DK2134685T3 - 7-usubstituerede indolderivater som MCL-1-inhibitorer - Google Patents

7-usubstituerede indolderivater som MCL-1-inhibitorer Download PDF

Info

Publication number
DK2134685T3
DK2134685T3 DK08745934.3T DK08745934T DK2134685T3 DK 2134685 T3 DK2134685 T3 DK 2134685T3 DK 08745934 T DK08745934 T DK 08745934T DK 2134685 T3 DK2134685 T3 DK 2134685T3
Authority
DK
Denmark
Prior art keywords
indole
propyl
carboxylic acid
naphthyloxy
methylphenyl
Prior art date
Application number
DK08745934.3T
Other languages
English (en)
Inventor
Milan Bruncko
Xiaohong Song
Hong Ding
Zhi-Fu Tao
Aaron R Kunzer
Steven W Elmore
Cheol-Min Park
David Madar
Xilu Wang
Andrew J Souers
Original Assignee
Abbvie 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 Abbvie Inc filed Critical Abbvie Inc
Application granted granted Critical
Publication of DK2134685T3 publication Critical patent/DK2134685T3/da

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
    • C07D209/30—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
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (4)

1. Forbindelse eller et terapeutisk acceptabelt salt deraf, hvor forbindelsen er valgt fra gruppen bestående af: 3-[3-(3-chlorphenoxy)propyl]-1 H-indol-2-carboxylsyre; 3-{3-[3-(trifluormethyl)phenoxy]propyl}-1 H-indol-2-carboxylsyre; 3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-[3-(2-benzylphenoxy)propyl]-1 H-indol-2-carboxylsyre; 3-[3-(2,3-dihydro-1 H-inden-5-yl-oxy)propyl]-1 H-indol-2-carboxylsyre; 3-{3-[(3-methyl-1-naphthyl)oxy]propyl}-1 H-indol-2-carboxylsyre; 3-{3-[(2-methyl-1-naphthyl)oxy]propyl}-1 H-indol-2-carboxylsyre; 3-[3-(1 -naphthylthio)propyl]-1 H-indol-2-carboxylsyre; 5-brom-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-(1 -naphthyloxy)propyl)-5-((1 E)-3-phenylprop-1 -enyl)-1 H-indol-2-carboxyl-syre; 3-(3-(1-naphthyloxy)propyl)-5-((E)-2-phenylvinyl)-1 H-indol-2-carboxylsyre; 5- (4-fluorphenyl)-3-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-(1-naphthyloxy)propyl)-5-(2-phenylethyl)-1 H-indol-2-carboxylsyre; 3-{3-[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]propyl}-1H-indol-2-carboxylsyre; 3- [3-(5,6,7,8-tetrahydronaphthalen-1-yl-oxy)propyl]-1 H-indol-2-carboxylsyre; 4- (4-fluorphenyl)-3-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-(1-naphthyloxy)propyl)-6-((E)-2-phenylvinyl)-1 H-indol-2-carboxylsyre; 3-(3-(1 -naphthyloxy)propyl)-6-((1 E)-3-phenylprop-1 -enyl)-1 H-indol-2-carboxyl-syre; 3- (3-(1 -naphthyloxy)propyl)-4-((1 E)-3-phenylprop-1 -enyl)-1 H-indol-2-carboxyl-syre; 6- (3-(benzyloxy)phenyl)-3-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 4- (3-(benzyloxy)phenyl)-3-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 5- brom-3-[4-(1 -naphthyloxy)butyl]-1 H-indol-2-carboxylsyre; 1 -methyl-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-(1 -naphthyloxy)propyl)-6-phenyl-1 H-indol-2-carboxylsyre; 6- (2-methylphenyl)-3-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 6-(3-methylphenyl)-3-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 6-(4-methylphenyl)-3-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(2-methylphenyl)-1-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(1 -naphthyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-(((3-(dimethylamino)propyl)amino)carbonyl)phenyl)-1 -(3-(1 -naph-thyloxy)propyl)-1H-indol-2-carboxylsyre; 3-(1,1 '-biphenyl-2-yl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(2-methylphenyl)-1-[3-(2-naphthyloxy)propyl]-1H-indol-2-carboxylsyre; 3-(2-methylphenyl)-1 -[3-(5,6,7,8-tetrahydronaphthalen-1 -yl-oxy)propyl]-1 H-in-dol-2-carboxylsyre; 3-(3-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-chlorphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-phenyl-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-(2-(trifluormethyl)phenyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-(3-(trifluormethyl)phenyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-(4-(trifluormethyl)phenyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-(4-(trifluormethoxy)phenyl)-1 H-indol-2-carboxyl-syre; 3-(2,3-dimethylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(2,5-dimethylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3,4-dimethylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3,5-dimethylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(2,5-dimethoxyphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3,4-dimethoxyphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(2-methylphenyl)-1 -[4-(1 -naphthyloxy)butyl]-1 H-indol-2-carboxylsyre; 3-(2-methylphenyl)-1-[4-(2-naphthyloxy)butyl]-1 H-indol-2-carboxylsyre; 1-[4-(2,3-dichlorphenoxy)butyl]-3-(2-methylphenyl)-1 H-indol-2-carboxylsyre: 1-[2-(2,4-dichlorphenoxy)ethyl]-3-(2-methylphenyl)-1 H-indol-2-carboxylsyre; 1-[3-(2,4-dichlorphenoxy)propyl]-3-(2-methylphenyl)-1H-indol-2-carboxylsyre; 1-[4-(2,4-dichlorphenoxy)butyl]-3-(2-methylphenyl)-1 H-indol-2-carboxylsyre; 3-benzyl-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(2-methylbenzyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-methylbenzyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(4-methylbenzyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(2-naphthylmethyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-(2-phenylethyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-(3-phenylpropyl)-1 H-indol-2-carboxylsyre; 3-(2-methylphenyl)-1 -[2-(1 -naphthyloxy)ethyl]-1 H-indol-2-carboxylsyre; 3-(2-methylphenyl)-1-[2-(2-naphthyloxy)ethyl]-1H-indol-2-carboxylsyre: 1-[2-(2,3-dichlorphenoxy)ethyl]-3-(2-methylphenyl)-1H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-((E)-2-phenylvinyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-((1 E)-3-phenylprop-1 -enyl)-1 H-indol-2-carboxyl-syre; 1 -(3-(1 -naphthyloxy)propyl)-3-(3-(piperidin-1 -yl-carbonyl)phenyl)-1 H-indol-2-car-boxylsyre; 3-(4-fluor-3-(morpholin-4-yl-carbonyl)phenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-in-dol-2-carboxylsyre; 3-(3-(((2-methoxyethyl)amino)carbonyl)phenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-((dimethylamino)sulfonyl)phenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(3-(morpholin-4-yl-methyl)phenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-car-boxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-piperidin-1 -yl-1 H-indol-2-carboxylsyre; 3-morpholin-4-yl-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-((3-(trifluormethoxy)phenyl)amino)-1 H-indol-2-car-boxylsyre; 3-(4-carboxypiperidin-1 -yl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-anilino-4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxyl-syre; 3-[3-(1 -naphthylthio)cyclohexyl]-1 H-indol-2-carboxylsyre; 3-[3-(1 -naphthyloxy)cyclohexyl]-1 H-indol-2-carboxylsyre; 1 -(2-methylbenzyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(2-(dimethylamino)ethyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(3-methylbenzyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(4-methylbenzyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1-(1,1 '-biphenyl-2-yl-methyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxyl-syre; 1-(1,1 '-biphenyl-3-yl-methyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxyl-syre; 1-(1,1 '-biphenyl-4-yl-methyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxyl-syre; 1 -(2,4-dimethylbenzyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(4-carboxybenzyl)-3-(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -((2S)-2-methyl-3-(1 -naphthyloxy)propyl)-4-(2-methylphenyl)-1 H-indol-2-car-boxylsyre; 1 -((2R)-2-methyl-3-(1 -naphthyloxy)propyl)-4-(2-methylphenyl)-1 H-indol-2-car-boxylsyre; 3-(3-(1 -naphthyloxy)propyl)-1 -(pyridin-4-yl-methyl)-1 H-indol-2-carboxylsyre; 3- (3-(1 -naphthyloxy)propyl)-1 -(pyridin-2-yl-methyl)-1 H-indol-2-carboxylsyre; 1 -(4-methoxybenzyl)-3-[2-(1 -naphthyloxy)ethoxy]-1 H-indol-2-carboxylsyre; 1 -(4-methoxybenzyl)-3-[3-(1 -naphthyloxy)prop-1 -ynyl]-1 H-indol-2-carboxylsyre; 4- (2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 4-(2,6-dimethylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-4-(1,3,5-trimethyl-1 H-pyrazol-4-yl)-1 H-indol-2-car-boxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-4-(2-oxocyclohexyl)-1 H-indol-2-carboxylsyre; 4-(2-methylphenyl)-3-(morpholin-4-yl-methyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-in-dol-2-carboxylsyre; 4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-3-(pyrrolidin-1 -yl-methyl)-1 H-in-dol-2-carboxylsyre; 3-((dimethylamino)methyl)-4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3- (((cyclohexylmethyl)amino)methyl)-4-(2-methylphenyl)-1-(3-(1-naph-thyloxy)propyl)-1 H-indol-2-carboxylsyre; 4- (2-morpholin-4-yl-cyclohexyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carbox-ylsyre; 4-(2-methylphenyl)-3-((4-methylpiperazin-1 -yl)methyl)-1 -(3-(1 -naphthyloxy)pro-pyl)-1 H-indol-2-carboxylsyre; 4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-3-(piperidin-1 -yl-methyl)-1 H-in-dol-2-carboxylsyre; 4-(2-methylphenyl)-3-((4-methylpiperidin-1 -yl)methyl)-1 -(3-(1 -naphthyloxy)pro-pyl)-1 H-indol-2-carboxylsyre; 3- ((benzyl(methyl)amino)methyl)-4-(2-methylphenyl)-1-(3-(1-naphthyloxy)pro-pyl)-1 H-indol-2-carboxylsyre; 4- (2-methylphenyl)-3-((methyl(pyridin-2-yl-methyl)amino)methyl)-1 -(3-(1 -naph-thyloxy)propyl)-1 H-indol-2-carboxylsyre; 4-(2-methylphenyl)-3-((methyl(pyridin-3-yl-methyl)amino)methyl)-1-(3-(1 -naph-thyloxy)propyl)-1 H-indol-2-carboxylsyre; 4-(2-methylphenyl)-3-((methyl(pyridin-4-yl-methyl)amino)methyl)-1 -(3-(1 -naph-thyloxy)propyl)-1 H-indol-2-carboxylsyre; 4-(2-(4-fluorphenyl)cyclohex-1 -en-1 -yl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 4-(2-methyl-6-nitrophenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 4-(2-chlor-6-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-4-(2-(4-nitrophenyl)cyclohex-1 -en-1 -yl)-1 H-indol-2-carboxylsyre; 4-(2-(3-methoxyphenyl)cyclohex-1 -en-1 -yl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-in-dol-2-carboxylsyre; 4-(5-fluor-2-methyl-3-((methylsulfonyl)methyl)phenyl)-1-(3-(1-naphthyloxy)pro-pyl)-1 H-indol-2-carboxylsyre; 4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-3-phenyl-1 H-indol-2-carboxyl-syre; 3- brom-4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 4- (2-methylphenyl)-3-((4-methylphenyl)amino)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(4-hydroxyphenyl)-4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3- (3-hydroxyphenyl)-4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 4- (2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-3-pyridin-4-yl-1 H-indol-2-car-boxylsyre; 4- (2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-3-pyridin-3-yl-1 H-indol-2-car-boxylsyre; 3-cyano-4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxyl-syre; 3- brom-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 5- (benzyloxy)-1 -(3-(1 -naphthyloxy)propyl)-3-(2-(trifluormethyl)phenyl)-1 H-indol- 2- carboxylsyre; 5-fluor-3-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 5-fluor-1 -(3-(1 -naphthyloxy)propyl)-3-(2-(trifluormethyl)phenyl)-1 H-indol-2-car-boxylsyre; 5-fluor-3-(2-isopropylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxyl- syre; 4- (2-methylphenyl)-1-(3-(1-naphthyloxy)propyl)-3-((3-(trifluormethoxy)phe-nyl)amino)-1 H-indol-2-carboxylsyre; 5- (benzyloxy)-1 -(3-(1 -naphthyloxy)propyl)-3-((3-(trifluormethoxy)phenyl)amino)-1 H-indol-2-carboxylsyre; 5-(benzyloxy)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 5-(benzyloxy)-3-(2-isopropylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-car-boxylsyre; 3- (2-(tert-butoxymethyl)phenyl)-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 5-fluor-1-(3-(1-naphthyloxy)propyl)-3-(2-((3-(trifluormethyl)phenoxy)methyl)phe-nyl)-1 H-indol-2-carboxylsyre; 5-chlor-3-(2-isopropylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxyl-syre; 5-chlor-3-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 5-hydroxy-3-(2-isopropylphenyl)-1-[3-(5,6,7,8-tetrahydronaphthalen-1-yl-oxy)propyl]-1 H indol-2-carboxylsyre; 5-hydroxy-3-(2-isopropylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carbox-ylsyre; 3-(2-isopropylphenyl)-5-(4-morpholin-4-yl-butoxy)-1-(3-(1-naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 5- fluor-1 -(3-(1 -naphthyloxy)propyl)-3-(1,3,5-trimethyl-1 H-pyrazol-4-yl)-1 H-indol- 2- carboxylsyre; 3- (2-isopropylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-5-phenyl-1 H-indol-2-carboxyl-syre; 3-(2,6-dimethylphenyl)-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxyl-syre; 3-(2-isopropylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-5-((1 E)-pent-1 -enyl)-1 H-indol-2-carboxylsyre; 3 -(2,6-dimethylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-3-(1,3,5-trimethyl-1 H-pyrazol-4-yl)-1 H-indol-2-car-boxylsyre; 3-(2-chlorphenyl)-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-((1 E)-5-(dimethylamino)pent-1 -enyl)-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-in-dol-2-carboxylsyre; 3-((1 E)-6-((2-carboxybenzoyl)amino)hex-1 -enyl)-5-fluor-1 -(3-(1 -naph-thyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-((1 E)-6-aminohex-1 -enyl)-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-car-boxylsyre; 3-(6-aminohexyl)-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(5-(dimethylamino)pentyl)-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-car-boxylsyre; 6- chlor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 3-(2-((1 E)-5-(dimethylamino)pent-1 -enyl)phenyl)-5-fluor-1 -(3-(1 -naph-thyloxy)propyl)-1 H-indol-2-carboxylsyre; og 3- (2-(dimethylamino)phenyl)-5-fluor-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-car-boxylsyre; 1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-carboxylsyre; 1 -methyl-5-(4-(2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-1 H-indol-2-yl)-1 H-pyrazol-3-ol; og 4- (2-methylphenyl)-1 -(3-(1 -naphthyloxy)propyl)-2-(1 H-tetraazol-5-yl)-1 H-indol.
2. Sammensætning indeholdende et excipiens og en terapeutisk virksom mængde af en forbindelse eller et terapeutisk acceptabelt salt ifølge krav 1.
3. Sammensætning til behandling af akut lymfoblastisk leukæmi, akut myelo-gen leukæmi, livmoderhalskræft, kronisk lymfocytisk leukæmi, kolorektal cancer, gastrisk karcinom, gestationel trofoblastisk sygdom, glioblastom, hoved- og halscancer, lungecancer, mesothiolom, multipelt myelom, non-Hodgkin's lymfom, oligodenrogliom, ovariecancer, pancreatisk cancer eller perifert T-celle lymfom hos et pattedyr, hvilken sammensætning indeholder et excipiens og en terapeutisk virksom mængde af en forbindelse eller et terapeutisk acceptabelt salt ifølge krav 1.
4. Forbindelse eller et terapeutisk acceptabelt salt ifølge krav 1 til anvendelse ved behandlingen af akut lymfoblastisk leukæmi, akut myelogen leukæmi, livmoderhalskræft, kronisk lymfocytisk leukæmi, kolorektal cancer, gastrisk karcinom, gestationel trofoblastisk sygdom, glioblastom, hoved- og halscancer, lungecancer, mesothiolom, multipelt myelom, non-Hodgkin's lymfom, oligodenrogliom, ovariecancer, pancreatisk cancer eller perifert T-celle lymfom hos et pattedyr, hvor en terapeutisk virksom mængde af forbindelsen eller et terapeutisk acceptabelt salt ifølge krav 1 og en terapeutisk virksom mængde af ét yderligere terapeutisk middel eller mere end ét yderligere terapeutisk middel skal indgives til pattedyret.
DK08745934.3T 2007-04-16 2008-04-16 7-usubstituerede indolderivater som MCL-1-inhibitorer DK2134685T3 (da)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US91204907P 2007-04-16 2007-04-16
US94968307P 2007-07-13 2007-07-13
PCT/US2008/060427 WO2008130970A1 (en) 2007-04-16 2008-04-16 7-nonsubstituted indole mcl-1 inhibitors

Publications (1)

Publication Number Publication Date
DK2134685T3 true DK2134685T3 (da) 2015-12-07

Family

ID=39683700

Family Applications (1)

Application Number Title Priority Date Filing Date
DK08745934.3T DK2134685T3 (da) 2007-04-16 2008-04-16 7-usubstituerede indolderivater som MCL-1-inhibitorer

Country Status (11)

Country Link
US (2) US7981888B2 (da)
EP (1) EP2134685B1 (da)
JP (2) JP5496876B2 (da)
CN (1) CN101711235A (da)
CA (2) CA2682354C (da)
DK (1) DK2134685T3 (da)
ES (1) ES2550753T3 (da)
MX (1) MX2009011210A (da)
PL (1) PL2134685T3 (da)
PT (1) PT2134685E (da)
WO (1) WO2008130970A1 (da)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2682356C (en) 2007-04-16 2016-06-14 Abbott Laboratories 7-substituted indole mcl-1 inhibitors
MX2011006000A (es) 2008-12-08 2011-07-20 Boehringer Ingelheim Int Compuestos para tratar cancer.
AU2009335818A1 (en) 2008-12-19 2011-07-21 Abbvie Inc. Compounds and methods of use
CA2747170C (en) * 2008-12-19 2017-07-18 Abbott Laboratories Tetrahydroisoquinoline derivatives and their uses to treat cancers and autoimmune disorders
EP2528893B1 (en) 2010-01-29 2018-10-10 Dana-Farber Cancer Institute, Inc. Small molecules for the modulation of mcl-1 and methods of modulating cell death, cell division, cell differentiation and methods of treating disorders
EP2487159A1 (en) 2011-02-11 2012-08-15 MSD Oss B.V. RorgammaT inhibitors
EP2567698B1 (en) 2011-09-07 2014-02-12 Rheinische Friedrich-Wilhelms-Universität Bonn GPR 17 agonists and screening assay
US8940737B2 (en) 2011-10-14 2015-01-27 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
AU2013235425B2 (en) 2012-03-20 2017-09-21 Dana Farber Cancer Institute, Inc. Inhibition of MCL-1 and/or BFL-1/A1
WO2014026330A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
WO2014026327A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. 4-heteroaryl substituted benzoic acid compounds as rorgammat inhibitors and uses thereof
WO2014026329A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. N-alkylated indole and indazole compounds as rorgammat inhibitors and uses thereof
US10093640B2 (en) 2012-09-21 2018-10-09 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
AU2015235944B2 (en) 2014-03-27 2020-06-25 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
AU2015337859B2 (en) 2014-10-29 2020-09-10 The Walter And Eliza Hall Institute Of Medical Research Use of therapeutic agents
CA2975997A1 (en) 2015-02-11 2016-08-18 Merck Sharp & Dohme Corp. Substituted pyrazole compounds as rorgammat inhibitors and uses thereof
WO2016200726A1 (en) 2015-06-08 2016-12-15 Texas Tech University System Inhibitors of mci-1 as drugs to overcome resistance to braf inhibitors and mek inhibitors
JP2018531958A (ja) 2015-10-27 2018-11-01 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． ＲＯＲγＴ阻害薬としてのヘテロアリール置換安息香酸及びその使用
CA3002850A1 (en) 2015-10-27 2017-05-04 Merck Sharp & Dohme Corp. Substituted indazole compounds as rorgammat inhibitors and uses thereof
AU2016344111A1 (en) 2015-10-27 2018-05-10 Merck Sharp & Dohme Corp. Substituted bicyclic pyrazole compounds as RORgammaT inhibitors and uses thereof
WO2017077535A1 (en) * 2015-11-02 2017-05-11 Carmel-Haifa University Economic Corporation Ltd. Apoptosis related protein in the tgf-beta signaling pathway (arts) mimetic compounds, compositions, methods and uses thereof in induction of differentiation and/or apoptosis of premalignant and malignant cells, thereby restoring their normal-like phenotype
KR102396177B1 (ko) 2016-03-04 2022-05-09 반더빌트유니버시티 치환된 인돌 ｍｃｌ-1 억제제
JP6894449B2 (ja) 2016-04-22 2021-06-30 アストラゼネカ・アクチエボラーグＡｓｔｒａｚｅｎｅｃａ Ａｋｔｉｅｂｏｌａｇ 癌を治療するためのマクロ環状ｍｃｌ１阻害剤
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
JP6910027B2 (ja) * 2017-03-29 2021-07-28 株式会社コーセー チロシナーゼ活性阻害剤、メラニン産生抑制剤及び美白剤
WO2018204286A1 (en) * 2017-04-30 2018-11-08 Development Center For Biotechnology An anti-cancer stemness drug
CN111757884B (zh) 2017-11-17 2023-12-19 拜耳股份公司 取代的大环吲哚衍生物
EP3710448A1 (en) 2017-11-17 2020-09-23 Bayer Aktiengesellschaft Macrocyclic chlorine substituted indole derivatives
UY37973A (es) 2017-11-17 2019-06-28 Bayer Ag Derivados de indol macrocíclicos
WO2019096914A1 (en) 2017-11-17 2019-05-23 Bayer Aktiengesellschaft Macrocyclic chlorine substituted indole derivatives
US11286263B2 (en) 2017-11-17 2022-03-29 The Broad Institute, Inc. Macrocyclic fluorine substituted indole derivatives
US20210253598A1 (en) 2017-11-17 2021-08-19 Bayer Aktiengesellschaft Aryl annulated macrocyclic indole derivatives
US20220041623A1 (en) * 2018-09-30 2022-02-10 Jiangsu Hengrui Medicine Co., Ltd. Indole macrocyclic derivative, preparation method thereof and application thereof in medicine
EP3781570A4 (en) * 2018-11-22 2021-06-02 Ascentage Pharma (Suzhou) Co., Ltd. MACROCYCLIC INDOLES SERVING AS MCL-1 INHIBITORS
CN114127079A (zh) 2019-05-17 2022-03-01 布罗德研究所有限公司 制备大环吲哚的方法
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
BR112022009754A2 (pt) 2019-11-21 2022-08-09 Janssen Pharmaceutica Nv Derivados macrocíclicos de sulfonila como inibidores de mcl-1
EP4061819A1 (en) 2019-11-21 2022-09-28 Janssen Pharmaceutica NV Macrocyclic indole derivatives as mcl-1 inhibitors
US20230014137A1 (en) 2019-11-29 2023-01-19 Ono Pharmaceutical Co., Ltd. Compound having lysophosphatidic acid receptor agonist activity and pharmaceutical use thereof
CN115335384B (zh) * 2020-03-30 2024-10-22 江苏恒瑞医药股份有限公司 一种吲哚类大环衍生物的结晶形式及其制备方法
CA3178283A1 (en) 2020-05-29 2021-12-02 Frederik Jan Rita Rombouts Macrocyclic 7-pyrazol-5-yl-indole derivatives as inhibitors of mcl-1
US20230234969A1 (en) 2020-06-19 2023-07-27 Janssen Pharmaceutica Nv N-linked macrocyclic 7-(pyrazol-5-yl)-indole derivatives as inhibiors of mcl-1
CA3222752A1 (en) 2021-06-11 2022-12-15 Gilead Sciences, Inc. Combination mcl-1 inhibitors with anti-body drug conjugates
EP4351564A1 (en) 2021-06-11 2024-04-17 Gilead Sciences, Inc. Combination mcl-1 inhibitors with anti-cancer agents

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3632805A (en) 1967-12-08 1972-01-04 Sumitomo Chemical Co Process for producing 1-aminoalkyl-benzodiazepine derivatives
FR2187318B1 (da) * 1972-06-08 1975-06-20 Delalande Sa
US4994477A (en) * 1988-03-24 1991-02-19 Abbott Laboratories Heterocyclic renin inhibitors
ATE255090T1 (de) * 1996-08-01 2003-12-15 Merckle Gmbh Acylpyrroldicarbonsäuren und acylindoldicarbonsäuren sowie ihre derivate als hemmstoffe der cytosolischen phospholipase a2
GB9716657D0 (en) 1997-08-07 1997-10-15 Zeneca Ltd Chemical compounds
EP1359138B1 (en) 1998-11-27 2006-02-08 Mitsubishi Chemical Corporation Process for the production of maleic anhydride
GB9902455D0 (en) 1999-02-05 1999-03-24 Zeneca Ltd Chemical compounds
GB9902452D0 (en) * 1999-02-05 1999-03-24 Zeneca Ltd Chemical compounds
GB0000626D0 (en) 2000-01-13 2000-03-01 Zeneca Ltd Chemical compounds
CA2427499A1 (en) 2000-10-10 2002-04-18 Smithkline Beecham Corporation Substituted indoles, pharmaceutical compositions containing such indoles and their use as ppar-.gamma. binding agents
DE10153346A1 (de) 2001-10-29 2004-04-22 Grünenthal GmbH Substituierte Indole
CA2468745A1 (en) 2001-11-30 2003-06-12 The Burnham Institute Induction of apoptosis in cancer cells
JP2005519915A (ja) * 2002-01-18 2005-07-07 セレテック・リミテッド・ライアビリティ・カンパニー Ｅｄｇ受容体に関連する症状の処置方法
EP1501797B1 (en) * 2002-04-23 2009-08-05 Aventis Pharmaceuticals Inc. 3-(substituted amino)-1h-indole-2-carboxylic acid ester and 3-(substituted amino)-benzo[b]thiophene-2-carboxylic acid ester derivatives as interleukin-4 gene expression inhibitors
GEP20084341B (en) 2003-02-26 2008-03-25 Sugen Inc Aminoheteroaryl compounds as protein kinase inhibitors
US7141600B2 (en) * 2003-04-15 2006-11-28 The Regents Of The University Of California Small molecule inhibition of a PDZ-domain interaction
SE0302035D0 (sv) * 2003-07-09 2003-07-09 Biolipox Ab New compound
US7268159B2 (en) * 2003-09-25 2007-09-11 Wyeth Substituted indoles
ITMI20040874A1 (it) * 2004-04-30 2004-07-30 Ist Naz Stud Cura Dei Tumori Derivati indolici ed azaindolici con azione antitumorale
CA2570363A1 (en) * 2004-06-18 2005-12-29 Biolipox Ab Indoles useful in the treatment of inflammation
EP1778633B1 (en) * 2004-06-18 2008-12-03 Biolipox AB Indoles useful in the treatment of inflammation
WO2005123675A1 (en) * 2004-06-18 2005-12-29 Biolipox Ab Indoles useful in the treatment of inflammation
WO2006041961A1 (en) * 2004-10-05 2006-04-20 GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTHAND HUMAN SERVICES Arylthioindole tubulin polymerization inhibitors and methods of treating or preventing cancer using same
FR2878849B1 (fr) 2004-12-06 2008-09-12 Aventis Pharma Sa Indoles substitues, compositions les contenant, procede de fabrication et utilisation
JP2008527030A (ja) * 2005-01-19 2008-07-24 バイオリポックス エービー 炎症の治療に有用なインドール類
AU2005325497A1 (en) * 2005-01-19 2006-07-27 Biolipox Ab Indoles useful in the treatment of inflammation
WO2007008627A2 (en) * 2005-07-07 2007-01-18 Abbott Laboratories Apoptosis promoters
TW200819447A (en) * 2006-08-31 2008-05-01 Smithkline Beecham Corp Chemical compounds
CA2682356C (en) 2007-04-16 2016-06-14 Abbott Laboratories 7-substituted indole mcl-1 inhibitors
CA2747170C (en) 2008-12-19 2017-07-18 Abbott Laboratories Tetrahydroisoquinoline derivatives and their uses to treat cancers and autoimmune disorders
AU2009335818A1 (en) 2008-12-19 2011-07-21 Abbvie Inc. Compounds and methods of use

Also Published As

Publication number Publication date
US7981888B2 (en) 2011-07-19
US8853209B2 (en) 2014-10-07
JP5895011B2 (ja) 2016-03-30
JP2014129396A (ja) 2014-07-10
EP2134685B1 (en) 2015-09-02
JP2010524955A (ja) 2010-07-22
CA2682354C (en) 2016-12-13
EP2134685A1 (en) 2009-12-23
US20110263599A1 (en) 2011-10-27
CN101711235A (zh) 2010-05-19
PL2134685T3 (pl) 2016-02-29
CA2682354A1 (en) 2008-10-30
CA2951295C (en) 2020-04-28
JP5496876B2 (ja) 2014-05-21
CA2951295A1 (en) 2008-10-30
WO2008130970A1 (en) 2008-10-30
ES2550753T3 (es) 2015-11-12
PT2134685E (pt) 2015-11-25
MX2009011210A (es) 2009-10-30
US20090124616A1 (en) 2009-05-14

Similar Documents

Publication Publication Date Title
DK2134685T3 (da) 7-usubstituerede indolderivater som MCL-1-inhibitorer
US9359296B2 (en) 7-substituted indole Mcl-1 inhibitors
ES2457418T3 (es) Indazoles, bencisoxazoles y bencisotiazoles como inhibidores de proteína cinasas
MX2010012260A (es) Inhibidores de proteina cinasas.
TW200932747A (en) 2-((R)-2-methylpyrrolidin-2-yl)-1H-benzimidazole-4-carboxamide Crystalline Form 1
ES2372559T3 (es) Compuestos heterocíclicos condensados como inhibidores de proteína quinasas.
EP2195298A1 (en) Crystalline indazole-derived chemotherepeutic
RU2473542C2 (ru) ИНГИБИТОРЫ Mcl-1 НА ОСНОВЕ 7-ЗАМЕЩЕННЫХ ИНДОЛОВ