JP2023520400A - アルファ-1-アンチトリプシン欠損症(aatd)を治療するためのアルファ-1-アンチトリプシンモジュレーターとしてのインドール誘導体 - Google Patents

アルファ-1-アンチトリプシン欠損症(aatd)を治療するためのアルファ-1-アンチトリプシンモジュレーターとしてのインドール誘導体 Download PDF

Info

Publication number
JP2023520400A
JP2023520400A JP2022559587A JP2022559587A JP2023520400A JP 2023520400 A JP2023520400 A JP 2023520400A JP 2022559587 A JP2022559587 A JP 2022559587A JP 2022559587 A JP2022559587 A JP 2022559587A JP 2023520400 A JP2023520400 A JP 2023520400A
Authority
JP
Japan
Prior art keywords
alkyl
compounds
pharmaceutically acceptable
cyano
optionally substituted
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.)
Pending
Application number
JP2022559587A
Other languages
English (en)
Japanese (ja)
Other versions
JP2023520400A5 (enExample
Inventor
サイモン ジルー,
マイケル フィリップ クラーク,
マイケル アーロン ブロドニー,
フィリップ マルセル ヌハント,
エミリー エリザベス アレン,
ロバート フランシス ジュニア フィモナリ,
マリアム ザキー,
マイケル ジョン ボイド,
デイビッド ディー. デイニンガー,
フー ジャン,
ホンボ デン,
フィリップ ノエル コリアー,
ブラッド マクスウェル,
ネイサン ディー. ワール,
スティーブン エム. ロンキン,
ジアン ワン,
チン タン,
ガブリエル シモーヌ フレミング,
ピーター ジョーンズ,
ダイアン マリー バウチャー,
レブ ティー.ディー. ファニング,
エイミー ビー. ホール,
デニス ジェイムズ ハーレー,
マック アーサー ジュニア ジョンソン,
ジョン パトリック マクスウェル,
レベッカ ジェーン スウェット,
ティモシー ルイス タプレイ,
スティーブン エー. トムソン,
ヴェロニク ダマグネス,
ケヴィン マイケル コットレル,
ユプル キールティ バンダレージ,
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.)
Vertex Pharmaceuticals Inc
Original Assignee
Vertex Pharmaceuticals Inc
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 Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc
Publication of JP2023520400A publication Critical patent/JP2023520400A/ja
Publication of JP2023520400A5 publication Critical patent/JP2023520400A5/ja
Pending legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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
    • A61K31/4151,2-Diazoles
    • A61K31/41621,2-Diazoles condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/08Bronchodilators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/10Expectorants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02Local antiseptics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/08Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D209/20Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/30Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/06Heterocyclic 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 only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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 two hetero rings
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/06Phosphorus compounds without P—C bonds
    • C07F9/08Esters of oxyacids of phosphorus
    • C07F9/09Esters of phosphoric acids
    • C07F9/117Esters of phosphoric acids with cycloaliphatic alcohols
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/50Organo-phosphines
    • C07F9/53Organo-phosphine oxides; Organo-phosphine thioxides
    • C07F9/5325Aromatic phosphine oxides or thioxides (P-C aromatic linkage)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/08Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05Isotopically modified compounds, e.g. labelled

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Nutrition Science (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Saccharide Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
JP2022559587A 2020-04-03 2021-04-02 アルファ-1-アンチトリプシン欠損症(aatd)を治療するためのアルファ-1-アンチトリプシンモジュレーターとしてのインドール誘導体 Pending JP2023520400A (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202063004717P 2020-04-03 2020-04-03
US63/004,717 2020-04-03
PCT/US2021/025614 WO2021203023A1 (en) 2020-04-03 2021-04-02 Indole derivatives as alpha-1 -antitrypsin modulators for treating alpha-1 -antitrypsin deficiency (aatd)

Publications (2)

Publication Number Publication Date
JP2023520400A true JP2023520400A (ja) 2023-05-17
JP2023520400A5 JP2023520400A5 (enExample) 2024-04-10

Family

ID=75919370

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2022559587A Pending JP2023520400A (ja) 2020-04-03 2021-04-02 アルファ-1-アンチトリプシン欠損症(aatd)を治療するためのアルファ-1-アンチトリプシンモジュレーターとしてのインドール誘導体

Country Status (13)

Country Link
US (1) US20230159502A1 (enExample)
EP (1) EP4132908A1 (enExample)
JP (1) JP2023520400A (enExample)
KR (1) KR20220165260A (enExample)
CN (1) CN115916748A (enExample)
AR (1) AR121745A1 (enExample)
AU (1) AU2021246526A1 (enExample)
BR (1) BR112022019792A2 (enExample)
CA (1) CA3177531A1 (enExample)
IL (1) IL296920A (enExample)
MX (1) MX2022011829A (enExample)
TW (1) TWI908788B (enExample)
WO (1) WO2021203023A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2023520396A (ja) * 2020-04-03 2023-05-17 バーテックス ファーマシューティカルズ インコーポレイテッド アルファ1-アンチトリプシンのモジュレーター

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3114672A1 (en) 2018-10-05 2020-04-23 Vertex Pharmaceuticals Incorporated Modulators of alpha-1 antitrypsin
US11884672B2 (en) 2019-05-14 2024-01-30 Vertex Pharmaceuticals Incorporated Modulators of alpha-1 antitrypsin
WO2022104353A1 (en) 2020-11-12 2022-05-19 Vertex Pharmaceuticals Incorporated Methods of monitoring alpha-1 antitrypsin (aat) deficiency by measuring polymerised aat
TW202440093A (zh) * 2023-03-06 2024-10-16 香港商英矽智能科技知識產權有限公司 Cdk8/19雙重抑制劑及其使用方法
EP4687883A2 (en) * 2023-04-05 2026-02-11 Caraway Therapeutics, Inc. Modulators of trpml, their compositions and methods of use

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996037467A1 (en) * 1995-05-22 1996-11-28 Merck Frosst Canada Inc. N-benzylindol-3-yl butanoic acid derivatives as cyclooxygenase-2 inhibitors
US20030165712A1 (en) * 2001-12-27 2003-09-04 Lightronik Technology Inc. Organic EL Device
JP2011512382A (ja) * 2008-02-19 2011-04-21 グラクソ グループ リミテッド エストロゲン様物質としての置換4−ヒドロキシ−n−(4−ヒドロキシフェニル)インドール
JP2011516602A (ja) * 2008-04-16 2011-05-26 カロ バイオ アクチェブラーグ 新規エストロゲン受容体リガンド
WO2012063753A1 (ja) * 2010-11-08 2012-05-18 日本電気株式会社 インドール系化合物、並びにこれを用いた光電変換用色素、半導体電極、光電変換素子および光電気化学電池
WO2012111610A1 (ja) * 2011-02-14 2012-08-23 日本電気株式会社 チアゾール系化合物及びその用途
WO2021203007A1 (en) * 2020-04-03 2021-10-07 Vertex Pharmaceuticals Incorporated Substituted 5-hydroxyindole compounds as modulators of alpha-1 antitrypsin

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002211901A1 (en) * 2000-10-10 2002-04-22 Smithkline Beecham Corporation Substituted indoles, pharmaceutical compositions containing such indoles and their use as PPAR-gamma binding agents
US7223785B2 (en) * 2003-01-22 2007-05-29 Boehringer Ingelheim International Gmbh Viral polymerase inhibitors
US20070203209A1 (en) * 2005-08-18 2007-08-30 Wilmin Bartolini Useful indole compounds
BRPI0710527B8 (pt) * 2006-04-04 2021-05-25 Fibrogen Inc compostos de pirrolo- e tiazolo-piridina e composição farmacêutica que os compreende
SG176477A1 (en) * 2006-08-07 2011-12-29 Ironwood Pharmaceuticals Inc Indole compounds
MX2020013853A (es) * 2018-06-22 2021-05-27 Ucl Business Ltd Compuestos innovadores.
TWI748194B (zh) * 2018-06-28 2021-12-01 德商菲尼克斯 Fxr有限責任公司 含有雙環核心部分之新穎lxr調節劑

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996037467A1 (en) * 1995-05-22 1996-11-28 Merck Frosst Canada Inc. N-benzylindol-3-yl butanoic acid derivatives as cyclooxygenase-2 inhibitors
US20030165712A1 (en) * 2001-12-27 2003-09-04 Lightronik Technology Inc. Organic EL Device
JP2011512382A (ja) * 2008-02-19 2011-04-21 グラクソ グループ リミテッド エストロゲン様物質としての置換4−ヒドロキシ−n−(4−ヒドロキシフェニル)インドール
JP2011516602A (ja) * 2008-04-16 2011-05-26 カロ バイオ アクチェブラーグ 新規エストロゲン受容体リガンド
WO2012063753A1 (ja) * 2010-11-08 2012-05-18 日本電気株式会社 インドール系化合物、並びにこれを用いた光電変換用色素、半導体電極、光電変換素子および光電気化学電池
WO2012111610A1 (ja) * 2011-02-14 2012-08-23 日本電気株式会社 チアゾール系化合物及びその用途
WO2021203007A1 (en) * 2020-04-03 2021-10-07 Vertex Pharmaceuticals Incorporated Substituted 5-hydroxyindole compounds as modulators of alpha-1 antitrypsin

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FARNAZ JAFARPOUR, ET AL.: "A Fast Track to Indoles and Annulated Indoles through ortho- vs ipso-Amination of Aryl Halides", ORGANIC LETTERS, vol. 21, JPN6025010336, 2019, pages 10143 - 10148, ISSN: 0005675439 *
LIN HE, ET AL.: "Transition-metal-free synthesis of multisubstituted N-arylindoles via reaction of arynes and a-amino", TETRAHEDRON, vol. 70, JPN6025010337, 2014, pages 2400 - 2405, ISSN: 0005675440 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2023520396A (ja) * 2020-04-03 2023-05-17 バーテックス ファーマシューティカルズ インコーポレイテッド アルファ1-アンチトリプシンのモジュレーター
JP7732999B2 (ja) 2020-04-03 2025-09-02 バーテックス ファーマシューティカルズ インコーポレイテッド アルファ1-アンチトリプシンのモジュレーター

Also Published As

Publication number Publication date
AR121745A1 (es) 2022-07-06
US20230159502A1 (en) 2023-05-25
CN115916748A (zh) 2023-04-04
AU2021246526A1 (en) 2022-11-03
EP4132908A1 (en) 2023-02-15
BR112022019792A2 (pt) 2022-12-06
MX2022011829A (es) 2022-12-15
WO2021203023A1 (en) 2021-10-07
TWI908788B (zh) 2025-12-21
KR20220165260A (ko) 2022-12-14
CA3177531A1 (en) 2021-10-07
IL296920A (en) 2022-12-01
TW202208332A (zh) 2022-03-01

Similar Documents

Publication Publication Date Title
JP2023520400A (ja) アルファ-1-アンチトリプシン欠損症(aatd)を治療するためのアルファ-1-アンチトリプシンモジュレーターとしてのインドール誘導体
JP7641238B2 (ja) α-1抗トリプシンモジュレーターとしての縮合三環系ピロール
US20230265080A1 (en) Modulators of alpha-1 antitrypsin
JP7573528B2 (ja) Apol1の阻害剤及びその使用方法
EP2556070B1 (en) Synthesis of chiral 2-(1h-indazol-6-yl)-spiro[cyclopropane-1,3'- indolin]-2'-ones
WO2020035065A1 (zh) 作为ret抑制剂的吡唑衍生物
TWI794880B (zh) 作為組蛋白去乙醯酶6抑制劑之新穎化合物及包含其之醫藥組合物
JP7733670B2 (ja) アルファ1-アンチトリプシンのモジュレーター
CN115715292B (zh) α-1-抗胰蛋白酶调节剂
JP2025516367A (ja) Parp1を選択的に阻害するフルオロキノキサリノン誘導体
JP2023520398A (ja) アルファ1-アンチトリプシンのモジュレーター
JP7791102B2 (ja) アルファ1-アンチトリプシンのモジュレーター
JP2023520396A (ja) アルファ1-アンチトリプシンのモジュレーター
CN115916749B (en) Alpha-1 antitrypsin modulators
WO2020119590A1 (zh) 3-氰基吡啶类化合物、包含其的药物组合物及其制备方法和用途
EA050129B1 (ru) Производные индола в качестве модуляторов альфа-1-антитрипсина для лечения дефицита альфа-1-антитрипсина (aatd)
WO2025252142A1 (zh) 一种血管紧张素ii型2受体激动剂及其用途
CN117940430A (zh) 作为Wee-1抑制剂的1,2-二氢-3H-吡唑[3,4-d]嘧啶-3-酮化合物

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20240328

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20240328

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20250220

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20250312

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20250612

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20250829

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20251201

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20251209

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20260109

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20260409

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20260422