EP0538312A1 - Antiandrogene [3,2-d]Triazolsteroide - Google Patents

Antiandrogene [3,2-d]Triazolsteroide

Info

Publication number
EP0538312A1
EP0538312A1 EP91912518A EP91912518A EP0538312A1 EP 0538312 A1 EP0538312 A1 EP 0538312A1 EP 91912518 A EP91912518 A EP 91912518A EP 91912518 A EP91912518 A EP 91912518A EP 0538312 A1 EP0538312 A1 EP 0538312A1
Authority
EP
European Patent Office
Prior art keywords
methyl
androst
mesyl
androsta
pyrazol
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP91912518A
Other languages
German (de)
English (en)
French (fr)
Inventor
Helmut Hofmeister
Dieter Bittler
Horst Michna
Ursula Habenicht
Karl-Heinrich Fritzemeier
Yukishige Nishino
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
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 Schering AG filed Critical Schering AG
Publication of EP0538312A1 publication Critical patent/EP0538312A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0036—Nitrogen-containing hetero ring
    • C07J71/0042—Nitrogen only
    • C07J71/0047—Nitrogen only at position 2(3)

Definitions

  • the present invention relates to [3,2-c] pyrazole and [3,2-d] triazole steroids of the general formula
  • X represents the group CH or a nitrogen atom
  • R 1 is an alkylsulfonyl group R-SO 2 - and, if X is the group CH, additionally an acyl group R-CO-, where R is in each case an alkyl group having 1 to 3
  • R 4 represents a hydrogen atom or, in the case of a C 4 -C 5 single bond, an ⁇ - or ⁇ -methyl group,
  • R 6 and R 6 ' each represent a hydrogen atom or together a 6,6-methylene or
  • R 7 is a hydrogen atom or, if R 6 and R 6 'are each hydrogen atoms, additionally a saturated or unsaturated ⁇ - or ⁇ -alkyl group with 1 to 4
  • R 6 and R 7 represent a 6 ⁇ , 7 ⁇ or 6 ⁇ , 7 ⁇ -methylene group or an additional bond between the carbon atoms 6 and 7 as well R 6 'is a hydrogen atom, R 11 is a hydrogen, fluorine or chlorine atom and R 11' is a hydrogen atom or R 11 and R 11 'are together a methylene group,
  • R 15 and R 16 each represent a hydrogen atom, a CC double bond, a 15 ⁇ , 16 ⁇ - or 15 ⁇ , 16 ⁇ -methylene group or -when R 4 and R 6 ' together for a 6,6-ethylene, 6,6-methylene or R 7 for an alkyl group with 1 to 4 carbon atoms or X stands for a nitrogen atom - additionally a CC single bond, and
  • R is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a
  • X is a CH group by an additional 15, 16 double bond, by an additional. ich ⁇ 15 ⁇ ( ⁇ ), 16 ⁇ ( ⁇ ) -methylene bridge and / or by an additional 6,6-methylene or 6,6-ethylene group and / or by an additional C 1 - to C 4 -alkyl group in 7 ⁇ - or ⁇ - Position of the steroid framework or
  • X is a nitrogen atom at least through this nitrogen atom.
  • the present invention also relates to a method for producing the
  • a) should be a CH group, a steroido [3,2-c] 1'H-pyrazole of the general
  • R 4 , R 6 , R 6 , R 7 , R 11 , R 11 , R 15 , R 16 and R 17 are those in formula I.
  • X a and X b is a chlorine or bromine atom or X a is the radical O-SO 2 -R or
  • the sulfonylation of the compounds of the general formula IIa is carried out using customary processes, for example those described in EP 0 207 375 A1 and resulting from the examples according to the invention.
  • the invention further relates to pharmaceutical preparations which have at least one
  • Carrier included.
  • the compounds according to the invention can be used primarily for the production of medicaments which are suitable for the therapy of benign prostatic hyperplasia and androgen-dependent prostate cancer. However, they can also be used to treat other androgen-dependent disorders and diseases.
  • the pharmaceutical preparations can be provided for oral, parenteral, transdermal, rectal or vaginal application and can be prepared in solid or liquid dosage form such as capsules, tablets, supposito ⁇ en, solutions, suspensions and emulsions.
  • Prostate cancer and other androgen-dependent disorders and diseases a daily dose of 10-1000 mg / day of a compound of general formula I is administered.
  • the active compounds of the general formula I are used in galenics using customary inert and pharmaceutically acceptable vehicles (carriers)
  • R 4 , R 6 , R 6 , R 7 , R 11 , R 11 ' R 15 , R 16 and R 17 are those in formula I.
  • Lithiumethinyl, Lithiumchlorethinyl or Lithiumpropinyl results in
  • Acetylene is passed into 200 ml of butyllithium solution (1.6 mol in hexane) in 600 ml of tetrahydrofuran at 0 ° C. for 45 min. Then add 20.0 g of 15 ⁇ -acetoxy-3-methoxy-androsta-3,5-diene 17-one in 400 ml of tetrahydrofuran. After 2 hours, carefully add saturated Ammonium chloride solution, diluted with ethyl acetate, washed with water, dried and concentrated i. Vacuum on. The crude product in 400 ml of methanol and 50 ml of water are added
  • reaction mixture is mixed with saturated ammonium chloride solution, diluted with ethyl acetate, washed with water, dried and i. Vacuum concentrated.
  • Propin is introduced at 0 ° C. in 150 ml of butyuithium solution (1.6 mol. In hexane) in 400 ml of tetrahydrofuran. 15 g of 15 ⁇ -acetoxy-3-methoxy-androsta-3,5, -dien-17-one in 300 ml of tetrahydrofuran are then added dropwise, the mixture is left to react and saturated ammonium chloride solution is added. It is diluted with ethyl acetate, washed with water, dried and i. Vacuum concentrated. The crude product is concentrated in a mixture of 300 ml of methanol and 20 ml of water at room temperature with 10 ml.
  • Example 7 17 ⁇ -ethynyl-17 ⁇ -hydroxy-4-methyl-androsta-4,15-dien-3-one a) 15 ⁇ -hydroxy-4- (phenylthiomethyl) -androst-4-en-3,17-dio ⁇ .
  • Hexane-ethyl acetate gradient gives 3 g of 17 ⁇ -hydroxy-17 ⁇ -methyl-7 ⁇ -vinyl-androst-4-en-3-one with a melting point of 116-117 ° C. (from isopropyl ether).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP91912518A 1990-07-04 1991-07-04 Antiandrogene [3,2-d]Triazolsteroide Withdrawn EP0538312A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE4021433 1990-07-04
DE4021433A DE4021433A1 (de) 1990-07-04 1990-07-04 Antiandrogene mit steroid(3,2-c)pyrazol-struktur

Publications (1)

Publication Number Publication Date
EP0538312A1 true EP0538312A1 (de) 1993-04-28

Family

ID=6409714

Family Applications (1)

Application Number Title Priority Date Filing Date
EP91912518A Withdrawn EP0538312A1 (de) 1990-07-04 1991-07-04 Antiandrogene [3,2-d]Triazolsteroide

Country Status (14)

Country Link
US (2) US5236912A (fi)
EP (1) EP0538312A1 (fi)
JP (1) JPH05508637A (fi)
CN (1) CN1059529A (fi)
AU (1) AU644201B2 (fi)
CA (1) CA2086678A1 (fi)
DE (1) DE4021433A1 (fi)
FI (1) FI925977A0 (fi)
HU (1) HUT64364A (fi)
IE (1) IE912333A1 (fi)
IL (1) IL98724A0 (fi)
PT (1) PT98199A (fi)
WO (1) WO1992000992A1 (fi)
ZA (1) ZA915193B (fi)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5879711A (en) * 1997-11-07 1999-03-09 Sequeira; Joel A. Stable antiandrogenic gel composition
CA2330611A1 (en) 1998-05-22 1999-12-02 The Board Of Trustees Of The Leland Stanford Junior University Bifunctional molecules and therapies based thereon
EP2671508B1 (en) 2005-04-28 2020-09-16 Proteus Digital Health, Inc. Pharma-informatics system
JP2009508494A (ja) 2005-09-16 2009-03-05 ラプトール ファーマシューティカル インコーポレイテッド Ｃｒを含むタンパク質に対して特異的な受容体−結合タンパク質（ｒａｐ）変異体を含む組成物およびその使用
US20080051380A1 (en) 2006-08-25 2008-02-28 Auerbach Alan H Methods and compositions for treating cancer
HUE059078T2 (hu) 2009-02-20 2022-10-28 Enhanx Biopharm Inc Glutation-alapú hatóanyagszállító rendszer
JP2012526144A (ja) 2009-05-06 2012-10-25 ラボラトリー スキン ケア インコーポレイテッド 活性物質−リン酸カルシウム粒子複合体を含む経皮送達組成物およびその使用方法
KR20240115925A (ko) 2016-07-29 2024-07-26 얀센 파마슈티카 엔브이 전립선암의 치료 방법
CN113024513A (zh) * 2021-03-22 2021-06-25 中国药科大学 新型雄激素受体降解剂、制备方法和医药用途

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL100550C (fi) * 1959-02-16
US3290293A (en) * 1961-12-01 1966-12-06 Merck & Co Inc 4-androsteno-[3, 2-c] pyrazoles
US3280112A (en) * 1963-01-28 1966-10-18 Sterling Drug Inc Steroido [2, 3-d] triazoles
US4297350A (en) * 1978-10-10 1981-10-27 The Upjohn Company Male contraceptive steroids and methods of use
US4684636A (en) * 1985-06-24 1987-08-04 Sterling Drug Inc. Antiandrogenic sulfonylsteroidopyrazoles and processes for preparation method of use and compositions thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9200992A1 *

Also Published As

Publication number Publication date
US5236912A (en) 1993-08-17
WO1992000992A1 (de) 1992-01-23
DE4021433A1 (de) 1992-01-09
IE912333A1 (en) 1992-01-15
PT98199A (pt) 1992-05-29
CN1059529A (zh) 1992-03-18
ZA915193B (en) 1992-04-29
JPH05508637A (ja) 1993-12-02
CA2086678A1 (en) 1992-01-05
FI925977A (fi) 1992-12-31
HU9204180D0 (en) 1993-09-28
IL98724A0 (en) 1992-07-15
FI925977A0 (fi) 1992-12-31
AU644201B2 (en) 1993-12-02
HUT64364A (en) 1993-12-28
US5389624A (en) 1995-02-14
AU8188091A (en) 1992-02-04

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Legal Events

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Free format text: ANTI-ANDROGENIC ??3,2-D TRIAZOLE STEROIDS