CN115916749B - α-1抗胰蛋白酶调节剂 - Google Patents

α-1抗胰蛋白酶调节剂

Info

Publication number
CN115916749B
CN115916749B CN202180039825.2A CN202180039825A CN115916749B CN 115916749 B CN115916749 B CN 115916749B CN 202180039825 A CN202180039825 A CN 202180039825A CN 115916749 B CN115916749 B CN 115916749B
Authority
CN
China
Prior art keywords
compounds
alkyl
mmol
fluoro
methyl
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
CN202180039825.2A
Other languages
English (en)
Chinese (zh)
Other versions
CN115916749A (zh
Inventor
S·吉鲁
M·P·克拉克
Q·唐
P·M·努汉特
P·琼斯
D·梅塞史密斯
U·K·班达拉格
K·M·科特雷尔
M·A·布罗德尼
G·S·弗莱明
J·王
J·徐
K·B·丹尼尔
M·J·博伊德
M·A·莫里斯
N·D·华尔
P·N·科利尔
S·凯萨万
S·M·朗金
H·邓
D·M·鲍彻
L·T·D·范宁
A·B·霍尔
D·J·赫利
M·A·小约翰逊
J·P·麦克斯韦
R·J·斯威特
T·L·塔普利
S·A·汤姆森
V·达马涅兹
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 CN115916749A publication Critical patent/CN115916749A/zh
Application granted granted Critical
Publication of CN115916749B publication Critical patent/CN115916749B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D209/22—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; 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
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/04—Heterocyclic 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
    • 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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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
    • C07D405/04—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/14—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/06—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Indole Compounds (AREA)
CN202180039825.2A 2020-04-03 2021-04-02 α-1抗胰蛋白酶调节剂 Active CN115916749B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202063004713P 2020-04-03 2020-04-03
US63/004713 2020-04-03
PCT/US2021/025591 WO2021203007A1 (en) 2020-04-03 2021-04-02 Substituted 5-hydroxyindole compounds as modulators of alpha-1 antitrypsin

Publications (2)

Publication Number Publication Date
CN115916749A CN115916749A (zh) 2023-04-04
CN115916749B true CN115916749B (zh) 2026-05-05

Family

ID=76444526

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202180039825.2A Active CN115916749B (zh) 2020-04-03 2021-04-02 α-1抗胰蛋白酶调节剂

Country Status (7)

Country Link
US (1) US20230339915A1 (enExample)
EP (1) EP4126817A1 (enExample)
JP (1) JP7733670B2 (enExample)
CN (1) CN115916749B (enExample)
AU (1) AU2021246104A1 (enExample)
CA (1) CA3177524A1 (enExample)
WO (1) WO2021203007A1 (enExample)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JOP20210060A1 (ar) 2018-10-05 2023-01-30 Vertex Pharma معدلات لمضاد تريبسين ألفا-1
US11884672B2 (en) 2019-05-14 2024-01-30 Vertex Pharmaceuticals Incorporated Modulators of alpha-1 antitrypsin
CN115697969B (zh) 2020-04-03 2026-08-11 弗特克斯药品有限公司 α-1抗胰蛋白酶调节剂
AU2021247285A1 (en) 2020-04-03 2022-10-27 Vertex Pharmaceuticals Incorporated Modulators of alpha-1 antitrypsin
CA3177531A1 (en) * 2020-04-03 2021-10-07 Vertex Pharmaceuticals Incorporated Indole derivatives as alpha-1 -antitrypsin modulators for treating alpha-1 -antitrypsin deficiency (aatd)
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
EP4188931A2 (en) 2020-07-27 2023-06-07 Vertex Pharmaceuticals Incorporated Processes for preparing 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
CN117384133A (zh) * 2023-10-11 2024-01-12 内蒙古益泽制药有限公司 一种2-溴-1-（吡啶-2-基）吲哚化合物及其制备方法
WO2026136445A1 (en) 2024-12-17 2026-06-25 Sub21, Inc. A1at modulators

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA200700243A1 (ru) 2004-07-14 2007-08-31 ПиТиСи ТЕРАПЬЮТИКС, ИНК. Способы лечения гепатита с
US8097644B2 (en) * 2006-03-28 2012-01-17 Allergan, Inc. Indole compounds having sphingosine-1-phosphate (S1P) receptor antagonist
JP5107589B2 (ja) * 2007-02-13 2012-12-26 旭化成株式会社 インドール誘導体
RS54165B1 (sr) * 2008-04-16 2015-12-31 Karo Bio Ab Novi ligandi za estrogenski receptor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SYNTHESIS OF ALDEHYDES AND NITI~ILES IN 5-HYDROXYINDOLE SERIES;A. N. Grinev, V. I. Shvedov等;Chemistry of Heterocyclic compounds;19751231;第11卷;1087-1090页 *

Also Published As

Publication number Publication date
CA3177524A1 (en) 2021-10-07
JP7733670B2 (ja) 2025-09-03
WO2021203007A1 (en) 2021-10-07
JP2023520207A (ja) 2023-05-16
AU2021246104A1 (en) 2022-10-20
EP4126817A1 (en) 2023-02-08
US20230339915A1 (en) 2023-10-26
CN115916749A (zh) 2023-04-04

Similar Documents

Publication Publication Date Title
JP7733670B2 (ja) アルファ１－アンチトリプシンのモジュレーター
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
AU2021286666A1 (en) Inhibitors of APOL1 and use of the same
AU2021246526A1 (en) Indole derivatives as alpha-1 -antitrypsin modulators for treating alpha-1 -antitrypsin deficiency (AATD)
US12502376B2 (en) Pyrano[4,3-b]indole derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD)
CN116348447A (zh) Apol1的抑制剂及其使用其的方法
TW202024091A (zh) α-1 抗胰蛋白酶之調節劑
JP7791102B2 (ja) アルファ１－アンチトリプシンのモジュレーター
CN101918376B (zh) 用作硬脂酰-辅酶a去饱和酶抑制剂的1，2，3-三唑衍生物
CN115715292B (zh) α-1-抗胰蛋白酶调节剂
CN114269755A (zh) 作为magl抑制剂的4,4a,5,7,8,8a-六吡啶并[4,3-b][1,4]噁嗪-3-酮化合物
CN101636386A (zh) 用作crth2拮抗剂和抗过敏剂的多环酸化合物
WO2021203010A1 (en) Pyrrolo[2,3-f]indazole and 2,4,5,10-tetrazatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8,11-pentaene derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (aatd)
CN116157393A (zh) Apol1的抑制剂及其用途
CN114907341A (zh) 吡啶并嘧啶酮类衍生物及其制备方法和用途
JP2002507999A (ja) トリアゾール化合物およびドーパミン−ｄ▲下３▼−リガンドとしてのその使用
CN120166990A (zh) α-1抗胰蛋白酶的调节剂
CN118974013A (zh) 吡咯烷化合物
US20080194584A1 (en) Nitrogen Heteroaromatic Compounds Which Bind To The Active Site Of Protein Kinase Enzymes
HK40062310A (en) 4,4a,5,7,8,8a-hexapyrido[4,3-b][1,4]oxazin-3-one compounds as magl inhibitors

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant