KR102489565B1 - 스테로이드 4,6-디엔의 6,7-알파-에폭시화를 위한 공정 및 중간체 - Google Patents

스테로이드 4,6-디엔의 6,7-알파-에폭시화를 위한 공정 및 중간체 Download PDF

Info

Publication number
KR102489565B1
KR102489565B1 KR1020187035835A KR20187035835A KR102489565B1 KR 102489565 B1 KR102489565 B1 KR 102489565B1 KR 1020187035835 A KR1020187035835 A KR 1020187035835A KR 20187035835 A KR20187035835 A KR 20187035835A KR 102489565 B1 KR102489565 B1 KR 102489565B1
Authority
KR
South Korea
Prior art keywords
formula
compound
alkyl
halo
group
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.)
Active
Application number
KR1020187035835A
Other languages
English (en)
Korean (ko)
Other versions
KR20190007011A (ko
Inventor
알렉산더 찰스 웨이머스-윌슨
조피아 콤스타
로라 월리스
티모시 에반스
Original Assignee
엔제트피 유케이 리미티드
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 엔제트피 유케이 리미티드 filed Critical 엔제트피 유케이 리미티드
Publication of KR20190007011A publication Critical patent/KR20190007011A/ko
Application granted granted Critical
Publication of KR102489565B1 publication Critical patent/KR102489565B1/ko
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

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
    • C07J71/0005—Oxygen-containing hetero ring
    • C07J71/001—Oxiranes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
    • C07J13/007—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 17 (20)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
    • 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
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl 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
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
    • 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
    • C07J41/0088—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing unsubstituted amino radicals
    • 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
    • C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
KR1020187035835A 2016-05-18 2017-05-18 스테로이드 4,6-디엔의 6,7-알파-에폭시화를 위한 공정 및 중간체 Active KR102489565B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1608776.9 2016-05-18
GBGB1608776.9A GB201608776D0 (en) 2016-05-18 2016-05-18 Methods and compounds
PCT/GB2017/051389 WO2017199036A1 (en) 2016-05-18 2017-05-18 Process and intermediates for the 6,7-alpha-epoxidation of steroid 4,6-dienes

Publications (2)

Publication Number Publication Date
KR20190007011A KR20190007011A (ko) 2019-01-21
KR102489565B1 true KR102489565B1 (ko) 2023-01-17

Family

ID=56320628

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020187035835A Active KR102489565B1 (ko) 2016-05-18 2017-05-18 스테로이드 4,6-디엔의 6,7-알파-에폭시화를 위한 공정 및 중간체

Country Status (14)

Country Link
US (1) US10766921B2 (enExample)
EP (1) EP3458467B1 (enExample)
JP (1) JP7034094B2 (enExample)
KR (1) KR102489565B1 (enExample)
CN (1) CN109415404B (enExample)
AU (1) AU2017265445B2 (enExample)
CA (1) CA3024283C (enExample)
DK (1) DK3458467T3 (enExample)
EA (1) EA038224B1 (enExample)
ES (1) ES2841324T3 (enExample)
GB (1) GB201608776D0 (enExample)
MX (1) MX378594B (enExample)
PT (1) PT3458467T (enExample)
WO (1) WO2017199036A1 (enExample)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201608777D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Compounds
GB201608776D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Methods and compounds
GB201812382D0 (en) 2018-07-30 2018-09-12 Nzp Uk Ltd Compounds
CN111560045A (zh) * 2020-06-23 2020-08-21 江苏佳尔科药业集团股份有限公司 一种以ba为原料合成石胆酸的方法
CN114957368B (zh) * 2021-09-08 2024-07-26 湖南科益新生物医药有限公司 中间体化合物及其制备方法和应用
CN114957372B (zh) * 2021-12-07 2023-10-31 湖南醇康医药科技有限公司 10α-甲基-5,7-二烯甾体化合物和地屈孕酮的制备方法

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2624748A (en) 1950-09-09 1953-01-06 Upjohn Co Bisnorchola-4, 6-dien-3-one-22-al
IT1088094B (it) 1976-10-14 1985-06-04 Hoffmann La Roche Derivati del pregnano
US4289872A (en) 1979-04-06 1981-09-15 Allied Corporation Macromolecular highly branched homogeneous compound based on lysine units
US5229490A (en) 1987-05-06 1993-07-20 The Rockefeller University Multiple antigen peptide system
DE3902357A1 (de) 1989-01-27 1990-08-02 Hoechst Ag Verwendung von rheniumorganischen verbindungen zur oxidation von c-c-mehrfachbindungen, darauf basierende oxidationsverfahren und neue rheniumorganische verbindungen
US5166372A (en) 1992-02-07 1992-11-24 Arco Chemical Technology, L.P. Epoxidation process
DE69312700T2 (de) 1992-04-14 1998-02-19 Cornell Res Foundation Inc Makromoleküle auf basis von dendritischen polymeren und verfahren zur herstellung
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
US5932462A (en) 1995-01-10 1999-08-03 Shearwater Polymers, Inc. Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
US5723636A (en) 1996-04-12 1998-03-03 National Starch And Chemical Investment Holding Corporation Methyltrioxorhenium-urea hydrogen peroxide epoxidation of olefins
DE60205891T2 (de) 2001-03-12 2006-06-22 Intercept Pharmaceuticals, Inc. Steroide als agonisten für fxr
US20090062256A1 (en) 2001-06-01 2009-03-05 Bristol-Myers Squibb Pharma Company LACTAMS SUBSTITUTED BY CYCLIC SUCCINATES AS INHIBITORS OF Abeta PROTEIN PRODUCTION
JP4758608B2 (ja) 2001-11-07 2011-08-31 ネクター セラピューティックス 分枝ポリマーおよびそれらの結合体
ITMI20030352A1 (it) 2003-02-27 2004-08-28 Chemi Spa Metodo per la sintesi di metiltriossorenio.
EP1568706A1 (en) 2004-02-26 2005-08-31 Intercept Pharmaceuticals, Inc. Novel steroid agonist for FXR
EP1775304A4 (en) 2004-07-13 2010-04-28 Mitsubishi Chem Corp PROCESS FOR THE PRODUCTION OF STEROIDS
ITMI20050912A1 (it) * 2005-05-19 2006-11-20 Erregierre Spa Processo di preparazione di acidi 3-a-ya(b)-diidrossi-6-a(b)-alchil-5b-colanici
JP2007210888A (ja) * 2006-01-12 2007-08-23 Mitsubishi Chemicals Corp ステロイド化合物の製造方法
PL2040713T3 (pl) 2006-06-27 2014-11-28 Intercept Pharmaceuticals Inc Pochodne kwasów żółciowych jako ligandy FXR do zapobiegania lub leczenia chorób lub stanów, w których pośredniczy FXR
US8796249B2 (en) 2008-07-30 2014-08-05 Intercept Pharmaceuticals, Inc. TGR5 modulators and methods of use thereof
ES2774368T3 (es) 2008-11-19 2020-07-20 Intercept Pharmaceuticals Inc Moduladores de TGR5 y métodos de uso de los mismos
EP2459581A4 (en) 2009-07-29 2012-12-26 Univ Chicago LIVER X-RECEPTOR AGONISTS
PT3336097T (pt) 2012-06-19 2020-10-29 Intercept Pharmaceuticals Inc Preparação da forma não cristalina de ácido obeticólico
CN108250264A (zh) 2012-10-26 2018-07-06 英特塞普特医药品公司 制备胆汁酸衍生物的方法
NZ708501A (en) 2012-11-28 2019-03-29 Intercept Pharmaceuticals Inc Treatment of pulmonary disease
US20140206657A1 (en) 2013-01-18 2014-07-24 City Of Hope Bile acid analog tgr5 agonists
US10166246B2 (en) 2014-05-27 2019-01-01 City Of Hope TGR5 agonist complexes for treating diabetes and cancer
EA033445B1 (ru) 2014-11-19 2019-10-31 Nzp Uk Ltd 5-бета-6-алкил-7-гидрокси-3-оновые стероиды в качестве промежуточных соединений для получения стероидных модуляторов fxr
EA033603B1 (ru) 2014-11-19 2019-11-08 Nzp Uk Ltd 6-альфа-алкил-6,7-дионовые стероиды в качестве промежуточных соединений для получения стероидных модуляторов fxr
WO2016079519A1 (en) 2014-11-19 2016-05-26 Dextra Laboratories Limited 6.alpha.-alkyl-3,7-dione steroids as intermediates for the production of steroidal fxr modulators
WO2016079517A1 (en) 2014-11-19 2016-05-26 Dextra Laboratories Limited 6-alkyl-7-hydroxy-4-en-3-one steroids as intermediates for the production of steroidal fxr modulators
US11578097B2 (en) 2014-11-26 2023-02-14 Enanta Pharmaceuticals, Inc. Tetrazole derivatives of bile acids as FXR/TGR5 agonists and methods of use thereof
CN105348365A (zh) 2014-12-03 2016-02-24 四川百利药业有限责任公司 一种胆酸衍生物及其制备方法、药物组合物和用途
GB201608777D0 (en) * 2016-05-18 2016-06-29 Dextra Lab Ltd Compounds
GB201608779D0 (en) * 2016-05-18 2016-06-29 Dextra Lab Ltd Methods and compounds
GB201608776D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Methods and compounds

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
Biosci. Biotechnol. Biochem.，2004.，Vol. 68，pp. 1332-1337
Chemistry and Physics of Lipids，2001.，Vol. 109，pp. 135-143
Eur. J. Org. Chem.，2001.，pp. 3731-3739
J. Org. Chem.，2002.，Vol. 67，pp. 6764-6771
Tetrahedron，1997.，Vol. 53， pp. 8129-8136
Tetrahedron: Asymmetry，1999.，Vol. 10，pp. 3977-3989

Also Published As

Publication number Publication date
WO2017199036A1 (en) 2017-11-23
AU2017265445B2 (en) 2020-12-03
EP3458467B1 (en) 2020-09-30
GB201608776D0 (en) 2016-06-29
EA201892516A1 (ru) 2019-05-31
CN109415404A (zh) 2019-03-01
AU2017265445A1 (en) 2018-11-15
JP2019516729A (ja) 2019-06-20
KR20190007011A (ko) 2019-01-21
ES2841324T3 (es) 2021-07-08
CN109415404B (zh) 2022-08-26
US20190309012A1 (en) 2019-10-10
JP7034094B2 (ja) 2022-03-11
EA038224B1 (ru) 2021-07-27
CA3024283A1 (en) 2017-11-23
MX2018014130A (es) 2019-04-29
MX378594B (es) 2025-03-11
BR112018073492A2 (pt) 2019-03-26
CA3024283C (en) 2024-07-02
DK3458467T3 (da) 2020-12-14
EP3458467A1 (en) 2019-03-27
US10766921B2 (en) 2020-09-08
PT3458467T (pt) 2021-01-05

Similar Documents

Publication Publication Date Title
KR102489565B1 (ko) 스테로이드 4,6-디엔의 6,7-알파-에폭시화를 위한 공정 및 중간체
KR102509432B1 (ko) 화학 중간체로서의 스테로이드 6.7.베타.-에폭사이드
KR102527821B1 (ko) 스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 6α-알킬-6,7-다이온 스테로이드
KR102458265B1 (ko) 담즙산 유도체, 특히 오베티콜산의 합성을 위한 중간체
KR102526631B1 (ko) 스테로이드 fxr 조절인자를 제조하기 위한 중간체로서의 6-알킬-7-하이드록시-4-엔-3-온 스테로이드
KR102526632B1 (ko) 스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 5β-6-알킬-7-하이드록시-3-온 스테로이드
KR102546748B1 (ko) 스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 6α-알킬-3,7-다이온 스테로이드
HK40006372B (en) Process for the 6,7-alpha-epoxidation of steroid 4,6-dienes
HK40006372A (en) Process for the 6,7-alpha-epoxidation of steroid 4,6-dienes
HK40055816A (en) Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid
HK40055816B (en) Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid
BR112018073492B1 (pt) Processos de preparo de compostos intermediários na síntese de derivados de ácido biliar com atividade farmacológica
HK40006370B (en) Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid
HK40006371B (en) Steroid 6.7.beta.-epoxides as chemical intermediates
HK40006371A (en) Steroid 6.7.beta.-epoxides as chemical intermediates

Legal Events

Date Code Title Description
PA0105 International application

Patent event date: 20181210

Patent event code: PA01051R01D

Comment text: International Patent Application

PG1501 Laying open of application
A201 Request for examination
PA0201 Request for examination

Patent event code: PA02012R01D

Patent event date: 20200512

Comment text: Request for Examination of Application

E902 Notification of reason for refusal
PE0902 Notice of grounds for rejection

Comment text: Notification of reason for refusal

Patent event date: 20220406

Patent event code: PE09021S01D

E701 Decision to grant or registration of patent right
PE0701 Decision of registration

Patent event code: PE07011S01D

Comment text: Decision to Grant Registration

Patent event date: 20221027

GRNT Written decision to grant
PR0701 Registration of establishment

Comment text: Registration of Establishment

Patent event date: 20230112

Patent event code: PR07011E01D

PR1002 Payment of registration fee

Payment date: 20230113

End annual number: 3

Start annual number: 1

PG1601 Publication of registration