CA2943815C - Substituted indole mcl-1 inhibitors - Google Patents

Substituted indole mcl-1 inhibitors Download PDF

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Publication number
CA2943815C
CA2943815C CA2943815A CA2943815A CA2943815C CA 2943815 C CA2943815 C CA 2943815C CA 2943815 A CA2943815 A CA 2943815A CA 2943815 A CA2943815 A CA 2943815A CA 2943815 C CA2943815 C CA 2943815C
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Prior art keywords
optionally substituted
cooh
nitrogen
sulfur
independently selected
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CA2943815A
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English (en)
French (fr)
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CA2943815A1 (en
Inventor
Taekyu Lee
Zhiguo BIAN
Johannes BELMAR
Plamen P. CHRISTOV
Nicholas F. Pelz
Subrata SHAW
Kwangho Kim
James C. Tarr
Edward T. Olejniczak
Bin Zhao
Stephen W. Fesik
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Vanderbilt University
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Vanderbilt University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered 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
    • A61K31/40—Heterocyclic 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
    • A61K31/403—Heterocyclic 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
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/40—Heterocyclic 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
    • A61K31/403—Heterocyclic 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
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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
    • A61K31/4155—1,2-Diazoles non 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine 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
    • A61K31/495—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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D401/14—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 three or more 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
    • C07D403/04—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
    • 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
    • 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
    • C07D403/14—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 three or more hetero rings
    • 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
    • C07D405/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D409/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D409/14—Heterocyclic 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
    • 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
    • C07D471/02—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 two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Indole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CA2943815A 2014-03-27 2015-03-26 Substituted indole mcl-1 inhibitors Active CA2943815C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201461971023P 2014-03-27 2014-03-27
US61/971,023 2014-03-27
PCT/US2015/022841 WO2015148854A1 (en) 2014-03-27 2015-03-26 Substituted indole mcl-1 inhibitors

Publications (2)

Publication Number Publication Date
CA2943815A1 CA2943815A1 (en) 2015-10-01
CA2943815C true CA2943815C (en) 2023-04-04

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CA2943815A Active CA2943815C (en) 2014-03-27 2015-03-26 Substituted indole mcl-1 inhibitors

Country Status (7)

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US (3) US10533010B2 (OSRAM)
EP (1) EP3122353B1 (OSRAM)
JP (1) JP6757312B2 (OSRAM)
CN (1) CN106456602B (OSRAM)
AU (1) AU2015235944B2 (OSRAM)
CA (1) CA2943815C (OSRAM)
WO (1) WO2015148854A1 (OSRAM)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2943815C (en) 2014-03-27 2023-04-04 Vanderbilt University Substituted indole mcl-1 inhibitors
US9949965B2 (en) 2014-10-17 2018-04-24 Vanderbilt University Tricyclic indole Mcl-1 inhibitors and uses thereof
US11306107B2 (en) 2016-02-25 2022-04-19 Amgen Inc. Compounds that inhibit MCL-1 protein
EP4292662A3 (en) * 2016-03-04 2024-02-21 Vanderbilt University Substituted indole mcl-1 inhibitors
MX386103B (es) 2016-04-22 2025-03-18 Astrazeneca Ab Inhibidores de mcl-1 y metodos de uso de los mismos.
EP3458459B1 (en) 2016-05-19 2022-04-27 Bayer Aktiengesellschaft Macrocyclic indole derivatives
WO2017198341A1 (en) 2016-05-19 2017-11-23 Bayer Aktiengesellschaft Macrocyclic indole derivatives
JOP20190024A1 (ar) 2016-08-26 2019-02-19 Gilead Sciences Inc مركبات بيروليزين بها استبدال واستخداماتها
JP6453507B2 (ja) * 2017-03-30 2019-01-16 アムジエン・インコーポレーテツド Ｍｃｌ−１タンパク質を阻害する化合物
TW201841888A (zh) * 2017-04-30 2018-12-01 財團法人生物技術開發中心 一種抗癌幹性之藥物
WO2019040511A1 (en) * 2017-08-22 2019-02-28 University Of Maryland Batimore DOUBLE INHIBITORS OF BCL-2 AND HDM2 FAMILIES BY CO-MIMETTISM OF ALPHA BH3 AND P53 PROPELLERS
AR113887A1 (es) 2017-11-17 2020-06-24 Bayer Ag Derivados de indol macrocíclicos sustituidos con cloro
EP3710450A1 (en) 2017-11-17 2020-09-23 Bayer Aktiengesellschaft Macrocyclic chlorine substituted indole derivatives
WO2019096907A1 (en) 2017-11-17 2019-05-23 Bayer Aktiengesellschaft Aryl annulated macrocyclic indole derivatives
UY37973A (es) 2017-11-17 2019-06-28 Bayer Ag Derivados de indol macrocíclicos
WO2019096909A1 (en) 2017-11-17 2019-05-23 The Broad Institute, Inc. Macrocyclic fluorine substituted indole derivatives as mcl-1 inhibitors, for use in the treatment of cancer
UY37971A (es) 2017-11-17 2019-06-28 Bayer Ag Derivados de indol macrocíclicos sustituidos
CN109988151B (zh) * 2017-12-29 2021-04-23 北京赛特明强医药科技有限公司 一种炔类化合物、制备方法及其应用
CA3091142C (en) 2018-02-26 2023-04-11 Gilead Sciences, Inc. Substituted pyrrolizine compounds and uses thereof
CN108251104B (zh) * 2018-02-27 2019-11-05 山东大学 一种取代吲哚-2-羧酸类Bcl-2小分子荧光探针及其应用
KR102732008B1 (ko) * 2018-05-14 2024-11-20 길리애드 사이언시즈, 인코포레이티드 Mcl-1 억제제
EP3810573A4 (en) 2018-06-25 2021-12-08 Suzhou Mednes Pharma Tech Co., Ltd. COMPOUNDS AND METHODS FOR THE TREATMENT OF CONDITIONS ASSOCIATED WITH THE HEDGEHOG ROUTE
BR112021005655A2 (pt) 2018-09-27 2021-06-29 Pierre Fabre Medicament ligantes à base de sulfomaleimida e conjugados correspondentes
US11691989B2 (en) 2018-11-22 2023-07-04 Ascentage Pharma (Suzhou) Co., Ltd. Macrocyclic indoles as Mcl-1 inhibitors
WO2020147802A1 (en) 2019-01-18 2020-07-23 Ascentage Pharma (Suzhou) Co., Ltd. Macrocyclic spiroethers as mcl-1 inhibitors
EP3969457B1 (en) 2019-05-17 2025-08-13 The Broad Institute Inc. Methods of preparing macrocyclic indoles
WO2021092061A1 (en) * 2019-11-08 2021-05-14 Unity Biotechnology, Inc. Combination treatment for senescence-associated diseases
WO2021092053A1 (en) * 2019-11-08 2021-05-14 Unity Biotechnology, Inc. Mcl-1 inhibitor macrocycle compounds for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
AU2023389065A1 (en) * 2022-12-06 2025-06-19 Captor Therapeutics S.A. Targeted protein degradation using bifunctional compounds that bind ubiquitin ligase and target mcl-1 protein
WO2024123195A1 (en) * 2022-12-06 2024-06-13 Captor Therapeutics S.A. Targeted protein degradation using prodrugs of bifunctional compounds that bind ubiquitin ligase and target mcl-1 protein
WO2025104079A1 (en) * 2023-11-17 2025-05-22 Helmholtz-Zentrum für Infektionsforschung GmbH Salicylic acid and picolinic acid derivatives as inhibitors of energy coupling factor (ecf) transporters for the treatment of bacterial infections

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4703053A (en) 1985-10-28 1987-10-27 Warner-Lambert Company Benzothiophenes and benzofurans and antiallergic use thereof
GB8531612D0 (en) 1985-12-23 1986-02-05 Beecham Wuelfing Gmbh & Co Kg Compounds
US4994477A (en) * 1988-03-24 1991-02-19 Abbott Laboratories Heterocyclic renin inhibitors
DE4128015A1 (de) 1991-08-23 1993-02-25 Kali Chemie Pharma Gmbh 1,7-anellierte 2-(piperazinoalkyl)indol-derivate sowie verfahren und zwischenprodukte zu ihrer herstellung und diese verbindugnen enthaltende arzneimittel
EP0639573A1 (de) 1993-08-03 1995-02-22 Hoechst Aktiengesellschaft Benzokondensierte 5-Ringheterocyclen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, ihre Verwendung als Diagnostikum, sowie sie enthaltendes Medikament
US5436264A (en) * 1993-08-19 1995-07-25 Syntex (U.S.A.) Inc. N-aryloxyalkyl tryptamine α1 -adrenergic receptor antagonists
JP3739432B2 (ja) 1994-02-25 2006-01-25 ダイセル化学工業株式会社 オゾン開裂反応
WO1997042188A1 (en) 1996-05-08 1997-11-13 Kumiai Chemical Industry Co., Ltd. Indolyl-substituted uracil derivatives and herbicides comprising them as active ingredients
CA2265853C (en) 1996-09-12 2010-08-03 Idun Pharmaceuticals, Inc. Inhibition of apoptosis using interleukin-1.beta.-converting enzyme (ice)/ced-3 family inhibitors
FR2761073B1 (fr) * 1997-03-20 1999-04-23 Synthelabo Derives de pyrazino[1,2-a]indole-1-one, leur preparation et leur application en therapeutique
FR2761070B1 (fr) 1997-03-20 1999-04-23 Synthelabo Derives de dihydropyrazino[1,2-a]indole-1-one, leur preparation et leur application en therapeutique
US6500853B1 (en) 1998-02-28 2002-12-31 Genetics Institute, Llc Inhibitors of phospholipase enzymes
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
FR2827287B1 (fr) 2001-07-13 2003-10-31 Servier Lab Nouveaux derives de benzene sulfonamide, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2005056522A2 (en) 2003-12-04 2005-06-23 National Health Research Institutes Indole compounds
US7429611B2 (en) 2004-09-23 2008-09-30 Bristol-Myers Squibb Company Indole inhibitors of 15-lipoxygenase
WO2007112322A2 (en) 2006-03-28 2007-10-04 Allergan, Inc. Indole compounds having sphingosine-1-phosphate (s1p) receptor agonist and/or antagonist biological activity
DE102006033109A1 (de) 2006-07-18 2008-01-31 Grünenthal GmbH Substituierte Heteroaryl-Derivate
PL2094662T3 (pl) 2006-12-14 2012-09-28 Astellas Pharma Inc Związki oparte na policyklicznych kwasach użyteczne jako antagoniści rCRTH2 oraz jako środki przeciwalergiczne
JP5496877B2 (ja) 2007-04-16 2014-05-21 アッヴィ・インコーポレイテッド ７−置換インドールＭｃｌ−１阻害薬
CA2951295C (en) * 2007-04-16 2020-04-28 Abbvie Inc. 7-nonsubstituted indole mcl-1 inhibitors
US20090270497A1 (en) 2008-04-24 2009-10-29 Pharmacyclics, Inc. Treatment of Non-Localized Inflammation with pan-HDAC Inhibitors
EP2161266A1 (en) 2008-08-22 2010-03-10 EVOTEC Neurosciences GmbH Benzofuran derivatives as orexin receptor antagonists
EP3124494B1 (en) 2008-12-09 2019-06-19 Dana-Farber Cancer Institute, Inc. Methods and compositions for specific modulation of mcl-1
FR2961393B1 (fr) 2010-06-16 2013-02-15 Oreal Procede de coloration capillaire a partir d'une composition comprenant au moins un compose indolique ou une indolinique, un sel metallique, du peroxyde d'hydrogene et un agent alcalinisant
CN103201263A (zh) 2010-09-08 2013-07-10 匹兹堡高等教育联邦体系大学 p53-Mdm2拮抗剂
AU2012226398B9 (en) 2011-03-06 2017-04-13 Merck Serono S.A. Low fucose cell lines and uses thereof
CN103974956B (zh) 2011-11-29 2016-07-06 南京奥昭生物科技有限公司 作为hdac6抑制剂和用作抗肿瘤剂的杂环酰胺化合物
WO2013112878A1 (en) * 2012-01-26 2013-08-01 The Penn State Research Foundation Mcl-1 modulating compositions
WO2014047427A2 (en) 2012-09-21 2014-03-27 Vanderbilt University Substituted benzofuran, benzothiophene and indole mcl-1 inhibitors
US10005728B2 (en) 2013-08-28 2018-06-26 Vanderbilt University Substituted indole Mcl-1 inhibitors
CA2943815C (en) 2014-03-27 2023-04-04 Vanderbilt University Substituted indole mcl-1 inhibitors
US9949965B2 (en) 2014-10-17 2018-04-24 Vanderbilt University Tricyclic indole Mcl-1 inhibitors and uses thereof
EP4292662A3 (en) 2016-03-04 2024-02-21 Vanderbilt University Substituted indole mcl-1 inhibitors

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