DK3204400T3 - 17alfa,21-diestere af cortexolon til anvendelse i behandling af tumorer - Google Patents
17alfa,21-diestere af cortexolon til anvendelse i behandling af tumorer Download PDFInfo
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- DK3204400T3 DK3204400T3 DK15778634.4T DK15778634T DK3204400T3 DK 3204400 T3 DK3204400 T3 DK 3204400T3 DK 15778634 T DK15778634 T DK 15778634T DK 3204400 T3 DK3204400 T3 DK 3204400T3
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- carcinoma
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- cortexolone
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
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Claims (23)
1. Forbindelse med formlen (I):
hvor: RerC(O)-Ri; Ri er et hydrogen eller en lineær alkylkæde, der indeholder 2 til 5 carbonatomer; og R' er en lineær alkylkæde, der indeholder 3 til 6 carbonatomer eller en eventuelt substitueret arylgruppe eller en eventuelt substitueret heteroarylgruppe; hvor Ri og R' ikke er ens.
2. Forbindelse ifølge krav 1, hvor den eventuelt substituerede arylgruppe er phenyl.
3. Forbindelse ifølge krav 1, hvor Ri er hydrogen eller CH2CH3, og R' er -(CH2)3-CH3 eller phenyl.
4. Forbindelse ifølge krav 1 med formlen:
Cortexolon 17a-valerat-21 -propionat
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse som et lægemiddel.
6. Forbindelsen til anvendelse ifølge krav 5 med formlen:
7. Forbindelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse i behandlingen af præcancerøse læsioner, dyspiasier, metaplasier og tumorsygdomme, der eventuelt indbefatter maligne neoplasier og metastaser.
8. Forbindelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse som et antitumormiddel.
9. Forbindelse til anvendelse ifølge krav 7 eller 8, hvor tumorsygdommene er solide tumorer, fortrinsvis epitheliale tumorer, mere fortrinsvis hvor de epitheliale tumorer er prostatakarcinom; mammakarcinom; pankreaskarcinom; lungekarcinom; karcinom i fordøjelseskanalen, såsom colonkarcinom; nyrecancer; thyroideakarcinom; uteruskarcinom eller binyrekarcinom.
10. Forbindelse til anvendelse ifølge krav 9, hvor de epitheliale tumorer er prostatakarcinom, hvor prostatakarcinomet fortrinsvis er eller bliver resistent over for anti-androgen-målrettet terapi, såsom enzalutamid; pankreaskarcinom, fortrinsvis eksokrint pankreaskarcinom; mammakarcinom, fortrinsvis triple-negativ brystcancer (TNBC), fortrinsvis hvor mammakarcinomet er triple-negativ brystcancer og individet har tilbagefald eller ikke reagerer på konventionel terapi; eller karcinom i fordøjelseskanalen, såsom colonkarcinom.
11. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 7 til 10, hvor forbindelsen er cortexolon 17a-valerat-21-propionat.
12. Forbindelse ifølge et hvilket som helst af kravene 1 til 4 til anvendelse som en glucocorticoidreceptor- (GR) modulator, fortrinsvis til anvendelse som en glucocorticoidantagonist.
13. Forbindelsen til anvendelse ifølge krav 12 med formlen:
14. Farmaceutisk sammensætning, der omfatter mindst én forbindelse ifølge et hvilket som helst af kravene 1 til 4 og mindst én fysiologisk acceptabel excipiens.
15. Farmaceutisk sammensætning ifølge krav 14, der endvidere omfatter mindst én anden aktiv bestanddel.
16. Farmaceutisk sammensætning ifølge krav 14 og mindst én anden aktiv bestanddel, fortrinsvis en kemoterapeutisk aktiv bestanddel, til simultan, separat eller sekventiel administration.
17. Farmaceutisk sammensætning ifølge et hvilket som helst af kravene 14 - 16 til anvendelse i behandlingen af præcancerøse læsioner, dyspiasier, metaplasier og tumorsygdomme, der eventuelt indbefatter maligne neoplasier og metastaser.
18. Farmaceutisk sammensætning ifølge et hvilket som helst af kravene 14 - 16 til anvendelse som et antitumormiddel.
19. Farmaceutisk sammensætning til anvendelse ifølge krav 17 eller 18, hvor tumorsygdommene er solide tumorer, fortrinsvis epitheliale tumorer, såsom prostatakarcinom; mammakarcinom; pankreaskarcinom; lungekarcinom; karcinom i fordøjelseskanalen, såsom colonkarcinom; nyrecancer; thyroideakarcinom; uteruskarcinom; binyrekarcinom.
20. Farmaceutisk sammensætning til anvendelse ifølge krav 19, hvor de epitheliale tumorer er prostatakarcinom, hvor prostatakarcinomet fortrinsvis er eller bliver resistent over for anti-androgen-målrettet terapi, såsom enzalutamid; pankreaskarcinom, fortrinsvis eksokrint pankreaskarcinom; mammakarcinom, fortrinsvis triple-negative brystcancer (TNBC), fortrinsvis hvor mammakarcinomet er triple-negativ brystcancer og individet har tilbagefald eller ikke reagerer på konventionel terapi; eller karcinom i fordøjelseskanalen, såsom colonkarcinom.
21. Farmaceutisk sammensætning ifølge et hvilket som helst af kravene 14 til 20, hvor forbindelsen er cortexolon 17 a-valerat-21-propionat.
22. Farmaceutisk sammensætning ifølge krav 14 til anvendelse som en glucocorticoidreceptor-(GR) modulator, fortrinsvis til anvendelse som en glucocorticoidantagonist.
23. Farmaceutisk sammensætning ifølge krav 22, hvor forbindelsen er cortexolon 17a-valerat-21-propionat.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14188063.3A EP3006453A1 (en) | 2014-10-08 | 2014-10-08 | 17alpha-monoesters and 17alpha,21-diesters of cortexolone for use in the treatment of tumors |
| PCT/EP2015/073172 WO2016055533A1 (en) | 2014-10-08 | 2015-10-07 | 17a,21-diesters of cortexolone for use in the treatment of tumors |
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| Publication Number | Publication Date |
|---|---|
| DK3204400T3 true DK3204400T3 (da) | 2019-03-04 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK18198653.0T DK3456330T3 (da) | 2014-10-08 | 2015-10-07 | Cortexolon-17alpha-valerat til anvendelse ved behandling af tumorer |
| DK15778634.4T DK3204400T3 (da) | 2014-10-08 | 2015-10-07 | 17alfa,21-diestere af cortexolon til anvendelse i behandling af tumorer |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK18198653.0T DK3456330T3 (da) | 2014-10-08 | 2015-10-07 | Cortexolon-17alpha-valerat til anvendelse ved behandling af tumorer |
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| AU (3) | AU2015329999B2 (da) |
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| CA (3) | CA3160391C (da) |
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| HR (2) | HRP20190194T1 (da) |
| HU (2) | HUE041503T2 (da) |
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| SI (2) | SI3204400T1 (da) |
| TR (1) | TR201901422T4 (da) |
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Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8859774B2 (en) | 2012-05-25 | 2014-10-14 | Corcept Therapeutics, Inc. | Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| US12226412B2 (en) | 2012-05-25 | 2025-02-18 | Corcept Therapeutics, Inc. | Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| 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 |
| US9943505B2 (en) | 2016-09-09 | 2018-04-17 | Corcept Therapeutics, Inc. | Glucocorticoid receptor modulators to treat pancreatic cancer |
| CA3055076C (en) | 2017-03-31 | 2022-02-22 | Corcept Therapeutics, Inc. | Glucocorticoid receptor modulators to treat cervical cancer |
| WO2020132046A1 (en) | 2018-12-19 | 2020-06-25 | Corcept Therapeutics Incorporated | Methods of treating cancer comprising administration of a glucocorticoid receptor modulator and a cancer chemotherapy agent |
| US11234971B2 (en) | 2018-12-19 | 2022-02-01 | Corcept Therapeutics Incorporated | Methods of treating cancer comprising administration of a glucocorticoid receptor modulator and a cancer chemotherapy agent |
| FI3897589T3 (fi) | 2018-12-19 | 2026-01-13 | Corcept Therapeutics Inc | Farmaseuttisia formulaatioita, jotka sisältävät relakorilanttia, heteroaryyliketonifusoitua atsekaliiniyhdistettä |
| CN110698527B (zh) * | 2019-11-19 | 2022-08-26 | 湖南新合新生物医药有限公司 | 一种高纯度氢化可的松-17-戊酸酯的制备方法 |
| US11285145B2 (en) | 2020-05-27 | 2022-03-29 | Corcept Therapeutics Incorporated | Concomitant administration of glucocorticoid receptor modulator relacorilant and paclitaxel, a dual substrate of CYP2C8 and CYP3A4 |
| CN112028956A (zh) * | 2020-09-10 | 2020-12-04 | 那路新 | 合成21-羟基-17-(1-氧代丙氧基)孕甾-4-烯-3,20-二酮的方法 |
| WO2022134033A1 (en) | 2020-12-25 | 2022-06-30 | Corcept Therapeutics Incorporated | Methods of preparing heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| CN114113603B (zh) * | 2021-06-30 | 2023-11-17 | 四川大学华西医院 | Cytl1作为胃癌预后标志物的应用 |
| WO2023088308A1 (zh) * | 2021-11-16 | 2023-05-25 | 石家庄迪斯凯威医药科技有限公司 | 一种具有抗耐药性的抗菌化合物 |
| IL319657A (en) | 2022-10-06 | 2025-05-01 | Corcept Therapeutics Inc | Glucocorticoid receptor modulator formulations |
| WO2024092195A1 (en) | 2022-10-28 | 2024-05-02 | Corcept Therapeutics Incorporated | Treatments for amyotrophic lateral sclerosis using dazucorilant |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE619180A (fr) * | 1961-06-24 | 1962-12-20 | Vismara Francesco Spa | 17-monoesters de 17 alpha, 21-dihydroxy stéroïdes et leur procédé de préparation |
| CH429716A (de) * | 1961-06-24 | 1967-02-15 | Vismara Francesco Spa | Verfahren zur Herstellung von 17a-Acyloxy-21-hydroxy-Steroiden |
| NL6605514A (da) | 1966-04-25 | 1967-10-26 | ||
| DE2748442C3 (de) | 1977-10-26 | 1981-08-27 | Schering Ag Berlin Und Bergkamen, 1000 Berlin | 17α-(3-Jodbenzoyloxy)-9α -chlor4-pregnen-3.20-dione, Zwischenprodukte und Verfahren zu ihrer Herstellung, 9α -chlor-17α, 21-dihydroxy-1,4-pregnadien-3,20-dion und dieses enthaltende Arzneimittel |
| EP0001737B1 (de) * | 1977-10-26 | 1981-01-07 | Schering Aktiengesellschaft | 17-Alpha-(3-Jodbenzoyloxy)-9-Alpha-chlor-4-pregnen-3.20-dione, deren D-Homo-analoga und Verfahren zu ihrer Herstellung |
| EP0054786B1 (de) * | 1980-12-23 | 1985-03-20 | Schering Aktiengesellschaft | Neue 6-alpha-Methylhydrocortison-Derivate, ihre Herstellung und Verwendung |
| CY1359A (en) | 1981-02-02 | 1987-08-07 | Schering Corp | Aromatic heterocyclic esters of steroids, their preparation and pharmaceutical compositions containing them |
| US4920216A (en) * | 1987-05-28 | 1990-04-24 | The Trustees Of Columbia In The City Of New York | Selective chlorination of steroids and other substrates directed by covalently linked pyridine derivatives acting as templates |
| US5990099A (en) | 1988-10-31 | 1999-11-23 | Alcon Laboratories, Inc. | Angiostatic agents and methods and compositions for controlling ocular hypertension |
| WO1990009394A2 (en) | 1989-02-07 | 1990-08-23 | The Upjohn Company | Dehalogenation of organic compounds using tin or lead |
| DE4121484A1 (de) | 1991-06-26 | 1993-01-07 | Schering Ag | Verfahren zur herstellung von 6-methylensteroiden |
| US6172054B1 (en) | 1995-06-15 | 2001-01-09 | Alcon Laboratories, Inc. | Combination therapy for lowering and controlling intraocular pressure |
| WO2000049993A2 (en) | 1999-02-24 | 2000-08-31 | Nitromed, Inc. | Nitrosated and nitrosylated steroids for the treatment of cardiovascular diseases and disorders |
| CA2377301C (en) * | 1999-06-14 | 2009-05-12 | Cosmo S.P.A. | Controlled release and taste masking oral pharmaceutical compositions |
| IT1314184B1 (it) | 1999-08-12 | 2002-12-06 | Nicox Sa | Composizioni farmaceutiche per la terapia di condizioni di stressossidativo |
| AU2001217709B2 (en) | 2000-11-16 | 2005-10-13 | Alcon Manufacturing, Ltd. | Combination therapy for lowering and controlling intraocular pressure |
| ITMI20011762A1 (it) * | 2001-08-10 | 2003-02-10 | Cosmo Spa | Esteri di 17alfa,21-diidrossipregnene, loro uso come agenti anti-androgenetici e procedimenti per la loro preparazione |
| ITMI20051695A1 (it) * | 2005-09-14 | 2007-03-15 | Cosmo Spa | Uso di 17a-esteri c3-c10 del 9,11-deidrocortexolone cme agenti anti-gonadotropinici |
| DE102006059063A1 (de) | 2005-12-24 | 2007-06-28 | Bayer Healthcare Ag | Verwendung von BAY 59-3074 zur Herstellung von Medikamenten zur Therapie von Hirntumoren sowie Kombinationen von BAY 59-3074 |
| US7687484B2 (en) | 2006-05-25 | 2010-03-30 | Bodor Nicholas S | Transporter enhanced corticosteroid activity |
| ITMI20071616A1 (it) * | 2007-08-03 | 2009-02-04 | Cosmo Spa | Processo enzimatico per l'ottenimento di 17-alfa monoesteri del cortexolone e/o suoi 9,11-deidroderivati. |
| CN101397317A (zh) | 2007-09-27 | 2009-04-01 | 天津药业研究院有限公司 | 一种新型硝酸酯类甾体化合物 |
| EP2231147A2 (en) * | 2007-12-13 | 2010-09-29 | Novartis AG | Combinations of therapeutic agents for treating cancer |
| JP2010515777A (ja) | 2008-03-18 | 2010-05-13 | シコール インコーポレイティド | 空気感受性ステロイドの精製 |
| AU2011260390B2 (en) * | 2010-06-01 | 2016-11-24 | Ernst-Moritz-Arndt Universitat Greifswald | Means and methods for diagnosing pancreatic cancer in a subject |
| US20120245552A1 (en) * | 2011-03-23 | 2012-09-27 | Pop Test Cortisol Llc | Combination Therapy |
| RU2506974C1 (ru) | 2012-11-06 | 2014-02-20 | Федеральное государственное бюджетное учреждение "Ростовский научно-исследовательский онкологический институт" Министерства здравоохранения Российской Федерации | Способ лечения первично нерезектабельного рака легкого |
| PL2945628T3 (pl) * | 2013-01-15 | 2020-09-21 | Aragon Pharmaceuticals, Inc. | Modulator receptorów androgenowych w skojarzeniu z octanem abirateronu i prednizonem do leczenia nowotworu stercza |
| 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 |
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