RU2668960C2 - Способ синтеза аналогов гормонов щитовидной железы и их полиморфов - Google Patents

Способ синтеза аналогов гормонов щитовидной железы и их полиморфов Download PDF

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RU2668960C2
RU2668960C2 RU2015114327A RU2015114327A RU2668960C2 RU 2668960 C2 RU2668960 C2 RU 2668960C2 RU 2015114327 A RU2015114327 A RU 2015114327A RU 2015114327 A RU2015114327 A RU 2015114327A RU 2668960 C2 RU2668960 C2 RU 2668960C2
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RU2015114327A
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RU2015114327A (ru
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II Д. Кит ХЕСТЕР
Роберт Дж. ДЬЮГИД
Марта КЕЛЛИ
Анна ЧАСНОФФ
Ган ДУН
Эдвин Л. КРОУ
Ребекка ТАУБ
Чарльз Х. РЕЙНОЛДС
Дук Соон ЧОЙ
Ляньхэ ШУ
Пин ВАН
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Мадригал Фармасьютикалз, Инк.
Ф.Хоффманн-Ля Рош Лтд.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/14—Oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/14—Oxygen atoms
    • C07D237/16—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Diabetes (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
RU2015114327A 2012-09-17 2013-09-17 Способ синтеза аналогов гормонов щитовидной железы и их полиморфов RU2668960C2 (ru)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261702137P 2012-09-17 2012-09-17
US61/702,137 2012-09-17
US201361790432P 2013-03-15 2013-03-15
US61/790,432 2013-03-15
PCT/US2013/060177 WO2014043706A1 (en) 2012-09-17 2013-09-17 Method of synthesizing thyroid hormone analogs and polymorphs thereof

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US (8) US9266861B2 (en:Method)
EP (4) EP4406594B1 (en:Method)
JP (7) JP6616688B2 (en:Method)
KR (4) KR102363776B1 (en:Method)
CN (2) CN108101851A (en:Method)
AR (1) AR092872A1 (en:Method)
AU (1) AU2013315017C1 (en:Method)
BR (2) BR112015005891A2 (en:Method)
CA (3) CA2884481C (en:Method)
DK (2) DK2895466T3 (en:Method)
ES (2) ES2795450T3 (en:Method)
IL (7) IL288133B2 (en:Method)
IN (1) IN2015DN03133A (en:Method)
MX (2) MX364661B (en:Method)
MY (1) MY170520A (en:Method)
NZ (2) NZ705827A (en:Method)
RU (2) RU2668960C2 (en:Method)
SG (3) SG10202006058QA (en:Method)
TW (4) TWI804870B (en:Method)
WO (1) WO2014043706A1 (en:Method)
ZA (1) ZA201501795B (en:Method)

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RU2809040C2 (ru) * 2018-12-13 2023-12-06 Тернс, Инк. АГОНИСТ РЕЦЕПТОРОВ THRβ И СПОСОБ ЕГО ПОЛУЧЕНИЯ И ПРИМЕНЕНИЕ
US12338232B2 (en) 2018-12-13 2025-06-24 Terns, Inc. THRβ receptor agonist compound and preparation method and use thereof
US12398127B2 (en) 2019-09-12 2025-08-26 Terns Pharmaceuticals, Inc. Thyroid hormone receptor beta agonist compounds

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CN108101851A (zh) * 2012-09-17 2018-06-01 马德里加尔制药公司 合成甲状腺激素类似物及其多形体的方法
JP2019533019A (ja) 2016-10-18 2019-11-14 マドリガル ファーマシューティカルズ インコーポレイテッドＭａｄｒｉｇａｌ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． Ｔｈｒ−ベータアゴニストで肝臓障害又は脂質障害を治療する方法
WO2019144835A1 (zh) * 2018-01-23 2019-08-01 深圳市塔吉瑞生物医药有限公司 取代的哒嗪酮化合物
EP3807267B1 (en) * 2018-06-12 2025-03-19 Xizang Haisco Pharmaceutical Co., Ltd. Thyroid hormone receptor agonists and uses thereof
WO2019242766A1 (zh) * 2018-06-22 2019-12-26 成都海创药业有限公司 氘代mgl-3196化合物及其用途
AR115666A1 (es) * 2018-07-02 2021-02-10 Madrigal Pharmaceuticals Inc Formas sólidas de 2-(3,5-dicloro-4-((5-isopropil-6-oxo-1,6-dihidropiridazin-3-il)oxi)fenil)-3,5-dioxo-2,3,4,5-tetrahidro-1,2,4-triazin-6-carbonitrilo
KR20210076932A (ko) * 2018-10-12 2021-06-24 인벤티스바이오 컴퍼니 리미티드 갑상선 호르몬 수용체 작용제
JP7445996B2 (ja) 2019-02-21 2024-03-08 ナンジン・ルイジェ・ファーマ・カンパニー・リミテッド 新規化合物及び甲状腺ホルモン受容体アゴニストとしてのそれらの使用
PT3965884T (pt) 2019-05-08 2025-03-31 Aligos Therapeutics Inc Moduladores de thr-beta com um grupo de cabeça dioxo-1,2,4-triazilo
WO2020228577A1 (zh) * 2019-05-10 2020-11-19 深圳微芯生物科技股份有限公司 一种哒嗪酮衍生物及其应用
WO2020239076A1 (zh) * 2019-05-29 2020-12-03 南京明德新药研发有限公司 作为甲状腺素受体-β激动剂的哒嗪酮类衍生物及其应用
CN112442013B (zh) * 2019-09-04 2022-07-26 广东东阳光药业有限公司 一种作为甲状腺激素β受体激动剂的化合物及其用途
WO2021063367A1 (zh) * 2019-09-30 2021-04-08 苏州科睿思制药有限公司 一种Resmetirom晶型及其制备方法和用途
CN112707892A (zh) * 2019-10-24 2021-04-27 苏州泽璟生物制药股份有限公司 哒嗪酮或哒嗪类化合物及其衍生物和药物组合物
WO2021104288A1 (zh) 2019-11-26 2021-06-03 昆药集团股份有限公司 1，2，4-三嗪-3，5-二酮类化合物及其制备方法和应用
TW202128668A (zh) * 2019-12-16 2021-08-01 大陸商江蘇恆瑞醫藥股份有限公司 并環類衍生物、其製備方法及其在醫藥上的應用
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CN114437034A (zh) * 2020-11-06 2022-05-06 深圳微芯生物科技股份有限公司 一种酞嗪类化合物的可药用盐、晶型及其制备方法
KR20230142523A (ko) 2021-02-01 2023-10-11 마드리갈 파마슈티칼스, 인크. 간 장애 또는 지질 장애의 치료를 위한 로수바스타틴 및 레스메티롬의 치료용 조합
CN114907327A (zh) * 2021-02-10 2022-08-16 杭州领业医药科技有限公司 Resmetirom的晶型及其制备方法和用途
CN115073429A (zh) * 2021-03-15 2022-09-20 昆药集团股份有限公司 一种1，2，4-三嗪-3，5-二酮类化合物的盐型、晶型及其制备方法
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CN116768802A (zh) * 2023-05-25 2023-09-19 杭州科巢生物科技有限公司 一种瑞司美替罗的合成方法
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CN117263870A (zh) * 2023-09-21 2023-12-22 江西同和药业股份有限公司 一种Resmetirom关键中间体III的制备方法
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RU2809040C2 (ru) * 2018-12-13 2023-12-06 Тернс, Инк. АГОНИСТ РЕЦЕПТОРОВ THRβ И СПОСОБ ЕГО ПОЛУЧЕНИЯ И ПРИМЕНЕНИЕ
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US12365669B2 (en) 2018-12-13 2025-07-22 Terns, Inc. THRβ receptor agonist compound and preparation method and use thereof
RU2820475C2 (ru) * 2019-08-21 2024-06-04 Хинова Фармасьютикалс Инк. Галогензамещенное фенилатное соединение и его применения
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