WO2007031349A1 - Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents. - Google Patents

Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents. Download PDF

Info

Publication number
WO2007031349A1
WO2007031349A1 PCT/EP2006/062995 EP2006062995W WO2007031349A1 WO 2007031349 A1 WO2007031349 A1 WO 2007031349A1 EP 2006062995 W EP2006062995 W EP 2006062995W WO 2007031349 A1 WO2007031349 A1 WO 2007031349A1
Authority
WO
WIPO (PCT)
Prior art keywords
use according
medicine
administered
hydrogen
dehydrocortexolone
Prior art date
Application number
PCT/EP2006/062995
Other languages
French (fr)
Inventor
Luigi Moro
Mauro Ajani
Giuseppe Celasco
Original Assignee
Cosmo Bio-Technologies Srl
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cosmo Bio-Technologies Srl filed Critical Cosmo Bio-Technologies Srl
Priority to JP2008530439A priority Critical patent/JP5061109B2/en
Priority to CA002622502A priority patent/CA2622502A1/en
Priority to US12/066,754 priority patent/US20090023696A1/en
Priority to CN200680033517.4A priority patent/CN101267826B/en
Priority to AU2006291445A priority patent/AU2006291445A1/en
Priority to NZ566580A priority patent/NZ566580A/en
Priority to EP06777284A priority patent/EP1959965A1/en
Publication of WO2007031349A1 publication Critical patent/WO2007031349A1/en
Priority to IL190045A priority patent/IL190045A0/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/16—Masculine contraceptives

Definitions

  • the gonadotrophins are hormones produced in humans by the hypophysis (anterior pituitary gland), whose action is in turn controlled by the hypothalamus which releases gonadotrophin releasing hormone (GnRH) by pulsed secretion.
  • the gonadotrophins stimulate the male gonads to produce androgenic hormones, particularly testosterone.
  • Some skin diseases such as alopecia, hirsutism, seborrhoea, prostate diseases such as benign prostatic hypertrophy, prostate cancer, and other medical conditions such as polycystic ovary syndrome and precocious puberty are controlled by androgenic hormones and/or by gonadotrophins.
  • the treatment strategy for the aforesaid diseases is: i) to inhibit gonadotrophin secretion and consequently the production of androgenic hormones; ii) to block the conversion of androgens to their biologically active metabolites; iii) to interfere with the direct action of the androgens in the tissues (Motta M., in: The
  • the first objective is normally achieved by using steroid hormones, or analogues and/or antagonists of the gonadotrophin releasing hormone (GnRH), both capable of suppressing gonadotrophin secretion and thus blocking the synthesis of hormones originating from the gonads.
  • GnRH gonadotrophin releasing hormone
  • the second objective is achieved by using androgen metabolism inhibitors which prevent the conversion of testosterone (T) to its principal metabolite, namely dihydrotestosterone (DHT).
  • DHT dihydrotestosterone
  • the third objective is achieved by the administration of substances, known as antiandrogens, which act as competitors at the receptors of the androgens, thus blocking the action of the androgens, regardless of their production site (testicles, ovaries, subrenal capsules).
  • hypophysial secretion of gonadotrophin is an extremely important mechanism in the treatment of pathologies such as tumours of the prostate, polycystic ovary syndrome, endometriosis, gonadotrophin- dependent precocious puberty, male contraception and aberrant sexual behaviour
  • These compounds act by blocking the conversion of androgens into their biologically active metabolites, and/or by interfering with the direct action of the androgenic hormones in the tissues, but are not found to have any inhibitory effect on gonadotrophin section.
  • U.S. patent 3,780,177 describes a process for obtaining new fluorinated steroids, mentioning some cortexolone derivatives such as 9,11-dehydrocortexonole 17 ⁇ - butyrate (diagram B) as intermediates of the synthesis.
  • some cortexolone derivatives such as 9,11-dehydrocortexonole 17 ⁇ - butyrate (diagram B) as intermediates of the synthesis.
  • CD invention C 3 -C 10 17 ⁇ -esters of 9,11-dehydrocortexolone having the formula (I) in which R 1 is hydrogen and R 2 is a linear or branched C 3 -C 10 acyl group show a powerful hypophysial activity, in addition to the characteristic antiandrogenic activity of the aforesaid family of substances; in fact, they act by significantly inhibiting gonadotrophs secretion.
  • the present invention therefore relates to the novel use Of C 3 -C 10 17 ⁇ -esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents.
  • the use OfC 3 -C 10 17 ⁇ -esters of 9,11 -dehydrocortexolone according to the present invention is specifically intended for the preparation of compounds for the treatment of disorders closely related to excess gonadotrophin production, such as prostate tumour, polycystic ovary and gonadotrophin-dependent precocious puberty, for the control of aberrant sexual behaviour, for male contraception, and/or in all medical practice requiring modulation of gonadotrophin secretion, for example in the fertilization procedure used to prevent premature hot flushes in women and ovarian stimulation in assisted fertilization methods.
  • the present invention relates specifically to the use of 9,11-dehydrocortexolone 17 ⁇ -butyrate of formula (II), corresponding to the compound of formula (I) in which R 1 is hydrogen and R 2 is a linear C 4 acyl,
  • the present invention therefore also proposes the pharmaceutical compounds containing as their active principle a compound belonging to the family of the C 3 - C 10 17 ⁇ -esters of 9,11-dehydrocortexolone, particularly 9,11-dehydrocortexolone 17 ⁇ -butyrate, in association with pharmacologically acceptable excipients and, optionally, any other active principles having a synergistic action.
  • the compounds of the invention can be formulated as injectable liquid pharmaceutical compounds such as monobasic or polyphase solutions and/or suspensions in solvents, or as solid pharmaceutical compounds such as tablets, capsules, pellets or liquid and/or semi- solid oral and/or topical pharmaceutical compounds such as solutions or suspensions, suppositories, globuli, vaginal suppositories, creams, ointments, lotions and/or gels, transdermal patches and sprays for cutaneous or nasal administration.
  • injectable liquid pharmaceutical compounds such as monobasic or polyphase solutions and/or suspensions in solvents
  • solid pharmaceutical compounds such as tablets, capsules, pellets or liquid and/or semi- solid oral and/or topical pharmaceutical compounds
  • solutions or suspensions suppositories, globuli, vaginal suppositories, creams, ointments, lotions and/or gels, transdermal patches and sprays for cutaneous or nasal administration.
  • the C 3 -C 10 17 ⁇ -esters of 9,11- dehydrocortexolone, and particularly 9,11-dehydrocortexolone 17 ⁇ -butyrate can be administered systematically in quantities varying from 0.1 to 1000 mg per unit dose, and preferably from 0.5 to 500 mg.
  • unit dose refers to a single form of administration, such as a tablet, a capsule and/or an injection.
  • the C 3 -C 10 17 ⁇ -esters of 9,11- dehydrocortexolone, and particularly 9,11-dehydrocortexolone 17 ⁇ -butyrate can also be administered topically in quantities varying from 0.01 to 25%, and preferably from 0.01 to 2%, of the total weight of the formulation (cream, ointment, lotion, gel, transdermal patch and/or cutaneous spray).
  • the anti-gonadotrophic action was evaluated in an animal model by evaluation of the hypersecretion of the gonads induced by castration in parabiotic rats ⁇ Shipley E.G., in: Methods in Hormone Research, R.I. Dorfman (ed.), vol. 2, pp 179-274. Academic Press, New York and London, 1962).
  • the results of the inhibitory action of 9-dehydrocortexolone 17 ⁇ -butyrate on the gonads are shown below in Table 1.
  • Wistar rats of both sexes with body weights of 50-60 g were used.
  • the males were castrated and, on the next day, were surgically united along the lateral body wall with intact females (parabiosis).
  • the castration of the males induces in them an immediate hypersecretion of gonadotrophin, which, on reaching the female via the parabiotic union, stimulates ovarian growth.
  • gonadotrophin which, on reaching the female via the parabiotic union, stimulates ovarian growth.
  • 9,11 -dehydrocortexolone 17 ⁇ -butyrate and its analogue, cortexolone 17 ⁇ -propionate were injected daily subcutaneously into the males in doses of 1 and 5 mg.
  • Progesterone was used as a positive control and was administered by the same procedure, in doses of 0.5 and 2 mg.
  • the ovaries and uteruses of each female rate were isolated and weighed.
  • the inhibitory action causing hypersecretion of gonadotrophin due to castration was evaluated via the capacity of the tested compound to oppose the increase of weight of the ovaries.
  • Table 1 above shows that 9,11-dehydrocortexolone 17 ⁇ -butyrate has a strong and significant dose-correlated inhibitory effect on gonadotrophin secretion. This effect is evident from the percentage decrease in weight of the ovaries of females in parabiotic union, which decreases by 59% when 1 mg of the trial compound is administered, and by 96% when 5 mg of the same compound is administered.
  • the anti-gonadotrophic effect of 9,11-dehydrocortexolone 17 ⁇ -butyrate is comparable to that shown by comparable doses of progesterone.
  • cortexolone 17 ⁇ -propionate has no anti-gonadotrophic action at all.

Abstract

The present invention relates to the use of C3-C10 17α-esters of 9,11- dehydrocortexolone as agents for inhibiting gonadotrophin secretion. The present invention therefore relates to the use of C3-C10 17 α-esters of 9,11- dehydrocortexolone for the preparation of a medicine for the treatment of disorders associated with the secretion of gonadotrophin and with the corresponding pharmaceutical compounds. The present invention relates specifically to the use of 9,11-dehydrocortexolone 17α-butyrate.

Description

Title
Use ofc3-c10 17α-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents.
Description
The gonadotrophins (LH and FSH) are hormones produced in humans by the hypophysis (anterior pituitary gland), whose action is in turn controlled by the hypothalamus which releases gonadotrophin releasing hormone (GnRH) by pulsed secretion.
In turn, the gonadotrophins stimulate the male gonads to produce androgenic hormones, particularly testosterone.
Some skin diseases such as alopecia, hirsutism, seborrhoea, prostate diseases such as benign prostatic hypertrophy, prostate cancer, and other medical conditions such as polycystic ovary syndrome and precocious puberty are controlled by androgenic hormones and/or by gonadotrophins.
The treatment strategy for the aforesaid diseases is: i) to inhibit gonadotrophin secretion and consequently the production of androgenic hormones; ii) to block the conversion of androgens to their biologically active metabolites; iii) to interfere with the direct action of the androgens in the tissues (Motta M., in: The
Medical Management of Prostate Cancer, L. Denis (ed.), pp 19-35. Springer-
Verlag, Berlin -1988).
The first objective is normally achieved by using steroid hormones, or analogues and/or antagonists of the gonadotrophin releasing hormone (GnRH), both capable of suppressing gonadotrophin secretion and thus blocking the synthesis of hormones originating from the gonads.
The second objective is achieved by using androgen metabolism inhibitors which prevent the conversion of testosterone (T) to its principal metabolite, namely dihydrotestosterone (DHT). The third objective is achieved by the administration of substances, known as antiandrogens, which act as competitors at the receptors of the androgens, thus blocking the action of the androgens, regardless of their production site (testicles, ovaries, subrenal capsules).
In particular, the inhibition of hypophysial secretion of gonadotrophin is an extremely important mechanism in the treatment of pathologies such as tumours of the prostate, polycystic ovary syndrome, endometriosis, gonadotrophin- dependent precocious puberty, male contraception and aberrant sexual behaviour
(Goodman & Gilman 's The Pharmacological Basis of Therapeutics. 9th Edition
1996, pp. 1379-1380. Ehrmann D.A., Polycystic ovary syndrome. N Engl J Med
2005; 352:1223-1236) and/or in all medical practice which requires modulation of gonadotrophin secretion, for example in fertilization procedures used to prevent hot flushes in women, and in ovarian stimulation in assisted fertility treatment
(Ron-El A. et al., Induction of ovulation after GnRH antagonists. Human
Reproduction Update 2000; 6:318-32).
International patent application WO03/014141 describes compounds belonging to the family of steroids structurally related to cortexolone (11-deoxy cortisone) as having high antiandrogenic activity.
These compounds, such as cortexolone 17α-propionate, act by blocking the conversion of androgens into their biologically active metabolites, and/or by interfering with the direct action of the androgenic hormones in the tissues, but are not found to have any inhibitory effect on gonadotrophin section.
U.S. patent 3,780,177 describes a process for obtaining new fluorinated steroids, mentioning some cortexolone derivatives such as 9,11-dehydrocortexonole 17α- butyrate (diagram B) as intermediates of the synthesis.
During the evaluation of new steroids structurally related to the cortexolone family, it was surprisingly found that, in accordance with the object of the present
Figure imgf000003_0001
CD invention, C3-C10 17α-esters of 9,11-dehydrocortexolone having the formula (I) in which R1 is hydrogen and R2 is a linear or branched C3-C10 acyl group show a powerful hypophysial activity, in addition to the characteristic antiandrogenic activity of the aforesaid family of substances; in fact, they act by significantly inhibiting gonadotrophs secretion. The present invention therefore relates to the novel use Of C3-C10 17α-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents.
The use OfC3-C10 17α-esters of 9,11 -dehydrocortexolone according to the present invention is specifically intended for the preparation of compounds for the treatment of disorders closely related to excess gonadotrophin production, such as prostate tumour, polycystic ovary and gonadotrophin-dependent precocious puberty, for the control of aberrant sexual behaviour, for male contraception, and/or in all medical practice requiring modulation of gonadotrophin secretion, for example in the fertilization procedure used to prevent premature hot flushes in women and ovarian stimulation in assisted fertilization methods. The present invention relates specifically to the use of 9,11-dehydrocortexolone 17α-butyrate of formula (II), corresponding to the compound of formula (I) in which R1 is hydrogen and R2 is a linear C4 acyl,
Figure imgf000004_0001
(H) as an anti-gonadotrophic agent capable of inhibiting gonadotrophin secretion.
The present invention therefore also proposes the pharmaceutical compounds containing as their active principle a compound belonging to the family of the C3- C10 17α-esters of 9,11-dehydrocortexolone, particularly 9,11-dehydrocortexolone 17α-butyrate, in association with pharmacologically acceptable excipients and, optionally, any other active principles having a synergistic action. The compounds of the invention can be formulated as injectable liquid pharmaceutical compounds such as monobasic or polyphase solutions and/or suspensions in solvents, or as solid pharmaceutical compounds such as tablets, capsules, pellets or liquid and/or semi- solid oral and/or topical pharmaceutical compounds such as solutions or suspensions, suppositories, globuli, vaginal suppositories, creams, ointments, lotions and/or gels, transdermal patches and sprays for cutaneous or nasal administration.
According to the present invention, the C3-C10 17α-esters of 9,11- dehydrocortexolone, and particularly 9,11-dehydrocortexolone 17α-butyrate, can be administered systematically in quantities varying from 0.1 to 1000 mg per unit dose, and preferably from 0.5 to 500 mg. According to the present invention, the term "unit dose" refers to a single form of administration, such as a tablet, a capsule and/or an injection.
According to the present invention, the C3-C10 17α-esters of 9,11- dehydrocortexolone, and particularly 9,11-dehydrocortexolone 17α-butyrate, can also be administered topically in quantities varying from 0.01 to 25%, and preferably from 0.01 to 2%, of the total weight of the formulation (cream, ointment, lotion, gel, transdermal patch and/or cutaneous spray). The anti-gonadotrophic action was evaluated in an animal model by evaluation of the hypersecretion of the gonads induced by castration in parabiotic rats {Shipley E.G., in: Methods in Hormone Research, R.I. Dorfman (ed.), vol. 2, pp 179-274. Academic Press, New York and London, 1962). The results of the inhibitory action of 9-dehydrocortexolone 17α-butyrate on the gonads are shown below in Table 1.
EXPERIMENTAL SECTION
Effect of 9,11 -dehydrocortexolone on the hypersecretion of gonadotrophin in the parabiotic rat
Wistar rats of both sexes with body weights of 50-60 g were used. The males were castrated and, on the next day, were surgically united along the lateral body wall with intact females (parabiosis). In this experimental procedure, the castration of the males induces in them an immediate hypersecretion of gonadotrophin, which, on reaching the female via the parabiotic union, stimulates ovarian growth. Starting on the day after parabiosis, 9,11 -dehydrocortexolone 17α-butyrate and its analogue, cortexolone 17α-propionate, were injected daily subcutaneously into the males in doses of 1 and 5 mg. Progesterone was used as a positive control and was administered by the same procedure, in doses of 0.5 and 2 mg.
Additional groups of pairs including intact males/intact females and castrated males/intact females were treated with the vehicle only and used as a control.
At the end of the treatment period, the pairs were killed and autopsies performed.
The ovaries and uteruses of each female rate were isolated and weighed.
The inhibitory action causing hypersecretion of gonadotrophin due to castration was evaluated via the capacity of the tested compound to oppose the increase of weight of the ovaries.
Table 1
Effect of 9,11-dehvdrocortexolone 17α-butyrate on the hypersecretion of gonadotrophin in the parabiotic rat
Treatment Daily dose Inhibition of ovarian
(mg) weight (%)
9,11- 1 59 a dehydrocortexolone 5 96 a
17α-butyrate cortexolone 17α- 1 5 propionate 5 5
progesterone 0.5 38 b
2 66 a a = P <0.01 b = P <0.05 against control* * an analysis of variance (ANOVA) was performed for each test and a value of P < 0.05 was selected as the limit for statistical significance. RESULTS
Table 1 above shows that 9,11-dehydrocortexolone 17α-butyrate has a strong and significant dose-correlated inhibitory effect on gonadotrophin secretion. This effect is evident from the percentage decrease in weight of the ovaries of females in parabiotic union, which decreases by 59% when 1 mg of the trial compound is administered, and by 96% when 5 mg of the same compound is administered. The anti-gonadotrophic effect of 9,11-dehydrocortexolone 17α-butyrate is comparable to that shown by comparable doses of progesterone. On the other hand, cortexolone 17α-propionate has no anti-gonadotrophic action at all.

Claims

1. Use of C3-C10 17α-esters of 9, 11 -dehydrocortexolone having the formula
Figure imgf000008_0001
(D in which R1 is hydrogen and R2 is C3-C10 acyl, for the preparation of a medicine with anti-gonadotrophic action.
2. Use according to Claim 1, in which R1 is hydrogen and R2 is linear or branched C4 acyl.
3. Use according to Claim 1, in which R1 is hydrogen and R2 is COCH2CH2CH3.
4. Use according to the preceding claims, in which the said medicine is used for the treatment of disorders associated with gonadotrophin secretion.
5. Use according to Claim 4, in which the said disorders are chosen from: prostate tumour, polycystic ovary and gonadotrophin-dependent precocious puberty, control of aberrant sexual behaviour, male contraception, hot flushes in women and/or in ovarian stimulation in assisted fertilization methods.
6. Use according to one of the preceding claims, in which the said medicine can be administered systematically.
7. Use according to Claim 6, in which the said systematic method is chosen from: injectable solutions and/or suspensions, tablets, capsules, pellets oral solutions and/or suspensions, globuli, nasal sprays, vaginal suppositories, and other suppositories.
8. Use according to Claim 6 and 7, in which the said medicine is administered in quantities varying from 0.1 to 1000 mg per unit dose.
9. Use according to Claim, in which the said medicine is administered in quantities varying from 0.5 to 500 mg per unit dose.
10. Use according to Claims 1-5, in which the said medicine can be administered topically.
11. Use according to Claim 10, in which the said topical method is chosen from: creams, ointments, lotions, gels, cutaneous sprays, and/or transdermal patches.
12. Use according to Claims 10 and 11, in which the said medicine is administered in quantities varying from 0.01 to 25% by weight.
13. Use according to Claim 12, in which the said medicine is administered in quantities varying from 0.01 to 2% by weight.
14. Pharmaceutical compounds containing as their active principle C3-C10 17α-esters of 9,11-dehydrocortexolone, having the formula
Figure imgf000009_0001
(I) in which R1 is hydrogen and R2 is C3-C10 acyl, in association with pharmacologically acceptable excipients.
15. Pharmaceutical compounds according to Claim 14, in which R1 is hydrogen and R2 is linear or branched C4 acyl.
16. Pharmaceutical compounds according to Claim 14, in which R1 is hydrogen and R2 is COCH2CH2CH3.
17. Pharmaceutical compounds according to the preceding claims for the treatment of disorders associated with gonadotrophin secretion.
18. Pharmaceutical compounds according to Claim 17, in which the said disorders are chosen from: prostate tumour, polycystic ovary, gonadotrophin- dependent precocious puberty, control of aberrant sexual behaviour, male contraception, hot flushes in women and/or in ovarian stimulation in assisted fertilization methods.
19. Pharmaceutical compounds according to the preceding claims, in the form of injectable solutions and/or suspensions, tablets, capsules, pellets oral solutions and/or suspensions, transdermal patches, suppositories, globuli, vaginal suppositories, creams, ointments, lotions, cutaneous and/or nasal sprays and/or gels.
PCT/EP2006/062995 2005-09-14 2006-06-08 Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents. WO2007031349A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP2008530439A JP5061109B2 (en) 2005-09-14 2006-06-08 C3-C1017α-esters of 9,11-cortexolone as antigonadal stimulants
CA002622502A CA2622502A1 (en) 2005-09-14 2006-06-08 Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents
US12/066,754 US20090023696A1 (en) 2005-09-14 2006-06-08 Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents
CN200680033517.4A CN101267826B (en) 2005-09-14 2006-06-08 Use of C3-C1017 α-ester of 9,11-dehydrodeoxydermosterol as an antiagonadotropic agent
AU2006291445A AU2006291445A1 (en) 2005-09-14 2006-06-08 Use of C3-C10 17alpha-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents.
NZ566580A NZ566580A (en) 2005-09-14 2006-06-08 Use of C3-C10 17alpha-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents
EP06777284A EP1959965A1 (en) 2005-09-14 2006-06-08 Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents
IL190045A IL190045A0 (en) 2005-09-14 2008-03-10 Use of c3-c10 17 alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI2005A001695 2005-09-14
IT001695A ITMI20051695A1 (en) 2005-09-14 2005-09-14 USE OF 17A-ESTERI C3-C10 OF 9,11-DEIDROCORTEXOLONE CME ANTI-GONADOTROPINIC AGENTS

Publications (1)

Publication Number Publication Date
WO2007031349A1 true WO2007031349A1 (en) 2007-03-22

Family

ID=37134232

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2006/062995 WO2007031349A1 (en) 2005-09-14 2006-06-08 Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents.

Country Status (11)

Country Link
US (1) US20090023696A1 (en)
EP (1) EP1959965A1 (en)
JP (1) JP5061109B2 (en)
KR (1) KR20080056719A (en)
CN (1) CN101267826B (en)
AU (1) AU2006291445A1 (en)
CA (1) CA2622502A1 (en)
IL (1) IL190045A0 (en)
IT (1) ITMI20051695A1 (en)
NZ (1) NZ566580A (en)
WO (1) WO2007031349A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013163683A (en) * 2007-08-03 2013-08-22 Cosmo Spa ENZYMATIC PROCESS FOR OBTAINING 17α-MONOESTER OF CORTEXOLONE AND/OR ITS 9,11-DEHYDRODERIVATIVE
EP3006453A1 (en) 2014-10-08 2016-04-13 Cosmo Technologies Ltd. 17alpha-monoesters and 17alpha,21-diesters of cortexolone for use in the treatment of tumors
US10603327B2 (en) 2015-06-22 2020-03-31 Cassiopea S.P.A. High concentration formulation

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003014141A1 (en) * 2001-08-10 2003-02-20 Cosmo S.P.A. 17alfa, 21-dihydroxypregnene esters as antiandrogenic agents

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3780177A (en) * 1967-06-16 1973-12-18 Warner Lambert Co 17-butyrate,21-ester derivatives of 6alpha,9alpha-difluoroprednisolone,compositions and use

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003014141A1 (en) * 2001-08-10 2003-02-20 Cosmo S.P.A. 17alfa, 21-dihydroxypregnene esters as antiandrogenic agents

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CELASCO GIUSEPPE ET AL: "Pharmacological profile of 9,11 dehydrocortexolone 17 alpha-butyrate (CB-03-04), a new androgen antagonist with antigonadotropic activity", ARZNEIMITTEL-FORSCHUNG, vol. 55, no. 10, 2005, pages 581 - 587, XP001247761, ISSN: 0004-4172 *
See also references of EP1959965A1 *

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10716796B2 (en) 2007-08-03 2020-07-21 Cassiopea S.P.A. Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives
US11938141B2 (en) 2007-08-03 2024-03-26 Cassiopea S.P.A. Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives
US9433628B2 (en) 2007-08-03 2016-09-06 Cassiopea Spa Enzymatic process for obtaining 17α-monoesters of cortexolone and/or its 9,11-dehydroderivatives
US9486458B2 (en) 2007-08-03 2016-11-08 Cassiopea Spa Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives
US10159682B2 (en) 2007-08-03 2018-12-25 Cassiopea S.P.A. Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives
US10166245B2 (en) 2007-08-03 2019-01-01 Cassiopea S.P.A. Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives
US11207332B2 (en) 2007-08-03 2021-12-28 Cassiopea S.P.A. Enzymatic process for obtaining 17 α-monoesters of cortexolone and/or its 9,11-dehydroderivatives
JP2013163683A (en) * 2007-08-03 2013-08-22 Cosmo Spa ENZYMATIC PROCESS FOR OBTAINING 17α-MONOESTER OF CORTEXOLONE AND/OR ITS 9,11-DEHYDRODERIVATIVE
US10993949B2 (en) 2014-10-08 2021-05-04 Cosmo Technologies Limited 17α-monoesters and 17α,21-diesters of cortexolone for use in the treatment of tumors
US10231980B2 (en) 2014-10-08 2019-03-19 Cosmo Technologies Ltd. Cortexolone 17alpha-benzoate for use in the treatment of tumours
EP3006453A1 (en) 2014-10-08 2016-04-13 Cosmo Technologies Ltd. 17alpha-monoesters and 17alpha,21-diesters of cortexolone for use in the treatment of tumors
US10646497B2 (en) 2014-10-08 2020-05-12 Cosmo Technologies Limited 17α-monoesters and 17α,21-diesters of cortexolone for use in the treatment of tumors
EP3456330A1 (en) 2014-10-08 2019-03-20 Cosmo Technologies Ltd Cortexolone 17alpha-valerate for use in the treatment of tumours
JP2021046418A (en) * 2014-10-08 2021-03-25 コスモ・テクノロジーズ・リミテツド COMPOSITIONS FOR USE IN TREATMENT OF TUMORS COMPRISING CORTEXOLONE 17α-VALERATE
US11712443B2 (en) 2014-10-08 2023-08-01 Cosmo Technologies Limited 17α-monoesters and 17α,21-diesters of cortexolone for use in the treatment of tumors
JP2019070033A (en) * 2014-10-08 2019-05-09 コスモ・テクノロジーズ・リミテツド COMPOSITIONS FOR USE IN TREATMENT OF TUMORS CONTAINING CORTEXOLONE 17α-VALERATE
US10183030B2 (en) 2014-10-08 2019-01-22 Cosmo Technologies Limited 17α,21-diesters of cortexolone for use in the treatment of tumors
JP7028809B2 (en) 2014-10-08 2022-03-02 コスモ・テクノロジーズ・リミテツド Composition for use in tumor treatment containing cortexolone 17α-valerate
US11213531B2 (en) 2015-06-22 2022-01-04 Cassiopea S.P.A. High concentration formulation
US10980819B2 (en) 2015-06-22 2021-04-20 Cassiopea S.P.A. High concentration formulation
US11883415B2 (en) 2015-06-22 2024-01-30 Cassiopea S.P.A. High concentration formulation
US10603327B2 (en) 2015-06-22 2020-03-31 Cassiopea S.P.A. High concentration formulation

Also Published As

Publication number Publication date
CA2622502A1 (en) 2007-03-22
ITMI20051695A1 (en) 2007-03-15
KR20080056719A (en) 2008-06-23
CN101267826B (en) 2010-12-01
CN101267826A (en) 2008-09-17
NZ566580A (en) 2011-03-31
JP2009507879A (en) 2009-02-26
AU2006291445A1 (en) 2007-03-22
EP1959965A1 (en) 2008-08-27
JP5061109B2 (en) 2012-10-31
IL190045A0 (en) 2008-12-29
US20090023696A1 (en) 2009-01-22

Similar Documents

Publication Publication Date Title
JP3350048B2 (en) Methods for treating androgen-related diseases
JP3332377B2 (en) Combination therapy for prevention and / or treatment of benign prostate hyperplasia
US5372996A (en) Method of treatment of androgen-related diseases
US6423698B1 (en) Combination therapy for the prophylaxis and/or treatment of benign prostatic hyperplasia
IE83638B1 (en) Method of treatment of androgen-related diseases
KR100270432B1 (en) Antiestrogen compounds as sex steroid activity inhibitors
JP6025301B2 (en) C-19 steroids for therapeutic use
Brodie et al. Aromatase inhibitors, their pharmacology and application
Celasco et al. Biological profile of cortexolone 17a-propionate (CB-03-01), a new topical and peripherally selective androgen antagonist
Brooks 12 Treatment of hirsutism with 5α-reductase inhibitors
US20090023696A1 (en) Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents
Rasmusson Chemical control of androgen action
US7939517B2 (en) 1,4,6-androstatriene-3,17-dione (“ATD”) for therapeutic uses
MX2008003589A (en) Use of c3-c10 17alfa-esters of 9,11-dehydrocortexolone as anti-gonadotrophic agents
Celasco et al. Pharmacological profile of 9, 11-dehydrocortexolone 17α-butyrate (CB-03-04), a new androgen antagonist with antigonadotropic activity
IE19990531A1 (en) Combination therapy for prophylaxis and/or treatment of benign prostatic hyperplasia
IE84077B1 (en) Combination therapy for prophylaxis and/or treatment of benign prostatic hyperplasia

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2006291445

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 190045

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 566580

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 200680033517.4

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: MX/a/2008/003589

Country of ref document: MX

Ref document number: 2622502

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2008530439

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 1020087007295

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2670/DELNP/2008

Country of ref document: IN

ENP Entry into the national phase

Ref document number: 2006291445

Country of ref document: AU

Date of ref document: 20060608

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 2006291445

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2006777284

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 12066754

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 2006777284

Country of ref document: EP