AU2015235944B2 - Substituted indole Mcl-1 inhibitors - Google Patents

Substituted indole Mcl-1 inhibitors Download PDF

Info

Publication number
AU2015235944B2
AU2015235944B2 AU2015235944A AU2015235944A AU2015235944B2 AU 2015235944 B2 AU2015235944 B2 AU 2015235944B2 AU 2015235944 A AU2015235944 A AU 2015235944A AU 2015235944 A AU2015235944 A AU 2015235944A AU 2015235944 B2 AU2015235944 B2 AU 2015235944B2
Authority
AU
Australia
Prior art keywords
optionally substituted
cancer
independently selected
nitrogen
sulfur
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.)
Ceased
Application number
AU2015235944A
Other languages
English (en)
Other versions
AU2015235944A1 (en
Inventor
Johannes BELMAR
Zhiguo BIAN
Plamen P. CHRISTOV
Stephen W. Fesik
Kwangho Kim
Taekyu Lee
Edward T. Olejniczak
Nicholas F. Pelz
Subrata SHAW
James C. Tarr
Bin Zhao
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.)
Vanderbilt University
Original Assignee
Vanderbilt University
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 Vanderbilt University filed Critical Vanderbilt University
Publication of AU2015235944A1 publication Critical patent/AU2015235944A1/en
Application granted granted Critical
Publication of AU2015235944B2 publication Critical patent/AU2015235944B2/en
Ceased legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Indole Compounds (AREA)
AU2015235944A 2014-03-27 2015-03-26 Substituted indole Mcl-1 inhibitors Ceased AU2015235944B2 (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
AU2015235944A1 AU2015235944A1 (en) 2016-10-13
AU2015235944B2 true AU2015235944B2 (en) 2020-06-25

Family

ID=54196421

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2015235944A Ceased AU2015235944B2 (en) 2014-03-27 2015-03-26 Substituted indole Mcl-1 inhibitors

Country Status (7)

Country Link
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
JP6757312B2 (ja) 2014-03-27 2020-09-16 ヴァンダービルト ユニバーシティー 置換インドールｍｃｌ−１阻害剤
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
BR112018067775B1 (pt) 2016-03-04 2024-02-15 Vanderbilt University Compostos inibidores de mcl-1 indol substituídos, composição farmacêutica compreendendo ditos compostos e usos terapêuticos dos mesmos
ME03729B (me) 2016-04-22 2021-01-20 Astrazeneca Ab Makrociklički mcl1 inhibitor! za tretman raka
WO2017198341A1 (en) 2016-05-19 2017-11-23 Bayer Aktiengesellschaft Macrocyclic indole derivatives
US10981932B2 (en) 2016-05-19 2021-04-20 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
WO2018204286A1 (en) * 2017-04-30 2018-11-08 Development Center For Biotechnology An anti-cancer stemness drug
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
EP3710449B1 (en) 2017-11-17 2022-07-06 The Broad Institute, Inc. Macrocyclic fluorine substituted indole derivatives as mcl-1 inhibitors, for use in the treatment of cancer
WO2019096905A1 (en) 2017-11-17 2019-05-23 Bayer Aktiengesellschaft Macrocyclic chlorine substituted indole derivatives
AR113886A1 (es) 2017-11-17 2020-06-24 Broad Inst Inc Derivados de indol macrocíclicos
WO2019096907A1 (en) 2017-11-17 2019-05-23 Bayer Aktiengesellschaft Aryl annulated macrocyclic indole derivatives
EP3710450A1 (en) 2017-11-17 2020-09-23 Bayer Aktiengesellschaft Macrocyclic chlorine substituted indole derivatives
JP7234250B2 (ja) 2017-11-17 2023-03-07 バイエル アクチェンゲゼルシャフト 置換大環状インドール誘導体
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
KR102526964B1 (ko) 2018-02-26 2023-04-28 길리애드 사이언시즈, 인코포레이티드 Hbv 복제 억제제로서의 치환된 피롤리진 화합물
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
PE20210004A1 (es) * 2018-05-14 2021-01-05 Gilead Sciences Inc Inhibidores de mcl-1
CN113329996B (zh) 2018-06-25 2023-03-10 博远医药(苏州)有限公司 用于治疗刺猬途径相关病症的化合物和方法
MX2021003295A (es) 2018-09-27 2021-07-16 Pf Medicament Enlazadores basados en sulfomaleimida y sus correspondientes conjugados.
CN110845520B (zh) 2018-11-22 2021-04-13 苏州亚盛药业有限公司 作为mcl-1抑制剂的大环吲哚
TWI745836B (zh) 2019-01-18 2021-11-11 大陸商蘇州亞盛藥業有限公司 作為mcl-1抑製劑的大螺環醚
WO2020236556A1 (en) 2019-05-17 2020-11-26 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
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
KR20250130610A (ko) * 2022-12-06 2025-09-02 캡터 테라퓨틱스 에스.에이. 유비퀴틴 리가제 및 표적 mcl-1 단백질에 결합하는 이작용성 화합물을 사용하는 표적화된 단백질 분해
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

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2761073A1 (fr) * 1997-03-20 1998-09-25 Synthelabo Derives de pyrazino[1,2-a]indole-1-one, leur preparation et leur application en therapeutique
WO1998042710A1 (fr) * 1997-03-20 1998-10-01 Sanofi-Synthelabo Derives de dihydropyrazino[1,2-a]indole-1-one, leur preparation et leur application en therapeutique
WO2008131000A2 (en) * 2007-04-16 2008-10-30 Abbott Laboratories 7-substituted indole mcl-1 inhibitors
WO2008130970A1 (en) * 2007-04-16 2008-10-30 Abbott Laboratories 7-nonsubstituted indole mcl-1 inhibitors
WO2014047427A2 (en) * 2012-09-21 2014-03-27 Vanderbilt University Substituted benzofuran, benzothiophene and indole mcl-1 inhibitors

Family Cites Families (29)

* 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
DE69734718T2 (de) 1996-09-12 2006-08-24 Idun Pharmaceuticals, Inc., San Diego Hemmung der apoptose unter verwendung von inhibitoren der interleukin-1 beta converting enzym (ice)/ced-3 familie
US6500853B1 (en) 1998-02-28 2002-12-31 Genetics Institute, Llc Inhibitors of phospholipase enzymes
PL366068A1 (en) 2000-10-10 2005-01-24 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
CN1886133B (zh) 2003-12-04 2010-12-01 财团法人卫生研究院 吲哚化合物
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
WO2008072784A1 (en) 2006-12-14 2008-06-19 Astellas Pharma Inc. Polycyclic acid compounds useful as crth2 antagonists and antiallergic agents
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
EP2358748B1 (en) 2008-12-09 2016-07-06 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
AU2011299551A1 (en) 2010-09-08 2013-03-21 University Of Pittsburgh - Of The Commonwealth System Of Higher Education P53-Mdm2 antagonists
EP2683821B1 (en) 2011-03-06 2018-07-25 Merck Serono SA Low fucose cell lines and uses thereof
JP6272773B2 (ja) 2011-11-29 2018-01-31 ナンジン アルゲン ファルマ カンパニー リミテッドＮａｎｊｉｎｇ Ａｌｌｇｅｎ Ｐｈａｒｍａ Ｃｏ． Ｌｔｄ． Ｈｄａｃ６阻害剤・抗腫瘍剤用複素環アミド化合物
WO2013112878A1 (en) 2012-01-26 2013-08-01 The Penn State Research Foundation Mcl-1 modulating compositions
EP3038618B1 (en) * 2013-08-28 2020-10-14 Vanderbilt University Substituted indole mcl-1 inhibitors
JP6757312B2 (ja) 2014-03-27 2020-09-16 ヴァンダービルト ユニバーシティー 置換インドールｍｃｌ−１阻害剤
US9949965B2 (en) 2014-10-17 2018-04-24 Vanderbilt University Tricyclic indole Mcl-1 inhibitors and uses thereof
BR112018067775B1 (pt) 2016-03-04 2024-02-15 Vanderbilt University Compostos inibidores de mcl-1 indol substituídos, composição farmacêutica compreendendo ditos compostos e usos terapêuticos dos mesmos

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2761073A1 (fr) * 1997-03-20 1998-09-25 Synthelabo Derives de pyrazino[1,2-a]indole-1-one, leur preparation et leur application en therapeutique
WO1998042710A1 (fr) * 1997-03-20 1998-10-01 Sanofi-Synthelabo Derives de dihydropyrazino[1,2-a]indole-1-one, leur preparation et leur application en therapeutique
WO2008131000A2 (en) * 2007-04-16 2008-10-30 Abbott Laboratories 7-substituted indole mcl-1 inhibitors
WO2008130970A1 (en) * 2007-04-16 2008-10-30 Abbott Laboratories 7-nonsubstituted indole mcl-1 inhibitors
WO2014047427A2 (en) * 2012-09-21 2014-03-27 Vanderbilt University Substituted benzofuran, benzothiophene and indole mcl-1 inhibitors

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
CAS Registry Number: 767271-11-4; STN Entry Date 22 October 2004; Pyrazino[1,2-a]indole-1,3(2H,4H)-dione,10-[2-[4-(6-fluoro-1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]- *
CAS Registry Number: 768344-03-2; STN Entry Date: 24 October 2004; Pyrazino[1,2-a]indol-1(2H)-one, 8-fluoro-10-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperidinyl]ethyl]-3,4-dihydro-2-methyl- *
CAS Registry Number: 769905-52-4; STN Entry Date: 26 October 2004; Pyrazino[1,2-a]indol-1(2H)-one, 10-[2-[4-(7-fluoro-1-isoquinolinyl)-1-piperazinyl]ethyl]-3,4-dihydro-8-methoxy-2-methyl- *
CAS Registry Number: 775268-85-4; STN Entry Date: 5 November 2004; Pyrazino[1,2-a]indol-1(2H)-one, 8-fluoro-10-[2-[4-(6-fluoro-1,2-benzisothiazol-3-yl)-1-piperidinyl]ethyl]-3,4-dihydro-2-(2-hydroxyethyl)- *
CAS Registry Number: 780737-91-9; STN Entry Date: 15 November 2004; Pyrazino[1,2-a]indole-2(1H)-acetamide, 8-fluoro-10-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-3,4-dihydro-1-oxo- *
CAS Registry Number: 781598-76-3; STN Entry Date: 16 November 2004; Pyrazino[1,2-a]indole-1,3(2H,4H)-dione,2-methyl-10-[2-(4-thieno[3,2-c]pyridin-4-yl-1-piperazinyl)ethyl]- *
CAS Registry Number: 785760-40-9; STN Entry Date: 22 November 2004; Pyrazino[1,2-a]indol-1(2H)-one, 10-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-3,4-dihydro-8-methoxy-2-methyl- *
CAS Registry Number: 793651-42-0; STN Entry Date: 07 December 2004; Pyrazino[1,2-a]indole-2(1H)-acetamide, 8-fluoro-10-[2-[4-(6-fluoro-1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-3,4-dihydro-N-methyl-1-oxo- *
FRIBERG,A. et al., Journal of Medicinal Chemistry, (2013), Vol.56, pages 15 - 30 *

Also Published As

Publication number Publication date
EP3122353B1 (en) 2020-10-28
US20200140447A1 (en) 2020-05-07
CA2943815C (en) 2023-04-04
AU2015235944A1 (en) 2016-10-13
US11208415B2 (en) 2021-12-28
JP2017510641A (ja) 2017-04-13
CN106456602A (zh) 2017-02-22
US20230039309A1 (en) 2023-02-09
US12195472B2 (en) 2025-01-14
CA2943815A1 (en) 2015-10-01
JP6757312B2 (ja) 2020-09-16
US20170174689A1 (en) 2017-06-22
WO2015148854A1 (en) 2015-10-01
EP3122353A4 (en) 2017-12-13
CN106456602B (zh) 2020-11-24
EP3122353A1 (en) 2017-02-01
US10533010B2 (en) 2020-01-14

Similar Documents

Publication Publication Date Title
AU2015235944B2 (en) Substituted indole Mcl-1 inhibitors
US10844032B2 (en) Substituted benzofuran, benzothiophene and indole Mcl-1 inhibitors
EP3038618B1 (en) Substituted indole mcl-1 inhibitors
ES2432029T3 (es) Inhibidores de quinasas de pirrolopiridina
ES2606640T3 (es) Inhibidores de cinasas de tipo piridopirimidinona
US9949965B2 (en) Tricyclic indole Mcl-1 inhibitors and uses thereof
US9181239B2 (en) Pyridopyrimidinone inhibitors of kinases
MX2011006509A (es) Compuestos heterociclicos y métodos de uso.
EP2640704A1 (en) Nampt inhibitors
WO2012045196A1 (en) Phosphoglycerate kinase inhibitors
CA2855510A1 (en) Nampt inhibitors
MX2012012059A (es) Inhibidores de pirrolopirazinona de cinasas.

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)
MK14 Patent ceased section 143(a) (annual fees not paid) or expired