Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07J—STEROIDS
  • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Definitions

• the present invention relates to pharmacologically active compounds and to their use as medicaments. More particularly it has been found that the compounds of the invention can be used for regulating the meiosis.
• Meiosis is the unique and ultimate event of germ cells on which sexual reproduction is based. Meiosis comprises two meiotic divisions. During the first division, exchange between maternal and paternal genes take place before the pairs of chromosomes are separated into the two daughter cells. These contain only half the number (1n) of chromosomes and 2c DNA. The second meiotic division proceeds without a DNA synthesis. This division therefore results in the formation of the haploid germ cells with only 1 c DNA.
• the meiotic events are similar in the male and female germ cells, but the time schedule and the differentiation processes which lead to ova and to spermatozoa differ profoundly.
• All female germ cells enter the prophase of the first meiotic division early in life, often before birth, but all are arrested as oocytes later in the prophase (dictyate state) until ovulation after puberty.
• the female has a stock of oocytes which is drawn upon until the stock is exhausted.
• Meiosis in females is not completed until after fertilisation, and results in only one ovum and two abortive polar bodies per germ cell.
• only some of the male germ cells enter meiosis from puberty and leave a stem population of germ cells throughout life. Once initiated, meiosis in the male cell proceeds without significant delay and produces four spermatozoa.
• MAS meiosis activating substance
• MPS meiosis preventing substance
• novel, stable compounds with interesting pharmacological properties.
• the compounds of the invention are useful for regulating the meiosis in oocytes and in male germ cells.
• R 1 , R 2 and R 3 independently, are hydrogen or methyl; R 4 and R 5 are either hydrogen or together they designate an additional bond between the carbon atoms to which they are bound.
• the present invention relates to a compound of the general formula (I) wherein R 1 is hydrogen.
• the present invention relates to a compound of the general formula (I) wherein R 1 is methyl.
• the present invention relates to a compound of the general formula (I) wherein R 2 is hydrogen.
• the present invention relates to a compound of the general formula (I) wherein R 2 is methyl.
• the present invention relates to a compound of the general formula (I) wherein R 3 is hydrogen.
• the present invention relates to a compound of the general formula (I) wherein R 3 is methyl.
• the present invention relates to a compound of the general formula (I) wherein R 4 and R5 are both hydrogen.
• the present invention relates to a compound of the general formula (I) wherein R 4 and R5 together designate an additional double bond between the carbon atoms to which they are bound.
• the present invention relates to the use of a compound of the general formula (I) in the manufacture of a medicament.
• the present invention relates to the use of a compound of the general formula (I) in the manufacture of a medicament for use in the regulation of meiosis.
• the expression "regulating the meiosis” is understood to indicate that the compounds can be used for stimulating the meiosis in vitro, in vivo, and ex vivo.
• the present invention relates to the use of a compound of the general formula (I) in the regulation of the meiosis of oocytes or male germ cells.
• the present invention relates to a method of regulating the meiosis in a mammalian germ cell which method comprises administering an effective amount of a compound of the general formula (I) above to a germ cell in need of such a treatment.
• the compounds of the present invention will induce resumption of meiosis in oocytes as well as in male germ cells.
• the existence of a meiosis inducing substance in nature has been known for some time. However, until recently the identity of the meiosis inducing substance or substances has been unknown.
• the compounds of the general formula (I) are used to stimulate the meiosis.
• the compounds of the general formula (I) are used to stimulate the meiosis in humans.
• the compounds of formula (I) are promising as new fertility regulating agents without the usual side effect on the somatic cells which are known from the hitherto used hormonal contraceptives which are based on estrogens and/or gestagens.
• a meiosis inducing substance can be administered so as to prematurely induce resumption of meiosis in oocytes while they are still in the growing follicle, before the ovulatory peak of gonadotropins occurs.
• the resumption of the meiosis can, for example, be induced a week after the preceding menstruation has ceased.
• the resulting overmature oocytes are then most likely not to be fertilised. The normal menstrual cycle is not likely to be affected.
• a meiosis inducing substance of the general formula (I) can be used in the treatment of certain cases of infertility in females, including women, by administration thereof to females who, due to an insufficient own production of MIS, are unable to produce mature oocytes. Also, when in vitro fertilisation is performed, better results can be achieved, when a meiosis inducing substance of the general formula (I) is added to the medium in which the oocytes are kept. Also, when infertility in males, including men, is caused by an insufficient own production of the meiosis inducing substance administration of a meiosis inducing substance of the general formula (I) can be used for relieving the problem.
• the route of administration of the compositions containing a compound of formula (I) may be any route which effectively transports the active compound to its site of action.
• compositions which comprises at least one compound of formula (I) in connection with a phar ⁇ maceutically acceptable carrier.
• a pharmaceutical composition which comprises at least one compound of formula (I) in connection with a phar ⁇ maceutically acceptable carrier.
• such compositions are preferably in the form of capsules or tablets.
• the pharmaceutical compositions may comprise carriers, diluents, abso ⁇ tion enhancers, preservatives, buffers, agents for adjusting the osmotic pressure, tablet disintegrating agents and other ingredients which are conventionally used in the art.
• solid carriers are magnesium carbonate, magnesium stearate, dextrin, lactose, sugar, talc, gelatine, pectin, tragacanth, methyl cellulose, sodium carboxymethyl cellulose, low melting waxes and cocoa butter.
• Liquid compositions include sterile solutions, suspensions and emulsions. Such liquid compositions may be suitable for injection or for use in connection with ex vivo and in vitro fertilisation.
• the liquid compositions may contain other ingredients which are conventionally used in the art, some of which are mentioned in the list above.
• composition for transdermal administration of a compound of this invention may be provided in the form of a patch and a composition for nasal administration may be provided in the form of a nasal spray in liquid or powder form.
• the dose of a compound of the invention to be used will be determined by a physician and will depend, inter alia, on the particular compound employed, on the route of administration and on the purpose of the use.
• the compounds of the general formula (I) can be synthesised by methods known per se.
• Examples of preferred compounds of the general formula (I) are the following:

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Priority Applications (1)

Applications Claiming Priority (2)

Publications (1)

Family

ID=8096873

Family Applications (1)

Country Status (3)

Cited By (2)

Citations (1)

• 1996
  • 1996-06-20 AU AU61226/96A patent/AU6122696A/en not_active Abandoned
  • 1996-06-20 WO PCT/DK1996/000271 patent/WO1997000883A1/en active Application Filing
  • 1996-06-24 ZA ZA965332A patent/ZA965332B/xx unknown

Patent Citations (1)

Non-Patent Citations (1)

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