JP6462865B2 - 第ｘｉａ因子阻害剤としてのピリミジノン - Google Patents

第ｘｉａ因子阻害剤としてのピリミジノン Download PDF

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Publication number
JP6462865B2
JP6462865B2 JP2017517766A JP2017517766A JP6462865B2 JP 6462865 B2 JP6462865 B2 JP 6462865B2 JP 2017517766 A JP2017517766 A JP 2017517766A JP 2017517766 A JP2017517766 A JP 2017517766A JP 6462865 B2 JP6462865 B2 JP 6462865B2
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mmol
pharmaceutically acceptable
methyl
chloro
tautomer
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JP2017530157A (ja
Inventor
アンドリュー・ケイ・ディルガー
ジェイムズ・アール・コート
インダワティ・デ・ルッカ
ファン・ティアナン
ウー・ヤン
ワン・ユーフェン
クマール・バラシャンムガ・パビセッティ
ウィリアム・アール・ユーイング
イェヘン・ジュー
ルース・アール・ウェクスラー
ドナルド・ジェイ・ピー・ピント
マイケル・ジェイ・オーワット
レオン・エム・スミス・ザ・セカンド
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Bristol Myers Squibb Co
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Bristol Myers Squibb Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • 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
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • 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
    • C07D403/10—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 carbon chain containing aromatic rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pulmonology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
JP2017517766A 2014-10-01 2015-07-29 第ｘｉａ因子阻害剤としてのピリミジノン Active JP6462865B2 (ja)

Priority Applications (1)

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JP2018244086A JP6937734B2 (ja) 2014-10-01 2018-12-27 第ｘｉａ因子阻害剤としてのピリミジノン

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462058316P 2014-10-01 2014-10-01
US62/058,316 2014-10-01
PCT/US2015/042576 WO2016053455A1 (en) 2014-10-01 2015-07-29 Pyrimidinones as factor xia inhibitors

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JP2017530157A JP2017530157A (ja) 2017-10-12
JP6462865B2 true JP6462865B2 (ja) 2019-01-30

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JP2017517766A Active JP6462865B2 (ja) 2014-10-01 2015-07-29 第ｘｉａ因子阻害剤としてのピリミジノン
JP2018244086A Active JP6937734B2 (ja) 2014-10-01 2018-12-27 第ｘｉａ因子阻害剤としてのピリミジノン
JP2021140618A Active JP7317905B2 (ja) 2014-10-01 2021-08-31 第ｘｉａ因子阻害剤としてのピリミジノン
JP2023117409A Pending JP2023134734A (ja) 2014-10-01 2023-07-19 第ｘｉａ因子阻害剤としてのピリミジノン

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JP2021140618A Active JP7317905B2 (ja) 2014-10-01 2021-08-31 第ｘｉａ因子阻害剤としてのピリミジノン
JP2023117409A Pending JP2023134734A (ja) 2014-10-01 2023-07-19 第ｘｉａ因子阻害剤としてのピリミジノン

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Cited By (3)

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JP2018525368A (ja) * 2015-07-29 2018-09-06 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ アルキルまたはシクロアルキルＰ２’基を担持する大員環の第ＸＩａ因子阻害剤
JP2019069989A (ja) * 2014-10-01 2019-05-09 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 第ｘｉａ因子阻害剤としてのピリミジノン
JP2019094354A (ja) * 2014-01-31 2019-06-20 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環

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EP3189047B1 (en) 2014-09-04 2018-12-26 Bristol-Myers Squibb Company Diamide macrocycles that are fxia inhibitors
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
SG11201702628XA (en) 2014-10-01 2017-04-27 Merck Patent Gmbh Boronic acid derivatives
JOP20160086B1 (ar) 2015-05-08 2021-08-17 2 Katholieke Univ Leuven Ku Leuven Research And Development مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
EP3310777B1 (en) 2015-06-19 2019-10-09 Bristol-Myers Squibb Company Diamide macrocycles as factor xia inhibitors
EP3328852B1 (en) 2015-07-29 2021-04-28 Bristol-Myers Squibb Company Factor xia macrocyclic inhibitors bearing a non-aromatic p2' group
JO3633B1 (ar) 2015-09-16 2020-08-27 Katholieke Univ Leuven Ku Leuven Research & Development مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
JOP20160198B1 (ar) 2015-09-16 2022-03-14 Janssen Pharmaceuticals Inc مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
US10752641B2 (en) 2016-03-02 2020-08-25 Bristol-Myers Squibb Company Diamide macrocycles having factor XIa inhibiting activity
EP3436435B1 (en) 2016-03-31 2021-05-12 Janssen Pharmaceuticals, Inc. Substituted indole derivatives as dengue viral replication inhibitors
EA201892216A1 (ru) 2016-03-31 2019-03-29 Янссен Фармасьютикалз, Инк. Замещенные производные индолина в качестве ингибиторов репликации вирусов денге
JOP20170069B1 (ar) 2016-04-01 2021-08-17 1 Janssen Pharmaceuticals Inc مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
EP3436004B1 (en) 2016-04-01 2024-12-11 Janssen Pharmaceuticals, Inc. Substituted indole compound derivatives as dengue viral replication inhibitors
CN110062757B (zh) * 2017-01-18 2022-03-04 广东东阳光药业有限公司 凝血因子XIa抑制剂及其用途
JOP20180026A1 (ar) 2017-03-31 2019-01-30 Univ Leuven Kath مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
JOP20180025B1 (ar) 2017-03-31 2021-08-17 Janssen Pharmaceuticals Inc مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
TWI771420B (zh) 2017-05-22 2022-07-21 美商健生醫藥公司 作為登革熱病毒複製抑制劑之經取代之吲哚啉衍生物（一）
CN110691773B (zh) 2017-05-22 2023-06-23 杨森制药公司 作为登革热病毒复制抑制剂的经取代的吲哚啉衍生物
US20220144835A1 (en) * 2019-04-11 2022-05-12 Bristol-Myers Squibb Company Enhanced performance of amorphous solid and solubilized formulations for achieving therapeutic plasma concentrations
KR20220045105A (ko) * 2019-04-11 2022-04-12 브리스톨-마이어스 스큅 컴퍼니 (6r,10s)-10-{4-[5-클로로-2-(4-클로로-1h-1,2,3-트리아졸-1-일)페닐]-6-옥소-1(6h)-피리미디닐}-1-(디플루오로메틸)-6-메틸-1,4,7,8,9,10-헥사히드로-11,15-(메테노)피라졸로[4,3-b][1,7]디아자시클로테트라데신-5(6h)-온의 제조를 위한 신규 합성 옵션
US12018027B2 (en) 2019-04-16 2024-06-25 China Resources Biopharmaceutical Company Limited Macrocyclic derivatives acting as XIa factor inhibitor
US20220281868A1 (en) * 2019-07-23 2022-09-08 Medshine Discovery Inc. Macrocyclic derivatives as factor xia inhibitors
CN116120240A (zh) * 2019-09-27 2023-05-16 深圳信立泰药业股份有限公司 FXIa抑制剂化合物及其制备方法和医药用途
KR20230008742A (ko) * 2020-04-10 2023-01-16 브리스톨-마이어스 스큅 컴퍼니 (9r,135s)-13-{4-[5-클로로-2-(4-클로로-1h,2,3-트리아졸-1-일)페닐]-6-옥소-1,6-디히드로피리미딘-1-일}-3-(디플루오로메틸)-9-메틸-3,4,7,15-테트라아자트리시클로[12.3.1.02·6]옥타데카-1(18),2(6),4,14,16-펜타엔-8-온의 결정질 형태
TW202229280A (zh) * 2020-10-12 2022-08-01 美商必治妥美雅史谷比公司 （６ｒ，１０ｓ）－１０－｛４－［５－氯－２－（４－氯－１ｈ－１，２，３－三唑－１－基）苯基］－６－側氧基－１（６ｈ）－嘧啶基｝－１－（二氟甲基）－６－甲基－１，４，７，８，９，１０－六氫－１１，１５－（亞甲橋基）吡唑并［４，３－ｂ］［１，７］二氮雜環十四炔－５（６ｈ）－酮之製備方法
CA3204552A1 (en) 2021-01-08 2022-07-14 Joseph M. LUETTGEN Antibodies and antigen binding peptides for factor xia inhibitors and uses thereof
CN115215867B (zh) * 2021-04-21 2023-12-26 上海美悦生物科技发展有限公司 FXIa抑制剂及其药物组合物、制备方法和用途
CN119894901A (zh) * 2023-06-30 2025-04-25 深圳信立泰药业股份有限公司 一种多取代的大环化合物及其制备方法与应用
WO2025099743A1 (en) * 2023-11-07 2025-05-15 Dr. Reddy’S Laboratories Limited Process for preparation of milvexian and solid-state forms thereof

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JP2019094354A (ja) * 2014-01-31 2019-06-20 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環
JP2021088610A (ja) * 2014-01-31 2021-06-10 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環
JP7325464B2 (ja) 2014-01-31 2023-08-14 ブリストル－マイヤーズ スクイブ カンパニー ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環
JP2023133468A (ja) * 2014-01-31 2023-09-22 ブリストル－マイヤーズ スクイブ カンパニー ヘテロ環式ｐ２’基を有する第ｘｉａ因子阻害剤としてのマクロ環
JP2019069989A (ja) * 2014-10-01 2019-05-09 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 第ｘｉａ因子阻害剤としてのピリミジノン
JP2021185182A (ja) * 2014-10-01 2021-12-09 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company 第ｘｉａ因子阻害剤としてのピリミジノン
JP7317905B2 (ja) 2014-10-01 2023-07-31 ブリストル－マイヤーズ スクイブ カンパニー 第ｘｉａ因子阻害剤としてのピリミジノン
JP2018525368A (ja) * 2015-07-29 2018-09-06 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ アルキルまたはシクロアルキルＰ２’基を担持する大員環の第ＸＩａ因子阻害剤

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