MX378591B - Intermedios para la sintesis de derivados de acido biliar, en particular, de acido obeticolico - Google Patents

Intermedios para la sintesis de derivados de acido biliar, en particular, de acido obeticolico

Info

Publication number
MX378591B
MX378591B MX2018014164A MX2018014164A MX378591B MX 378591 B MX378591 B MX 378591B MX 2018014164 A MX2018014164 A MX 2018014164A MX 2018014164 A MX2018014164 A MX 2018014164A MX 378591 B MX378591 B MX 378591B
Authority
MX
Mexico
Prior art keywords
sup
intermediates
synthesis
obeticholic
acid derivatives
Prior art date
Application number
MX2018014164A
Other languages
English (en)
Other versions
MX2018014164A (es
Inventor
Alexander Charles Weymouth-Wilson
Carl Otter
Ieuan Davies
Laura Wallis
Rhys Batchelor
Timothy Evans
Zofia Komsta
Original Assignee
Nzp Uk Ltd
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 Nzp Uk Ltd filed Critical Nzp Uk Ltd
Publication of MX2018014164A publication Critical patent/MX2018014164A/es
Publication of MX378591B publication Critical patent/MX378591B/es

Links

Classifications

    • 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
    • C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J21/005—Ketals
    • C07J21/006—Ketals at position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J21/005—Ketals
    • C07J21/008—Ketals at position 17
    • 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
    • C07J33/00—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J33/00—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J33/002—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
    • 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
    • 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
    • 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
    • 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)

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)

Abstract

La invencion se refiere a los compuestos de formula general (I): (Ver formula I) en donde: , R1, R2, R3, R4, R5, R6 y Y son como se definen aqui; los compuestos son intermedios en la sintesis de acidos biliares sinteticos que son utiles en el tratamiento de afecciones como la enfermedad hepatica.
MX2018014164A 2016-05-18 2017-05-18 Intermedios para la sintesis de derivados de acido biliar, en particular, de acido obeticolico MX378591B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB1608777.7A GB201608777D0 (en) 2016-05-18 2016-05-18 Compounds
PCT/GB2017/051385 WO2017199033A1 (en) 2016-05-18 2017-05-18 Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid

Publications (2)

Publication Number Publication Date
MX2018014164A MX2018014164A (es) 2019-04-01
MX378591B true MX378591B (es) 2025-03-11

Family

ID=56320629

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2018014164A MX378591B (es) 2016-05-18 2017-05-18 Intermedios para la sintesis de derivados de acido biliar, en particular, de acido obeticolico

Country Status (15)

Country Link
US (2) US10968250B2 (es)
EP (2) EP3458469B1 (es)
JP (1) JP7034093B2 (es)
KR (1) KR102458265B1 (es)
CN (1) CN109415407B (es)
AU (1) AU2017266539B2 (es)
CA (1) CA3024281A1 (es)
EA (1) EA037584B1 (es)
ES (2) ES2878577T3 (es)
GB (1) GB201608777D0 (es)
HR (1) HRP20211128T1 (es)
HU (1) HUE054851T2 (es)
MX (1) MX378591B (es)
PT (1) PT3458469T (es)
WO (1) WO2017199033A1 (es)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201608776D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Methods and compounds
EP3431486A1 (en) * 2017-07-18 2019-01-23 Bionice, S.L.U. Process and intermediates for the synthesis of obeticholic acid and derivatives thereof
GB201812382D0 (en) 2018-07-30 2018-09-12 Nzp Uk Ltd Compounds
CN111138509B (zh) * 2018-11-02 2022-12-06 东莞东阳光药物研发有限公司 奥贝胆酸的制备方法
CN111072744B (zh) * 2019-12-03 2021-09-14 江苏佳尔科药业集团股份有限公司 一种以ba为原料合成熊去氧胆酸的方法
CN114315945A (zh) * 2020-09-28 2022-04-12 四川澄华生物科技有限公司 一种胆甾酸及其衍生物的除杂方法
CN112341516B (zh) * 2020-11-14 2022-07-15 湖南科瑞生物制药股份有限公司 5,6-环氧类固醇类化合物及其制备方法和应用
EP4423105A2 (en) * 2021-11-02 2024-09-04 Sandhill One, LLC High purity non-animal derived udca

Family Cites Families (47)

* 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
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
EP0636156B1 (en) 1992-04-14 1997-07-30 Cornell Research Foundation, Inc. Dendritic based macromolecules and method of production
WO1994019366A1 (en) 1993-02-26 1994-09-01 Magainin Pharmaceuticals Inc. Chemical synthesis of squalamine
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
EP1392714B1 (en) 2001-03-12 2005-08-31 Intercept Pharmaceuticals, Inc. Steroids as agonists for 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
AU2002352524B2 (en) 2001-11-07 2007-10-04 Nektar Therapeutics Branched polymers and their conjugates
EP1568706A1 (en) 2004-02-26 2005-08-31 Intercept Pharmaceuticals, Inc. Novel steroid agonist for FXR
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
CN101374854A (zh) * 2006-01-12 2009-02-25 三菱化学株式会社 甾类化合物的制备方法
WO2007095174A2 (en) 2006-02-14 2007-08-23 Intercept Pharmaceuticals, Inc. Bile acid derivatives as fxr ligands for the prevention or treatment of fxr-mediated diseases or conditions
CA2656320C (en) 2006-06-27 2015-04-28 Intercept Pharmaceuticals, Inc. Bile acid derivatives as fxr ligands for the prevention or treatment of fxr-mediated diseases or conditions
EA017714B1 (ru) 2007-01-19 2013-02-28 Интерсепт Фармасьютикалз, Инк. Модуляторы tgr5 и способы их применения
CA2732323C (en) 2008-07-30 2017-06-27 Intercept Pharmaceuticals, Inc. Tgr5 modulators and methods of use thereof
EP2373673B1 (en) 2008-11-19 2016-07-27 Intercept Pharmaceuticals, Inc. Tgr5 modulators and methods of use thereof
PL2698375T3 (pl) 2008-11-19 2018-08-31 Intercept Pharmaceuticals, Inc. Modulatory TGR5 i sposób ich zastosowania
JP2013500986A (ja) 2009-07-29 2013-01-10 ザ・ユニバーシティ・オブ・シカゴ 肝臓ｘ受容体アゴニスト
SG10201607230SA (en) 2012-06-19 2016-10-28 Intercept Pharmaceuticals Inc Preparation, Uses And Solid Forms Of Obeticholic Acid
US9777038B2 (en) 2012-10-26 2017-10-03 Intercept Pharmaceuticals, Inc. Process for preparing bile acid derivatives
AU2013352288B2 (en) 2012-11-28 2017-11-23 Intercept Pharmaceuticals, Inc. Treatment of pulmonary disease
US20140206657A1 (en) * 2013-01-18 2014-07-24 City Of Hope Bile acid analog tgr5 agonists
PL2997035T3 (pl) 2013-05-14 2018-10-31 Intercept Pharmaceuticals, Inc. 11-hydroksy-6-podstawione pochodne kwasów żółciowych i ich koniugaty aminokwasowe jako modulatory receptorów farnezoidu x
JP2016520199A (ja) 2013-05-24 2016-07-11 ネステク ソシエテ アノニム 過敏性腸症候群を診断するための経路特異的マーカー
US10166246B2 (en) * 2014-05-27 2019-01-01 City Of Hope TGR5 agonist complexes for treating diabetes and cancer
PT3149019T (pt) 2014-05-29 2020-02-19 Bar Pharmaceuticals S R L Derivados de colano para utilização no tratamento e/ou na prevenção de doenças mediadas por fxr e tgr5/gp-bar1
SG11201703717SA (en) 2014-11-06 2017-06-29 Enanta Pharm Inc Bile acid analogs an fxr/tgr5 agonists and methods of use thereof
ES2748692T3 (es) 2014-11-19 2020-03-17 Nzp Uk Ltd Esteroides 6.alfa.-alquil-3,7-diona como intermedios para la producción de moduladores FXR de esteroides
EA033427B1 (ru) 2014-11-19 2019-10-31 Nzp Uk Ltd 6-алкил-7-гидрокси-4-ен-3-оновые стероиды в качестве промежуточных соединений для получения стероидных модуляторов fxr
PL3221332T3 (pl) * 2014-11-19 2019-10-31 Nzp Uk Ltd Steroidy, 5.beta.-6-alkilo-7-hydroksy-3-ony jako związki pośrednie do wytwarzania steroidowych modulatorów fxr
KR102527821B1 (ko) 2014-11-19 2023-05-02 엔제트피 유케이 리미티드 스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 6α-알킬-6,7-다이온 스테로이드
US10208081B2 (en) 2014-11-26 2019-02-19 Enanta Pharmaceuticals, Inc. Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof
KR20170099909A (ko) 2014-11-26 2017-09-01 이난타 파마슈티칼스, 인코포레이티드 Fxr/tgr5 작용제로서의 담즙산 유사체 및 이의 이용 방법
WO2016086134A1 (en) 2014-11-26 2016-06-02 Enanta Pharmaceuticals, Inc. Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof
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
CN106279328A (zh) 2015-05-20 2017-01-04 重庆药友制药有限责任公司 一种制备6α-烷基鹅去氧胆酸的方法
CA2989167A1 (en) 2015-06-19 2016-12-22 Intercept Pharmaceuticals, Inc. Tgr5 modulators and methods of use thereof
CN106397522A (zh) 2015-07-31 2017-02-15 中国人民解放军军事医学科学院毒物药物研究所 3,7‑二（叔丁基二甲基硅基氧基）‑6‑烯‑5β‑胆烷‑24‑酸甲酯
CN106478759A (zh) 2015-08-31 2017-03-08 陕西合成药业股份有限公司 奥贝胆酸衍生物及其制备方法和用途
CN106478756A (zh) 2015-09-02 2017-03-08 中美华世通生物医药科技（武汉）有限公司 Oca-e单晶及其制备方法和用途
CN106518946A (zh) 2015-09-10 2017-03-22 上海迪诺医药科技有限公司 磺酰脲衍生物、其药物组合物及应用
GB201608776D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Methods and compounds
GB201608779D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Methods and compounds

Also Published As

Publication number Publication date
KR102458265B1 (ko) 2022-10-25
EA037584B1 (ru) 2021-04-16
ES2970336T3 (es) 2024-05-28
GB201608777D0 (en) 2016-06-29
WO2017199033A1 (en) 2017-11-23
US20210179661A1 (en) 2021-06-17
EP3458469B1 (en) 2021-04-14
KR20190009322A (ko) 2019-01-28
EP3848382C0 (en) 2023-11-29
EP3848382B1 (en) 2023-11-29
MX2018014164A (es) 2019-04-01
ES2878577T3 (es) 2021-11-19
HUE054851T2 (hu) 2021-10-28
CN109415407B (zh) 2021-08-17
US20190284227A1 (en) 2019-09-19
EP3458469A1 (en) 2019-03-27
EA201892514A1 (ru) 2019-05-31
JP2019516720A (ja) 2019-06-20
BR112018073488A2 (pt) 2019-04-09
US11479577B2 (en) 2022-10-25
PT3458469T (pt) 2021-06-11
AU2017266539A1 (en) 2018-11-15
CN109415407A (zh) 2019-03-01
EP3848382A1 (en) 2021-07-14
CA3024281A1 (en) 2017-11-23
JP7034093B2 (ja) 2022-03-11
US10968250B2 (en) 2021-04-06
HRP20211128T1 (hr) 2022-01-07
AU2017266539B2 (en) 2021-04-15

Similar Documents

Publication Publication Date Title
MX378591B (es) Intermedios para la sintesis de derivados de acido biliar, en particular, de acido obeticolico
PH12017502331A1 (en) 1,4-substituted piperidine derivatives
IN2014KN00929A (es)
TN2019000192A1 (en) Pyrazole derivatives as malt1 inhibitors
WO2015200481A8 (en) Mnk inhibitors and methods related thereto
MX2020003458A (es) Derivados radiomarcados de un compuesto de 2-amino-6-fluoro-n-[ 5-fluoro-piridin-3-il]-pirazolo[1,5-a]pirimidin-3- carboxamida util como inhibidor de ataxia telangiectasia mutada y rad3 relacionado (atr) cinasa, preparacion de tal compuesto y diferentes formas solidas del mismo.
EP4321513A3 (en) Pyrrolotriazine compounds as tam inhibitors
PH12019550140A1 (en) Piperidine-substituted mnk inhibitors and methods related thereto
WO2014164533A8 (en) Methods of stereoselective synthesis of substituted nucleoside analogs
EP3778605A3 (en) Lrrk2 inhibitors and methods of making and using the same
WO2016168682A3 (en) Bromodomain inhibitor
MX378717B (es) Acidos carboxilicos heterociclicos como activadores de guanilato ciclasa soluble.
PH12016501977A1 (en) 2-AMINO-6-METHYL-4,4a,5,6-TETRAHYDROPYRANO[3,4-d][1,3]THIAZIN-8a(8H)-YL-1,3-THIAZOL-4-YL AMIDES
EA201691794A1 (ru) Конденсированные [1,4]диазепиновые соединения в качестве ингибиторов продукции аутотаксина (atx) и лизофосфатидиловой кислоты (lpa)
EA201691141A1 (ru) Соединения против ccr6
EA201500298A1 (ru) Алкоксипиразолы в качестве активаторов растворимой гуанилатциклазы
PH12017500841A1 (en) 2-amino-6-(difluoromethyl)- 5,5-difluoro-6-phenyl-3,4,5,6-tetrahydropyridines as bace1 inhibitors
EA201500182A1 (ru) 4-МЕТИЛ-2,3,5,9,9b-ПЕНТААЗАЦИКЛОПЕНТА[a]НАФТАЛИНЫ
MX350211B (es) Proceso para la preparacion del etil-ester del acido n- (4-ciclohexil-3-trifluoro-metil-benciloxi) -acetimidico.
MX379846B (es) Derivados de 4-bencil y 4-benzoil piperidina sustituidos.
MX387443B (es) Compuestos de heteroarilcarboxamida como inhibidores de ripk2
MX377644B (es) 6.7.beta-epóxidos esteroideos como intermedios químicos.
MX378555B (es) Proceso para la preparacion de derivados del acido biliar de las sulfonilureas
MX392586B (es) Derivados de la espiropiperidina.
TN2017000342A1 (en) Novel cyclopropabenzofuranyl pyridopyrazinediones