WO1998005679A3 - Mixed agonists of the progesterone receptor and assays therefor - Google Patents

Mixed agonists of the progesterone receptor and assays therefor Download PDF

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Publication number
WO1998005679A3
WO1998005679A3 PCT/US1997/013754 US9713754W WO9805679A3 WO 1998005679 A3 WO1998005679 A3 WO 1998005679A3 US 9713754 W US9713754 W US 9713754W WO 9805679 A3 WO9805679 A3 WO 9805679A3
Authority
WO
WIPO (PCT)
Prior art keywords
mixed
agonist
progesterone receptor
mixed agonists
assays
Prior art date
Application number
PCT/US1997/013754
Other languages
French (fr)
Other versions
WO1998005679A9 (en
WO1998005679A2 (en
Inventor
Donald P Mcdonnell
Brandee L Wagner
Original Assignee
Univ Duke
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 Univ Duke filed Critical Univ Duke
Publication of WO1998005679A2 publication Critical patent/WO1998005679A2/en
Publication of WO1998005679A3 publication Critical patent/WO1998005679A3/en
Publication of WO1998005679A9 publication Critical patent/WO1998005679A9/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • C07J1/0051—Estrane derivatives
    • C07J1/0081—Substituted in position 17 alfa and 17 beta
    • C07J1/0088—Substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being an unsaturated hydrocarbon group
    • C07J1/0096—Alkynyl derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0077—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom
    • C07J41/0083—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom substituted in position 11-beta by an optionally substituted phenyl group not further condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
    • C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
    • C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
    • C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
    • C07J7/0025—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa substituted in position 16
    • C07J7/003—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group

Landscapes

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

Abstract

A third class of PR-ligand (i.e. mixed agonist) is identified which induces a progesterone receptor conformation distinct from that induced by a PR agonist or antagonist. PR mixed agonists exhibit partial agonist activity which is influenced by cell context. These compounds provide useful pharmacological profiles for treating progesterone related diseases and/or conditions. Assays are provided to screen for PR mixed agonists. Molecular designs are provided to convert a PR antagonist to a PR mixed agonist.
PCT/US1997/013754 1996-08-05 1997-08-05 Mixed agonists of the progesterone receptor and assays therefor WO1998005679A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2320696P 1996-08-05 1996-08-05
US60/023,206 1996-08-05

Publications (3)

Publication Number Publication Date
WO1998005679A2 WO1998005679A2 (en) 1998-02-12
WO1998005679A3 true WO1998005679A3 (en) 1998-03-12
WO1998005679A9 WO1998005679A9 (en) 1998-06-11

Family

ID=21813689

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/013754 WO1998005679A2 (en) 1996-08-05 1997-08-05 Mixed agonists of the progesterone receptor and assays therefor

Country Status (1)

Country Link
WO (1) WO1998005679A2 (en)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PE20010581A1 (en) * 1999-08-31 2001-06-04 Schering Ag MESOPROGESTINES (MODULAR PROGESTERONE RECEPTORS) AS COMPONENTS OF COMPOSITIONS USED FOR HORMONE SUBSTITUTION THERAPY (HRT)
US8193252B1 (en) 1999-08-31 2012-06-05 Bayer Pharma AG Mesoprogestins (progesterone receptor modulators) for the treatment and prevention of benign hormone dependent gynecological disorders
KR20020038745A (en) * 1999-08-31 2002-05-23 타우버트 디터, 레흐만 흘거,디테르 타우베르트 홀게르 레만 Mesoprogestins (Progesterone Receptor Modulators) as a Component of Female Contraceptives
EA007854B1 (en) * 1999-08-31 2007-02-27 Шеринг Акциенгезельшафт Mesoprogestins (progesterone receptor modulators) for the treatment and prevention of benign hormone dependent gynecological disorders
US6750015B2 (en) 2000-06-28 2004-06-15 Kathryn B. Horwitz Progesterone receptor-regulated gene expression and methods related thereto
DE102006054535A1 (en) 2006-11-15 2008-05-21 Bayer Schering Pharma Aktiengesellschaft Progesterone receptor antagonist
DE102009034367A1 (en) 2009-07-20 2011-01-27 Bayer Schering Pharma Aktiengesellschaft 17-Hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-benzylidene derivatives, process for their preparation and their use for the treatment of diseases
DE102009034366A1 (en) 2009-07-20 2011-01-27 Bayer Schering Pharma Aktiengesellschaft 17-Hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-methyleneoxyalkylene aryl derivatives, process for their preparation and their use for the treatment of diseases
DE102009034362A1 (en) 2009-07-20 2011-01-27 Bayer Schering Pharma Aktiengesellschaft 17-Hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-aryl derivatives, process for their preparation and their use for the treatment of diseases
DE102009034368A1 (en) 2009-07-20 2011-01-27 Bayer Schering Pharma Aktiengesellschaft 17-Hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-acyloxyalkylenephenyl derivatives, process for their preparation and their use for the treatment of diseases
DE102009034526A1 (en) 2009-07-21 2011-02-10 Bayer Schering Pharma Aktiengesellschaft 17-Hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-ethynylphenyl derivatives, process for their preparation and their use for the treatment of diseases
DE102009034525A1 (en) 2009-07-21 2011-01-27 Bayer Schering Pharma Aktiengesellschaft 17-Hydroxy-17-pentafluoroethyl-estra-4,9 (10) -diene-11-aryl derivatives, process for their preparation and their use for the treatment of diseases
DE102010007719A1 (en) 2010-02-10 2011-08-11 Bayer Schering Pharma Aktiengesellschaft, 13353 Progesterone receptor antagonist
DE102010007722A1 (en) 2010-02-10 2011-08-11 Bayer Schering Pharma Aktiengesellschaft, 13353 Progesterone receptor antagonist
WO2016090139A1 (en) * 2014-12-03 2016-06-09 Evestra, Inc. Combination of estrogens plus antiprogestins with significant partial agonistic effect as an effective treatment of menopausal symptoms and for prevention of the occurrence of breast cancer

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989012448A1 (en) * 1988-06-23 1989-12-28 Research Triangle Institute 11beta-SUBSTITUTED PROGESTERONE ANALOGS
WO1993023431A1 (en) * 1992-05-14 1993-11-25 Baylor College Of Medicine Mutated steroid hormone receptors, methods for their use and molecular switch for gene therapy

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989012448A1 (en) * 1988-06-23 1989-12-28 Research Triangle Institute 11beta-SUBSTITUTED PROGESTERONE ANALOGS
WO1993023431A1 (en) * 1992-05-14 1993-11-25 Baylor College Of Medicine Mutated steroid hormone receptors, methods for their use and molecular switch for gene therapy

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
B. WAGNER ET AL: "16.alpha.-Substituted Analogs of the Antiprogestin RU486 induce a Unique Conformation in the Human Progesterone Receptor Resulting in Mixed Agonist Activity", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA., vol. 93, no. 16, 6 August 1996 (1996-08-06), WASHINGTON US, pages 8739 - 8744, XP002046549 *
CHEMICAL ABSTRACTS, vol. 109, no. 15, 10 October 1988, Columbus, Ohio, US; abstract no. 122708, N. TERAKAWA ET AL: "RU 486, A Progestin Antagonist, binds to Progesterone Receptors in a Human Endometrial Cancer Cell Line and Reverses the Growth Inhibition by Progestins" page 86; column 1; XP002046550 *
COOK C E ET AL: "REVERSAL OF ACTIVITY PROFILE IN ANALOGS OF THE ANTIPROGESTIN RU 486: EFFECT OF A 16ALPHA-SUBSTITUENT ON PROGESTATIONAL (AGONIST) ACTIVITY", LIFE SCIENCES, vol. 52, no. 2, 1 January 1993 (1993-01-01), pages 155 - 162, XP000577581 *
H. KLOOSTERBROER ET AL: "Screening of Anti-Progestagens by Receptor Studies and Bioassays", JOURNAL OF STEROID BIOCHEMISTRY, vol. 31, no. 4B, October 1988 (1988-10-01), pages 567 - 571, XP002046784 *
JOURNAL OF STEROID BIOCHEMISTRY, vol. 31, no. 2, 1988, pages 161 - 166 *
T. GARCIA ET AL: "Switching Agonistic, Antagonistic and Mixed Transcriptional Responses to 11.beta.-Substituted Progestins by Mutation of the Progesterone Receptor", MOLECULAR ENDOCRINOLOGY, vol. 6, no. 12, December 1992 (1992-12-01), pages 2071 - 2078, XP002046548 *

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Publication number Publication date
WO1998005679A2 (en) 1998-02-12

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