additional bond or a hydrogen atom, if Rβ and R9 or R8 and R14 remain together for an additional bond, R8 is together with R7 or with R9 or with R14 an additional bond, R9 is together with R8 an additional bond or a hydrogen atom, if R7 and R8 or R8 and R14 remain together for an additional bond, R14 is, together with R8 an additional bond or a hydrogen atom, if R7 and R8 or R8 and R9 remain together for an additional bond, R17 is hydrogen in the alpha position, R19 is methyl in the beta position, R20 is methyl in the alpha position, then R22 is 3-methylbutyl;; with the proviso that the following compounds are discarded: cholesta-4, 7-dien-3-one; cholesta-4, 8-dien-3-one; cholesta-4, 8 (14) -dien-3-one; cholesta-4, 7-dien-3a-ol; cholesta-4, 7-dien-3ß-ol; 5-cyano-5β-cholest-7-en-3-one; 5-cyano-5β-cholest-7-en-3β-ol; 5-methyl-5β-cholest-7-en-3-one; 5-methyl-5β-cholest-7-en-3a-ol; 5-methyl-5β-cholest-7-en-3β-ol; 3β, 7α-dihydroxycholest-5-ene; 3β, 7β-dihydroxycholest-5-ene; 3β-hydroxycholest-5-en-7-one; 3β-hydroxycholest-7-one; 7a-hydroxycholest-4-en-3-one; cholest-3, 6-dione; 3β-hydroxycholest-6-one; 3β, 6β-dihydroxylestanol; cholest-4-en-3, 6-dione; 3β, 5α, 6β-trihydroxylestanol; 3β, 5α-dihydroxycholestane; 3β, 4β-dihydroxycholest-5-ene; cholest-2-en-6-one; cholest-4, 6-dien-3-one; cholest-4,7-dien-3-one; cholest-3, 5-dien-7-one; 19-nor-21-methylpregna-4,9-dien-17a-hydroxy-3,20-dione; 19-nor-21-methylpregna-4,9-dien-17a-acetoxy-3,20-dione; 19-nor-21, 21-dimethylpregna-4,9-dien-17a-hydroxy-3,20-dione; 17a-21, 21-dimethyl-19-nor-pregna-4, 9-dien-3, 20-dione; 3a-acetoxy-24-nor-coian-23-one; 3a-hydroxy-26, 27-di-nor-23-trans-5β-cholest-23-en-25-carboxylic acid methyl ester; 3a-hydroxy-26,27 methyl ester, di-nor-5β-cholesta-25-carboxylic acid; 3-keto-26, 27-di-nor-5β-cholesta-25-carboxylic acid methyl ester; 3-keto-4-bromo-26,27-di-nor-5β-cholesta-25-carboxylic acid methyl ester; 3-keto-26, 27-di-nor-cholest-4-en-25-carboxylic acid methyl ester; 3β-Acetoxy-26,27-di-nor-cholesta-3,5-dien-25-carboxylic acid methyl ester; 3β-hydroxy-26,27-di-nor-cholest-5-en-25-carboxylic acid methyl ester; 3-keto-26, 27-di-nor-cholest-, 6-dien-25-carboxylic acid methyl ester; 3β-hydroxy-26,27-di-nor-cholesta-3,5,7-trien-25-carboxylic acid methyl ester; and 3-hydroxy-26,27-di-nor-cholesta-5,7-diene-25-carboxylic acid methyl ester; 3ß, 22-diacetoxy-cholesta-5-en-25-ol; 3ß, 22-diacetoxy-25- fluorocholesterol-5-ene; 22-hydrocholesterol-5-en-25-fluoro-3-hemisuccinate; 3β, 22-diacetoxy-25-dichlorocholesterol-5-ene; 3β, 22-dihydroxy-25-chlorocholesterol-5-ene; 22-hydroxy-25-chlorocholesterol-5-en-3β-hemisuccinate; 3β, 22-di-hydroxy-25-bromocholesterol-5-ene; 3β, 22-dihydroxy-25-fluorocholesterol-5-ene; Edenic acid; 3ß-acetoxycholesta-5-en-25-des-dimeti1-24-one; 3,24-diacetoxicolesta-25-des-dimethyl-5,23-diene; 3β-acetoxylesta-25-de-methyl-5-en-24-difluoro-25-one; 3β-acetoxy-24-di-fluorocholesterol-5, 7-dien-25-ol; 3β-hydroxycholest-5-en-24-one; 3ß-acetoxylest-5-en-24-one; 5ß-cholest-24-one; 5β-cholestan-24a-homo-24-one; 3a, 6a-dihydroxy-5β-cholest-24-one; 3a, 6a-diacetoxy-5β-cholest-24-one; 3a, 6a-diacetoxy-5β-cholest-24a-homo-24-one; 3a, 6a-dihydroxy-5β-cholest-24a, 24β-bis-homo-24-one; 3a-hydroxy-5β-cholest-24-one; 3a-acetoxy 5β-cholesta-24-one; 3a-benzyloxy-5β-cholesta-24-one; 3a-ethyloxycarbonyloxy-5β-cholesta-24-one; 3a-hydroxy-5β-cholestan-24a-homo-24-one; 3a-hydroxy-24a-24β-bis-homo-5β-cholestane; 3β-hydroxycholesta-5, 7-dien-24-one; 3ß-acetoxycholesta-5, 7-dien-24-one; la, 3β-dihydroxycholesta-5, 7-dien-24-one; la, 3β-diacetoxicolesta-5, 7-dien-24-one; chenodeoxycholic acid; ursodeoxycholic acid; trimebutine salt of chenodeoxycholic acid; Get ouf of trimebutine of ursodeoxycholic acid; 3ß, 25-dihydroxycholest-5-en-24-one; 3ß-acetoxy-cholest-5-en-24-one; 3ß-acetoxy-25-hydroxycholest-5-en-24-one; 3ß, 25-dihydroxycholest-5-en-24-one; 3β-hydroxycholest-5-en-24-one; 3ß-hydroxy-25-hydroperoxylest-5-en-24-one, 3ß, 24, 25-trihydroxycholest-5-ene; la, 3ß-dihydroxicolest-5-en-24-one; la, 3β, 25-trihydroxy-cholest-5-en-24-one; la, 3β, 24, 25-tetrahydroxicolest-5-en-24-one; 3a-acetoxy-7a-bromo-cholest-5-ene; 3a-actoxicolesta-5, 7-diene; 3a-acetoxy-25-hydroxycholesta-5,7-diene; 3β, 25-dihydroxy-26,27-hexafluoro-cholest-5-ene; la, 3β, 25-trihydroxy-26,27-hexafluoro-cholest-5-ene; 3a, 7a, 12a, 24R, 26,27-hexahydrocholetane; 3a-hydroxy-7-calanic acid; 3a, a-dihydroxycalanic acid; 3a, 7β-dihydroxycalanic acid; and 3a, 7β-lithium dihydroxycholate; cholesta-1, 4,6-trien-3-one; cholest-5-en-la, 3β-diol; la-hydroxycholesta-4,6-dien-3-one; la, 3β-dihydroxycholest-5-ene; 25-hydroxycholesta-l, 6-triene-3-one; la, 3ß-25-trihydroxycholest-5-ene; 3a, 7β-dihydroxy-toxicolic acid; 3a, 7a-dihydroxy-toxicolic acid; 7-ketodeoxycholic acid; 3a, 7β-dihydroxy-toxicolic acid; colic acid; 7-ketocholic acid; 3a, 7β, 12a-colic acid; 12-ketocholic acid; colic acid; 3a-hydroxy-7- acid ketocholic; 3a, 7a-diacetoxycholic acid; 3a, 7a-diacetoxy-12-ketocholic acid; 3a, 7a-dihydroxy-toxicolic acid; 7-ketodeoxycholic acid; 3a-7β-dihydroxy-toxicolic acid; 3a, ß-dihydroxy-12-ketocholic acid; colic acid, methyl ester of cholic acid; 3-acetylcholic acid methyl ester; 3- (2-propenyl) -cholic acid methyl ester; 3-methyl ester of 3- (3-hydroxypropyl) -colic acid; deoxycholic acid; 12-ketodeoxycholic acid; 3β-acetyloxy-12-keto-deoxycholic acid; 3β- (hydroxyethyloxy) -cholic acid methyl ester; 3β- (hydroxypropyloxy) cholic acid methyl ester; 3β (hydroxybutyloxy) cholic acid methyl ester; 3β- (hydroxy-phenyloxy) -cholic acid methyl ester; 3β- (hydroxyhexyloxy) cholic acid methyl ester; 3β (hydroxydecanoyloxy) cholic acid methyl ester; 3β- (2-hydroxyethyloxyethyloxy) cholic acid methyl ester; 3β- (2-hydroxypropyloxy) cholic acid methyl ester; 3β- (hydroxyethyloxy) deoxycholic acid methyl ester; 3β- (hydroxypropyloxy) deoxycholic acid methyl ester; 3β- (hydroxy-phenyloxy) -deoxycholic acid methyl ester; 3β- (hydroxydecyloxy) deoxycholic acid methyl ester; 3β- (2-hydroxyethyloxy) chenodeoxycholic acid methyl ester; 3β- (3-hydroxypropyloxy) chenodeoxycholic acid methyl ester; 3β- (5-hydroxypenthyloxy) chenodeoxycholic acid methyl ester; 3β- (10-hydroxydecyloxy) chenodeoxycholic acid methyl ester; 3β- (2-hydroxyethyl-oxy) lithocholic acid methyl ester; 3β- (3-hydroxypropyloxy) lithocholic acid methyl ester; 3β- (5-hydroxypentyloxy) lithocholic acid methyl ester; 3β- (10-hydroxydecayloxy) lithocholic acid methyl ester; 3β- (benzyloxyethyloxy) cholic acid methyl ester; 3β- (benzyloxyethyloxy) cholic acid terbutyl ester; 3-β- (2-hydroxyethyloxy) cholic acid tert-butyl ester; 3β- (2-hydroxyethyloxy) -7a, 12a-diacetyloxycholic acid methyl ester; 3β- (propionyloxy) -7a, 12a-diacetyloxy-24-carboxylic acid methyl ester; chenodeoxycholic acid; Sitosterol; 3a-hydroxycholestane; 3β-hydroxycholestane; 25-fluorocolest-5-en-3β-22, diol; 25-chlorocholest-5-en-3β, 22-diol; 22-hydroxy-25-fluorocolest-5-en-3β-hemi succinate; 22-hydroxy-25-chlorocholest-5-en-3β-hemisuccinate; cholesta-5-en-3β, 22.25-triol; (3ß, 5a, 20R) -4,, 20-trimethyl-21- phenylpregna-8, 14-dien-3-ol; (3β, 5a, 20R) -4,4-20-trimethy1-21 (3-methylphenyl) pregna-8,14-dien-3-ol; and (3β, 5a, 20R) -4,4-dimethyl-23-phenyl-24-norcola-8,14-dien-3-ol; and the esters, salts, active metabolites and prodrugs thereof.

2. The compounds according to claim 1, characterized in that R22 represents phenyl optionally substituted with one or more of the following groups whose substituents can be identical or different: hydroxyl, lower alkoxy, halogen, amino, N-alkylamino, N, N- dialkylamino, cyano, carboxyl or oxo; benzyl optionally substituted with one or more of the following groups whose substituents may be identical or different: hydroxyl, lower alkoxy, halogen, amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; cyclohexyl optionally substituted with one or more of the following groups whose substituents may be identical or different; hydroxyl, alkoxy, halogen, amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; cyclohexylalkyl optionally substituted with one or more of the following groups whose substituents may be identical or different: hydroxyl, lower alkoxy, halogen, amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; alkyl optionally substituted with one or more of the following groups whose substituents may be identical or different: hydroxyl, alkoxy, halogen, amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; alkenyl optionally substituted with one or more of the following groups whose substituents may be identical or different: hydroxyl, lower alkoxy, halogen, amino, N-alkylamino, N, N-dialkylamino, cyano, carboxyl or oxo; and the remaining substituents are as defined in accordance with claim 1.

3. The compounds according to any of claims 1 and 2, characterized in that they are (20R) -20-methyl-21-phenyl-5a-pregna-8, 14-dien-3β-ol; (20R) -20-methyl-21- (3-methylphenyl) -5a-pregna-8,1-dieth-3ß-ol; (20RJ-20-methyl-21- (3-hydroxyphenyl) -5a-pregna-8, 14-dien-3β-ol; (20R) -20-methyl-21- (cyclopentyl) -5a-pregna-8, 14 -dien-3ß-ol; 24-nor-cholest-8, 14-dien-3ß-ol; (20R) -20-methyl-21- (cyclohexyl) -5a-pregna-8, 14-dien-3ß-ol; (20R) -20-methyl-22-phenyl-5a-pregna-8, 14-dien-3β-ol; 23,24-dinor-cholest-8, 14-dien-3ß-ol; (20R) -2 O-methyl-21- (cyclobutyl) -5a-pregna-8, 14-dien-3β-ol; 4, -dimethyl-17β- ((IR) -methyl-3-methyl-2-butenyl) androsta-8, 14-dien-3-β-ol; (20R) -20-methyl-23-dimethylamino-5a-pregna-8, 14-dien-3β-ol; N, N-dimethylamide of 3β-hydroxy-5a-cyanocol-8-en-24-oic acid; N, N-dimethylamide of 5β-methylcol-8-en-3-on-24-oic acid; N, N-dimethylamide of 3β-hydroxy-4,4-dimethyl-5a-14β-cola-8,15-dien-24-oic acid; 3β-hydroxy-5α-cyano-cholest-8-en-24-one; 5β-methylcol-8-en-3, 24-dione; 3β-hydroxy-4,4-dimethyl-5a, 14β-cholesta-8,15-dien-24-one; 3-hydroxy-5a-cyanocol-8-en-24-oic acid cyclohexyl ester; 5β-methylcol-8-en-3-on-24-oic acid cyclohexyl ester; 3-hydroxy-4,4-dimethyl-5a, 1β-cola-8,15-dien-24-oic acid cyclohexyl ester; N- (4-methylpiperazinyl) amide of 3β-hydroxy-5a-cola-8,14-dien-24-oic acid; N- (4-methylpiperazinyl) amide of 3β-hydroxychola-5, 7-diene-24-oic acid; N- (4-methylpiperazinyl) amide of 3β-hydroxy-5a-cyanocol-8-en-24-oic acid; N- (4-methyl-piperazinyl) -amide of 5-methyl-8-en-3-on-24-oic acid; 3- (4-Hydroxy-4,4-dimethyl-5a, 14β-collat-8,15-dien-24-oic acid N- (4-ethylpiperazinyl) -amide; (20RJ-20-methyl-21-phenyl-5a-pregna-5, 7-dien-3β-ol; (20RJ-20- ? ÍÍ? ÍJ .I -JÍ methyl-21- (3-methylphenyl) -5a-pregna-5, 7-dien-3β-o1; (20R) -20-methyl-21- (3-hydroxy phenyl) -5a-pregna-5, 7-dien-3β-ol; (20R) -20-methyl-21- (cyclopentyl) -5a-pregna-5, 7-dien-3β-ol; 24-nor-cholest-5, 7-dien-3ß-ol; (20R) -20-methyl-21- (cyclohexyl) -5a-pregna-5, 7-diene-3β-ol; (20R) -20-methyl-22-phenyl-5a-pregna-5, 7-dien-3β-ol; 23,24-dinorcolest-5, 7-dien-3ß-ol; (20RJ-20-methyl-21- (cyclobutyl) -5a-pregna-5, -dien-3β-o1; 4,4-dimethyl-17β- ((IR) -methyl-3-methyl-2-butenyl) androsta -5, 7-dien-3ß-ol; (20R) -20-methyl-23-dimethylamino-5a-pregna-5, 7-dien-3ß-ol; cholesta-5, 7-dien-25-chloro-3β -ol; cholesta-5, 7-dien-26-chloro-3-ß-ol; cholesta-5, 7-dien-26-ol; nor-24-cholesta-8, ll-dien-3ß-ol; cholesta -4, 8-dien-3ß-ol, cholesta-4, 8-dien-3a-ol, cholesta-4, 8 (14) -dien-3ß-ol, cholesta-, 8 (14) -dien-3a- ol; 5-cyano-5a-cholest-7-en-3a-ol; 5-cyano-5a-cholest-7-en-3β-ol; 5-cyano-5-cholest-7-en-3a-ol; • 5-cyano-5a-cholest-8-en-3a-ol; 5-cyano-5a-cholest-8-en-3β-ol; 5-cyano-5β-cholest-8-en-3a-ol; -cyano-5β-cholest-8-en-3β-ol; 5-cyano-5a-cholest-8 (14) -in-3a-ol; 5-cyano-5a-cholest-8 (14) -in-3β -ol; 5-cyano-5β-cholest-8 (14) -in-3a-ol; 5-cyano-5-cholest-8 (14) -in-3β-ol; 3 ', 4a-dihydrocyclopropa [4, 5] -5β-cholest-7-en-3β-ol; 3 ', 4β-dihydrocyclopropa [4,5] -5a-cholest-7-en-3a-ol; 3', 4a-dihydrocyclopropa [4,5] -5ß-cholest-8-en-3ß-ol; 3 ', 4ß- dihydrocyclopropa [4,5] -5a-cholest-8-en-3a-ol; 3 ', 4a-dihydrocyclopropa [4,5] -5β-cholest-8 (14) -en-3β-ol; 3 ', 4β-dihydrocyclopropa [4,5] -5a-cholest-8 (14) -en-3a-ol; 5- (hydroxymethyl) -5a-cholest-7-en-3β-ol; 5- (hydroxymethyl) -5β-cholest-7-en-3a-ol; 5- (hydroxymethyl) -5a-cholest-en-3ß-ol; 5- (hydroxymethyl) -5β-cholest-8-en-3a-ol; 5- (hydroxymethyl) -5a-cholest-8 (14) -en-3ß-ol; 5- (hydroxymethyl) -5β-cholest-8 (14) -en-3a-ol; 5-methyl-5β-cholest-8-en-3-one; 5-methyl-5β-cholest-8-en-3β-ol; 5-methyl-5β-cholest-8-en-3a-ol; 5-methyl-5β-cholest-8 (14) -en-3-one; 5-methyl-5β-cholest-8 (14) -en-3ß-ol; 5-methyl-5β-cholest-8 (14) -in-3a-ol; 3a- (trifluoromethyl) cholesta-4,7-dien-3β-ol; 3β- (trifluoromethyl) cholesta-4,7-diene-3a-ol; 3a- (trifluoromethyl) cholesta-4,8-dien-3β-ol; 3β- (trifluoromethyl) cholesta-4,8-dien-3a-ol; 3a- (trifluoromethyl) -4,8 (14) -dien-3β-ol; 3β- (trifluoromethyl) cholesta-4,8 (14) dien-3a-ol; 5-methyl-24-ñor-5β-cholest-8 (14) -en-3-one; (20R) -5, 20-dimethyl-21-phenyl-5β-pregn-8 (14) -en-3-one; (20R) -21-cyclohexyl-5,20-dimethyl-5β-pregn-8 (14) -en-3-one; 5-methyl-24-nor-5β-cholesta-8 (14) -23-dien-3-one; 4,4-dimethyl-24-benzoylamido-5a-cola-8, 14-dien-3β-ol; 3-Hydroxy-4,4-dimethyl-5a-cola-8,14-dien-2 -oic acid N-phenylaninamide; mono (3ß-hydroxy-, 4-dimethyl- 5a-cola-8, 14-dien) -24-succinate; (l-methyl-4-hydroxypiperidinyl) ester of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; N- (norleucin) 3-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide; N- (arginine) 3-hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide; N- (glutamic acid) 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid amide; N- (leucine) 3-hydroxy-4, -dimethyl-5a-cola-8, 14-dien-24-oic acid amide; 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid methyl ester; 3-hydroxy-4,4-dimethyl-5,7-dien-24-oic acid methyl ester; 3-hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid ethyl ester; 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; 3-hydroxy-4, -dimethyl-5a-cola-8,14-dien-24-oic acid cyclohexyl ester; 3β-hydroxy-4,4-dimethyl-5a-cholesta-8, 14-dien-24-one; 3β-hydroxy-4,4,24-trimethyl-5a-cola-8, 14-dien-24-one; 3β-hydroxy-4,4-dimethyl-24-phenyl-5a-cola-8,14-dien-24-one; 3β-hydroxy-4,4-dimethyl-24- (3-pentyl) -5a-cola-8,14-dien-24-one; N-phenylamide of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid amide; 4, 4-dimethyl-24-phenylamino-5a-cola-8, 14-dien-3β-ol; 4, 4-dimethyl-24-amino-5a-cola-8, 14-dien-3β-ol; 4,4-dimethyl-5a-cola-8, 14-dien-3β, 24-diol; 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-aldehyde; 4, 4-dimethyl-17β- ((IR) -methyl-4-methyl-3-pentenyl) -androsta-8, 14-diene-3β-ol; 4, 4-dimethyl-5a-cholesta-14, 16,24-trien-3β-ol; 4, 4-dimethyl-17β- ((IR) -methi 1-3-methyl-2-butenyl) androsta-8,14-dien-3β-ol; (20R) -4,4, 20-trimethyl-21- (4-methyl phenyl) -5a-pregna-8, 14-dien-3β-ol; (20R) -4,4-trimethyl-21- (2-methylphenyl) -5a-pregna-8,14-dien-3ß-ol, (20R) -4,4-trimethyl-21- (cyclohexyl) ) -5a-pregna-8, 14-dien-3ß-ol; (20R) -4,4, 20-trimethyl 1-21- (3-hydroxyphenyl) -5a-pregna-8,1-dieth-3β-ol; (20R) -4, 4, 20-trimethy1-22- (cyclohexyl) -5a-pregna-8, 14-diene-3β-ol; 24-γ-4, 4-dimethyl-5a-cholest-8, 14-dien-3β-ol; 27-nor-4, 4-dimethyl-5a-cholest-8, 14, 25-trien-3ß-ol; (20R) -4,4-trimethyl-21- (cyclobutyl) -5a-pregna-8,14-dien-3ß-ol; (20R) -4,4, 20-trimethyl-21- (cyclopentyl) -5a-pregna-8, 14-dien-3β-ol; 25-chloro-4,4-dimethyl-5a-cholesta-8,14-dien-3β-ol; 4, 4-dimethyl-24- (N, N-dimethylamino) -24-cyano-5a-cholesta-8, 14-diene-3β-ol; 4, 4-dimethylcholest-8, 14,25-trien-3β-ol; 4, 4-dimethy1-17β- ((IR) -methyl-4-iodobutyl) androsta-8, 14-dien-3β-ol; 4, 4-dimethyl-17β- ((IR) -methylbutyl) androsta-8, 14-dien-3β-ol; 4,4-dimethyl-17β- ((IR) -methyl-4-cyanobutyl) androsta-8, 14- dien-3ß-ol; 4, -dimethyl-17β- ((IR) -methi-4-cyanobutyl) androsta-8, 14-dien-3β-ol; benzyl ester of 27-nor-3β-hydroxy-4,4-dimethyl-5a-cholesta-8,14-dien-26-oic acid; N- (methionine methyl ester) 3-hydroxy-4, -dimethyl-5a-cola-8, 14-dien-24-oic acid amide; N- (methionine) amide of 3β-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; N- (4-methyl-piperazinyl) -amide of 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid; 3-Hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid N-tert-butylamide; N- (isonipecotic acid ethyl ester) 3β-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide; N- (isonipecotic acid) 3-hydroxy-4,4-dimethyl-5a-cola-8,14-dien-24-oic acid amide; N- (3-hydroxy-4, 4-dimethyl-5a-cola-8, 14-dien-24-oic acid amide of the phenylalanm) 3-hydroxy-4-amide; 3β-hydroxy-4,4-dimethyl-5,7,7-dien-24-oic acid; 3-Hydroxy-, -dimethyl-5,7-dien-24-oic acid N-dimethylamide; 4, 4-dimethyl-24-acetamido-5a-cola-8, 14-dien-3β-ol;

4-dimethyl-24-acetoxy-5a-cola-8, 14-dien-3β-ol; 4,4-dimethyl-24-methoxy-5a-cola-8, 14-dien-3β-ol; 4, 4-dimethyl-24-benzyloxy-5a-cola-8, 14-dien-3β-ol; benzyl ester of 3β-hydroxy-4,4-dimethyl-5a-cola-8, 14-dien-24-oic acid; 26, 27-diethyl-3β-hydroxy-4, 4- dimethyl-5a-cholesta-8, 14-diene-26, 27-dioate; 3β-hydroxy-4,4-dimethyl-5a-cholesta-8, 14-diene-26,27-dioic acid; and 27-nor-3β-hydroxy-4,4-dimethyl-5a-cholesta-8,14-dien-26-oic acid. . The compounds according to any of claims 1 or 2, with the proviso that when R7 R2, R5 »R6, R7» 8 / R9 »R", R12, R14, R15, R16 and R22 are each hydrogen, R '3 is hydrogen, and R3 is hydroxyl, alkoxy, acyloxy or sulfonyloxy, or R3 together with R' 3 is = NOR38 wherein R38 is hydrogen or alkyl, R4 and R'4 are hydrogen or alkyl, R6 plus R7, R7 more RB, R8 plus R9, R8 plus R14 and / or R14 plus R15 is / are one or more additional double bonds R20 and R'20 are hydrogen or alkyl, then R22 is different from phenyl optionally substituted with hydroxyl, alkoxy, halogen, amino , N-alkylamino or N, N-dialkylamino or from benzyl optionally substituted by hydroxyl, alkoxy, halogen, amino, N-dialkylamino or N, N-dialkyl mino.

5. The use of the compounds of the general formula Ib characterized in that R is hydrogen, halogen, methyl, hydroxyl, or oxo; R2 is selected from the group comprising hydrogen, hydroxyl, alkyl of 1 to 3 carbon atoms, vmilo, alkoxy of 1 to 3 carbon atoms and halogen, or R2 designates together with R3, an additional bond between the carbon atoms in the which are placed R2 and R3; R3 is selected from the group consisting of hydrogen, optionally substituted alkoxy, acyloxy, sulfonyloxy, phosphonyloxy, halogen, lower alkyl or a perfluoro (lower alkyl) group; or R3 together with R2 designates an additional bond between the two carbon atoms in which R2 is placed and R3; or R3 designates, together with R'3, oxo or a group of the general formula = NOR38 wherein R38 is hydrogen or lower alkyl; R '3 designates hydrogen or hydroxyl, with the proviso that R3 and R'3 are not simultaneously hydrogen; R4 and R'4, which are different or identical with the proviso that they are not both hydroxyl, are selected from the group comprising hydrogen, halogen, hydroxyl and alkyl of 1 to 6 carbon atoms which may be substituted with halogen , hydroxyl or cyano, or wherein R4 and R'4 together designate methylene or oxo or, together with the carbon atom to which they are attached, form a cyclopropane ring, a cyclopentane ring, a cyclohexane ring; or R4 designates, together with R '4 and R5, a methane bridge between the carbon atoms in the 4 and 5 position or an additional bond between the carbon atoms in the 4 and 5 position; R5 is hydrogen, halogen, hydroxyl, lower alkyl, cyano, hydroxymethyl, a carbaldehyde, an oxime derived from a carbaldehyde, a carboxylic acid, a primary or secondary amide derived from a carboxylic acid, a ester with an alcohol group of 1 to 6 carbon atoms; or R5 designates together with R6, an additional bond between the carbon atoms in which R5 and R6 are placed; R6 is hydrogen, hydroxyl, halogen or oxo, or R6 designates, together with R5 or R7, an additional bond between the carbon atoms in which R6 and R5 or R7 are placed; R7 is selected from the group comprising hydrogen, hydroxyl, lower alkoxy, acyloxy, halogen and lower alkyl; or R7 designates, together with Rd or R8, an additional bond between the carbon atoms in which R7 and R6 or R8 are placed; R'7 is hydrogen, or, if R7 is lower alkyl, R '7 is hydrogen or hydroxyl; or R7 designates together with R'7, methylene, oxo or a group of the general formula = NOR36, wherein R36 is hydrogen or lower alkyl; R8 is hydrogen, hydroxyl or halogen, or R8 designates together with R7, R9 or R14, an additional bond between the carbon atoms in which RB and R7, R9 or R14 are placed; R9 is hydrogen, hydroxyl or halogen, or R9 designates together with R8 or R11, an additional bond between the carbon atoms in which R9 and R8 or R11 are placed; R11 is selected from the group comprising hydrogen, hydroxyl, lower alkoxy, acyloxy, halogen and lower alkyl, or R11 designates, together with R9 or R12, an additional bond between the carbon atoms in which R11 and R9 or R12 are placed; R'11 is hydrogen, or, if R11 is lower alkyl, R 'is hydrogen or hydroxyl, or R11 designates, together with R'11, methylene, oxo or a group of the general formula = NOR37, wherein R37 is hydrogen or lower alkyl; R12 is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 4 carbon atoms, methylene, hydroxyl, lower alkoxy, acyloxy, oxo and a group of the general formula = NOR33 wherein R33 is hydrogen or alkyl of 1 to 3 carbon atoms, or R12 designates, together with R11, an additional bond between the carbon atoms in which R11 and R12 are placed; R14 is hydrogen or hydroxyl, or R14 designates together with R15, an additional bond between the carbon atoms, in which R14 and R15 are placed; R15 is selected from the group comprising hydrogen, halogen, lower alkyl, methylene, hydroxyl, lower alkoxy, oxo and a group of the general formula = NOR32 wherein R32 is hydrogen or alkyl of 1 to 3 carbon atoms, or R15 designates, together with R14, an additional bond between the carbon atoms in which R15 and R14 are placed; R16 is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 3 carbon atoms, methylene, hydroxyl, lower alkoxy, oxo and a group of the general formula = NOR34 wherein R34 is hydrogen or lower alkyl, or R16 designates together with R17, an additional bond between the carbon atoms in which R16 and R17 are placed; R17 is hydrogen or hydroxyl, or R17 designates, together with R16, an additional bond between the carbon atoms in which R17 and R16 are placed; R20 is selected from the group consisting of hydrogen, lower alkyl and hydroxymethyl, or R20 and R'20 together designate methylene or oxo; R'20 is hydrogen, halogen, lower alkyl or hydroxyl; R '22 is hydrogen, hydroxyl or oxo; R22 represents phenyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the formula general -COOR, N-alkylamino or N, N-dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; benzyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, - dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; cyclohexyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N- dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; cyclohexylalkyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR, oxo, N-alkylamino or N, -dialkylamino wherein the N-alkylamino or N, -dialkylamino is optionally substituted with carboxyl , lower alkoxy or lower alkylthio; alkyl optionally substituted with one or more of the following groups, which substituents may be different or identical: hydroxyl, alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-acylamino, N-alkylamino or N, N-dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; alkenyl optionally substituted with one or more of the following groups, which substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N-dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; and R39 represents lower alkyl or aralkyl, and further, when R7 R2. R'7 R5, RU R12, R15, R16, R'20 and R'22 are each hydrogen, R3 is hydrogen, lower alkyl or perfluoro (lower alkyl), R'3 is hydroxyl, or R3 designates, together with R '3, oxo, R4 is hydrogen or together with R5 is a methane bridge or together with R5 an additional bond, R5 is lower alkyl, cyano, hydroxymethyl, a carbaldehyde, an oxime derived from a carbaldehyde, a carboxylic acid, a primary amide or secondary derivative of a carboxylic acid, an ester with an alcohol group of 1 to 6 carbon atoms or together with R4 a methane bridge, or together with R4 an additional bond, R7 is together with R8 an additional bond or a hydrogen atom , if R8 and R9 or R8 and R14 remain together for an additional bond, R8 is together with R7 or with R9 or with R14 an additional bond, R9 is together with R8 an additional bond or a hydrogen atom, if R7 and R8 or R8 and R14 remain together for an additional bond, R14 is together with R8 an additional bond or a hydrogen atom, if R7 and R8 or R8 and R9 remain together for an additional bond, R17 is hydrogen in the alpha position, R19 is methyl in the beta position, and R20 is methyl in the alpha position, then R22 is 3-methylbutyl; with the proviso that the following compounds are renounced: 3β-7a-dihydroxycholest-5-ene; 3β, 7β-dihydroxycholest-5-ene; 3β-hydroxycholest-5-en-7-one; 3β-hydroxycholest-7-one; 7a-hydroxycholest-4-en-3-one; cholest-3, 6-dione; 3β-hydroxycholest-6-one; 3β, 6β-dihydroxylestanol; cholest-4-en-3, 6-dione; 3β, 5α, 6β-trihydroxylestanol; 3β, 5α-dihydroxy-cholestane; 3β, 4β-dihydroxycholest-5-ene; cholest-2-en-6-one; cholest-4, 6-dien-3-one; cholest-, 7-dien-3-one; cholest-3, 5-dien-7-one; 19-nor-21-methylpregna-4,9-dien-17a-hydroxy-3,20-dione; 19-nor-21-methylpregna-4,9-diene-17a-acetoxy-3,20-dione; 19-nor-21,21-dimethylpregna-4,9-dien-17a-hydroxy-3,20-dione; 17a-21, 21-dimethyl-19-nor-pregna-4, 9-dien-3, 20-dione; 3β, 22-diacetoxicolesta-5-en-25-ol; 3β, 22-diacetoxy-25-fluorocholesterol-5-ene; 22-hydroxycholesta-5-en-25-fluoro-3-hemisuccinate; 3β, 22-diacetoxy-25-dichlorocholesterol-5-ene; 3β, 22-dihydroxy-25-chlorocholesterol-5-ene; 22-hydroxy-25-chlorocholesterol-5-en-3β-hemisuccinate; 3β, 22-dihydroxy-25-bromocholesterol-5-ene; 3β, 22-dihydroxy-25-fluorocholesterol-5-ene; chenodeoxycholic acid; ursodeoxycholic acid; trimebutine salt of chenodeoxycholic acid; Get ouf of trimebutine of ursodeoxycholic acid; a, 7a, 12a, 24R, 26, 27-hexahydrocholetane; 3a, 7β-dihydroxy-toxicolic acid; chenodeoxycholic acid; Sitosterol; campesterol; 3a-hydroxycholestane; 3β-hydroxycholestane; 25-fluorocolest-5-en-3β, 22-diol; 25-chlorocholest-5-en-3β, 22-diol; 22-hydroxy-25-fluorocolest-5-en-3β-hemisuccinate; 22-hydroxy-25-chlorocholest-5-en-3β-hemisuccinate; cholesta-5-en-3β, 22, 25-triol; (3β, 5a-20R) -4,4-trimethyl-21-phenylpregna-8,14-dien-3-ol; (3β, 5a, 20R) -4,4-20-trimethyl-21 (3-methylphenyl) pregna-8,14-dien-3-ol; and (3ß, 5a, 20R) -4,4-dimethy1-23-pheny1-24 -organic- 8, 14-dien-3-ol; as a medicine.

6. The use according to the previous claim, wherein the compound is the compounds according to claim 2.

7. The use according to any of the two previous claims, wherein the compound is the compounds according to claim 3.

8. The use in accordance with any of the three previous claims, wherein the compound is any of the compounds according to claim 4.

9. The compounds of the general formula characterized in that R1 is hydrogen, halogen, methyl, hydroxyl, or oxo; R2 is selected from the group consisting of hydrogen, hydroxyl, alkyl of 1 to 3 carbon atoms, vinyl, alkoxy of 1 to 3 carbon atoms and halogen, or R2 designates together with R3, an additional bond between the carbon atoms in the which are placed R2 and R3; R3 is selected from the group consisting of hydrogen, optionally substituted alkoxy, acyloxy, sulfonyloxy, phosphonyloxy, halogen, lower alkyl or a perfluoro (lower alkyl) group; or R3 designates together with R2 an additional bond between the two carbon atoms in which R2 and R3 are placed; or R3 designates, together with R'3, oxo or a group of the general formula = NOR38 wherein R38 is hydrogen or lower alkyl; R '3 designates hydrogen or hydroxyl, with the proviso that R3 and R' 3 are not simultaneously hydrogen; R4 and R'4, which are different or identical with the proviso that they are not both hydroxyl, are selected from the group comprising hydrogen, halogen, hydroxyl and alkyl of 1 to 6 carbon atoms which may be substituted with halogen , hydroxyl or cyano, or wherein R4 and R '4 together designate methylene or oxo or, together with the carbon atom to which they are attached, form a cyclopropane ring, a cyclopentane ring, a cyclohexane ring; or R4 designates, together with R'4 and R5, a methane bridge between the carbon atoms in the 4 and 5 position or an additional bond between the carbon atoms in the 4 and 5 position; R5 is hydrogen, halogen, hydroxyl, lower alkyl, cyano, hydroxymethyl, a carbaldehyde, an oxime derived from a carbaldehyde, a carboxylic acid, a primary or secondary amide derived from a carboxylic acid, an ester with an alcohol group from 1 to 6 carbon atoms; or R5 designates together with R6, an additional bond between the carbon atoms in which R5 and R6 are placed; R6 is hydrogen, hydroxyl, halogen or oxo, or R6 designates, together with R5 or R7, an additional bond between the carbon atoms in which R6 and R5 or R7 are placed; R7 is selected from the group comprising hydrogen, hydroxyl, lower alkoxy, acyloxy, halogen and lower alkyl; or R7 designates, together with R6 or R8, an additional bond between the carbon atoms in which R7 and R6 or R8 are placed; R'7 is hydrogen, or, if R7 is lower alkyl, R '7 is hydrogen or hydroxyl; or R7 designates together with R'7, methylene, oxo or a group of the general formula = NOR36, wherein R36 is hydrogen or lower alkyl; R8 is hydrogen, hydroxyl or halogen, or R8 designates together with R7, R9 or R14, an additional bond between the carbon atoms in which R8 and R7, R9 or R14 are placed; R9 is hydrogen, hydroxyl or halogen, or R9 designates together with R8 or R11, an additional bond between the carbon atoms in which R9 and R8 or R "are placed; R11 is selected from the group consisting of hydrogen, hydroxyl, lower alkoxy , acyloxy, halogen and lower alkyl, or R11 designates, together with R9 or R12, an additional bond between the carbon atoms in which R11 and R9 or R12 are placed; R'11 is hydrogen, or, if R11 is lower alkyl, R'11 is hydrogen or hydroxyl, or R11 designates, together with R'11, methylene, oxo or a group of the general formula = NOR37, wherein R37 is hydrogen or lower alkyl; R12 is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 4 carbon atoms, methylene, hydroxyl, lower alkoxy, acyloxy, oxo and a group of the general formula = NOR33 wherein R33 is hydrogen or alkyl of 1 to 3 carbon atoms, or R12 designates, together with R11, an additional bond between the carbon atoms in which R11 and R12 are placed; R14 is hydrogen or hydroxyl, or R14 designates together with R15, an additional bond between the carbon atoms, in which R14 and R15 are placed; R15 is selected from the group consisting of hydrogen, halogen, lower alkyl, methylene, hydroxyl, lower alkoxy, oxo and a group of the general formula = NOR32 wherein R32 is hydrogen or alkyl of 1 to 3 carbon atoms, or R15 designates, together with R14 an additional bond between the carbon atoms in which R15 and R14 are placed; R16 is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 3 carbon atoms, methylene, hydroxyl, lower alkoxy, oxo and a group of the general formula = NOR34 wherein R34 is hydrogen or lower alkyl, or R16 designates together with R17, an additional bond between the carbon atoms in which Rld and R17 are placed; R17 is hydrogen or hydroxyl, or R17 designates, together with R16, an additional bond between the carbon atoms in which R17 and R16 are placed; R20 is selected from the group consisting of hydrogen, lower alkyl and hydroxymethyl, or R20 and R'20 together designate methylene or oxo; R '20 is hydrogen, halogen, lower alkyl or hydroxyl; R'22 is hydrogen, hydroxyl or oxo; R22 represents phenyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, N-alkylamino or N, N - dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; benzyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N - dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; cyclohexyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N- dialkylamino where the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; cyclohexylalkyl optionally substituted with one or more of the following groups whose substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N - dialkylamino wherein the N-alkylamino or N, -dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; alkyl optionally substituted with one or more of the following groups, which substituents may be different or identical: hydroxyl, alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-acylamino, N-alkylamino or N, N-dialkylamino wherein the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; alkenyl optionally substituted with one or more of the following groups, which substituents may be different or identical: hydroxyl, lower alkoxy, halogen, amino, cyano, carboxyl, a group of the general formula -COOR39, oxo, N-alkylamino or N, N-dialkylamino where the N-alkylamino or N, N-dialkylamino substituent is optionally substituted with carboxyl, lower alkoxy or lower alkylthio; and R39 represents lower alkyl or aralkyl, and further, when R7 R2, R'7 R5 »R", R12 / R15, R16, R'20 and R'22 are each hydrogen, R3 is hydrogen, lower alkyl or perfluoro ( lower alkyl), R '3 is hydroxyl, or R3 designates, together with R'3, oxo, R4 is hydrogen or together with R5 is a methane bridge or together with R5 is an additional bond, R5 is lower alkyl, cyano, hydroxymethyl, a carbaldehyde, an oxime derived from a carbaldehyde, a carboxylic acid, a primary or secondary amide derived from a carboxylic acid, an ester with an alcohol group of 1 to 6 carbon atoms or together with R4 a methane bridge, or together with R4 an additional bond, R7 is together with RB an additional bond or a hydrogen atom, if R8 and R9 or R8 and R14 remain together for an additional bond, R8 is together with R7 or with R9 or with R14 an additional bond, R9 is together with R8 an additional bond or a hydrogen atom, if R7 and R8 or R8 and R14 remain together for an additional bond, R is together with R an additional bond or a hydrogen atom, if R7 and R8 or R8 and R9 remain together for an additional bond, R17 is hydrogen in the alpha position, R19 is methyl 'in the beta position , R20 is methyl in the alpha position, then R22 is 3-methylbutyl; with the proviso that the following compounds are discarded: (3ß, 5a, 20R) -4,4-20-trimethyl-21-phenylpregna-8,14-dien-3-ol; (3β, 5a, 20R) -4,4,20-trimethyl-21- (3-methylphenyl) pregna-8, 14-dien-3-ol; and (3β, 5a, 20R) -4,4-dimethyl-23-phenyl-24-norcola-8, 14-dien-3-ol; for use in the regulation of meiosis.

10. The compound according to the previous claim, characterized in that the compound is the compounds according to claim 2.

11. The compound according to any of the two previous claims, characterized in that the compound is the compounds according to claim 3.

12. The compound according to any of the three previous claims, characterized in that the compound is any of the compounds according to claim 4.

13. The use of a compound of the general formula described above for the preparation of a medicament regulating meiosis.

14. The use of a compound of the general formula described above for the preparation of a medicament for the treatment of infertility in mammals, preferably in humans (men and women).

15. The use of a compound of the general formula described above for the preparation of a contraceptive agent, preferably for humans (men and women).

16. The use of a compound of the general formula described above in a fertilization culture medium that also contains a mammalian germ cell, preferably a human cell.

17. The use according to any one of the previous use claims, wherein the compound is the compound according to claim 2.

18. The use according to any one of the previous use claims, wherein the compound is the compound according to claim 3.

19. The use according to any of the previous use claims, wherein the compound is any of the compounds according to claim 4.

20. A method for regulating meiosis, characterized in that it comprises administering to a subject in need of such regulation, an effective amount of a compound of the formula described above.

21. A method for regulating meiosis in a mammalian germ cell, characterized in that the method comprises administering an effective amount of a compound of the general formula described above to a germ cell in need of such treatment.

22. A method, characterized in that a compound of the general formula described above is administered to a germ cell by administering it to a mammal that hosts said cell.

23. A method according to any of the preceding claims, characterized in that the germ cell, the meiosis of which is to be regulated, is an oocyte.

24. A method according to any one of the previous method claims, characterized in that a compound of the general formula described above is administered to an exo ve or in vitro oocyte.

25. A method according to any of the previous method claims, characterized in that the germ cell, the meiosis of which is to be regulated, is a male germ cell.

26. A method of conformance with any of the prior method reivinations, characterized in that the mature male germ cells are produced by the administration of a compound of the general formula I described above to the testicular tissue, in vi ve, ex vi ve or in vi tro .

27. A method according to any of the previous method claims, characterized in that the compound is the compounds according to claim 2.

28. A method according to any of the previous method claims, characterized in that the compound is the compounds according to claim 3.

29. A method according to any of the previous method claims, characterized in that the compounds are any of the compounds according to claim 4.

30. Any novel feature or combination of the features described herein.