CN1242017A - Meiosis regulating compounds - Google Patents

Abstract

Certain compounds that are structurally related to natural products, such as those extracted from bovine testis and human follicular fluid, can be used to regulate meiosis in oocytes and male germ cells.

Description

Compounds that regulate meiosis

field of invention

The present invention relates to pharmacologically active compounds and their use as medicines. More specifically, it has been found that the sterol derivatives described herein can be used to regulate meiosis.

Background of the invention

5α-bromocholestane-3β,6β-diol, 7α-bromocholestane-3β,6α-diol, 7α-bromocholestane-3β, 6β-diol, 7α-bromocholestane-3β, 5α-diol-6-one, 7β-bromocholestane-3β, 5α-diol-6 -ketone, 3β-bromocholestan-2α-ol, 5α-chlorocholestane-3β, 6α-diol, 5α-chlorocholestane-3β, 6β-diol, 6β-chlorocholestane sterane-3β,5α-diol, ^Δ7,9(11) -cholestadiene-3β,6α-diol, ^Δ7,9(11) -cholestadiene-3β,6β-diol, Cholestan-2α, 3α-diol, Cholestan-2α, 3β-diol, Cholestan-2β, 3α-diol, Cholestan-2β, 3β-diol, Cholestan-3α, 4α-diol, cholestane-3α, 4β-diol, cholestane-3β, 4β-diol, cholestane-3α, 5α-diol, cholestane-3β, 5α-diol, cholesterol Stanane-3β, 6α-diol, Cholesterane-3β, 6β-diol, Cholesterane-3β, 22α-diol, Cholesterane-3β, 22β-diol, Cholesterane-3β, 7α , 8α-triol, Δ ⁵ -cholestene-3β, 4α-diol, Δ ⁵ -cholestene-3β, 4β-diol, Δ ⁵ -cholestene-3β, 20α-diol, Δ ⁵ -cholestene-3β,22α-diol, ^Δ5 -cholestene-3β,22β-diol, ^Δ5 -cholestene-3β,24α-diol, ^Δ5 -cholestene-3β,24β -diol, Δ ⁶ -cholestene-3β,5α-diol, Δ ⁸⁽¹⁴⁾ -cholestene-3β,9α-diol, Δ ¹¹ -cholestene-3α,24-diol, Δ ⁵ -cholestene-3β, 6-diol-7-one, Δ ⁵ -cholestene-4α-ol-3-one, Δ ⁵ -cholestene-3β, 4β, 7α-triol, coprosterol Alkane-3α, 5β-diol, Coprostan-3β, 5β-diol, Coprostan-3β, 6β-diol, Coprostan-4β, 5β-diol-3-one and 20β-hydroxy- 20-isocholesterol.

In Example 5 of German Patent Application Publication No. 1,183,079 a method for the preparation of 4α-hydroxy-5α-cholestan-3-one is mentioned without claiming that this compound has any other use than as an intermediate.

Cholesta-3β, 5α, 6β-triol-3β-hemisuccinate, cholesta-3β, 5α, 6β-triol are mentioned in Examples 1-5 of German Patent Application Publication No. 1,224,738, respectively -3β-hemisuccinate-6β-acetate, cholestan-3β,5α,6β-triol-3β-hemisuccinate-6β-formate, cholestan-3β,5α,6β- Triol-3β-sulfate and cholestan-3β,5α,6β-triol-3β-phosphate, it is also mentioned that these compounds described therein are useful in the treatment of arteriosclerosis.

A process for the preparation of insecticides such as 2β, 3β, 14α, 22(R), 25-pentahydroxycholest-7-en-6-one is described in German Patent Application Publication No. 2,201,991 C2.

German Patent Application Publication No. 2,236,778 B2 relates to a new insecticide cholest-7-ene-2β, 3β, 5β, 11α, 14α, 20(R), 22(R)-heptahydroxy-6- ketone.

5,24-Cholestadien-3β-ol, 5-cholestadiene-3β, 24 , 25-triol-3β-acetate, 5-cholestene-3β, 24,25-triol-3β,24-diacetate, 5,25-cholestadien-3β-ol acetate ester, 5-cholestene-3β, 25,26-triol-3β-acetate and 5-cholestene-3β, 25,26-triol, also mentioning that these compounds described therein are 24, 25 (or 25,26)-dihydroxycholecalciferol is a very useful intermediate in the preparation technology.

Cholesta-5α-alkane-3β,6α-diol, Cholesta-5β-alkane-3β,6β-diol, Cholesta-5α-alkane-3β,6β-diol, Cholesta-5α- Alkane-3,6-dione, cholesta-5[alpha]-alkane-6[beta]-ol-3-one and cholesta-5[alpha]-alkane-2[alpha]-bromo-6[beta]-ol-3-one were used as intermediates.

In German Patent Application Publication No. 2,415,676, cholestane-3β, 25-diol-3β-acetate, cholestane-3β are mentioned as compounds III, IV, X, XI, XII and XIII, respectively, 5α,25-triol-3β-acetate, cholestane-3β,5α,25-triol, cholestane-5α,25-diol-3-one, cholestane-4-ene-25- Alcohol-3-one and cholesta-4,6-dien-25-ol-3-one, suggesting that these compounds described therein may be substantially more potent than vitamin _D3 .

The preparation of 1α, 3β-dihydroxycholest-5-ene and 1α, 3β-dihydroxycholest-6-ene is mentioned in Example 1 (Compounds V and II) of German Patent Application Publication No. 2,546,715 A1. method, suggesting that the compounds described therein can be used as food additives and in vitamin compositions.

3α,6α-dihydroxy-5β-cholestan-24-one, 3α,6α,24- Trihydroxy-5β-cholestane, 3-chlorocholest-5,24-diene, 3β-hydroxycholest-5-en-24-one acetate and 3-chlorocholest-5-ene -24-ones, it is also mentioned that these compounds described therein can be used as intermediates in the preparation of streptosterols, their derivatives and other active vitamin D.

Cholestan-25-fluoro-3β,22(S)-diol, cholestane-25- Chloro-3β,22(S)-diol, Cholesta-25-methyl-3β,22-diol, Cholesta-25-methyl-3β,22-diol-3-hydrobutanedioic acid Esters and cholestane-25-methyl-3β,22-diol-dihydrosuccinate, it is also mentioned that these compounds described therein inhibit the activity of HMGCOA reductase and the formation of cholesterol in the blood.

In German Patent Application Publication No. 3,390,016C2, a process for the preparation of 1α,52-dihydroxy-26,26,26,27,27,27-hexafluorocholest-5-ene is described, also mentioned This compound can be easily converted into a compound with similar activity to vitamin _D3 .

In Danish Patent Application Publication No. 123,767, a process for the preparation of 2β, 3β, 14α, 22,25-pentahydroxy- ^Δ7-5β -cholesten-6-one is mentioned, and the effect of this compound on the central The nervous system has a role to play.

Mentioned in Examples 1, 1, 4, 4, 5ii, 5(1), 6i, 7, 7(2), 8iii, 8iv, 8iv, 9iii and 9iv of European Patent Application Publication No. 15,122B1 25-Hydroxy-3β-[(tetrahydro-2H-pyran-2-yl)oxy]cholest-5-en-24-one, 3β-[(tetrahydro-2H-pyran-2-yl) Oxy]cholest-5-en-24-one, 25-hydroxy-24-oxocholesterol-3β-acetate, 24-oxocholesterol-3β-acetate, 25-hydroxy-24- Oxycholesterol, 24,25-dihydroxycholesterol, 3α,6α,25-trihydroxy-24-oxo-5β-cholestane, 1α,25-dihydroxy-24-oxocholesterol, 1α, 24,25-trihydroxycholesterol, 3β-hydroxy-24-oxocholesta-5,7-diene, 3β,25-dihydroxy-24-oxocholesta-5,7-diene, 3β -Hydroxy-24-oxocholesta-5,7-diene, 1α,3β-dihydroxy-24-oxocholesta-5,7-diene and 1α,3β,25-trihydroxy-24-oxo Substituted cholesta-5,7-diene. It is also mentioned that the compounds described therein are useful as intermediates which can be converted into active vitamin _D3 .

(24R))-3β,24,25-trihydroxycholest-5-ene, (24RS)-3β,24, 25-trihydroxycholest-5-ene and (24R)-1β,3β,24,25-4hydroxycholest-5-ene, also mentioning that the compounds described therein can be used as the preparation of vitamin _D3 derivatives intermediate.

4,4-Dimethyl-24-methylene-3β- Sulfonyloxy-12α-acetoxycholesta-8,14-diene-2α,11β-diol, 4,4-dimethyl-24methylene-3β-sulfonyloxy-12α-acetyl Oxycholest-8-ene-2α,11β-diol, 4,4-dimethyl-24methylene-12α-acetoxycholest-8,14-diene-2α,3β,11β- Triol, 4,4-Dimethyl-24-methylene-12α-acetoxycholesta-8,14-diene-3β,11β-diol, 4,4-Dimethyl-24-methylene -12α-Acetoxycholest-8-ene-2α,3β,11β-triol, 4,4-Dimethyl-24-methylene-12α-acetoxycholest-8-ene-3β,11β -diol, 4,4-dimethyl-24-methylenecholest-8-ene-2,3β,11β,12α-tetrol, 4,4-dimethyl-24-methylene-3β-sulfo Acyloxycholesta-8,14-diene-2α,11β,12α-triol, 4,4-dimethyl-24methylenecholesta-8,14-diene-2α,3β,11β, 12α-tetrol, 4,4-dimethyl-24methylene-3β-sulfonyloxy-12α-acetoxycholest-8-en-2-ol-11-one and mono(4,4 -Dimethyl-24-methylene-12α-acetoxycholesta-8,14-diene-2α,11β-diol)-3β-succinate, also mentioned that said compound has anti-inflammatory effect .

1α, 3β-dihydroxycholest-5-ene and 1α, 3β, 24-trihydroxycholest-5-ene are mentioned in Examples 1 and 2, respectively, of European Patent Application Publication No. 349,869A2, and also The latter compound can then be used for the production of α,24-dihydroxy-vitamin _D3 .

Cholesta-5,7-diene-3β,23(R),25-triol and cholesta-5,7-diene-3β are mentioned in Example 1 of British Patent Application Publication No. 2,089,810A , 23(S), 25-triol, also mentioned that the compounds described therein should be used as a substitute for 25-hydroxyvitamin _D3 in various medical applications.

1α,3β-Dihydroxycholest-5-ene and 1α,3β,25-trihydroxycholest-5-ene are mentioned respectively in Examples 1 and 3 of Norwegian Patent Application Publication No. 144,264, and also The compounds described therein find use in the veterinary field.

The use of Δ ⁷ -cholestene-2β, 3β-diol-6-one as starting material (preparation of Δ ⁷ -coprostanene-2β, 3β, 14 -triol-6-one), the latter compound has activity against insecticide allergens.

2β, 3β, 14α, 22(R), 25-pentahydroxy- ^Δ7-5β -cholesten-6-one and 2β are mentioned in Examples 4 and 5 of Swedish Patent Application Publication No. 330,883, respectively, 3β, 14α, 22(S), 25-pentahydroxy- ^Δ7-5β -cholesten-6-one, also mentioned that the compounds described therein have very useful pharmacological properties, but did not specify which pharmacological properties performance.

Cholester-5-ene-3β, 22(R,S), 25-triol, cholest-5 -ene-25-fluoro-3β,22(R,S)-diol, cholest-5-ene-25-fluoro-22(R,S)-alcohol-3β-hemisuccinate, cholester- 5-ene-25-chloro-3β,22-diol and cholest-5-ene-25-chloro-22-ol-3β-hemisuccinate, also mentioning that the compounds described therein have pharmacological activity, such as Inhibits the activity of (HMG-CoA) reductase.

3α, 7α, 12α, 24, 25-pentahydroxyfungostane, 3α, 7α, 12α, 25-tetrahydroxyfungostane, 3α, 7α, 25- Trihydroxyfungostane, 3α, 7α, 24, 25-tetrahydroxyfungostane, 5β-cholestane-3α, 7α, 12α, 24α, 25-pentol, 5β-cholestane-3α, 7α, 12α , 24β, 25-pentol, 5β-cholestane-3α, 7α, 12α, 25, 26-pentol and 5β-cholestane-3α, 7α, 12α, 25-tetrol, also referring to the The compounds are useful in the preparation of compositions having antibacterial, antibacterial and bacteriostatic properties.

1α,2α,3β-trihydroxycholesta-5,7-diene and 1α,2α-dihydroxy-3β-acetoxycholesterol as intermediates are described in Examples 1 and 3 of U.S. Patent No. 4,011,250, respectively Ste-5-ene.

Cholesta-5-ene-2β-fluoro-1α,3β-diol is mentioned as compound 3 in US Patent No. 4,254,045, and it is also mentioned that the compound described therein has vitamin D-like activity.

The preparation of 24-cyclopropylcholest-5-ene-3β, 22(S)-diol-3-acetate, 24-cyclopropylcholest-5-ene-3β, 24-cyclopropylcholest-5-ene, Ste-5-ene-3β, 22(S)-diol, 24-cyclopropylcholest-5-ene-3β, 22(S)-diol-3-hydro-succinate and 24-cyclo Propyl-5α-cholestane-3β,22(S)-diol, also mentions that the compounds described therein inhibit the activity of HMG-CoA reductase.

Cholesta-1,4,6-trien-3-one, 1α,3β-dihydroxycholesta -5-ene, 1α,3β-dihydroxy-5α-cholestane, 1α,3β-dihydroxycholesta-5,7-diene, 1α,3β,25-trihydroxycholesta-5-ene, 1α , 25-dihydroxycholesterol and 1α, 25-dihydroxycholesterol-3-benzoate, and mentions that the compounds described therein have medical uses.

Other known compounds are cholest-5-ene-3β,20(S)-diol (Sigma, St.Louis, Mo, USA, Cat.No.H6378), cholest-5-ene-3β,22 (S)-diol (Sigma, St.Louis, Mo, USA, Cat.No.H5884), cholest-5-ene-3β, 4β-diol (SteraloidInc., Wilton, NH, USA, Cat.No .C6410, Batch L1066)), cholest-5-ene-3β, 22(R)-diol (Sigma, St.Louis, Mo, USA, Cat.No.H9384) and 2β, 3β, 14α, 22( R), 25-pentahydroxycholest-7-en-6-one.

The above-mentioned documents do not mention compounds capable of regulating meiosis, and the contents of the above-mentioned documents are hereby incorporated by reference,

Meiosis is a fundamental activity unique to germ cells that underlies sexual reproduction. Meiosis consists of two meiotic divisions. During the first division, before the chromosome pairs separate into two daughter cells, an exchange occurs between maternal and paternal genes. These daughter cells contain only half (1n) of chromosomes and 2c DNA. DNA synthesis does not occur during the second meiotic division, so this division forms haploid germ cells containing only 1c DNA.

The meiotic activity of male and female germ cells is similar, but the timing and differentiation process of egg and sperm production are quite different. All female germ cells enter prophase of the first meiotic division early in life, usually before birth, but are later arrested into oocytes in the prophase (dictyate state) before ovulation after maturation. Thus, from early in life, females have a stockpile of oocytes from which oocytes are drawn until the stockpile is depleted. Meiosis in females is complete only after fertilization and one germ cell produces only one egg and two aborted polar bodies. In contrast, throughout life, only some male germ cells mature from puberty into meiosis, leaving behind a predominant number of germ cells. Once initiated, meiosis of the male cell proceeds without significant delay and produces 4 spermatozoa.

Little is known about the mechanisms governing the initiation of male and female meiosis. In oocytes, new studies suggest that follicular purines, panxanthines, or adenines may be responsible for arresting meiosis (Downs, S.M. et al., Dev Biol 82 (1985) 454-458; Eppig, J.J. et al., Dev Biol 119 (1986) 313-321; and Downs, S.M. Mol Reprod Dev 35 (1993) 82-94). For the first time, Byskov et al. described the presence of substances controlling diffuse meiosis in a culture system of fetal mouse gonads (Byskov, A.G. et al., Dev Biol 52 (1976) 193-200). When meiosis occurs, the fetal mouse ovary secretes meiosis-activating substance (MAS), and releases meiosis-inhibiting substance (MPS) from morphologically differentiated testes containing dormant non-meiotic cells, suggesting that MAS and Relative concentrations of MPS regulate the initiation, arrest and occurrence of meiosis in male and female germ cells (Byskov, A.G. et al., The Physiology of Reproduction (Knobil, E. and Neil, J.D., Raven Press, New York (1994) ). Clearly, if meiosis can be regulated, replication can be controlled. A recent article (Byskov, A.G. et al., Nature 374 (1995), 559-562) describes the isolation of Unfortunately, these cholesterols are not so stable, so it will be greatly convenient to take advantage of this interesting discovery if more stable meiosis activating compounds can be obtained.

Compounds known to stimulate meiosis and which differ from the compounds claimed in the present application are described in WO 96/27658.

The compounds described in the present invention have several advantages over known compounds.

Summary of the invention

It is an object of the present invention to provide compounds and methods for alleviating infertility in males and females, especially mammals, more particularly humans.

Another object of the present invention is to provide compounds and methods for use as contraceptives for males and females, especially mammals, more particularly humans.

The present invention provides novel compounds with interesting pharmacological properties, in particular compounds of formula Ia, Ib and Ic useful for modulating meiosis in oocytes and male germ cells.

One aspect of the present invention relates to compounds of general formula Ia in claim 1 below.

In another embodiment of the present invention, it relates to an ester of a compound of general formula Ia, which is generally obtained by esterification of one or more hydroxyl groups of a compound of formula Ia with an acid, for example, the acid can be selected from succinic acid And other aliphatic dicarboxylic acids, nicotinic acid, isonicotinic acid, ethyl carbonate, phosphoric acid, sulfonic acid, sulfamic acid, benzoic acid, acetic acid, propionic acid and other aliphatic monocarboxylic acids.

In a preferred embodiment of the present invention, it relates to compounds of general formula Ib and esters thereof for use as medicaments.

In another preferred embodiment of the present invention, it relates to a compound of general formula Ic or an ester thereof for use in the manufacture of a medicament for use in regulating meiosis.

In yet another preferred embodiment of the present invention, it relates to the use of the above-mentioned compound of formula Ic or its ester as a drug, especially as a drug for regulating meiosis. The compound can be used pure or in the form of a liquid or solid composition containing auxiliaries commonly used in the art.

In the present invention, the term "modulates meiosis" is used to indicate that certain compounds of the present invention can be used to stimulate meiosis in test tube, in vivo or in vitro. Therefore, these compounds can be used as agonists of substances that activate naturally occurring meiosis, and can be used to treat infertility caused by lack of sufficient stimulation of meiosis in both males and females. Other compounds of the invention may be antagonists of substances that activate naturally occurring meiosis and may be used in a manner to regulate meiosis, preferably in living organisms, making them suitable for use as contraceptives, in such In the present case, "modulation" refers to partial or total inhibition.

In another aspect of the present invention, it relates to the use of a compound of the above formula Ic or an ester thereof for regulating meiosis of oocytes, especially mammalian oocytes, more particularly human oocytes.

In yet another aspect of the present invention, it relates to the use of the above-mentioned compound of formula Ic or an ester thereof in stimulating meiosis of oocytes, especially mammalian oocytes, more particularly human oocytes.

In yet another aspect of the present invention, it relates to the use of the compound of the above formula Ic or an ester thereof for inhibiting meiosis of oocytes, especially mammalian oocytes, more particularly human oocytes.

In yet another aspect of the present invention, it relates to the use of the above-mentioned compound of formula Ic or an ester thereof in regulating meiosis of male germ cells, especially mammalian male germ cells, more particularly human male germ cells.

In yet another aspect of the present invention, it relates to the use of the above-mentioned compound of formula Ic or its ester in stimulating meiosis of male germ cells, especially mammalian male germ cells, more particularly human male germ cells.

In yet another aspect of the present invention, it relates to the use of the above-mentioned compound of formula Ic or its ester in inhibiting the meiosis of male germ cells, especially mammalian male germ cells, more particularly human male germ cells,

Still another aspect of the present invention relates to a method of regulating meiosis of mammalian germ cells, which method comprises administering an effective amount of the compound of formula Ic or an ester thereof to the germ cells in need of such treatment.

Still another aspect of the present invention relates to a method for regulating meiosis of germ cells in mammals, wherein the compound of formula Ic or an ester thereof is administered to the mammal hosting said cells so as to introduce the compound into the germ cells.

Still another aspect of the present invention relates to a method for regulating meiosis of germ cells using the compound of formula Ic or its esters above, wherein the germ cells are oocytes.

Another aspect of the present invention relates to a method of regulating meiosis of an oocyte, wherein the above-mentioned compound of formula Ic or an ester thereof is administered to the oocyte in vitro.

Another aspect of the present invention relates to a method of modulating meiosis in male germ cells, wherein the germ cells are administered a compound of formula Ic above or an ester thereof.

Another aspect of the present invention relates to a method for producing mature male germ cells by administering the above-mentioned compound of formula Ic or its ester to testicular tissue containing immature cells in vivo or in vitro.

Detailed description of the invention

Preferred compounds of formula Ia, Ib and Ic are those wherein ^R1 and ^R2 are both hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein one of R ^{and R} is hydrogen and the other is methyl,

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R1 and ^R2 are both methyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹ is branched or unbranched C ₁ -C ₆ alkyl optionally substituted by halogen, hydroxy or cyano.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ² is branched or unbranched C ₁ -C ₆ alkyl optionally substituted by halogen, hydroxy or cyano.

Other preferred compounds of formulas Ia, Ib and Ic are those wherein ^R1 is hydroxy and ^R2 is selected from hydrogen and branched or unbranched _C1 - _C6 optionally substituted by halogen, hydroxy or cyano alkyl.

Other preferred compounds of formulas Ia, Ib and Ic are those wherein ^R2 is hydroxy and ^R1 is selected from hydrogen and branched or unbranched _C1 - _C6 optionally substituted by halogen, hydroxy or cyano alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹ and R ² together represent methylene.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R1 and ^R2 together with the carbon atoms to which they are attached form a cyclopropane ring.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R1 and ^R2 together with the carbon atoms to which they are attached form a cyclopentane ring.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R1 and ^R2 together with the carbon atoms to which they are attached form a cyclohexane ring.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 is methylene.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 is methoxy or acetoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 is =NOH.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ³ is =NOR ²⁶ , wherein R ²⁶ is C ₁ -C ₃ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 is hydroxyl and _C1 - _C4 alkyl attached to the same carbon atom of the cholesteric backbone.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 and ^R9 together represent an additional bond between the carbon atoms at ^R3 and ^R9 .

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R3 and ^R14 together represent an additional bond between ^R3 and the carbon atom at ^R14 .

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R4 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁴ is methylene.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R4 is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R4 is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R4 is methoxy or acetoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R4 is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R4 is =NOH.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁴ is =NOR ²⁷ , wherein R ²⁷ is C ₁ -C ₃ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R4 is hydroxyl and _C1 - _C4alkyl attached to the same carbon atom of the cholesteric backbone.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁴ and R ¹³ together represent an additional bond between R ⁴ and the carbon atom at R ¹³ .

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁴ and R ¹⁵ together represent an additional bond between the carbon atoms at R ⁴ and R ¹⁵ .

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R5 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R5 is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁵ is C ₁ -C ₄ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁵ is methylene.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R5 is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁵ is methoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁵ is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R5 is =NOH.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁵ is =NOR ²² , wherein R ²² is C ₁ -C ₃ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R5 and ^R6 together represent an additional bond between the carbon atoms at ^R5 and ^R6 .

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R6 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R6 is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁶ and R ¹⁴ together represent an additional bond between R ⁶ and the carbon atom at R ¹⁴ .

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R9 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R9 is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R9 is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R9 is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ⁹ and R ¹⁰ together represent an additional bond between the carbon atoms at R ⁹ and R ¹⁰ .

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁰ is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁰ is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁰ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is hydroxy.

Other preferred compounds of formulas Ia, Ib and Ic are those wherein R is ^alkoxy , arylalkoxy, alkoxyalkoxy or alkanoyloxyalkyl and each group contains up to 10 carbon atoms , preferably compounds containing up to 8 carbon atoms.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is C ₁ -C ₄ alkoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is methoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is ethoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is CH ₃ OCH ₂ O—.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is pivaloyloxymethoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R11 is an acyloxy group derived from a carboxylic acid containing 1 to 20 carbon atoms.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R is selected from the group consisting of acetoxy, benzoyloxy, pivaloyloxy, butyryloxy, nicotinoyloxy, isonicotinoyloxy, Hemisuccinyloxy, hemiglutaryloxy, butylcarbamoyloxy, phenylcarbamoyloxy, butoxycarbonyloxy, tert-butoxycarbonyloxy and ethoxycarbonyloxy The compound of acyloxy group.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is sulfonyloxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is phosphoryloxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is =NOH.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is =NOR ²⁸ , wherein R ²⁸ is C ₁ -C ₃ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ is halogen.

Other preferred compounds of formulas Ia, Ib and Ic are those wherein R ¹¹ is hydroxyl and C ₁ -C ₄ alkyl attached to the same carbon atom of the cholesteric backbone.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹¹ and R ¹² together represent an additional bond between the carbon atoms at R ¹¹ and R ¹² .

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹² is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹² is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹² is C ₁ -C ₃ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹² is C ₁ -C ₃ alkoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹² is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹³ is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹³ is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹³ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹³ and R ¹⁴ together represent an additional bond between the carbon atoms at R ¹³ and R ¹⁴ .

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁴ is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁴ is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁴ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is C ₁ -C ₄ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is methylene.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is methoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is =NOH.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁵ is =NOR ²³ , wherein R ²³ is C ₁ -C ₃ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is C ₁ -C ₃ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is methylene.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is methoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is =NOH.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ is =NOR ²⁴ , wherein R ²⁴ is C ₁ -C ₃ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁶ and R ¹⁷ together represent an additional bond between the carbon atoms at R ¹⁶ and R ¹⁷ .

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R17 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁷ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R18 and ^R19 are both hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein one of ^R18 and ^R19 is hydrogen and the other is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein one of ^R18 and ^R19 is hydrogen and the other is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein one of ^R18 and ^R19 is hydrogen and the other is methoxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein one of R ^{and R} is fluorine and the other is hydrogen,

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ¹⁸ and R ¹⁹ together represent oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ²⁵ is hydroxymethyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ²⁵ is C ₁ -C ₄ alkyl.

Other preferred compounds of the formulas Ia, Ib and Ic are those wherein R ²⁵ together with R ³¹ represent methylene.

Other preferred compounds of the formulas Ia, Ib and Ic are those wherein R ²⁵ together with R ³¹ represents oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ²⁹ is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ²⁹ is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ²⁹ is methyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ²⁹ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ²⁹ is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ³⁰ is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ³⁰ is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ³⁰ is methyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ³⁰ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R31 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein ^R31 is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ³¹ is methyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein R ³¹ is hydroxy.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R7 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R7 is a hydroxyl group.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R7 is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and R ⁷ and R ⁸ together represent an additional bond between the carbon atoms at R ⁷ and R ⁸ .

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R8 is hydrogen.

Other preferred compounds of formulas Ia, Ib and Ic are those wherein A is a carbon atom and R ⁸ is C ₁ -C ₄ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and R ⁸ is methylene.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R8 is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and R ⁸ is cyano.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R8 is halogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R8 is a hydroxyl group.

Other preferred compounds of formulas Ia, Ib and Ic are those wherein A is a carbon atom and ^R20 is _C1 - _C4alkyl .

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R20 is trifluoromethyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and R ²⁰ is C ₃ -C ₆ cycloalkyl.

Other preferred compounds of the formulas Ia, Ib and Ic are those wherein A is a carbon atom and ^R21 is _C1 - _C4alkyl .

Other preferred compounds of formulas Ia, Ib and Ic are those wherein A is a carbon atom and R ²¹ is C ₁ -C ₄ hydroxyalkyl.

Other preferred compounds of the formulas Ia, Ib and Ic are those wherein A is a carbon atom and R ²¹ is a C ₁ -C ₄ haloalkyl group containing up to 3 halogen atoms.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and ^R21 is methoxymethyl or acetoxymethyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a carbon atom and R ²¹ is C ₃ -C ₆ cycloalkyl.

Other preferred compounds of formulas Ia, Ib and Ic are those wherein A is a carbon atom, and R ^{and R} together with the carbon atoms to which they are attached form a _C3 - _C6 cycloalkyl ring, preferably a cyclopropyl ring, Compounds with cyclopentyl ring or cyclohexyl ring.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a nitrogen atom.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a nitrogen atom and ^R8 is hydrogen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a nitrogen atom and ^R8 is a hydroxyl group.

Other preferred compounds of formulas Ia, Ib and Ic are those wherein A is a nitrogen atom and R ⁸ is C ₁ -C ₄ alkyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a nitrogen atom and ^R8 is oxygen.

Other preferred compounds of formula Ia, Ib and Ic are those wherein A is a nitrogen atom and ^R20 and ^R21 are independently selected from _C1 - _C4 alkyl, cyclopropyl, cyclopentyl and cyclohexyl.

Other preferred compounds of formula Ia, Ib and Ic are those wherein the long side chain at position 17 is in the beta position.

It should be understood that the preferred substituents mentioned above can be combined with each other in any manner.

More preferred embodiments are mentioned in the appended claims.

The term C ₁ -C ₃ alkyl used in the specification and claims of the present invention represents an alkyl group containing 1-3 carbon atoms, preferred examples of which are methyl, ethyl and propyl, more preferred examples are methyl and ethyl. Similarly, the term C ₁ -C ₄ alkyl represents an alkyl group containing 1 to 4 carbon atoms, preferred examples of which are methyl, ethyl, propyl, isopropyl and butyl, more preferred examples are methyl base and ethyl. The term C ₁ -C ₆ alkyl represents an alkyl group containing 1 to 6 carbon atoms, preferred examples of which are methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl and hexyl, more Preferred examples are methyl, ethyl, propyl, isopropyl, butyl and tert-butyl, more preferred examples are methyl and ethyl.

The term C ₁ -C ₃ alkoxy used in the description and claims of the present invention represents an alkoxy group containing 1 to 3 carbon atoms, preferred examples of which are methoxy, ethoxy and propoxy, More preferred examples are methoxy and ethoxy.

The term halogen as used in the description and claims of the present invention preferably represents fluorine and chlorine, more preferably fluorine.

The term C ₁ -C ₄ alkanediyl as used in the description and claims of the present invention represents a branched or unbranched alkane from which two hydrogen atoms have been removed. As can be seen from formula I, in these alkanediyl groups, two free bonds are attached to the same carbon atom of the cholesteric backbone. The general terms for alkanediyl are considered alkylidene and alkylene. Examples of preferred alkanediyl groups are methylene, ethylene, propylene, propylidene, isopropylidene, sec-butylidene and 1,4-butylene.

The term C ₃ -C ₆ cycloalkyl used in the description and claims of the present invention represents a cycloalkyl group having 3 to 6 carbon atoms in the ring, and preferred examples are cyclopropyl and cyclopentyl.

The term acyloxy as used in the description and claims of the present invention represents a monovalent substituent containing an optionally substituted C ₁ -C ₆ alkyl or phenyl group attached through a carbonyloxy group, such as acetoxy group, propionyloxy, butyryloxy, isobutyryloxy, pivaloyloxy, valeryloxy, benzoyl, etc.

The compound molecule of claim 1 contains several chiral centers, so there are several isomers, and all these isomers and their mixtures are within the protection scope of the present invention.

Compounds of general formula I can be prepared in a similar manner to known compounds. Thus, the synthesis of compounds of formula I can be carried out following well-established synthetic routes described in the review literature of cholesterol and cholesterol analogues. The following books can be used as key source materials for the synthesis: Steroids by L.F. Fieser & M. Fieser: Reinhold Publishing Corporation, NY 1959; Rood's Chemistry of Carbon Compounds (edited by S. Coffrey): Elsevier Publishing Company, 1971; and especially the Dictionary of Steroids (Eds. R.A. Hill, D.N. Kirk, H.L.J. Makin, and G.M. Murphy): Chapmann & Hall. The last of these contains an extensive indexed bibliography covering original literature prior to 1990. All of these books, including the last cited citation, are incorporated by reference.

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

The existence of meiosis-inducing substances in nature has been known for some time, however the identity of the meiosis-inducing substances has not been known until recently.

Possibilities for affecting meiosis are manifold. According to a preferred embodiment of the present invention, the compound according to claim 1 or its ester is used to stimulate meiosis. According to another preferred embodiment of the present invention, the compounds according to claim 1 or their esters are used to stimulate meiosis in humans. Accordingly, the compounds of claim 1 or their esters are expected to be used as new fertility regulators without the hitherto known effects on somatic production of hormonal contraceptives based on estrogens and/or progestogens. side effects.

When used as a female contraceptive, meiosis-inducing substances can be taken to induce meiosis in oocytes that are still growing follicles before ovulation produces gonadotropin peak and before maturation. For example, meiosis can be induced one week after the woman's previous menstrual cessation. At ovulation, the resulting over-mature oocyte is most likely not to be fertilized. Normal menstrual cycle is unlikely to be affected. It is therefore important to note that in cultured human granulosa cells (the somatic cells of the follicle), progesterone biosynthesis is unaffected by the presence of meiosis-inducing substances, whereas hormonal contraceptives used to date The estrogens and progestogens used in the drug have adverse effects on the biosynthesis of progesterone.

According to another aspect of the present invention, by administering the meiosis-inducing substance or its ester according to claim 1 to females who cannot produce mature oocytes due to their own inability to produce sufficient meiosis-activating substances, they can be It is used to treat certain infertility conditions in females, including women. In addition, when fertilization is carried out in vitro, better results can be obtained when the compound of claim 1 or its ester is added to the medium for preserving oocytes.

When male (including male) infertility is caused by the lack of mature germ cells due to the male's inability to produce enough substances for activating meiosis, taking the compound of claim 1 or its ester can alleviate the symptoms.

Another method different from the above method is to prevent females from producing mature oocytes by taking the compound of claim 1 or its esters capable of inhibiting meiosis to achieve the purpose of female contraception. Similarly, the purpose of male contraception can be achieved by taking the compound of claim 1 or its ester which can inhibit meiosis, so that males cannot produce mature germ cells.

The route of administration of the composition containing the compound of claim 1 or an ester thereof may be any method effective to deliver the active compound to its site of action.

Accordingly, when a compound of the present invention is administered to a mammal, the compound is conveniently provided in the form of a pharmaceutical composition comprising at least one compound of claim 1 or an ester thereof and a pharmaceutically acceptable carrier . For oral administration, such compositions are preferably in the form of capsules or tablets.

From the foregoing it will be appreciated that the required dosing regimen will depend on the condition to be treated. Thus, when used to treat infertility, the administration can be done once or for a limited period of time, eg until conception. When the compound of claim 1 or its ester is used as a contraceptive, it must be administered continuously or periodically. Timing of administration in relation to ovulation is important when used as a female contraceptive without continuous dosing.

Examples of preferred compounds of the invention are given below:

Cholesta-5-ene-3α, 1β-diol, Cholesta-5-ene-3α, 1α-diol, Cholesta-5-ene-3α, 2β-diol, Cholesta-5-ene-3α , 2α-diol, cholest-5-ene-3α, 4β-diol, cholest-5-ene-3α, 4α-diol, cholest-5-ene-3α, 7β-diol, cholesterol -5-ene-3α, 7α-diol, cholest-5-ene-3α, 11β-diol, cholest-5-ene-3α, 11α-diol, cholest-5-ene-3α, 12β -diol, cholest-5-ene-3α, 12α-diol, cholest-5-ene-3α, 15β-diol, cholest-5-ene-3α, 15α-diol, cholest-5 -ene-3α, 16β-diol, cholest-5-ene-3α, 16α-diol, cholest-5-ene-3α, 17β-diol, cholest-5-ene-3α, 17α-diol alcohol, cholest-5-ene-3α, (20R)-diol, cholest-5-ene-3α, (20S)-diol, cholest-5-ene-3α, 21-diol, cholesterol -5-ene-3α, (22R)-diol, cholest-5-ene-3α, (22S)-diol, cholest-5-ene-3α, (23R)-diol, cholest-5 -ene-3α, (23S)-diol, cholest-5-ene-3α, (24R)-diol, cholest-5-ene-3α, (24S)-diol, cholest-5-ene -3α, 25-diol, (25R) cholest-5-ene-3α, 26-diol, (25S) cholest-5-ene-3α, 26-diol, cholest-5-ene-3β , 1β-diol, cholest-5-ene-3β, 1α-diol, cholest-5-ene-3β, 2β-diol, cholest-5-ene-3β, 2α-diol, cholesterol -5-ene-3β,4β-diol, cholest-5-ene-3β,4α-diol, cholest-5-ene-3β,7β-diol, cholest-5-ene-3β,7α -diol, cholest-5-ene-3β, 11β-diol, cholest-5-ene-3β, 11α-diol, cholest-5-ene-3β, 12β-diol, cholest-5 -ene-3β, 12α-diol, cholest-5-ene-3β, 15β-diol, cholest-5-ene-3β, 15α-diol, cholest-5-ene-3β, 16β-diol alcohol, cholest-5-ene-3β, 16α-diol, cholest-5-ene-3β, 17β-diol, cholest-5-ene-3β, 17α-diol, cholest-5-diol -3β, (20R)-diol, cholest-5-ene-3β, (20S)-diol, cholest-5-ene-3β, 21-diol, cholest-5-ene-3β, ( 22R)-diol, cholest-5-ene-3β, (22S)-diol, cholest-5-ene-3β, (23R)-diol, cholest-5-ene-3β, (23S) -diol, cholest-5-ene-3β, (24R)-diol, cholest-5-ene-3β, (24S)-diol, cholest-5-ene-3β, 25-diol, (25S)-cholesta-5-ene-3β,26-diol, cholesta-5,24-diene-3α,1β-diol, cholesta-5,24-diene-3α,1α-diol alcohol, cholesta-5,24-diene-3α,2β-diol, cholesta-5,24-diene-3α,2α-diol, cholesta-5,24-diene-3α,4β- Diol, Cholesta-5,24-diene-3α,4α-diol, Cholesta-5,24-diene-3α,1β-diol, Cholesta-5,24-diene-3α,7β -diol, cholesta-5,24-diene-3α, 7α-diol, cholesta-5,24-diene-3α, 11β-diol, cholesta-5,24-diene-3α, 11α-diol, cholesta-5,24-diene-3α, 12β-diol, cholesta-5,24-diene-3α, 12α-diol, cholesta-5,24-diene-3α , 15β-diol, cholesta-5,24-diene-3α, 15α-diol, cholesta-5,24-diene-3α, 16β-diol, cholesta-5,24-diene- 3α, 16α-diol, cholesta-5,24-diene-3α, 17β-diol, cholesta-5,24-diene-3α, 17α-diol, cholesta-5,24-diene -3α, (20R)-diol, cholesta-5, 24-diene-3α, (20S)-diol, cholesta-5, 24-diene-3α, 21-diol, cholesta-5 , 24-diene-3α, (22R)-diol, cholesta-5, 24-diene-3α, (22S)-diol, cholesta-5, 24-diene-3α, (23R)- Diol, Cholesta-5,24-diene-3α, (23S)-diol, Cholesta-5,24-diene-3α, 26-diol, Cholesta-5,24-diene-3β , 1β-diol, cholesta-5,24-diene-3β, 1α-diol, cholesta-5,24-diene-3β, 2β-diol, cholesta-5,24-diene- 3β,2α-diol, cholesta-5,24-diene-3β,4β-diol, cholesta-5,24-diene-3β,4α-diol, cholesta-5,24-diene -3β,7β-diol, cholesta-5,24-diene-3β,7α-diol, cholesta-5,24-diene-3β,11β-diol, cholesta-5,24-diol ene-3β, 11α-diol, cholesta-5,24-diene-3β, 12β-diol, cholesta-5,24-diene-3β, 12α-diol, cholesta-5,24-diol Diene-3β, 15β-diol, cholesta-5,24-diene-3β, 15α-diol, cholesta-5,24-diene-3β, 16β-diol, cholesta-5,24 -diene-3β, 16α-diol, cholesta-5, 24-diene-3β, 17β-diol, cholesta-5, 24-diene-3β, 17α-diol, cholesta-5, 24-diene-3β, (20R)-diol, cholesta-5,24-diene-3β, (20S)-diol, cholesta-5,24-diene-3β, 21-diol, Cholesta-5,24-diene-3β, (22R)-diol, Cholesta-5,24-diene-3β, (22S)-diol, Cholesta-5,24-diene-3β, (23R)-diol, cholesta-5,24-diene-3β, (23S)-diol, cholesta-5,24-diene-3β,26-diol, 4,4-dimethyl Cholesta-5-ene-3α, 1β-diol, 4,4-Dimethylcholest-5-ene-3α, 1α-diol, 4,4-Dimethylcholest-5-ene-3α , 2β-diol, 4,4-dimethylcholest-5-ene-3α, 2α-diol, 4,4-dimethylcholest-5-ene-3α, 7β-diol, 4, 4-Dimethylcholest-5-ene-3α, 7α-diol, 4,4-Dimethylcholest-5-ene-3α, 11β-diol, 4,4-Dimethylcholesta- 5-ene-3α, 11α-diol, 4,4-dimethylcholest-5-ene-3α, 12β-diol, 4,4-dimethylcholest-5-ene-3α, 12α- Diol, 4,4-dimethylcholest-5-ene-3α, 15β-diol, 4,4-dimethylcholest-5-ene-3α, 15α-diol, 4,4-diol Methylcholest-5-ene-3α, 16β-diol, 4,4-Dimethylcholest-5-ene-3α, 16α-diol, 4,4-Dimethylcholest-5-ene -3α, 17β-diol, 4,4-dimethylcholest-5-ene-3α, 17α-diol, 4,4-dimethylcholest-5-ene-3α, (20R)-di alcohol, 4,4-dimethylcholest-5-ene-3α, (20S)-diol, 4,4-dimethylcholest-5-ene-3α, 21-diol, 4,4- Dimethylcholest-5-ene-3α, (22R)-diol, 4,4-Dimethylcholest-5-ene-3α, (22S)-diol, 4,4-Dimethylcholesterol Ste-5-ene-3α, (23R)-diol, 4,4-Dimethylcholest-5-ene-3α, (23S)-diol, 4,4-Dimethylcholest-5- ene-3α, (24R)-diol, 4,4-dimethylcholest-5-ene-3α, (24S)-diol, 4,4-dimethylcholest-5-ene-3α, 25-diol, (25R)-4,4-dimethylcholest-5-ene-3α, 26-diol, (25S)-4,4-dimethylcholest-5-ene-3α, 26-diol, 4,4-dimethylcholest-5-ene-3β,1β-diol, 4,4-dimethylcholest-5-ene-3β,1α-diol, 4,4 -Dimethylcholest-5-ene-3β,2β-diol, 4,4-Dimethylcholest-5-ene-3β,2α-diol, 4,4-Dimethylcholest-5- -ene-3β,7β-diol, 4,4-dimethylcholest-5-ene-3β,7α-diol, 4,4-dimethylcholest-5-ene-3β,11β-diol alcohol, 4,4-dimethylcholest-5-ene-3β, 11α-diol, 4,4-dimethylcholest-5-ene-3β, 12β-diol, 4,4-dimethyl Cholester-5-ene-3β, 12α-diol, 4,4-dimethylcholest-5-ene-3β, 15β-diol, 4,4-dimethylcholest-5-ene- 3β, 15α-diol, 4,4-dimethylcholest-5-ene-3β, 16β-diol, 4,4-dimethylcholest-5-ene-3β, 16α-diol, 4 , 4-Dimethylcholest-5-ene-3β, 17β-diol, 4,4-Dimethylcholest-5-ene-3β, 17α-diol, 4,4-Dimethylcholesterol -5-ene-3β, (20R)-diol, 4,4-dimethylcholest-5-ene-3β, (20S)-diol, 4,4-dimethylcholest-5-ene -3β, 21-diol, 4,4-dimethylcholest-5-ene-3β, (22R)-diol, 4,4-dimethylcholest-5-ene-3β, (22S) -diol, 4,4-dimethylcholest-5-ene-3β, (23R)-diol, 4,4-dimethylcholest-5-ene-3β, (23S)-diol, 4,4-Dimethylcholest-5-ene-3β, (24R)-diol, 4,4-Dimethylcholest-5-ene-3β, (24S)-diol, 4,4- Dimethylcholest-5-ene-3β,25-diol, (25S)-4,4-di-methylcholest-5-ene-3β,26-diol, 4,4-dimethyl Cholesta-5,24-diene-3α,1β-diol, 4,4-Dimethylcholesta-5,24-diene-3α,1α-diol, 4,4-Dimethylcholesterol -5,24-diene-3α,2β-diol, 4,4-dimethylcholesta-5,24-diene-3α,2α-diol, 4,4-dimethylcholesta-5 , 24-diene-3α,7β-diol, 4,4-dimethylcholesta-5,24-diene-3α,7α-diol, 4,4-dimethylcholesta-5,24 -diene-3α, 11β-diol, 4,4-dimethylcholesta-5,24-diene-3α, 11α-diol, 4,4-dimethylcholesta-5,24-diol ene-3α, 12β-diol, 4,4-dimethylcholesta-5,24-diene-3α, 12α-diol, 4,4-dimethylcholesta-5,24-diene- 3α, 15β-diol, 4,4-dimethylcholesta-5,24-diene-3α, 15α-diol, 4,4-dimethylcholesta-5,24-diene-3α, 16β-diol, 4,4-dimethylcholesta-5,24-diene-3α, 16α-diol, 4,4-dimethylcholesta-5,24-diene-3α, 17β- Diol, 4,4-dimethylcholesta-5,24-diene-3α, 17α-diol, 4,4-dimethylcholesta-5,24-diene-3α, (20R)- Diol, 4,4-dimethylcholesta-5,24-diene-3α, (20S)-diol, 4,4-dimethylcholesta-5,24-diene-3α, 21- Diol, 4,4-dimethylcholesta-5,24-diene-3α, (22R)-diol, 4,4-dimethylcholesta-5,24-diene-3α, (22S )-diol, 4,4-dimethylcholesta-5,24-diene-3α, (23R)-diol, 4,4-dimethylcholesta-5,24-diene-3α, (23S)-diol, 4,4-dimethylcholesta-5,24-diene-3α, 26-diol, 4,4-dimethylcholesta-5,24-diene-3β, 1β-diol, 4,4-dimethylcholesta-5,24-diene-3β,1α-diol, 4,4-dimethylcholesta-5,24-diene-3β,2β- Diol, 4,4-Dimethylcholesta-5,24-diene-3β,2α-diol, 4,4-Dimethylcholesta-5,24-diene-3β,7β-diol , 4,4-dimethylcholesta-5,24-diene-3β,7α-diol, 4,4-dimethylcholesta-5,24-diene-3β,11β-diol, 4 , 4-dimethylcholesta-5,24-diene-3β,11α-diol, 4,4-dimethylcholesta-5,24-diene-3β,12β-diol, 4,4 -Dimethylcholesta-5,24-diene-3β,12α-diol, 4,4-dimethylcholesta-5,24-diene-3β,15β-diol, 4,4-diol Methylcholesta-5,24-diene-3β,15α-diol, 4,4-dimethylcholesta-5,24-diene-3β,16β-diol, 4,4-dimethyl Cholesta-5,24-diene-3β,16α-diol, 4,4-Dimethylcholesta-5,24-diene-3β,17β-diol, 4,4-Dimethylcholesterol -5,24-diene-3β,17α-diol, 4,4-dimethylcholesta-5,24-diene-3β,(20R)-diol, 4,4-dimethylcholesta -5,24-diene-3β, (20S)-diol, 4,4-dimethylcholesta-5,24-diene-3β,21-diol, 4,4-dimethylcholesta -5,24-diene-3β, (22R)-diol, 4,4-dimethylcholesta-5,24-diene-3β, (22S)-diol, 4,4-dimethyl Cholesta-5,24-diene-3β, (23R)-diol, 4,4-dimethylcholesta-5,24-diene-3β, (23S)-diol, 4,4-diol Methylcholesta-5,24-diene-3β,26-diol, spiro[cholesta-5-ene-3α,7β-diol-4,1′-cyclopropane], spiro[cholesta-5 -ene-3α,7α-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α,11β-diol-4,1′-cyclopropane], spiro[cholesta-5- -ene-3α,11α-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α,12β-diol-4,1′-cyclopropane], spiro[cholesta-5- -ene-3α,12α-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α,15β-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3α, 15α-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α, 16β-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3α, 16α-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α, 17β-diol-4,1′-cyclopropane], spiro[cholesteryl -5-ene-3α, 17α-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α, (20R)-diol-4,1′-cyclopropane], spiro[ Cholesta-5-ene-3α, (20S)-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α, 21-diol-4,1′-cyclopropane], Spiro[cholest-5-ene-3α, (22R)-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α, (22S)-diol-4,1′- cyclopropane], spiro[cholest-5-ene-3α, (23R)-diol-4, 1′-cyclopropane], spiro[cholest-5-ene-3α, (23S)-diol-4 , 1′-cyclopropane], spiro[cholest-5-ene-3α, (24R)-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α, (24S)- Diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α,25-diol-4,1′-cyclopropane], spiro[(25R)-cholest-5-ene- 3α,26-diol-4,1′-cyclopropane], spiro[(25S)-cholest-5-ene-3α,26-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3β,7β-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3α,7α-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3β, 11β-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β, 11α-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3β, 12β-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β, 12α-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3β, 15β-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β, 15α-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3β, 16β-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β, 16α-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3β, 17β-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β, 17α-diol-4,1′-cyclopropane], spiro[cholesta- 5-ene-3β, (20R)-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β, (20S)-diol-4,1′-cyclopropane], spiro [cholest-5-ene-3β,21-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β,(22R)-diol-4,1′-cyclopropane] , spiro[cholest-5-ene-3β, (22S)-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β, (23R)-diol-4,1′ -cyclopropane], spiro[cholest-5-ene-3β, (23S)-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β, (24R)-diol- 4,1′-cyclopropane], spiro[cholest-5-ene-3β, (24S)-diol-4,1′-cyclopropane], spiro[cholest-5-ene-3β,25-di Alcohol-4,1′-cyclopropane], spiro[(25R)-cholest-5-ene-3β,26-diol-4,1′-cyclopropane], spiro[(25S)-cholest-5-ene -ene-3β,26-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,7β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,7β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,7β-diol-4,1′-cyclopropane], Steta-5,24-diene-3α,7α-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,11β-diol-4,1′-cyclopropane] propane], spiro[cholesta-5,24-diene-3α,11α-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,12β-diol- 4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,12α-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α , 15β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,15α-diol-4,1′-cyclopropane], spiro[cholesta-5, 24-diene-3α, 16β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α, 16α-diol-4,1′-cyclopropane], spiro [cholesta-5,24-diene-3α,7β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,7α-diol-4,1′ -cyclopropane], spiro[cholesta-5,24-diene-3α, (20R)-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α, ( 20S)-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,21-diol-4,1′-cyclopropane], spiro[cholesta-5, 24-diene-3α, (22R)-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α, (22S)-diol-4,1′-cyclopropane] propane], spiro[cholesta-5,24-diene-3α, (23R)-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α, (23S) -diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3α,26-diol-4,1′-cyclopropane], spiro[cholesta-5,24- Diene-3β, 7β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β,7α-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β,7α-diol-4,1′-cyclopropane], spiro[cholestera ster-5,24-diene-3β,11β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β,11α-diol-4,1′-cyclopropane] propane], spiro[cholesta-5,24-diene-3β,12β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β,12α-diol- 4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β,15β-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β , 15α-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β,16β-diol-4,1′-cyclopropane], spiro[cholesta-5, 24-diene-3β, 16α-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β, 17β-diol-4,1′-cyclopropane], spiro [cholesta-5,24-diene-3β,17α-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β,(20R)-diol-4, 1′-cyclopropane], spiro[cholesta-5,24-diene-3β, (20S)-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β , 21-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β, (22R)-diol-4,1′-cyclopropane], spiro[cholesta- 5,24-diene-3β, (22S)-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β, (23R)-diol-4,1′ -cyclopropane], spiro[cholesta-5,24-diene-3β,(23S)-diol-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3β,26 -diol-4,1′-cyclopropane], 3α-hydroxycholest-5-en-1-one, 3α-hydroxycholest-5-en-2-one, 3α-hydroxycholest-5-ene -7-one, 3α-hydroxycholest-5-en-11-one, 3α-hydroxycholest-5-en-12-one, 3α-hydroxycholest-5-en-15-one, 3α-hydroxy Cholester-5-en-16-one, 3α-hydroxycholest-5-en-22-one, 3α-hydroxycholest-5-en-23-one, 3α-hydroxycholest-5-ene-24 -ketone, 3β-hydroxycholest-5-en-1-one, 3β-hydroxycholest-5-en-2-one, 3β-hydroxycholest-5-en-7-one, 3β-hydroxycholesterol -5-en-11-one, 3β-hydroxycholest-5-en-12-one, 3β-hydroxycholest-5-en-15-one, 3β-hydroxycholest-5-en-16-one , 3β-hydroxycholest-5-en-22-one, 3β-hydroxycholest-5-en-23-one, 3β-hydroxycholest-5-en-24-one, 3α-hydroxycholest-5 , 24-dien-1-one, 3α-hydroxycholesta-5,24-dien-2-one, 3α-hydroxycholesta-5,24-dien-7-one, 3α-hydroxycholesta- 5,24-dien-11-one, 3α-hydroxycholesta-5,24-dien-12-one, 3α-hydroxycholesta-5,24-dien-15-one, 3α-hydroxycholesterol -5,24-dien-16-one, 3α-hydroxycholesta-5,24-dien-22-one, 3α-hydroxycholesta-5,24-dien-23-one, 3β-hydroxycholesta-23-one ster-5,24-dien-1-one, 3β-hydroxycholesta-5,24-dien-2-one, 3β-hydroxycholesta-5,24-dien-7-one, 3β-hydroxy Cholesta-5,24-dien-11-one, 3β-hydroxycholesta-5,24-dien-12-one, 3β-hydroxycholesta-5,24-dien-15-one, 3β- Hydroxycholesta-5,24-dien-16-one, 3β-hydroxycholesta-5,24-dien-22-one, 3β-hydroxycholesta-5,24-dien-23-one, 4 , 4-Dimethyl-3α-hydroxycholest-5-en-1-one, 4,4-dimethyl-3α-hydroxycholest-5-en-2-one, 4,4-dimethyl -3α-hydroxycholest-5-en-7-one, 4,4-dimethyl-3α-hydroxycholest-5-en-11-one, 4,4-dimethyl-3α-hydroxycholesterol -5-en-12-one, 4,4-dimethyl-3α-hydroxycholest-5-en-15-one, 4,4-dimethyl-3α-hydroxycholest-5-ene-16 -ketone, 4,4-dimethyl-3α-hydroxycholest-5-en-22-one, 4,4-dimethyl-3α-hydroxycholest-5-en-23-one, 4,4 -Dimethyl-3α-hydroxycholest-5-en-24-one, 4,4-dimethyl-3β-hydroxycholest-5-en-1-one, 4,4-dimethyl-3β -Hydroxycholest-5-en-2-one, 4,4-Dimethyl-3β-hydroxycholest-5-en-7-one, 4,4-Dimethyl-3β-hydroxycholest-5 -en-11-one, 4,4-dimethyl-3β-hydroxycholest-5-en-12-one, 4,4-dimethyl-3β-hydroxycholest-5-en-15-one , 4,4-dimethyl-3β-hydroxycholest-5-en-16-one, 4,4-dimethyl-3β-hydroxycholest-5-en-22-one, 4,4-di Methyl-3β-hydroxycholest-5-en-23-one, 4,4-dimethyl-3β-hydroxycholest-5-en-24-one, 4,4-dimethyl-3α-hydroxy Cholesta-5,24-dien-1-one, 4,4-dimethyl-3α-hydroxycholesta-5,24-dien-2-one, 4,4-dimethyl-3α-hydroxy Cholesta-5,24-dien-7-one, 4,4-dimethyl-3α-hydroxycholesta-5,24-dien-11-one, 4,4-dimethyl-3α-hydroxy Cholesta-5,24-dien-12-one, 4,4-dimethyl-3α-hydroxycholesta-5,24-dien-15-one, 4,4-dimethyl-3α-hydroxy Cholesta-5,24-dien-16-one, 4,4-dimethyl-3α-hydroxycholesta-5,24-dien-22-one, 4,4-dimethyl-3α-hydroxy Cholesta-5,24-dien-23-one, 4,4-dimethyl-3β-hydroxycholesta-5,24-dien-1-one, 4,4-dimethyl-3β-hydroxy Cholesta-5,24-dien-2-one, 4,4-dimethyl-3β-hydroxycholesta-5,24-dien-7-one, 4,4-dimethyl-3β-hydroxy Cholesta-5,24-dien-11-one, 4,4-dimethyl-3β-hydroxycholesta-5,24-dien-12-one, 4,4-dimethyl-3β-hydroxy Cholesta-5,24-dien-15-one, 4,4-dimethyl-3β-hydroxycholesta-5,24-dien-16-one, 4,4-dimethyl-3β-hydroxy Cholesta-5,24-dien-22-one, 4,4-dimethyl-3β-hydroxycholesta-5,24-dien-23-one, spiro[3α-hydroxycholesta-5-ene -7-keto-4,1′-cyclopropane], spiro[3α-hydroxycholest-5-en-11-one-4,1′-cyclopropane], spiro[3α-hydroxycholest-5-ene -12-keto-4,1′-cyclopropane], spiro[3α-hydroxycholest-5-en-15-one-4,1′-cyclopropane], spiro[3α-hydroxycholest-5-ene -16-keto-4,1′-cyclopropane], spiro[3α-hydroxycholest-5-en-22-one-4,1′-cyclopropane], spiro[3α-hydroxycholest-5-ene -23-keto-4,1′-cyclopropane], spiro[3α-hydroxycholest-5-en-24-one-4,1′-cyclopropane], spiro[3β-hydroxycholest-5-ene -7-keto-4,1′-cyclopropane], spiro[3β-hydroxycholest-5-en-11-one-4,1′-cyclopropane], spiro[3β-hydroxycholest-5-ene -12-keto-4,1′-cyclopropane], spiro[3β-hydroxycholest-5-en-15-one-4,1′-cyclopropane], spiro[3β-hydroxycholest-5-ene -16-keto-4,1′-cyclopropane], spiro[3β-hydroxycholest-5-en-22-one-4,1′-cyclopropane], spiro[3β-hydroxycholest-5-ene -23-keto-4,1′-cyclopropane], spiro[3β-hydroxycholest-5-en-24-one-4,1′-cyclopropane], spiro[3α-hydroxycholesta-5,24 -diene-7-one-4,1′-cyclopropane], spiro[3α-hydroxycholesta-5,24-diene-11-one-4,1′-cyclopropane], spiro[3α-hydroxy Cholesta-5,24-dien-12-one-4,1′-cyclopropane], spiro[3α-hydroxycholesta-5,24-dien-15-one-4,1′-cyclopropane] , spiro[3α-hydroxycholesta-5,24-diene-16-one-4,1′-cyclopropane], spiro[3α-hydroxycholesta-5,24-diene-22-one-4, 1′-cyclopropane], spiro[3β-hydroxycholesta-5,24-dien-7-one-4,1′-cyclopropane], spiro[3β-hydroxycholesta-5,24-diene- 11-keto-4,1′-cyclopropane], spiro[3β-hydroxycholesta-5,24-diene-12-one-4,1′-cyclopropane], spiro[3β-hydroxycholesta-5 , 24-diene-15-one-4,1′-cyclopropane], spiro[3β-hydroxycholesta-5,24-diene-16-one-4,1′-cyclopropane], spiro[3β -Hydroxycholest-5,24-diene-22-one-4,1′-cyclopropane], 4,4-dimethylcholest-5-ene-1,3-dione, 4,4- Dimethylcholest-5-ene-3,7-dione, 4,4-dimethylcholest-5-ene-3,11-dione, 4,4-dimethylcholest-5- ene-3,12-dione, 4,4-dimethylcholest-5-ene-3,15-dione, 4,4-dimethylcholest-5-ene-3,16-dione , 4,4-dimethylcholest-5-ene-3,22-dione, 4,4-di-methylcholest-5-ene-3,23-dione, 4,4-dimethyl Cholesta-5-ene-3,24-dione, 4,4-dimethylcholesta-5,24-diene-1,3-dione, 4,4-dimethylcholesta-5 , 24-diene-3,7-dione, 4,4-dimethylcholesta-5,24-diene-3,11-dione, 4,4-dimethylcholesta-5,24 -diene-3,12-dione, 4,4-dimethylcholesta-5,24-diene-3,15-dione, 4,4-dimethylcholesta-5,24-dione ene-3,16-dione, 4,4-dimethylcholesta-5,24-diene-3,22-dione, 4,4-dimethylcholesta-5,24-diene- 3,23-dione, spiro[cholest-5-ene-3,7-dione-4,1′-cyclopropane], spiro[cholest-5-ene-3,11-dione-4, 1′-cyclopropane], spiro[cholest-5-ene-3,12-dione-4,1′-cyclopropane], spiro[cholest-5-ene-3,15-dione-4, 1′-cyclopropane], spiro[cholest-5-ene-3,16-dione-4,1′-cyclopropane], spiro[cholest-5-ene-3,22-dione-4, 1′-cyclopropane], spiro[cholest-5-ene-3,23-dione-4,1′-cyclopropane], spiro[cholest-5-ene-3,24-dione-4, 1′-cyclopropane], spiro[cholesta-5,24-diene-3,7-dione-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3,11 -diketo-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3,12-dione-4,1′-cyclopropane], spiro[cholesta-5,24- Diene-3,15-dione-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3,16-dione-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3,16-dione-4,1′-cyclopropane], Steta-5,24-diene-3,22-dione-4,1′-cyclopropane], spiro[cholesta-5,24-diene-3,23-dione-4,1′-cyclopropane propane], 4,4-dimethyl-1β-hydroxycholest-5-en-3-one, 4,4-dimethyl-1α-hydroxycholest-5-en-3-one, 4,4 -Dimethyl-2β-hydroxycholest-5-en-3-one, 4,4-dimethyl-2α-hydroxycholest-5-en-3-one, 4,4-dimethyl-7β -Hydroxycholest-5-en-3-one, 4,4-Dimethyl-7α-hydroxycholest-5-en-3-one, 4,4-Dimethyl-11β-hydroxycholest-5 -en-3-one, 4,4-dimethyl-11α-hydroxycholest-5-en-3-one, 4,4-dimethyl-12β-hydroxycholest-5-en-3-one , 4,4-Dimethyl-12α-hydroxycholest-5-en-3-one, 4,4-dimethyl-15β-hydroxycholest-5-en-3-one, 4,4-di Methyl-15α-hydroxycholest-5-en-3-one, 4,4-dimethyl-16β-hydroxycholest-5-en-3-one, 4,4-dimethyl-16α-hydroxy Cholester-5-en-3-one, 4,4-Dimethyl-17β-hydroxycholest-5-en-3-one, 4,4-Dimethyl-17α-hydroxycholest-5-ene -3-one, 4,4-dimethyl-(20R)-hydroxycholest-5-en-3-one, 4,4-dimethyl-(20S)-hydroxycholest-5-ene-3 -ketone, 4,4-dimethyl-21-hydroxycholest-5-en-3-one, 4,4-dimethyl-(22R)-hydroxycholest-5-en-3-one, 4 , 4-Dimethyl-(22S)-hydroxycholest-5-en-3-one, 4,4-dimethyl-(23R)-hydroxycholest-5-en-3-one, 4,4 -Dimethyl-(23S)-hydroxycholest-5-en-3-one, 4,4-dimethyl-(24R)-hydroxycholest-5-en-3-one, 4,4-di Methyl-(24S)-hydroxycholest-5-en-3-one, 4,4-dimethyl-25-hydroxycholest-5-en-3-one, 4,4-dimethyl-1β -Hydroxycholesta-5,24-dien-3-one, 4,4-Dimethyl-1α-hydroxycholesta-5,24-dien-3-one, 4,4-Dimethyl-2β -Hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-2α-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-7β -Hydroxycholesta-5,24-dien-3-one, 4,4-Dimethyl-7α-hydroxycholesta-5,24-dien-3-one, 4,4-Dimethyl-11β -Hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-11α-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-12β -Hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-12α-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-15β -Hydroxycholesta-5,24-dien-3-one, 4,4-Dimethyl-15α-hydroxycholesta-5,24-dien-3-one, 4,4-Dimethyl-16β -Hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-16α-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-17β -Hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-17α-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-( 20R)-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-(20S)-hydroxycholesta-5,24-dien-3-one, 4,4-di Methyl-21-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-(22R)-hydroxycholesta-5,24-dien-3-one, 4,4 -Dimethyl-(22S)-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-(23R)-hydroxycholesta-5,24-dien-3-one , 4,4-Dimethyl-(23S)-hydroxycholesta-5,24-dien-3-one, 4,4-dimethyl-26-hydroxycholesta-5,24-diene-3 -keto, spiro[7β-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[7α-hydroxycholest-5-en-3-one-4,1′-cyclopropane propane], spiro[11β-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[11α-hydroxycholest-5-en-3-one-4,1′-cyclopropane] propane], spiro[12β-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[12α-hydroxycholest-5-en-3-one-4,1′-cyclopropane] propane], spiro[15β-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[15α-hydroxycholest-5-en-3-one-4,1′-cyclopropane] propane], spiro[16β-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[16α-hydroxycholest-5-en-3-one-4,1′-cyclopropane] propane], spiro[17β-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[17α-hydroxycholest-5-en-3-one-4,1′-cyclopropane] propane], spiro[(20R)-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[(20S)-hydroxycholest-5-en-3-one-4, 1′-cyclopropane], spiro[21-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[(22R)-hydroxycholest-5-en-3-one- 4,1′-cyclopropane], spiro[(22S)-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[(23R)-hydroxycholest-5-ene- 3-keto-4,1′-cyclopropane], spiro[(23S)-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[(24R)-hydroxycholest- 5-en-3-one-4,1′-cyclopropane], spiro[(24S)-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[25-hydroxycholesterol Ste-5-en-3-one-4,1′-cyclopropane], spiro[(25R)-26-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[ (25S)-26-hydroxycholesta-5-en-3-one-4,1′-cyclopropane], spiro[7β-hydroxycholesta-5,24-hydroxycholesta-5,24-dien-3-one-4,1′ -cyclopropane], spiro[7α-hydroxycholesta-5,24-dien-3-one-4,1′-cyclopropane], spiro[11β-hydroxycholesta-5,24-diene-3- Keto-4,1′-cyclopropane], spiro[11α-hydroxycholesta-5,24-dien-3-one-4,1′-cyclopropane], spiro[12β-hydroxycholesta-5,24 -dien-3-one-4,1′-cyclopropane], spiro[12α-hydroxycholesta-5,24-dien-3-one-4,1′-cyclopropane], spiro[15β-hydroxy Cholesta-5,24-dien-3-one-4,1′-cyclopropane], spiro[15α-hydroxycholesta-5,24-dien-3-one-4,1′-cyclopropane] , spiro[16β-hydroxycholesta-5,24-dien-3-one-4,1′-cyclopropane], spiro[16α-hydroxycholesta-5,24-dien-3-one-4, 1′-cyclopropane], spiro[17β-hydroxycholesta-5,24-dien-3-one-4,1′-cyclopropane], spiro[17α-hydroxycholesta-5,24-diene- 3-keto-4,1′-cyclopropane], spiro[(20R)-hydroxycholesta-5,24-dien-3-one-4,1′-cyclopropane], spiro[(20S)-hydroxy Cholesta-5,24-dien-3-one-4,1′-cyclopropane], spiro[21-hydroxycholesta-5,24-dien-3-one-4,1′-cyclopropane] , spiro[(22R)-hydroxycholest-5,24-dien-3-one-4,1′-cyclopropane], spiro[(22S)-hydroxycholest-5-en-3-one-4 , 1′-cyclopropane], spiro[(23R)-hydroxycholest-5-en-3-one-4,1′-cyclopropane], spiro[(23S)-hydroxycholest-5,24-di en-3-one-4,1'-cyclopropane] and spiro[26-hydroxycholesta-5,24-dien-3-one-4,1'-cyclopropane].

pharmaceutical composition

The pharmaceutical composition comprising the compound of claim 1 or its ester may also contain carriers, diluents, absorption enhancers, preservatives, buffers, agents for adjusting osmotic pressure, tablet disintegrating agents and other commonly used compounds in the art. components. Examples of solid carriers are magnesium carbonate, magnesium stearate, dextrin, lactose, sugar, talc, gelatin, pectin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax and cocoa butter.

Liquid compositions include sterile solutions, suspensions and emulsions. This liquid composition is suitable for injection or use in connection with in vitro and in vitro fertilization. Liquid compositions may contain other ingredients commonly used in the art, some of which have been mentioned above.

Additionally, compounds of the present invention for subcutaneous administration may be provided in the form of tablets, and compositions for nasal administration may be provided as liquid or powder nasal sprays.

The amount of a compound of the invention to be used will be at the discretion of the physician and will depend particularly on the particular compound employed, on the mode of administration and the purpose of use.

The compound of claim 1 and its esters can be synthesized by known methods.

The present invention can be further illustrated by the following examples, but the examples should not be construed as limiting the scope of protection. The features disclosed in the preceding description and the following examples can be combined in any way to form materials for carrying out the invention in various ways.

Example

Example 1

In the oocyte test, cholest-5-ene-3β,4β-diol was tested as a meiosis activating substance.

animal

Oocytes were obtained from immature female mice (C57BI/6J×DBA/2J F1-hybrid, Bomholtgaard, Denmark) weighing 13-16 g and reared under controlled light and temperature. Gonadotropin (Gonal-F.Serono, Solna, Sweden, containing 20 IU FSH, in addition, Puregon, Organon, Swords, Ireland, containing 20 IU FSH) was injected intraperitoneally to the mouse in 0.2 ml, after 48 hours, by decapitation kill animals.

Oocyte collection and culture

Ovaries were dissected and oocytes were isolated by manual puncturing of follicles with a pair of 27 gauge needles under a stereomicroscope in Hx-medium (see below). The spherical oocytes with complete blastocysts were divided into cumulus-enclosed oocytes (CEO) and naked oocytes (NO) and placed in 3mM hypoxanthine (Sigma Cat.No.H-9377), 8mg/ml human serum albumin (HSA, StateSerum Institute, Denmark), 0.23mM pyruvate (Sigma Cat.No.S-8636), 2mM glutamine (Fow Cat.No.16-801), 100IU/ml penicillin and 100 μg/ml streptomycin (FowCat.No.16-700) in α-minimal essential medium (α-MEM without ribonucleotides, GibcoBRL, Cat.No.22561), this medium is called Hx-medium .

The oocytes were washed 3 times in Hx-medium, and the oocytes with uniform size were divided into CEO and NO groups. CEO and NO were cultured in 4-well multiwell plates (Nunclon, Denmark) containing 0.4 ml of Hx-medium and 35-45 oocytes per well. Usually at the same time as the test culture tests are carried out, a set of control (ie 35-45 oocytes cultured in Hx-medium without the addition of the test compound) tests are carried out. Test cultures were formulated with various concentrations of test compounds as indicated in the table below.

Cultivate at 37° C. and 100% humidity and air containing 5% CO ₂ for 22-24 hours.

check oocytes

At the end of the culture, count the number of oocytes containing blastocysts (GV) or blastocyst bursts (GVB) and oocytes containing polar bodies (PB) using a stereomicroscope or an inverted microscope with differential interference contrast equipment Number of. The percentage of oocytes containing GVB in the total oocytes and the percentage of oocytes containing PB in the total oocytes in the test culture were calculated and compared with the control culture.

Activation of meiosis in oocytes with cholest-5-ene-3β,4β-diol: compound source: Steraloids Inc., Wilton, NH, USA, catalog number: C6410, lot number: L1066. The results are shown in the table below:

NO: %GVB %PB Test concentration μM 18.6 1.7 control 50.2 17.2 7.0

CEO: %GVB %PB Test concentration μM 27.0 10.8 control 44.4 25.9 7.0

As shown in the table above, cholest-5-ene-3β,4β-diol induced meiosis in both naked oocytes and cumulus-encased oocytes cultured in vitro.

Example 2

In the oocyte assay, compounds are tested for inhibition of meiosis.

Blastocyst (GV) oocytes were obtained from immature FSH-treated female mice following the same method as described in Example 1 (supra). Oocytes were washed three times in Hx-medium, and oocytes of uniform size were divided into CEO and NO groups. 4,4-Dimethylcholesta-8,14,24-trien-3β-ol (FF-MAS) has previously been shown to induce meiosis of CEO and NO in test tubes (Byskov, A.G. et al., Nature 374 (1995) 559-562). In 4-well multiwell plates (Nunclon, Denmark), CEO and NO were co-incubated with different concentrations of test compounds in Hx-medium supplemented with 0.7-7.0 μM FF-MAS, wherein each well contained 0.4 ml of Hx-medium and 35-45 oocytes. Usually at the same time as experiments with test cultures supplemented with different concentrations of test compounds, experiments with a set of controls (i.e. 35-45 oocytes cultured in Hx-medium containing FF-MAS without the addition of test compounds) were performed . Test cultures were formulated with various concentrations of test compounds as indicated in the table below.

The test results of inhibiting oocyte meiosis with cholest-5-ene-3β, (22R)-diol (hereinafter referred to as "22R") are shown in the table below:

NO: %GVB %PB FF-MAS concentration μM 22R concentration μM Concentration ratio FF-MAS: 22R 19.5 9.5 1.2 - control 4.6 0 1.2 25 1:20 33.0 7.8 0.7 - control 16.9 0 0.7 13 1:19 2.9 0 0.7 25 1:36

CEO: %GVB %PB FF-MAS concentration μM 22R concentration μM Concentration ratio FF-MAS: 22R 21.7 10.8 0.7 - control 6.9 3.4 0.7 25 1:36 39.0 18.9 7 - control twenty one 3.5 7 12.5 1:2

As can be seen from the table, 22R antagonized FF-MAS-induced meiosis in a dose-related manner.

The present invention can be carried out in other forms or manners without departing from the essence or essential characteristics of the present invention, so the description of the present invention should be considered in all respects as illustrative and not as restrictive of the appended claims of the present invention. Any changes within the equivalent meaning and range of the specified protection scope are included in the present invention.

Example 3

4,4-Dimethylcholesta-5,8-dien-3-one

The D-8 double bond was introduced according to the method described in the literature [J. Lip. Res. 37, 1529, (1996)]. According to the method in the literature, cholesta-5,8-dien-3β-alcohol is prepared according to the 3-step method, and the alcohol is oxidized with the classic Oppenauer oxidation [Hev. Sta-4,8-dien-3-one, which was used as a starting material for some of the compounds listed below.

Potassium tert-butyrate (550mg) was dissolved in 13ml of tert-butanol at 45°C, and a solution of cholesta-4,8-dien-3-one (470mg) dissolved in 1.5ml of tetrahydrofuran was added dropwise. After 10 minutes, iodomethane (0.63ml) was added and the reaction mixture was stirred for 1 hour. After treatment with water and purification by column chromatography, 4,4-dimethyl-cholesta-5,8-dien-3-one (310 mg) was isolated.

¹ H-NMR (CDCl ₃ ): δ=0.64ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 1.04(s, 3H, H-19); 1.24(s, 3H, 4-CH ₃ ); 1.29(s, 3H, 4-CH ₃ ); 2.63(m, 2H, H- 7); 5.69 (t, J=3Hz, 1H, H-6). C ₂₉ H ₄₆ = MW (molecular weight): 410.684.

Example 4

4,4-Dimethylcholesta-5,8-dien-3β-ol

4,4-Dimethyl-cholesta-5,8-dien-3-one (100 mg) was reduced with lithium aluminum hydride (5 mg) in 2 ml tetrahydrofuran at room temperature. The solution was stirred for 1 hour, treated with water and purified by column chromatography to isolate 4,4-dimethyl-cholesta-5,8-dien-3β-one (60 mg).

¹ H-NMR (CDCl ₃ ): δ=0.63ppm(s, 3H, H-18); 0.86(s×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 1.12(s, 3H, H-19); 1.15(s, 3H, 4-CH ₃ ) 1.21(s, 3H, 4-CH ₃ ); 2.56(m, 2H, H-7 ); 3.82(dd, J=10Hz, J=5Hz, 1H H-3); 5.75(t, J=3Hz, 1H, H-6).C ₂₉ H ₄₈ O, MW: 412.700.

Example 5

Cholesta-5,8-dien-3β-yl acetate

¹ H-NMR (CDCl ₃ ): δ=0.64ppm(s, 3H, H-18); 0.87(2×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 1.20(s, 3H, H-19); 2.03(s, 3H, 3-Oac) 2.28(m, 2H, H-4); 2.53(m, 2H, H-7); 4.61(m, 1H, H-3); 5.45(m, 1H, H-6). C ₂₉ H ₄₆ O ₂ , MW: 426.683. J. Lipid Res. 37, 1529, (1996).

Example 6

5β-cholest-8-ene-3β,5β-diol

Epoxidation of cholesta-5,8-dien-3-one was carried out in a similar manner to the literature method [J.Med.Chem.39, 5092 (1996)] to give 4α,5-epoxy-5α-cholesterol Ste-8-en-3-one, the compound is reduced as follows:

4α, 5-epoxy-5α-cholest-8-en-3-one (75mg) was dissolved in 3ml of tetrahydrofuran, lithium aluminum hydride (30mg) was added at room temperature, the reaction mixture was stirred for 15 minutes, treated with water, column After chromatographic purification, 5[beta]-cholest-8-ene-3[beta],5[beta]-diol (19 mg) and 5[beta]-cholest-8-ene-3[alpha],5[beta]-diol (24 mg) were isolated.

¹ H-NMR (CDCl ₃ ): δ=0.63ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 1.06(s, 3H, H-19); 2.53(broad, 1H, OH) 4.09(m, 1H, H-3).C ₂₇ H ₄₆ O ₂ , MW: 402.661.

Example 7

5β-cholest-8-ene-3α, 5β-diol

¹ H-NMR (CDCl ₃ ): δ=0.63ppm(s, 3H, H-18); 0.87(2×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 0.99(s, 3H, H-19); 3.97(m, 1H, H-3).C ₂₇ H ₄₆ O ₂ , MW: 402.661.

Example 8

4,4-Dimethylcholesta-5,7,14-trien-3-one

¹ H-NMR (CDCl ₃ ): δ-0.87(2×d, J=7Hz, 6H, H-26/27); 0.94(s, H3); 0.95(d, J=7Hz, 3H, H-21 ); 1.09(s, 3H); 1.17(s, 3H, 4-CH ₃ ); 1.36(s, 3H, 4-CH ₃ ); 5.69(s, 1H, H-14); 6.05(d, J= 10Hz, 1H, H-7); 6.57 (d, J=10Hz, 1H, H-6); C ₂₉ H ₄₄ O, MW: 408.668.J.Chem.Soc.PT1, 812, (1977).

Example 9

3β-(Acetoxy)-5α-cholest-8-en-6α-ol

Cholesta-5,8-dien-3β-yl acetate (1.0g) was dissolved in 250ml of ether, the reaction mixture was cooled to 0°C, and 2.35ml of borane-dimethylsulfide complex ( 2M solution in tetrahydrofuran), the reaction mixture was warmed to room temperature within 2 hours, then 26 ml of water, 26 ml of sodium hydroxide solution (10% aqueous solution) and 3.65 ml of hydrogen peroxide were added at 0°C. After treatment with water and purification by column chromatography, 3β-(acetoxy)-5α-cholest-8-en-6α-ol (140 mg) was isolated.

¹ H-NMR (CDCl ₃ ): δ=0.59ppm(s, 3H, H-18); 0.87(2×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 0.99(s, H3, H-19); 2.03(s, 3H, 3-Oac); 2.26(m, 1H); 2.48(m, 1H); -6); 4.69 (m, 1H, H-3); C ₂₉ H ₄₈ O ₃ , MW: 444.698.

Example 10

5α-cholest-7-ene-3β,5α,6β-triol

¹ H-NMR (CDCl ₃ ): δ=0.59ppm(s, 3H, H-18); 0.87(2×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 1.08(s, H3, H-19); 3.63(m, 1H, H-6); 4.08(m, 1H, H-3); 5.35(m, 1H, H-7) .C ₂₇ H ₄₆ O ₃ , MW: 418.660. J.Org.Chem.50, 1835, (1985).

Example 11

Cholesta-5,8,14-trien-3β-ol

Cholesta-5,8-diene-3β-ol (1.54g) was dissolved in 50ml of dichloromethane, and a solution of chloroperoxybenzoic acid (1.04g) dissolved in 50ml of dichloromethane was added at room temperature, stirred The reaction mixture was treated with water for 5 hours and 8α,9α-epoxycholest-5-en-3β-ol (740 mg) was isolated after column chromatography.

Dissolve 8α, 9α-epoxycholest-5-en-3β-ol (200mg) in dichloromethane, cool the solution to 0°C, and add 1.5ml of diethylaluminum cyanide (1M solution in toluene) dropwise solution, and the reaction mixture was allowed to warm to room temperature and stirred for an additional 18 hours. After treatment with base and purification by column chromatography, cholesta-5,8,14-trien-3β-ol (51 mg) was isolated.

¹ H-NMR (CDCl ₃ ): δ=0.84ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 1.22(s, H3, H-19); 2.59(m, 1H, H-7); 2.88(m, 1H, H-7); 3.57(m, 1H, H-3) ;5.38(m, 1H, H-15); 5.52(m, 1H, H-6).C ₂₇ H ₄₂ O, MW: 382.630.

Example 12

1α-Hydroxy-5β-cholestan-3-one

¹ H-NMR (CDCl ₃ ): δ=0.68ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.90(d, J=7Hz, 3H, H-21); 1.21 (s, H3, H-19); 3.62 (m, 1H, H-1).C ₂₇ H ₄₆ O ₂ , MW: 402.661.J.Chem.Soc.PT1, 2488, (1977).

Example 13

Cholesta-5-ene-3β,9α-diol

8α,9α-epoxycholest-5-en-3β-ol (200 mg) was dissolved in 13 ml of diethylamine at -20°C, lithium (100 mg) was added in small portions, and the reaction mixture was stirred for 3 hours. After treatment with water, the crude product (207 mg) was isolated and recrystallized from diisopropyl ether to give cholest-5-ene-3[beta],9[alpha]-diol (62 mg).

¹ H-NMR (CDCl ₃ ): δ=0.68ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.93(d, J=7Hz, 3H, H-21); 1.15(s, H3, H-19) _; 2.37(m, 1H); 3.52(m, 1H, H-3); ₄₆ O ₂ , MW: 402.661.

Example 14

5α-cholest-7-ene-3β,5α-diol

¹ H-NMR (CDCl ₃ ): δ=0.56ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.92(s, 3H, H- 19); 0.94(d, J=7Hz, 3H, H-21); 2.24(m, 1H); 4.05(m, 1H, H-3); 5.08(m, 1H, H-7) _{.C27H 46} O ₂ , MW: 402.661.biochem.J.105, 1194, (1967).

Example 15

5β-cholestane-1α,3α-diol

Dissolve 1α-hydroxyl-5β-cholestan-3-one [J.Chem.Soc.Perkin.Trans.1, 1977, 2488] (110mg) in 6ml of ethanol, add sodium borohydride ( 52 mg), the reaction mixture was stirred for 4 hours, treated with water and purified by column chromatography to isolate 5β-cholestane-1α,3α-diol (75 mg).

¹ H-NMR (CDCl ₃ ): δ=0.64ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.88(d, J=7Hz, 3H, H-21); 1.12(s, 3H, H-19); 3.29(dd, J=12Hz, J=3Hz, 1H, H-1); 3.77(m, 1H, H-3).C ₂₇ H ₄₈ O ₂ , MW: 404.677.

Example 16

5α-cholestane-3β, 5β-diol

¹ H-NMR (CDCl ₃ ): δ=0.65ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.92(d, J=7Hz, 3H, H-21); 0.95(s, 3H, H-19); 2.01(m, 1H, H-4); 2.20(dd, J=15Hz, J=4Hz, 1H, H-4); 3.00( Broad peak, 1H, OH); 4.13 (m, 1H, H-3). C ₂₇ H ₄₈ O ₂ , MW: 404.677. J.Org.Chem.27, 1433, (1962).

Example 17

5β-cholestane-3α, 5β-diol

¹ H-NMR (CDCl ₃ ): δ=0.64ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.89(s, 3H, H- 19); 0.91 (d, J=7Hz, 3H, H-21); 4.02 (m, 1H, H-3). C ₂₇ H ₄₈ O ₂ , MW: 404.677.J.Org.Chem.27, 1433, (1962).

Example 18

5α-cholestane-3α, 5α-diol

¹ H-NMR (CDCl ₃ ): δ=0.65ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 6H, H-26/27); 0.92(d, J=7Hz, 3H, H-21); 0.95(s, 3H, H-19); 3.25(b, 1H, OH); 4.10(m, 1H, H-3). C ₂₇ H ₄₈ O ₂ , MW; 404.677.J .Chem.Soc., 4482, (1961).

Example 19

3β-(benzoyloxy)-22-hydroxy-4,4-dimethyl-5α-cholesta-8(14)-ene-15,24-dione

¹ H-NMR (CDCl ₃ ): δ=0.85ppm (s, 3H, H-18); 0.96-1-16 (m, 18H, H-19, H-21, 2x4-CH3, H-26/27 ); 2.6(m, 1H, H-25); 3.3(d, J=2Hz, 1H, 22-OH); 4.06(m, 1H, H-22); 4.22(m, 1H, H-7); 4.8 (dd, J=11Hz, J=5Hz, 1H, H-3). C ₃₆ H ₅₀ O ₅ , MW: 562.790. J.Am.Chem.Soc.11(1989), 278.

Example 20

3β-(benzoyloxy)-4,4-dimethyl-5α-cholesta-8(14)-ene-15,24-dione

¹ H-NMR (CDCL ₃ ): δ=0.85ppm(s, 3H, H-18); 0.97-1-14(m, 18H, 2x4-CH3, H-19, H-21, H-26/27 ); 2.6(m, 1H, H-25); 4.21(m, 1H, H-7); 4.8(dd, J=11Hz, J=5Hz, 1H, H-3). C ₃₆ H ₅₀ O ₄ , MW: 546.791.J.Am.Chem.Soc.11(1989), 278.

Example 21

3β-(benzoyloxy)-24-hydroxy-4,4-dimethyl-5α-cholest-8(14)-en-15-one

¹ H-NMR (CDCl ₃ ): δ=0.85ppm (s, 3H, H-18); 0.88-1-04 (m, 18H, H-19, H-21, 2x4-CH3, H-26/27 ); 2.38(m, 1H, H-16); 3.31(m, 1H, H-24); 4.21(m, 1H, H-7); 4.8(dd, J=11Hz, J=5Hz, 1H, H -3). C ₃₆ H ₅₂ O ₄ , MW: 548.807. J.Am.Chem.Soc.11(1989), 278.

Example 22

5β-cholest-7-ene-3β,5β-diol

Dissolve 5,6β-epoxy-5β-cholest-7-en-3β-ol [J.Org.Chem.50 (1985), 1835] (150mg) in 2.5ml of potassium hydroxide solution (5% methanol solution), the reaction mixture was refluxed for 1 hour. Treatment with water, extraction with ethyl acetate and purification by column chromatography gave 5β-cholest-7-ene-3β,5β-diol (54 mg).

¹ H-NMR (CDCl ₃ ): δ=0.55ppm(s, 3H, H-18); 0.86(2×d, J=7Hz, 9H, H-26/27); 0.92(s, 3H, H- 19); 0.94(d, J=7Hz, 3H, H-21); 4.16(m, 1H, H-3); 5.05(m, 1H, H-7). C ₂₇ H ₄₆ O ₂ , MW: 402.661 .

Example 23

5β-cholest-6-ene-3β, 5β, 8β-triol

¹ H-NMR (CDCl ₃ ): δ=0.66ppm(s, 3H, H-18); 0.87(3×d, J=7Hz, 9H, H-21/26/27); 1.28(s, 3H, H-19); 2.24(m, 1H); 2.77(m, 1H); 3.48(m, 1H, H-3); 5.64(d, J=11Hz, 1H); 5.88(d, J=11Hz, 1H ).C ₂₇ H ₄₆ O ₃ , MW: 418.660. J.Org.Chem.50(1961), 1835.

Example 24

5α-cholest-8-ene-3β,6α-diol

¹ H-NMR (CDCl ₃ ): δ=0.60ppm(s, 3H, H-18); 0.87(2×d, J=7Hz, 6H, H-26/27); 0.94(d, J=7Hz, 3H, H-21); 0.98(s, 3H, H-19); 2.48(m, 1H); 3.62(m, 1H, H-3); 3.75(m, 1H, H-6) _{. 46} O ₂ , MW: 402.661. Proc. Chem. Soc. London, 450, (1961).

Example 25

5β-cholest-8-ene-3β,6β-diol

Dissolve 3β-(acetoxy)-5α-cholest-8-en-6α-ol (124mg) in 20ml of ethanol, add solid potassium hydroxide (710mg), stir the reaction mixture for 2 hours, treat with water, separate 5β-cholest-8-ene-3β,6β-diol (96 mg).

¹ H-NMR (CDCl ₃ ): δ=0.65ppm(s, 3H, H-18); 0.87(2×d, J=7Hz, 6H, H-26/27); 0.93(d, J=7Hz, 3H, H-21); 1.14(s, 3H, H-19); 2.33(m, 2H); 3.83(m, 2H, H-3/6). C ₂₇ H ₄₆ O ₂ , MW: 402.661.

Example 26

(24R,S)-4,4-Dimethyl-5α-cholesta-8,14-diene-3β,24-diol

¹ H-NMR (CDCl ₃ ): 5.36ppm (s, 1H); 3.33 (m, 1H); 3.23 (dd, 1H); 1.05 (s, 3H); 1.02 (s, 3H); ); 0.84(s, 3H); 0.81(s, 3H).

The compound was separated into (24R) and (24S) isomers.

Claims (9)

1. Compounds of general formula Ia:

wherein ^R1 and ^R2 are different or the same, with the proviso that they are not both hydroxy, selected from the group consisting of hydrogen, halogen, hydroxy and branched or unbranched _C1 -C which may be substituted by halogen, hydroxy or cyano ₆ alkyl, or wherein R ¹ and R ² together represent a methylene group or oxygen, or form a cyclopropane ring, a cyclopentane ring or a cyclohexane ring together with the carbon atoms connected to them; R ³ is selected from hydrogen, Methylene, hydroxy, methoxy, acetoxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (attached to the same carbon atom of the cholesteric backbone) and =NOR ²⁶ , where R ²⁶ is hydrogen or C ₁ -C ₃ alkyl, or R ³ and R ⁹ or R ¹⁴ together represent another bond between R ³ and the carbon atom at R ⁹ or R ¹⁴ ; R ⁴ is selected from hydrogen, methylene, hydroxyl, methyl Oxygen, acetoxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (attached to the same carbon atom of the cholesteric skeleton) and =NOR ²⁷ , wherein R ²⁷ is hydrogen or C ₁ -C ₃ alkyl, Or R ⁴ and R ¹³ or R ¹⁵ together represent another bond between R ⁴ and the carbon atom at R ¹³ or R ¹⁵ ; R ⁵ is selected from hydrogen, halogen, C ₁ -C ₄ alkyl, methylene, Hydroxy, methoxy, oxygen and =NOR ²² , wherein R ²² is hydrogen or C ₁ -C ₃ alkyl, or R ⁵ and R ⁶ together represent another bond between the carbon atoms at R ⁵ and R ⁶ ; ^R6 is selected from hydrogen or hydroxyl, or ^R6 and ^R5 together represent another bond between ^R5 and the carbon atom at ^R6 ; ^R9 is hydrogen, hydroxyl, halogen or oxygen, or ^R9 and ^R3 or R ¹⁰ together represents another bond between R ⁹ and R ³ or the carbon atom at R ¹⁰ ; R ¹⁰ is hydrogen halogen or hydroxyl, or R ¹⁰ and R ⁹ together represent between R ¹⁰ and the carbon atom at R ⁹ Another bond; R ¹¹ is selected from hydroxyl, optionally substituted alkoxy, acyloxy, sulfonyloxy, phosphoryloxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (with bile the same carbon atom of the sterol skeleton) and =NOR ²⁸ , wherein R ²⁸ is hydrogen or C ₁ -C ₃ alkyl, or R ¹¹ and R ¹² together represent another path between the carbon atoms at R ¹¹ and R ¹² bond; R ¹² is selected from hydrogen, hydroxyl, C ₁ -C ₃ alkyl, vinyl, C ₁ -C ₃ alkoxy and halogen, or R ¹² and R ¹¹ together represent one of the carbon atoms at R ¹¹ and R ^{12 R13} is hydrogen, hydroxyl or halogen, or ^R13 and ^R4 or ^R14 together represent another bond between ^R13 and the carbon atom at ^R4 or ^R14 ; ^R14 is hydrogen, Hydroxy or halogen, or R ¹⁴ and R ³ or R ⁶ or R ¹³ together represent another bond between R ¹⁴ and R ³ or R ⁶ or the carbon atom at R ¹⁴ ; R ¹⁵ is selected from hydrogen, halogen, C ₁ -C ₄ alkyl, methylene, hydroxyl, methoxy, acetoxy, oxygen and =NOR ²³ , wherein R ²³ is hydrogen or C ₁ -C ₃ alkyl, or R ¹⁵ and R ⁴ together represent R ¹⁵ and another bond between the carbon atom at ^R4 ; ^R16 is selected from the group consisting of hydrogen, halogen, _C1 - _C3 alkyl, methylene, hydroxyl, methoxyl, oxygen and = ^NOR24 , wherein ^R24 is hydrogen or C ₁ -C ₃ alkyl, or R ¹⁶ and R ¹⁷ together represent another bond between R ¹⁷ and the carbon atom at R ¹⁶ ; R ¹⁷ is hydrogen or hydroxyl, or R ¹⁷ and R ¹⁶ together represent R An additional bond between ¹⁷ and the carbon atom at ^R16 ; both ^R18 and ^R19 are hydrogen, or one of ^R18 and ^R19 is hydrogen and the other is halogen, hydroxy, or methoxy, or R ¹⁸ and R ¹⁹ together represent oxygen; R ²⁵ is selected from C ₁ -C ₄ alkyl and hydroxymethyl, or R ²⁵ and R ³¹ together represent methylene or oxygen; R ²⁹ is hydrogen, halogen, methyl, hydroxyl or Oxygen; R ³⁰ is hydrogen, halogen, methyl or hydroxyl; R ³¹ is hydrogen, halogen, methyl, hydroxyl, or R ³¹ and R ²⁵ together represent methylene or oxygen; and A is a carbon atom or a nitrogen atom; and When A is a carbon atom, ^R7 is selected from hydrogen, hydroxy and halogen; and ^R8 is selected from hydrogen, halogen, hydroxy, _C1 - _C4 alkyl, methylene and oxygen, or ^R7 and ^R8 together represent Another bond between the carbon atoms at ^R7 and ^R8 ; ^R20 is selected from _C1 - _C4 alkyl, trifluoromethyl and _C3 - _C6 cycloalkyl; ^R21 is selected from _C1 -C ₄ alkyl, C ₁ -C ₄ hydroxyalkyl, C ₁ -C ₄ haloalkyl containing up to three halogen atoms, methoxymethyl, acetoxymethyl and C ₃ -C ₆ cycloalkyl, or R ²⁰ and R ²¹ form a C ₃ -C ₆ cycloalkyl ring together with their carbon atoms; when A is a nitrogen atom, R ⁷ represents a pair of lone electrons; and R ⁸ is selected from hydrogen, hydroxyl , C ₁ -C ₄ alkyl, cyano and oxygen; while R ²⁰ and R ²¹ are independently C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl; the general conditions are: R ¹ , R ² , At least one of R ⁶ , R ^{8 ,} R ⁹ , R ¹⁰ , R ¹² , R ¹³ , R ¹⁴ , R 18 , R ¹⁹ , R ²⁹ , R ³⁰ and R ³¹ is hydroxyl, or R ²⁵ is hydroxymethyl, A further general condition is that: R ⁹ , R ¹⁰ and R ¹¹ are not all hydroxyl groups, and a further general condition is that it is not 5α-bromocholestane-3β, 6β-diol, 7α-bromocholestane- 3β, 6α-diol, 7α-bromocholestane-3β, 6β-diol, 7α-bromocholestane-3β, 5α-diol-6-one, 7β-bromocholestane-3β , 5α-diol-6-one, 3β-bromocholestan-2α-ol, 5α-chlorocholestane-3β, 6α-diol, 5α-chlorocholestane-3β, 6β-diol alcohol, 6β-chlorocholestane-3β,5α-diol, ^Δ7,9(11) -cholestadiene-3β,6α-diol, ^Δ7,9(11) -cholestadiene- 3β, 6β-diol, cholestane-2α, 3α-diol, cholestane-2α, 3β-diol, cholestane-2β, 3α-diol, cholestane-2β, 3β-diol , cholestane-3α, 4α-diol, cholestane-3α, 4β-diol, cholestane-3β, 4β-diol, cholestane-3α, 5α-diol, cholestane-3β , 5α-diol, cholestane-3β, 6α-diol, cholestane-3β, 6β-diol, cholestane-3β, 22α-diol, cholestane-3β, 22β-diol, Cholesterane-3β,7α,8α-triol, Δ5-cholestene-3β,4α-diol, ^Δ5 -cholestene-3β,4β-diol, ^{Δ5 -} cholestene-3β, 20α-diol, Δ ⁵ -cholestene-3β, 22α-diol, Δ ⁵ -cholestene-3β, 22β-diol, Δ ⁵ -cholestene-3β, 24α-diol, Δ ⁵ - Cholesterene-3β, 24β-diol, Δ ⁶ -cholestene-3β, 5α-diol, Δ ⁸⁽¹⁴⁾ -cholestene-3β, 9α-diol, Δ ¹¹ -cholestene-3α , 24-diol, Δ ⁵ -cholestene-3β, 6-diol-7-one, Δ ⁵ -cholestene-4α-ol-3-one, Δ ⁵ -cholestene-3β, 4β, 7α-triol, Coprostan-3α, 5β-diol, Coprostan-3β, 5β-diol, Coprostan-3β, 6β-diol, Coprostan-4β, 5β-diol-3 -ketone, 20β-hydroxy-20-isocholesterol, 4α-hydroxy-5α-cholestan-3-one, cholestan-3β, 5α, 6β-triol-3β-hemisuccinate, cholesteryl- 3β, 5α, 6β-triol-3β-hemisuccinate-6β-acetate, cholesteryl-3β, 5α, 6β-triol-3β-hemisuccinate-6β-formate, bile Steranes-3β, 5α, 6β-triol-3β-sulfate, Cholesta-3β, 5α, 6β-triol-3β-phosphate, 2β, 3β, 14α, 22(R), 25-pentahydroxycholesterol Ste-7-en-6-one, cholest-7-en-2β, 3β, 5β, 11α, 14α, 20(R), 22(R)-heptahydroxy-6-one, 5,24-cholesteryl Dien-3β-ol, 5-cholestene-3β,24,25-triol-3β-acetate, 5-cholestene-3β,24,25-triol-3β,24-diacetate Esters, 5,25-cholestadien-3β-ol acetate, 5-cholestene-3β,25,26-triol-3β-acetate, 5-cholestene-3β,25,26 -triol, 24,25(or 25,26)-dihydroxycholecalciferol, cholestan-5α-alkane-3β,6α-diol, cholestan-5β-alkane-3β,6β-diol, cholesterol -5α-alkane-3,6-dione, cholestan-5α-alkane-6β-ol-3-one, cholestan-5α-alkane-2α-bromo-6β-ol-3-one, cholestane- 3β,25-diol-3β-acetate, cholestane-3β,5α,25-triol-3β-acetate, cholestane-3β,5α,25-triol, cholestane-5α , 25-diol-3-one, cholest-4-en-25-ol-3-one, cholesta-4,6-dien-25-ol-3-one, 1α, 3β-dihydroxycholesterol Ste-5-ene, 1α,3β-dihydroxycholest-6-ene, 3α,6α-dihydroxy-5β-cholestan-24-one, 3α,6α,24-trihydroxy-5β-cholestan alkanes, 3-chlorocholest-5,24-diene, 3β-hydroxycholest-5-en-24-one acetate, 3-chlorocholest-5-en-24-one, cholesterol alkane-25-fluoro-3β,22(S)-diol, cholestane-25-chloro-3β,22(S)-diol, cholestane-25-methyl-3β,22-diol, Cholesterane-25-methyl-3β, 22-diol-3-hydrosuccinate, cholestane-25-methyl-3β, 22-diol-bis-hydrosuccinate, 1α, 52-Dihydroxy-26, 26, 26, 27, 27, 27-hexafluorocholest-5-ene, 2β, 3β, 14α, 22, 25-pentahydroxy-Δ ⁷ -5β-cholestene-6- Ketone, 25-hydroxy-3β-[(tetrahydro-2H-pyran-2-yl)oxy]cholest-5-en-24-one, 3β-[(tetrahydro-2H-pyran-2- Base) oxy]cholest-5-en-24-one, 25-hydroxy-24-oxocholesterol-3β-acetate, 24-oxocholesterol-3β-acetate, 25-hydroxy- 24-oxocholesterol, 24,25-dihydroxycholesterol, 3α,6α,25-trihydroxy-24-oxo-5β-cholestane, 1α,25-dihydroxy-24-oxocholesterol, 1α,24,25-trihydroxycholesterol, 3β-hydroxy-24-oxocholesta-5,7-diene, 3β,25-dihydroxy-24-oxocholesta-5,7-diene, 3β-hydroxy-24-oxocholesta-5,7-diene, 1α,3β-dihydroxy-24-oxocholesta-5,7-diene, 1α,3β,25-trihydroxy-24- Oxycholesta-5,7-diene, 24(R)-3β,24,25-trihydroxycholest-5-ene, (24RS)-3β,24,25-trihydroxycholest-5-ene , (24R)-1β,3β,24,25-tetrahydroxycholest-5-ene, 4,4-dimethyl-24methylene-3β-sulfonyloxy-12α-acetoxycholest- 8,14-Diene-2α,11β-diol, 4,4-Dimethyl-24-methylene-3β-sulfonyloxy-12α-acetoxycholest-8-ene-2α,11β- Diol, 4,4-dimethyl-24methylene-12α-acetoxycholesta-8,14-diene-2α,3β,11β-triol, 4,4-dimethyl-24methylene Methyl-12α-acetoxycholest-8,14-diene-3β,11β-diol, 4,4-dimethyl-24methylene-12α-acetoxycholest-8-ene- 2α, 3β, 11β-triol, 4,4-dimethyl-24 methylene-12α-acetoxycholest-8-ene-3β, 11β-diol, 4,4-dimethyl-24 Methylenecholest-8-ene-2,3β,11β,12α-tetraol, 4,4-dimethyl-24methylene-3β-sulfonyloxycholesta-8,14-diene- 2α, 11β, 12α-triol, 4,4-dimethyl-24methylene-8,14-diene-2α, 3β, 11β, 12α-tetrol, 4,4-dimethyl-24methylene Methyl-3β-sulfonyloxy-12α-acetoxycholest-8-en-2-ol-11-one, mono(4,4-dimethyl-24methylene-12α-acetoxy Cholesta-8,14-diene-2α,11β-diol)-3β-succinate, 1α,3β-dihydroxycholest-5-ene, 1α,3β,24-trihydroxycholest-5 -ene, cholesta-5,7-diene-3β,23(R),25-triol, cholesta-5,7-diene-3β,23(S),25-triol, 1α,3β -dihydroxycholest-5-ene, 1α,3β,25-trihydroxycholest-5-ene, Δ ⁷ -cholestene-2β,3β-diol-6-one, 2β,3β,14α,22 (R), 25-pentahydroxy-Δ ⁷ -5β-cholesten-6-one, 2β, 3β, 14α, 22(S), 25-pentahydroxy-Δ ⁷ -5β-cholesten-6-one , Cholesta-5-ene-3β, 22(R, S), 25-triol, Cholesta-5-ene-25-fluoro-3β, 22(R, S)-diol, Cholesta-5- ene-25-fluoro-22(R,S)-alcohol-3β-hemisuccinate, cholest-5-ene-25-chloro-3β,22-diol, cholest-5-ene-25- Chloro-22-ol-3β-hemisuccinate, 3α, 7α, 12α, 24, 25-pentahydroxynaprostanes, 3α, 7α, 12α, 25-tetrahydroxynaprostanes, 3α, 7α, 25- Trihydroxyfungostane, 3α, 7α, 24, 25-tetrahydroxyfungostane, 5β-cholestane-3α, 7α, 12α, 24α, 25-pentol, 5β-cholestane-3α, 7α, 12α , 24β, 25-pentol, 5β-cholestane-3α, 7α, 12α, 25, 26-pentol, 5β-cholestane-3α, 7α, 12α, 25-tetrol, 1α, 2α, 3β- Trihydroxycholesta-5,7-diene, 1α,2α-dihydroxy-3β-acetoxycholest-5-ene, cholest-5-ene-2β-fluoro-1α,3β-diol, 24 -Cyclopropylcholest-5-ene-3β, 22(S)-diol-3-acetate, 24-cyclopropylcholest-5-ene-3β, 22(S)-diol, 24 -Cyclopropylcholest-5-ene-3β, 22(S)-diol-3-hydro-succinate, 24-cyclopropyl-5α-cholestane-3β, 22(S)-di alcohol, cholest-1,4,6-trien-3-one, 1α,3β-dihydroxycholest-5-ene, 1α,3β-dihydroxy-5α-cholestane, 1α,3β-dihydroxy Cholesta-5,7-diene, 1α,3β,25-trihydroxycholest-5-ene, 1α,25-dihydroxycholesterol, 1α,25-dihydroxycholesterol-3-benzoate, Cholesta-5-ene-3β, 20(S)-diol, 2β, 3β, 14α, 22(R), 25-pentahydroxycholest-7-en-6-one and cholest-5-ene- 3β, 22(S)-diol, cholest-5-ene-3β, 20(S)-diol, cholest-5-ene-3β, 22(S)-diol, cholest-5-ene -3β,4β-diol, cholest-5-ene-3β,22(R)-diol and 2β,3β,14α,22(R),25-pentahydroxycholest-7-en-6-one. 2. the compound of general formula Ib is as the purposes of medicine:

wherein ^R1 and ^R2 are different or the same, provided that they are not all hydroxy, selected from hydrogen, halogen, hydroxy and branched or unbranched _C1 - _C6 which may be substituted by halogen, hydroxy or cyano Alkyl, or wherein R ¹ and R ² together represent a methylene group or oxygen, or form a cyclopropane ring, a cyclopentane ring or a cyclohexane ring together with the carbon atoms connected to them; R ³ is selected from hydrogen, ethylene Methyl, hydroxy, methoxy, acetoxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (attached to the same carbon atom of the cholesteric skeleton) and =NOR ²⁶ , where R ²⁶ is hydrogen or C ₁ -C ₃ alkyl, or R ³ and R ⁹ or R ¹⁴ together represent another bond between R ³ and the carbon atom at R ⁹ or R ¹⁴ ; R ⁴ is selected from hydrogen, methylene, hydroxyl, methoxy radical, acetoxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (attached to the same carbon atom of the cholesteric backbone) and =NOR ²⁷ , wherein R ²⁷ is hydrogen or C ₁ -C ₃ alkyl, or R ⁴ and R ¹³ or R ¹⁵ together represent another bond between R ⁴ and the carbon atom at R ¹³ or R ¹⁵ ; R ⁵ is selected from hydrogen, halogen, C ₁ -C ₄ alkyl, methylene, hydroxyl , methoxy, oxygen and =NOR ²² , wherein R ²² is hydrogen or C ₁ -C ₃ alkyl, or R ⁵ and R ⁶ together represent another bond between the carbon atoms at R ⁵ and R ⁶ ; R ⁶ is selected from hydrogen or hydroxyl, or ^R6 and ^R5 together represent another bond between ^R5 and the carbon atom at ^R6 ; ^R9 is hydrogen, hydroxyl, halogen or oxygen, or ^R9 and ^R3 or R ¹⁰ together represents another bond between ^R9 and ^R3 or the carbon atom at ^R10 ; ^R10 is hydrogen halogen or hydroxyl, or ^R10 and ^R9 together represent the bond between ^R10 and the carbon atom at ^R9 Another bond; R ¹¹ is selected from hydroxyl, optionally substituted alkoxy, acyloxy, sulfonyloxy, phosphoryloxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (with cholesterol the same carbon atom of the backbone) and =NOR ²⁸ , where R ²⁸ is hydrogen or C ₁ -C ₃ alkyl, or R ¹¹ and R ¹² together represent another bond between the carbon atoms at R ¹¹ and R ¹² ; R ¹² is selected from hydrogen, hydroxyl, C ₁ -C ₃ alkyl, vinyl, C ₁ -C ₃ alkoxy and halogen, or R ¹² and R ¹¹ together represent between R ¹¹ and carbon atoms at R ^{12 R13} is hydrogen, hydroxyl or halogen, or ^R13 and ^R4 or ^R14 together represent another bond between ^R13 and the carbon atom at ^R4 or ^R14 ; ^R14 is hydrogen, hydroxyl or halogen, or R ¹⁴ and R ³ or R ⁶ or R ¹³ together represent another bond between R ¹⁴ and R ³ or R ⁶ or the carbon atom at R ¹⁴ ; R ¹⁵ is selected from hydrogen, halogen, C ₁ - C ₄ alkyl, methylene, hydroxyl, methoxy, acetoxy, oxygen and =NOR ²³ , wherein R ²³ is hydrogen or C ₁ -C ₃ alkyl, or R ¹⁵ and R ⁴ together represent R ¹⁵ and An additional bond between the carbon atoms at ^R4 ; ^R16 is selected from the group consisting of hydrogen, halogen, _C1 - _C3 alkyl, methylene, hydroxyl, methoxy, oxygen and = ^NOR24 , where ^R24 is hydrogen or C ₁ -C ₃ alkyl, or R ¹⁶ and R ¹⁷ together represent another bond between R ¹⁷ and the carbon atom at R ¹⁶ ; R ¹⁷ is hydrogen or hydroxyl, or R ¹⁷ and R ¹⁶ together represent R ¹⁷ and an additional bond between the carbon atom at ^R16 ; both ^R18 and ^R19 are hydrogen, or one of ^R18 and ^R19 is hydrogen and the other is halogen, hydroxy, or methoxy, or ^R18 and R ¹⁹ together represent oxygen; R ²⁵ is selected from C ₁ -C ₄ alkyl and hydroxymethyl, or R ²⁵ and R ³¹ together represent methylene or oxygen; R ²⁹ is hydrogen, halogen, methyl, hydroxy or oxygen ; R ³⁰ is hydrogen, halogen, methyl or hydroxyl; R ³¹ is hydrogen, halogen, methyl, hydroxyl, or R ³¹ and R ²⁵ together represent methylene or oxygen; and A is a carbon atom or a nitrogen atom; and when When A is a carbon atom, R ⁷ is selected from hydrogen, hydroxy and halogen; and R ⁸ is selected from hydrogen, halogen, hydroxy, C ₁ -C ₄ alkyl, methylene and oxygen, or R ⁷ and R ⁸ together represent R ⁷ and another bond between the carbon atoms at R ⁸ ; R ²⁰ is selected from C ₁ -C ₄ alkyl, trifluoromethyl and C ₃ -C ₆ cycloalkyl; R ²¹ is selected from C ₁ -C ₄ Alkyl, C ₁ -C ₄ hydroxyalkyl, C ₁ -C ₄ haloalkyl containing up to three halogen atoms, methoxymethyl, acetoxymethyl and C ₃ -C ₆ cycloalkyl, or R ²⁰ and R ²¹ form a C ₃ -C ₆ cycloalkyl ring together with their carbon atoms; when A is a nitrogen atom, R ⁷ represents a pair of lone electron pairs; and R ⁸ is selected from hydrogen, hydroxyl, C ₁ -C ₄ alkyl, cyano and oxygen; while R ²⁰ and R ²¹ are independently C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl; the general proviso is: R ¹ , R ² , R ⁶ , at least ^one of R ⁸ , R ⁹ , R ¹⁰ , R ¹² , R ¹³ , R ¹⁴ , R 18 , R ¹⁹ , R ²⁹ , R ³⁰ and R ³¹ is a hydroxyl group, or R ²⁵ is a hydroxymethyl group, further The general condition is: R ⁹ , R ¹⁰ and R ¹¹ are not all hydroxyl groups, and the further general condition is: it is not cholesteryl-3β, 5α, 6β-triol-3β-succinate, cholesteryl-3β , 5α, 6β-triol-3β-hemisuccinate-6β-acetate, cholesteryl-3β, 5α, 6β-triol-3β-hemisuccinate-6β-formate, cholesteryl -3β, 5α, 6β-triol-3β-sulfate, cholestane-3β, 5α, 6β-triol-3β-phosphate, cholestane-3β, 25-diol-3β-acetate, cholesterol Stelane-3β,5α,25-triol-3β-acetate, Cholesterane-3β,5α,25-triol, Cholesterane-5α,25-diol-3-one, Cholesta-4 -en-25-ol-3-one, cholesta-4,6-dien-25-ol-3-one, 1α,3β-dihydroxycholest-5-ene, 1α,3β-dihydroxycholesterol -6-ene, 3α, 6α-dihydroxy-5β-cholestan-24-one, 3α, 6α, 24-trihydroxy-5β-cholestane, 3-chlorocholesta-5,24-di ene, 3β-hydroxycholest-5-en-24-one acetate, 3-chlorocholest-5-en-24-one, cholestane-25-fluoro-3β, 22(S)-di alcohol, cholestane-25-chloro-3β, 22(S)-diol, cholestane-25-methyl-3β, 22-diol, cholestane-25-methyl-3β, 22-diol Alcohol-3-hydrosuccinate, cholestane-25-methyl-3β,22-diol-bis-hydrosuccinate, 2β,3β,14α,22,25-pentahydroxy- ^Δ7- 5β-cholesten-6-one, (24R)-3β,24,25-trihydroxycholest-5-ene, (24RS)-3β,24,25-trihydroxycholest-5-ene, (24R )-1β,3β,24,25-tetrahydroxycholest-5-ene, 4,4-dimethyl-24methylene-3β-sulfonyloxy-12α-acetoxycholest-8,14 -diene-2α, 11β-diol, 4,4-dimethyl-24-methylene-3β-sulfonyloxy-12α-acetoxycholest-8-ene-2α, 11β-diol, 4,4-Dimethyl-24-methylene-12α-acetoxycholesta-8,14-diene-2α,3β,11β-triol, 4,4-dimethyl-24-methylene- 12α-Acetoxycholest-8,14-diene-3β,11β-diol, 4,4-Dimethyl-24methylene-12α-acetoxycholest-8-ene-2α,3β , 11β-triol, 4,4-dimethyl-24-methylene-12α-acetoxycholest-8-ene-3β, 11β-diol, 4,4-dimethyl-24-methylene Cholesta-8-ene-2,3β,11β,12α-tetrol, 4,4-dimethyl-24methylene-3β-sulfonyloxycholesta-8,14-diene-2α,11β , 12α-triol, 4,4-dimethyl-24-methylenecholesta-8,14-diene-2α, 3β, 11β, 12α-tetrol, 4,4-dimethyl-24-methylene -3β-sulfonyloxy-12α-acetoxycholest-8-en-2-ol-11-one, mono(4,4-dimethyl-24methylene-12α-acetoxychol ster-8,14-diene-2α,11β-diol)-3β-succinate, cholesta-5,7-diene-3β,23(R),25-triol, cholesta-5 , 7-diene-3β, 23(S), 25-triol, 2β, 3β, 14α, 22(R), 25-pentahydroxy-Δ7-5β-cholesten- ⁶ -one, 2β, 3β , 14α, 22(S), 25-pentahydroxy-Δ ⁷ -5β-cholesten-6-one, cholest-5-ene-3β, 22(R, S), 25-triol, cholest- 5-ene-25-fluoro-3β,22(R,S)-diol, cholest-5-ene-25-fluoro-22(R,S)-ol-3β-hemisuccinate, cholesteryl -5-ene-25-chloro-3β,22-diol, cholest-5-ene-25-chloro-22-ol-3β-hemisuccinate, 3α,7α,12α,24,25-penta Hydroxystanne, 3α, 7α, 12α, 25-tetrahydroxystanne, 3α, 7α, 25-trihydroxystanne, 3α, 7α, 24,25-tetrahydroxystanne, 5β-cholestane -3α, 7α, 12α, 24α, 25-pentaol, 5β-cholestane-3α, 7α, 12α, 24β, 25-pentaol, 5β-cholestane-3α, 7α, 12α, 25, 26-penta Alcohol, 5β-cholestane-3α, 7α, 12α, 25-tetraol, cholest-5-ene-2β-fluoro-1α, 3β-diol, 24-cyclopropylcholest-5-ene-3β , 22(S)-diol-3-acetate, 24-cyclopropylcholest-5-ene-3β, 22(S)-diol, 24-cyclopropylcholest-5-ene-3β , 22(S)-diol-3-hydro-succinate, 24-cyclopropyl-5α-cholestane-3β, 22(S)-diol, cholestane-1,4,6-tri En-3-one, 1α,3β-dihydroxycholesta-5-ene, 1α,3β-dihydroxy-5α-cholestane, 1α,3β-dihydroxycholesta-5,7-diene, 1α, 3β,25-trihydroxycholest-5-ene, 1α,25-dihydroxycholesterol, and 1α,25-dihydroxycholesterol-3-benzoate.

wherein ^R1 and ^R2 are different or the same, provided that they are not all hydroxy, selected from hydrogen, halogen, hydroxy and branched or unbranched _C1 - _C6 which may be substituted by halogen, hydroxy or cyano Alkyl, or wherein R ¹ and R ² together represent a methylene group or oxygen, or form a cyclopropane ring, a cyclopentane ring or a cyclohexane ring together with the carbon atoms connected to them; R ³ is selected from hydrogen, ethylene Methyl, hydroxy, methoxy, acetoxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (attached to the same carbon atom of the cholesteric skeleton) and =NOR ²⁶ , where R ²⁶ is hydrogen or C ₁ -C ₃ alkyl, or R ³ and R ⁹ or R ¹⁴ together represent another bond between R ³ and the carbon atom at R ⁹ or R ¹⁴ ; R ⁴ is selected from hydrogen, methylene, hydroxyl, methoxy radical, acetoxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (attached to the same carbon atom of the cholesteric backbone) and =NOR ²⁷ , wherein R ²⁷ is hydrogen or C ₁ -C ₃ alkyl, or R ⁴ and R ¹³ or R ¹⁵ together represent another bond between R ⁴ and the carbon atom at R ¹³ or R ¹⁵ ; R ⁵ is selected from hydrogen, halogen, C ₁ -C ₄ alkyl, methylene, hydroxyl , methoxy, oxygen and =NOR ²² , wherein R ²² is hydrogen or C ₁ -C ₃ alkyl, or R ⁵ and R ⁶ together represent another bond between the carbon atoms at R ⁵ and R ⁶ ; R ⁶ is selected from hydrogen or hydroxyl, or ^R6 and ^R5 together represent another bond between ^R5 and the carbon atom at ^R6 ; ^R9 is hydrogen, hydroxyl, halogen or oxygen, or ^R9 and ^R3 or R ¹⁰ together represents another bond between ^R9 and ^R3 or the carbon atom at ^R10 ; ^R10 is hydrogen halogen or hydroxyl, or ^R10 and ^R9 together represent the bond between ^R10 and the carbon atom at ^R9 Another bond; R ¹¹ is selected from hydroxyl, optionally substituted alkoxy, acyloxy, sulfonyloxy, phosphoryloxy, oxygen, halogen, C ₁ -C ₄ alkanediyl (with cholesterol the same carbon atom of the backbone) and =NOR ²⁸ , where R ²⁸ is hydrogen or C ₁ -C ₃ alkyl, or R ¹¹ and R ¹² together represent another bond between the carbon atoms at R ¹¹ and R ¹² ; R ¹² is selected from hydrogen, hydroxyl, C ₁ -C ₃ alkyl, vinyl, C ₁ -C ₃ alkoxy and halogen, or R ¹² and R ¹¹ together represent between R ¹¹ and carbon atoms at R ^{12 R13} is hydrogen, hydroxyl or halogen, or ^R13 and ^R4 or ^R14 together represent another bond between ^R13 and the carbon atom at ^R4 or ^R14 ; ^R14 is hydrogen, hydroxyl or halogen, or R ¹⁴ and R ³ or R ⁶ or R ¹³ together represent another bond between R ¹⁴ and R ³ or R ⁶ or the carbon atom at R ¹⁴ ; R ¹⁵ is selected from hydrogen, halogen, C ₁ - C ₄ alkyl, methylene, hydroxyl, methoxy, acetoxy, oxygen and =NOR ²³ , wherein R ²³ is hydrogen or C ₁ -C ₃ alkyl, or R ¹⁵ and R ⁴ together represent R ¹⁵ and An additional bond between the carbon atoms at ^R4 ; ^R16 is selected from the group consisting of hydrogen, halogen, _C1 - _C3 alkyl, methylene, hydroxyl, methoxy, oxygen and = ^NOR24 , where ^R24 is hydrogen or C ₁ -C ₃ alkyl, or R ¹⁶ and R ¹⁷ together represent another bond between R ¹⁷ and the carbon atom at R ¹⁶ ; R ¹⁷ is hydrogen or hydroxyl, or R ¹⁷ and R ¹⁶ together represent R ¹⁷ and an additional bond between the carbon atom at ^R16 ; both ^R18 and ^R19 are hydrogen, or one of ^R18 and ^R19 is hydrogen and the other is halogen, hydroxy, or methoxy, or ^R18 and R ¹⁹ together represent oxygen; R ²⁵ is selected from C ₁ -C ₄ alkyl and hydroxymethyl, or R ²⁵ and R ³¹ together represent methylene or oxygen; R ²⁹ is hydrogen, halogen, methyl, hydroxy or oxygen ; R ³⁰ is hydrogen, halogen, methyl or hydroxyl; R ³¹ is hydrogen, halogen, methyl, hydroxyl, or R ³¹ and R ²⁵ together represent methylene or oxygen; and A is a carbon atom or nitrogen atom; and When A is a carbon atom, ^R7 is selected from hydrogen, hydroxy and halogen; and ^R8 is selected from hydrogen, halogen, hydroxy, _C1 - _C4 alkyl, methylene and oxygen, or ^R7 and ^R8 together represent Another bond between the carbon atoms at ^R7 and ^R8 ; ^R20 is selected from _C1 - _C4 alkyl, trifluoromethyl and _C3 - _C6 cycloalkyl; ^R21 is selected from _C1 -C ₄ alkyl, C ₁ -C ₄ hydroxyalkyl, C ₁ -C ₄ haloalkyl containing up to three halogen atoms, methoxymethyl, acetoxymethyl and C ₃ -C ₆ cycloalkyl, or R ²⁰ and R ²¹ form a C ₃ -C ₆ cycloalkyl ring together with their carbon atoms; when A is a nitrogen atom, R ⁷ represents a pair of lone electrons; and R ⁸ is selected from hydrogen, hydroxyl , C ₁ -C ₄ alkyl, cyano and oxygen; while R ²⁰ and R ²¹ are independently C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl; the general conditions are: R ¹ , R ² , At least one of R ⁶ , R ^{8 ,} R ⁹ , R ¹⁰ , R ¹² , R ¹³ , R ¹⁴ , R 18 , R ¹⁹ , R ²⁹ , R ³⁰ and R ³¹ is hydroxyl, or R ²⁵ is hydroxymethyl, It is a further general proviso that ^R9 , ^R10 and ^R11 are not all hydroxyl groups, and it is a further general proviso that it is not used to regulate meiosis. 4. Use of the compound of the above general formula Ic in the preparation of a medicament for regulating meiosis in mammals. 5. A method of modulating meiosis in mammalian germ cells, the method comprising administering an effective amount of a compound of formula Ic above to germ cells in need of such treatment. 6. A method wherein the compound is administered to a germ cell host mammal by administering the compound of the above general formula Ic to the cell. 7. A method according to any one of the preceding two claims, wherein the meiosis-regulated germ cell is an oocyte. 8. A method according to any one of the preceding claims, wherein a compound according to any one of the preceding product claims is administered to the oocyte in vitro. 9. A method according to any one of the preceding claims, wherein the meiosis-regulated germ cell is a male germ cell. 10. The method according to any one of the preceding claims, wherein the compound of any one of the preceding product claims is administered to the testicular tissue in vivo or in vitro.