HRP20100230T1 - NOVI 2-SUPSTITUIRANI D-HOMO-ESTRA-1,3,5(10)-TRIENI KAO INHIBITORI 17ß-HIDROKSISTEROIDNE DEHIDROGENAZE TIPA 1 - Google Patents

NOVI 2-SUPSTITUIRANI D-HOMO-ESTRA-1,3,5(10)-TRIENI KAO INHIBITORI 17ß-HIDROKSISTEROIDNE DEHIDROGENAZE TIPA 1 Download PDF

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HRP20100230T1
HRP20100230T1 HR20100230T HRP20100230T HRP20100230T1 HR P20100230 T1 HRP20100230 T1 HR P20100230T1 HR 20100230 T HR20100230 T HR 20100230T HR P20100230 T HRP20100230 T HR P20100230T HR P20100230 T1 HRP20100230 T1 HR P20100230T1
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homo
estra
oxo
trien
substituted
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Gege Christian
Regenhardt Wilko
Peters Olaf
Hillisch Alexander
Adamski Jerzy
M�ller Gabriele
Deluca Dominga
Elger Walter
Schneider Birgitt
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Bayer Schering Pharma Aktiengesellschaft
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J63/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J63/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/008Expansion of ring D by one atom, e.g. D homo steroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30Oestrogens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/32Antioestrogens

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Reproductive Health (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

2-Supstituirani D-homo-estratrieni opće formule I, gdje je R2 je zasićena ili nezasićena C1-C8-alkilna skupina, aralkil ili alkilaril radikal, C1-C8-alkiloksi skupina ili atom halogena, R13 je atom vodika ili metilna skupina, R17 je vodik ili atom fluora, gdje isprekidane linije u B prstenu i D prstenu steroidne molekule mogu biti dodatne dvostruke veze, i njihove farmaceutski prihvatljive soli s izuzetkom spoja 2-metoksi-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ola. Patent sadrži još 13 patentnih zahtjeva.

Claims (14)

1. 2-Supstituirani D-homo-estratrieni opće formule I, [image] gdje je R2 je zasićena ili nezasićena C1-C8-alkilna skupina, aralkil ili alkilaril radikal, C1-C8-alkiloksi skupina ili atom halogena, R13 je atom vodika ili metilna skupina, R17 je vodik ili atom fluora, gdje isprekidane linije u B prstenu i D prstenu steroidne molekule mogu biti dodatne dvostruke veze, i njihove farmaceutski prihvatljive soli s izuzetkom spoja 2-metoksi-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ola.
2. 2-Supstituirani D-homo-estra-1,3,5(10)-trieni prema zahtjevu 1, naznačeni time da R2 je C1-C5-alkoksi, C1-C5-alkil ili C2-C3-alkenil radikal ili je brom ili klor.
3. 2-Supstituirani D-homo-estra-1,3,5(10)-trieni prema zahtjevu 1, naznačeni time da R2 je metoksi ili etoksi radikal, metil, etil ili propil radikal, i alil radikal.
4. 2-Supstituirani D-homo-estra-1,3,5(10)-trieni prema zahtjevu 1, naznačeni time da R13 je atom vodika.
5. 2-Supstituirani D-homo-estra-1,3,5(10)-trieni prema zahtjevu 1, naznačeni time da su 2) 2-etoksi-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 3) 2-kloro-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 2 4) 2-bromo-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 3 5) 2-jodo-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 4 6) 2-kloro-17α-floro-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 5a 7) 2-kloro-17β-floro-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 5b 8) 2-bromo-17α-floro-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 9) 2-bromo-17β-floro-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 10) 2-(2-feniletil)-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 6 11) 2-alil-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 7 12) 2-alil-17α-floro-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 13) 2-alil-17β-floro-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 14) 2-kloro-17a-okso-17a-homo-estra-1,3,5(10),16-tetraen-3-ol 15) 2-bromo-17a-okso-17a-homo-estra-1,3,5(10),16-tetraen-3-ol 8 16) 2-alil-17a-okso-17a-homo-estra-1,3,5(10),16-tetraen-3-ol 17) 2-propil-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol 18) 2-metoksi-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 19) 2-etoksi-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 20) 2-kloro-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 21) 2-bromo-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 22) 2-jodo-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 23) 2-kloro-17α-floro-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 24) 2-kloro-17β-floro-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 25) 2-bromo-17α-floro-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 26) 2-bromo-17β-floro-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 27) 2-alil-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 28) 2-alil-17α-floro-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 29) 2-alil-17β-floro-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol 30) 2-kloro-17a-okso-17a-homo-18a-homo-estra-1,3,5(10),16-tetraen-3-ol 31) 2-bromo-17a-okso-17a-homo-18a-homo-estra-1,3,5(10),16-tetraen-3-ol 32) 2-alil-17a-okso-17a-homo-18a-homo-estra-1,3,5(10),16-tetraen-3-ol 33) 2-propil-17a-okso-17a-homo-18a-homo-estra-1,3,5(10)-trien-3-ol
6. 2-Supstituirani D-homo-estra-1,3,5(10)-trieni prema jednom od zahtjeva 1 do 5 ili 2-metoksi-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol naznačeni time da su za proizvodnju lijeka.
7. Upotreba 2-supstituiranih D-homo-estra-1,3,5(10)-triena prema jednom od zahtjeva 1 to 5 ili 2-metoksi-17a-okso-17a-homo-estra-1,3,5(10)-trien-3-ol naznačena time da je za proizvodnju lijeka za profilaksu i terapiju bolesti ovisnih o estrogenu na koje pozitivno utječe inhibicija 17β-hidroksisteroidnih dehidrogenaza.
8. Upotreba 2-supstituiranih D-homo-estra-1,3,5(10)-triena prema zahtjevu 7, naznačena time da se barem jedan daljnji aktivni spoj koristi u kombinaciji za proizvodnju lijeka.
9. Upotreba 2-supstituiranih D-homo-estra-1,3,5(10)-triena prema zahtjevu 8, naznačena time da je daljnji aktivni spoj antiandrogen, anti-gestagen, inhibitor aromataze ili anti-estrogen.
10. Upotreba 2-supstituiranih D-homo-estra-1,3,5(10)-triena prema jednom od zahtjeva 7 do 9, naznačena time da je za proizvodnju lijeka za profilaksu i terapiju hormonski-ovisnih tumora muških i ženskih gonada, te muških i ženskih spolnih organa, uključujući mliječne žlijezde.
11. Upotreba 2-supstituiranih D-homo-estra-1,3,5(10)-triena prema zahtjevu 10 naznačena time da je za proizvodnju lijeka za profilaksu i terapiju karcinoma dojke.
12. Upotreba 2-supstituiranih D-homo-estra-1,3,5(10)-triena prema zahtjevu 10 naznačena time da je za proizvodnju lijeka za liječenje karcinoma prostate.
13. Upotreba 2-supstituiranih D-homo-estra-1,3,5(10)-triena prema zahtjevu 10 naznačena time da je za proizvodnju lijeka za liječenje endometrioze.
14. Farmaceutski pripravci koji sadrže barem jedan spoj opće formule I prema jednom od zahtjeva 1 do 5 ili 2-metoksi-17a-okso-17a-homoestra-1,3,5(10)-trien-3-ol i po potrebi barem jednog daljnjeg aktivnog spoja zajedno sa farmaceutski prihvatljivim ekscipijentima i/ili nosačima, te je daljnji aktivni spoj antiandrogen, anti-gestagen, inhibitor aromataze ili anti-estrogen.
HR20100230T 2004-07-02 2010-04-20 NOVI 2-SUPSTITUIRANI D-HOMO-ESTRA-1,3,5(10)-TRIENI KAO INHIBITORI 17ß-HIDROKSISTEROIDNE DEHIDROGENAZE TIPA 1 HRP20100230T1 (hr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102004032673A DE102004032673A1 (de) 2004-07-02 2004-07-02 Neue 2-substituierte D-Homo-estra-1,3,5(10)-triene als Inhibitoren der 17ß-Hydroxysteroiddehydrogenase Typ 1
PCT/EP2005/007314 WO2006003012A1 (de) 2004-07-02 2005-07-04 NEUE 2-SUBSTITUIERTE D-HOMO ESTRA-1,3,5(10)-TRIENE ALS INHIBITOREN DER 17ß-HYDROXYSTEROIDDEHYDROGENASE TYP 1

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EP (1) EP1763534B1 (hr)
JP (1) JP4871274B2 (hr)
KR (1) KR20070035059A (hr)
CN (1) CN1980949B (hr)
AT (1) ATE458744T1 (hr)
AU (1) AU2005259329B8 (hr)
BR (1) BRPI0511394A (hr)
CA (1) CA2571760C (hr)
CR (1) CR8854A (hr)
DE (2) DE102004032673A1 (hr)
DK (1) DK1763534T3 (hr)
EA (1) EA011455B1 (hr)
EC (1) ECSP077160A (hr)
ES (1) ES2340401T3 (hr)
HK (1) HK1103745A1 (hr)
HR (1) HRP20100230T1 (hr)
IL (1) IL180171A0 (hr)
MX (1) MX2007000108A (hr)
NO (1) NO20070605L (hr)
NZ (1) NZ552515A (hr)
PL (1) PL1763534T3 (hr)
PT (1) PT1763534E (hr)
UA (1) UA92324C2 (hr)
WO (1) WO2006003012A1 (hr)
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US8030298B2 (en) 2005-05-26 2011-10-04 Abbott Products Gmbh 17β-HSD1 and STS inhibitors
US8080540B2 (en) 2006-09-19 2011-12-20 Abbott Products Gmbh Therapeutically active triazoles and their use
US8288367B2 (en) 2006-11-30 2012-10-16 Solvay Pharmaceuticals Gmbh Substituted estratriene derivatives as 17BETA HSD inhibitors
DE102007015169A1 (de) 2007-03-27 2008-10-02 Universität des Saarlandes Campus Saarbrücken 17Beta-Hydroxysteroid-Dehydrogenase-Typ1-Inhibitoren zur Behandlung hormonabhängiger Erkrankungen
DE102007040243A1 (de) 2007-08-25 2009-02-26 Universität des Saarlandes 17Beta-Hydroxysteriod-Dehydrogenase Typ1 Inhibitoren zur Behandlung hormonabhängiger Erkrankungen
US9850272B2 (en) 2013-06-25 2017-12-26 Forendo Pharma Ltd. Therapeutically active estratrienthiazole derivatives as inhibitors of 17.beta-hydroxy-steroid dehydrogenase, type 1
US10377791B2 (en) 2013-06-25 2019-08-13 Forendo Pharma Ltd. Therapeutically active estratrienthiazole derivatives as inhibitors of 17 B-hydroxysteroid dehydrogenase, type 1
US9663549B2 (en) 2013-06-25 2017-05-30 Forendo Pharma Ltd. Therapeutically active 17-nitrogen substituted estratreinthiazole derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase
CN107207562B (zh) 2014-12-23 2020-03-06 佛恩多制药有限公司 17β-HSD1抑制剂的前药
CN107207561B (zh) 2014-12-23 2020-03-31 佛恩多制药有限公司 17β-HSD1–抑制剂的前药
CZ307437B6 (cs) 2016-06-07 2018-08-22 Ăšstav organickĂ© chemie a biochemie AV ÄŚR, v.v.i. 15β-substituované deriváty estronu jako selektivní inhibitory 17β-hydroxysteoiddehydrogenáz
UA126342C2 (uk) 2017-06-08 2022-09-21 Форендо Фарма Лтд 15-бета-[3-пропанамідо]-заміщені естра-1,3,5(10)-трієн-17-он-сполуки і їх 17-оксими для використання в інгібуванні 17-бета-гідроксистероїддегідрогеназ
SG11202105795XA (en) 2018-12-05 2021-06-29 Forendo Pharma Ltd Estra-1,3,5(10)-triene compounds condensed in position 16(17) with a pyrazole ring as inhibitors of 17-hsd1

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GB1346691A (en) * 1970-06-12 1974-02-13 Inst Khim Prirodnykh Soedineny Stereospecific method for preparing estrane compounds of natural configuration
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ES2340401T3 (es) 2010-06-02
CA2571760A1 (en) 2006-01-12
AU2005259329B8 (en) 2011-11-24
AU2005259329A1 (en) 2006-01-12
MX2007000108A (es) 2007-03-09
DK1763534T3 (da) 2010-05-17
CN1980949B (zh) 2010-05-05
PT1763534E (pt) 2010-04-27
EP1763534B1 (de) 2010-02-24
ZA200700958B (en) 2008-07-30
CN1980949A (zh) 2007-06-13
EP1763534A1 (de) 2007-03-21
WO2006003012A1 (de) 2006-01-12
KR20070035059A (ko) 2007-03-29
PL1763534T3 (pl) 2010-07-30
CR8854A (es) 2007-08-28
UA92324C2 (en) 2010-10-25
ATE458744T1 (de) 2010-03-15
DE102004032673A1 (de) 2006-01-26
JP2008504337A (ja) 2008-02-14
JP4871274B2 (ja) 2012-02-08
IL180171A0 (en) 2007-06-03
EA200700103A1 (ru) 2007-08-31
CA2571760C (en) 2011-11-22
EA011455B1 (ru) 2009-04-28
NO20070605L (no) 2007-02-01
NZ552515A (en) 2010-07-30
HK1103745A1 (en) 2007-12-28
DE502005009091D1 (de) 2010-04-08
BRPI0511394A (pt) 2007-12-04
AU2005259329B2 (en) 2011-11-10
ECSP077160A (es) 2007-02-28

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