DK2684880T3 - Dispiropyrrolidinderivat - Google Patents

Dispiropyrrolidinderivat Download PDF

Info

Publication number
DK2684880T3
DK2684880T3 DK12755073.9T DK12755073T DK2684880T3 DK 2684880 T3 DK2684880 T3 DK 2684880T3 DK 12755073 T DK12755073 T DK 12755073T DK 2684880 T3 DK2684880 T3 DK 2684880T3
Authority
DK
Denmark
Prior art keywords
group
compound
chloro
mmol
oxo
Prior art date
Application number
DK12755073.9T
Other languages
English (en)
Inventor
Yuuichi Sugimoto
Kouichi Uoto
Masaki Miyazaki
Masaki Setoguchi
Toru Taniguchi
Keisuke Yoshida
Akitake Yamaguchi
Shoko Yoshida
Takanori Wakabayashi
Original Assignee
Daiichi Sankyo Co Ltd
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 Daiichi Sankyo Co Ltd filed Critical Daiichi Sankyo Co Ltd
Application granted granted Critical
Publication of DK2684880T3 publication Critical patent/DK2684880T3/da

Links

Classifications

    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/20—Spiro-condensed systems
    • 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
    • C07D487/12—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 three hetero rings
    • C07D487/20—Spiro-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
    • A61K31/395—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
    • A61K31/407—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 other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • 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
    • A61K31/495—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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not 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
    • A61K31/535—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
    • 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
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Neurology (AREA)
  • Oncology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Hematology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pulmonology (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Claims (24)

  1. DISPIROPYRROLIDINDERIVAT
    1. Forbindelse, der er repræsenteret ved den almene formel (1) eller et salt deraf: hvor
    ring A repræsenterer en spirobundet 4- til 6-leddet mættet carbonhydridring der kan have én eller flere substituenter, der er udvalgt fra gruppe 1, eller en spirobundet 6-leddet mættet heterocyklisk ring, der kan have én eller flere substituenter, der er udvalgt fra gruppe 1; ring B repræsenterer en benzenring, der kan have én eller flere substituenter, der er udvalgt fra gruppe 2, en pyridinring, der kan have én eller flere substituenter, der er udvalgt fra gruppe 2, eller en pyrimidinring, der kan have én eller flere substituenter, der er udvalgt fra gruppe 2; R1 repræsenterer en arylgruppe, der kan have én eller flere substituenter, der er udvalgt fra gruppe 3, en heteroarylgruppe, der kan have én eller flere substituenter, der er udvalgt fra gruppe 3, en C3-C6-cycloalkylgruppe, der kan have én eller flere substituenter, der er udvalgt fra gruppe 3, eller en C3-C6-cycloalkenylgruppe, der kan have én eller flere substituenter, der er udvalgt fra gruppe 3; R2 repræsenterer en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer eller ét til tre hydroxygrupper, eller et hydrogenatom og R3 repræsenterer en gruppe, der er repræsenteret ved følgende almene formler (2), (3) eller (4):
    (2) (3) (4) hvor i formel (2), R4 og R5 hver uafhængigt repræsenterer en hydroxygruppe, en Ci-C6-alkylgruppe, eller en Ci-C6-alkoxygruppe, eller R4 og R5 sammen med de carbonatomer, hvortil henholdsvis R4- og R5-gruppeme er bundet, kan danne en 4- til 6-leddet mættet carbonhydridring; i formel (3), den brudte linje i ringstrukturen indikerer, at bindingen kan være en dobbeltbinding, R6 repræsenterer en Ci-C6-alkylgruppe, der kan have én eller flere substituenter, der er udvalgt fra gruppe 4, en carbamoylgruppe, der kan have én eller flere substituenter, der er udvalgt fra gruppe 5, en 5- eller 6-leddet nitrogenholdig heteroarylgruppe, der kan være substitueret med en oxogruppe eller én eller flere Ci-C6-alkylgrupper, der kan være substitueret med en oxogruppe eller én hydroxygruppe, en hydroxygruppe, eller -NR'R", hvor R' og R" hver uafhængigt repræsenterer en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, en oxogruppe, eller en til tre hydroxygrupper, en C3-C4-cycloalkylgruppe, der kan være substitueret med et til tre halogenatomer eller en til tre hydroxygrupper, eller et hydrogenatom, eller R' og R" sammen med det nitrogenatom, hvortil R' og R" er bundet, kan danne en 4- til 7-leddet nitrogenholdig heterocyklisk gruppe, der kan have én eller flere substituenter, der er udvalgt fra en Ci-C6-alkylgruppe og en hydroxygruppe, R7 repræsenterer en Ci-C6-alkylgruppe, der kan være substitueret med en hydroxygruppe, en hydroxygruppe eller et hydrogenatom, eller R6 og R7 sammen kan danne en spirobundet 4- til 6-leddet carbonhydridring eller en spirobundet 4-til 6-leddet nitrogenholdig heterocyklisk ring, R8 er fraværende eller repræsenterer én eller flere substituenter, der er udvalgt fra en hydroxygruppe, en Ci-C6-alkylgruppe og en C i -CV,-alkoxygruppc, og Z repræsenterer CH2, NH eller et oxygenatom; og i formel (4), R9 repræsenterer en Ci-C6-alkylgruppe, der kan have én eller flere substituenter, der er udvalgt fra gruppe 4, en carbamoylgruppe, der kan have én eller flere substituenter, der er udvalgt fra gruppe 5, en 5-eller 6-leddet nitrogenholdig heteroarylgruppe, der kan være substitueret med en oxogruppe eller én eller flere Ci-C6-alkylgrupper der kan være substitueret med en oxogruppe eller én hydroxygruppe, en hydroxygruppe, eller -NR'R", hvor R' og R" hver uafhængigt repræsenterer en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, en oxogruppe, eller en til tre hydroxygrupper, en C3-C4-cycloalkylgruppe, der kan være substitueret med et til tre halogenatomer eller en til tre hydroxygrupper, eller et hydrogenatom, eller R' og R" sammen med det nitrogenatom, hvortil R' og R" er bundet, kan danne en 4- til 7-leddet nitrogenholdig heterocyklisk gruppe, der kan have én eller flere substituenter, der er udvalgt fra en Ci-C6-alkylgruppe og en hydroxygruppe, R10 repræsenterer en Ci-C6-alkylgruppe, der kan være substitueret med én hydroxygruppe, en hydroxygruppe, eller et hydrogenatom, eller R9 og R10 sammen kan danne en spirobundet 4- til 6-leddet carbonhydridring eller en spirobundet 4- til 6-leddet nitrogenholdig heterocyklisk ring, og R11 er fraværende eller repræsenterer én eller flere substituenter, der er udvalgt fra en hydroxygruppe, en Ci-C6-alkylgruppe og en Ci-C6-alkoxygruppe: Gruppe 1: et halogenatom, en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, en Ci-C6-alkoxygruppe, og en cyangruppe, Gruppe 2: et halogenatom, en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, en C3-C4-cycloalkylgruppe, der kan være substitueret med et til tre halogenatomer, en vinylgruppe, en ethynylgruppe, en cyangruppe og en Ci-C6-alkoxygruppe, Gruppe 3: et halogenatom, en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer eller en til tre hydroxygrupper, en C3-C4-cycloalkylgruppe, der kan være substitueret med et til tre halogenatomer eller en til tre hydroxygrupper, avinylgruppe, en ethynylgruppe, en cyangruppe, -OR', -NR'R ", -COOR' og -CONHR', hvor R' og R" hver uafhængigt repræsenterer en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer eller en til tre hydroxygrupper, en C3-C4-cycloalkylgruppe, der kan være substitueret med et til tre halogenatomer eller en til tre hydroxygrupper, eller et hydrogenatom, eller R' og R" sammen med det nitrogenatom, hvortil R' og R" er bundet, kan danne en 4- til 7-leddet nitrogenholdig heterocyklisk gruppe, der kan have én eller flere substituenter, der er udvalgt fra en Ci-C6-alkylgruppe og en hydroxygruppe, Gruppe 4: et halogenatom, en hydroxygruppe, en carbamoylgruppe, en morpholingruppe, en Cr C6-alkoxygruppe, en Ci-C6-alkylsulfonylgruppe og -NR'R", hvor R' og R" hver uafhængigt repræsenterer en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, en til tre hydroxygrupper, eller en oxogruppe, en C3-C4-cycloalkylgruppe, der kan være substitueret med et til tre halogenatomer eller en til tre hydroxygrupper, eller et hydrogenatom, eller R' og R" sammen med det nitrogenatom, hvortil R' og R" er bundet, kan danne en 4- til 7-leddet nitrogenholdig heterocyklisk gruppe, der kan have én eller flere substituenter, der er udvalgt fra en Ci-C6-alkylgruppe og en hydroxygruppe, og Gruppe 5: en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, en til tre hydroxygrupper, eller en Ci-C6-alkoxygruppe, en C3-C6-cycloalkylgruppe, en Ci-C6-alkoxygruppe og en tetrahydropyranylgruppe.
  2. 2. Forbindelse ifølge krav 1, hvor ring B repræsenterer en benzenring, der kan have én eller flere substituenter, der er bundet til 5- eller 6-positionen udvalgt fra et halogenatom, en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, en cyangruppe og en Ci-C6-alkoxygruppe.
  3. 3. Forbindelse ifølge krav 1, hvor ring B repræsenterer en pyridinring der kan have én substituent, der er bundet til 6-positionen udvalgt fra et halogenatom, en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, en cyangruppe og en Ci-C6-alkoxygruppe.
  4. 4. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R1 repræsenterer en phenylgruppe, der kan have ét chloratom, der er bundet til 3-positionen eller et chloratom og et fluoratom, der er bundet til henholdsvis 3- og 2-positionerne.
  5. 5. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor R1 repræsenterer en pyridylgruppe, der kan have ét chloratom, der er bundet til 2-positionen eller et chloratom og et fluoratom, der er bundet til henholdsvis 2- og 3-positionerne.
  6. 6. Forbindelse ifølge krav 1, der er repræsenteret ved den almene formel (7) eller et salt deraf: hvor
    ring A, R2 og R3 har de samme betydninger som henholdsvis ring A, R2, og R3 i krav 1; R12, R13 og R16 repræsenterer en gruppe, der er udvalgt fra et halogenatom, en Ci-C6-alkylgrappe, der kan være substitueret med et til tre halogenatomer, og en cyangruppe; og R14 er fraværende eller repræsenterer én eller flere substituenter, der er udvalgt fra et halogenatom, en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, og en cyangruppe.
  7. 7. Forbindelse ifølge krav 1, der er repræsenteret ved den almene formel (8) eller et salt deraf: hvor
    ring A, R2 og R3 har de samme betydninger som henholdsvis ring A, R2, og R3 i krav 1; R12, R13 og R16 repræsenterer en gruppe, der er udvalgt fra et halogenatom, en Ci-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer, og en cyangruppe; og R14 er fraværende eller repræsenterer én eller flere substituenter, der er udvalgt fra et halogenatom, en C i-C6-alkylgruppe, der kan være substitueret med et til tre halogenatomer og en cyangruppe.
  8. 8. Forbindelse ifølge krav 1, der er udvalgt fra følgende erunne eller et salt deraf:
  9. 9. Forbindelse ifølge krav 1, der er (3'R,4'S,5,R)-N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6”-chlor-4'-(2-chlor-3-fluorpyridin-4-yl)-4,4-dimethyl-2"-oxo-l",2"-dihydrodispiro[cyclohexan-l,2,-pyrrolidin-3 ',3" -indol] -5 '-carboxamidhydrochlorid.
  10. 10. Forbindelse ifølge krav 1, der er (3'R,4'S,5'R)-N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6"-chlor-4'-(2-chlor-3-fluorpyridin-4-yl)-4,4-dimethyl-2"-oxo-l",2"-dihydrodispiro[cyclohexane-l,2'-pyrrolidin-3 ',3" -indol] -5 '-carboxamidsulfat.
  11. 11. Forbindelse ifølge krav 1, der er (3'R,4'S,5'R)-N-[(3R,6S)-6-carbamoyltetrahydro-2F[-pyran-3-yl]-6"-chlor-4'-(2-chlor-3-fluorpyridin-4-yl)-4,4-dimethyl-2"-oxo-l",2"-dihydrodispiro[cyclohexane-l,2,-pyrrolidin-3 ',3" -indol] -5 '-carboxamidmethansulfonat.
  12. 12. Forbindelse ifølge krav 1, der er (3'R,4'S,5'R)-N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6"-chlor-4'-(2-chlor-3-fluorpyridin-4-yl)-4,4-dimethyl-2"-oxo-l",2"-dihydrodispiro[cyclohexane-l,2'-pyrrolidin-3 ',3" -indol] -5 '-carboxamidethansulfonat.
  13. 13. Forbindelse ifølge krav 1, der er (3,R,4'S,5'R)-N-[(3R,6S)-6-carbamoyltetrahydro-2F[-pyran-3-yl]-6"-chlor-4'-(2-chlor-3-fluorpyridin-4-yl)-4,4-dimethyl-2"-oxo-l",2"-dihydrodispiro[cyclohexane-l,2,-pyrrolidin-3 ',3" -indol] -5 '-carboxamidbenzensulfonat.
  14. 14. Forbindelse ifølge krav 1, der er (3'R,4'S,5'R)-N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6"-chlor-4'-(2-chlor-3-fluorpyridin-4-yl)-4,4-dimethyl-2"-oxo-l",2"-dihydrodispiro[cyclohexane-l,2'-pyrrolidin-3 ',3" -indol] -5 '-carboxamid-p-toluensulfonat.
  15. 15. Forbindelse ifølge krav 1, der er (3'R,4'S,5'R)-6"-chlor-4'-(2-chlor-3-fluorpyridin-4-yl)-N-{(3R,6S)-6-[ 1 -hydroxyethyl]tetrahydro-2H-pyran-3-yl} -4,4-dimethyl-2"-oxo-l ",2"-dihydrodispiro[cyclohexan-1,2'-pyrrolidin-3 ',3" -indol] -5 '-carboxamidbenzensulfonat. 16. (2S,5R)-5-({[(3'R,4'S,5'R)-6"-chlor-4'-(2-chlor-3-fluorpyridin-4-yl)-4,4-dimethyl-2"-oxo-l",2"-dihydrodispiro[cyclohexan-l,2'-pyrrolidm-3',3"-indol]-5'-yl]carbonyl}amino)tetrahydro-2H-pyran-2-carboxylsyre.
  16. 17. Medikament, der omfatter en forbindelse ifølge et hvilket som helst af kravene 1 til 8 eller et salt deraf eller forbindelse ifølge et hvilket som helst af kravene 9 til 16 som en aktiv ingrediens.
  17. 18. Farmaceutisk sammensætning, der omfatter en forbindelse ifølge et hvilket som helst af kravene 1 til 8 eller et salt deraf eller forbindelse ifølge et hvilket som helst af kravene 9 til 16 og en farmaceutisk acceptabel bærer.
  18. 19. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 eller et salt deraf eller forbindelse ifølge et hvilket som helst af kravene 9 til 16 til anvendelse som en hæmmer af Mdm2.
  19. 20. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 eller et salt deraf eller forbindelse ifølge et hvilket som helst af kravene 9 til 16 til anvendelse som en hæmmer af Mdm2-ubiquitinligase.
  20. 21. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 eller et salt deraf eller forbindelse ifølge et hvilket som helst af kravene 9 til 16 til anvendelse som en hæmmer af p53-Mdm2-binding.
  21. 22. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 eller et salt deraf eller forbindelse ifølge et hvilket som helst af kravene 9 til 16 til anvendelse som en hæmmer af p53-transskriptionsaktivitet.
  22. 23. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 eller et salt deraf eller forbindelse ifølge et hvilket som helst af kravene 9 til 16 til anvendelse som en hæmmer af p5 3-nedbrydning.
  23. 24. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 eller et salt deraf eller forbindelse ifølge et hvilket som helst af kravene 9 til 16 til anvendelse i behandling af cancer.
  24. 25. Forbindelse til anvendelse ifølge krav 24, hvor canceren er lungecancer, brystcancer, prostatacancer, coloncancer, akut myeloid leukæmi, malignt lymfom, malignt melanom, retinoblastom, neuroblastom eller sarkom.
DK12755073.9T 2011-03-10 2012-03-09 Dispiropyrrolidinderivat DK2684880T3 (da)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2011052687 2011-03-10
US201161546805P 2011-10-13 2011-10-13
PCT/JP2012/056066 WO2012121361A1 (ja) 2011-03-10 2012-03-09 ジスピロピロリジン誘導体

Publications (1)

Publication Number Publication Date
DK2684880T3 true DK2684880T3 (da) 2018-05-22

Family

ID=46798312

Family Applications (1)

Application Number Title Priority Date Filing Date
DK12755073.9T DK2684880T3 (da) 2011-03-10 2012-03-09 Dispiropyrrolidinderivat

Country Status (28)

Country Link
US (4) US8629133B2 (da)
EP (1) EP2684880B1 (da)
JP (1) JP5792279B2 (da)
KR (1) KR101779644B1 (da)
CN (2) CN103635473B (da)
AU (1) AU2012226890B2 (da)
BR (1) BR112013023175B1 (da)
CA (1) CA2829188C (da)
CO (1) CO6781539A2 (da)
DK (1) DK2684880T3 (da)
ES (1) ES2666870T3 (da)
HR (1) HRP20180646T1 (da)
HU (1) HUE038714T2 (da)
IL (1) IL228322A (da)
LT (1) LT2684880T (da)
MX (1) MX342958B (da)
MY (1) MY172862A (da)
PH (1) PH12015501860A1 (da)
PL (1) PL2684880T3 (da)
PT (1) PT2684880T (da)
RS (1) RS57158B1 (da)
RU (1) RU2612534C2 (da)
SG (2) SG193002A1 (da)
SI (1) SI2684880T1 (da)
TR (1) TR201807311T4 (da)
TW (1) TWI494312B (da)
WO (1) WO2012121361A1 (da)
ZA (1) ZA201306552B (da)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008095063A1 (en) 2007-01-31 2008-08-07 Dana-Farber Cancer Institute, Inc. Stabilized p53 peptides and uses thereof
KR101623985B1 (ko) 2007-03-28 2016-05-25 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 스티칭된 폴리펩티드
GB0811643D0 (en) 2008-06-25 2008-07-30 Cancer Rec Tech Ltd New therapeutic agents
RU2582678C2 (ru) 2010-08-13 2016-04-27 Эйлерон Терапьютикс, Инк. Пептидомиметические макроциклы
SI2684880T1 (en) * 2011-03-10 2018-08-31 Daiichi Sankyo Company, Limited DERIVAT DISPIROPYROLIDINE
ES2624808T3 (es) * 2011-05-11 2017-07-17 The Regents Of The University Of Michigan Antagonistas de MDM2 espirooxindólicos
TWI643868B (zh) 2011-10-18 2018-12-11 艾利倫治療公司 擬肽巨環化合物
WO2013123266A1 (en) 2012-02-15 2013-08-22 Aileron Therapeutics, Inc. Peptidomimetic macrocycles
CA2864120A1 (en) 2012-02-15 2013-08-22 Aileron Therapeutics, Inc. Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles
TWI586668B (zh) 2012-09-06 2017-06-11 第一三共股份有限公司 二螺吡咯啶衍生物之結晶
SG11201503052RA (en) 2012-11-01 2015-05-28 Aileron Therapeutics Inc Disubstituted amino acids and methods of preparation and use thereof
US9181271B2 (en) 2012-11-01 2015-11-10 Incyte Holdings Corporation Tricyclic fused thiophene derivatives as JAK inhibitors
MX2015008196A (es) 2012-12-20 2015-09-16 Merck Sharp & Dohme Imidazopiridinas sustituidas como inhibidores de doble minuto 2 humana.
US10030028B2 (en) * 2013-09-04 2018-07-24 Daiichi Sankyo Company, Limited Method for producing a spirooxindole derivative
EP3116501A1 (en) 2014-03-13 2017-01-18 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing cftr activity
US9745292B2 (en) 2014-03-13 2017-08-29 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
CA2945527C (en) * 2014-04-17 2022-05-17 The Regents Of The University Of Michigan Mdm2 inhibitors and therapeutic methods using the same
EP3137471A1 (en) 2014-04-30 2017-03-08 Incyte Corporation Processes of preparing a jak1 inhibitor and new forms thereto
WO2015189799A1 (en) 2014-06-12 2015-12-17 Adamed Sp. Z O.O. Compounds comprising 1,1',2,5'-tetrahydrospiro[indole-3,2'-pyrrole]-2,5'-dione system as inhibitors p53-mdm2 protein-protein interaction
CA2952862A1 (en) 2014-06-19 2015-12-23 Proteostasis Therapeutics, Inc. Compounds, compositions and methods of increasing cftr activity
WO2016001376A1 (en) 2014-07-03 2016-01-07 Boehringer Ingelheim International Gmbh New spiro[3h-indole-3,2´-pyrrolidin]-2(1h)-one compounds and derivatives as mdm2-p53 inhibitors
US9701685B2 (en) 2014-08-18 2017-07-11 Hudson Biopharma Inc. Spiropyrrolidines as MDM2 inhibitors
US10471120B2 (en) 2014-09-24 2019-11-12 Aileron Therapeutics, Inc. Peptidomimetic macrocycles and uses thereof
MX2017003819A (es) 2014-09-24 2017-06-15 Aileron Therapeutics Inc Macrociclos peptidomimeticos y formulaciones de los mismos.
EP3204514A1 (en) * 2014-10-09 2017-08-16 Daiichi Sankyo Co., Ltd. Algorithms for gene signature-based predictor of sensitivity to mdm2 inhibitors
US10738011B2 (en) 2014-12-23 2020-08-11 Proteostasis Therapeutics, Inc. Derivatives of 5-(hetero)arylpyrazol-3-carboxylic amide or 1-(hetero)aryltriazol-4-carboxylic amide useful for the treatment of inter alia cystic fibrosis
MA41253A (fr) 2014-12-23 2017-10-31 Proteostasis Therapeutics Inc Composés, compositions et procédés pour augmenter l'activité du cftr
WO2016105468A1 (en) 2014-12-23 2016-06-30 Proteostasis Therapeutics, Inc. Derivatives of 3-heteroarylisoxazol-5-carboxylic amide useful for the treatment of inter alia cystic fibrosis
US10392378B2 (en) 2014-12-23 2019-08-27 Proteostasis Therapeutics, Inc. Derivatives of 5-phenyl- or 5-heteroarylathiazol-2-carboxylic amide useful for the treatment of inter alia cystic fibrosis
TWI711452B (zh) * 2015-02-20 2020-12-01 日商第一三共股份有限公司 癌症的倂用治療法
CN107614003A (zh) 2015-03-20 2018-01-19 艾瑞朗医疗公司 拟肽大环化合物及其用途
US10485794B2 (en) 2015-04-13 2019-11-26 Daiichi Sankyo Company, Limited Treatment method by combined use of MDM2 inhibitor and BTK inhibitor
CN108135168B (zh) 2015-05-21 2021-07-20 凯莫森特里克斯股份有限公司 Ccr2调节剂
US10548878B2 (en) 2015-07-24 2020-02-04 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods of increasing CFTR activity
US10023613B2 (en) 2015-09-10 2018-07-17 Aileron Therapeutics, Inc. Peptidomimetic macrocycles as modulators of MCL-1
GB201517217D0 (en) 2015-09-29 2015-11-11 Astex Therapeutics Ltd And Cancer Res Technology Ltd Pharmaceutical compounds
GB201517216D0 (en) 2015-09-29 2015-11-11 Cancer Res Technology Ltd And Astex Therapeutics Ltd Pharmaceutical compounds
NZ741093A (en) 2015-10-06 2022-12-23 Proteostasis Therapeutics Inc Compounds, compositions, and methods for modulating cftr
LT3359542T (lt) 2015-10-09 2021-05-25 Boehringer Ingelheim International Gmbh Spiro[3h-indolo-3,2 -pirolidin]-2(1h)-ono junginiai ir dariniai, kaip mdm2-p53 inhibitoriai
TW201722428A (zh) * 2015-10-23 2017-07-01 第一三共股份有限公司 用於治療急性骨髓性白血病（ａｍｌ）之醫藥組成物及對有此需要者進行急性骨髓性白血病治療之方法
TW202332444A (zh) * 2015-10-23 2023-08-16 日商第一三共股份有限公司 用於治療癌症之醫藥組成物
CN105693738A (zh) * 2016-01-14 2016-06-22 绍兴文理学院 3’-苯基螺[吲哚啉-3,2’-吡咯烷]-2-酮类衍生物及其制备方法和应用
GB201603779D0 (en) * 2016-03-04 2016-04-20 Mission Therapeutics Ltd Novel compounds
US9486444B1 (en) 2016-03-21 2016-11-08 King Saud University Anti-cancer compound
EP3440066B1 (en) 2016-04-06 2022-11-30 The Regents of The University of Michigan Mdm2 protein degraders
BR112018070747B1 (pt) 2016-04-07 2024-01-09 Proteostasis Therapeutics, Inc Átomos de silicone contendo análogos de ivacaftor, composições farmacêuticas e usos terapêuticos
JP2019522633A (ja) 2016-05-20 2019-08-15 ジェネンテック， インコーポレイテッド Ｐｒｏｔａｃ抗体コンジュゲート及び使用方法
AU2017280206A1 (en) 2016-06-21 2019-01-17 Proteostasis Therapeutics, Inc. Compounds, compositions, and methods for increasing CFTR activity
JPWO2018074387A1 (ja) * 2016-10-17 2019-08-08 第一三共株式会社 Ｍｄｍ２阻害剤とｄｎａメチルトランスフェラーゼ阻害剤との併用治療法
GB201704965D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
GB201704966D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
AU2018313850B2 (en) 2017-08-09 2022-12-22 Denali Therapeutics Inc. Compounds, compositions and methods
PT3676297T (pt) * 2017-09-01 2023-08-29 Denali Therapeutics Inc Compostos, composições e métodos
KR102616949B1 (ko) 2017-09-14 2023-12-22 다이이찌 산쿄 가부시키가이샤 고리형 구조를 갖는 화합물
AU2018335486B2 (en) 2017-09-25 2024-07-04 Chemocentryx, Inc. Combination therapy using a Chemokine Receptor 2 (CCR2) antagonist and a PD-1/PD-L1 inhibitor
US20190269664A1 (en) 2018-01-08 2019-09-05 Chemocentryx, Inc. Methods of treating solid tumors with ccr2 antagonists
US11154556B2 (en) 2018-01-08 2021-10-26 Chemocentryx, Inc. Methods of treating solid tumors with CCR2 antagonists
EP3511334A1 (en) * 2018-01-16 2019-07-17 Adamed sp. z o.o. 1,2,3',5'-tetrahydro-2'h-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrole]-2,3'-dione compounds as therapeutic agents activating tp53
US11304949B2 (en) 2018-03-30 2022-04-19 Incyte Corporation Treatment of hidradenitis suppurativa using JAK inhibitors
CN108864113B (zh) * 2018-08-03 2021-08-13 南方科技大学 一种mdm2-hdac双靶点抑制剂、药物组合物及其制备和用途
TWI837231B (zh) 2018-11-29 2024-04-01 日商第一三共股份有限公司 含有ｅｚｈ１／２雙重抑制劑之醫藥組合及其用途
CA3129609A1 (en) 2019-02-13 2020-08-20 Denali Therapeutics Inc. Eukaryotic initiation factor 2b modulators
EP3924341A4 (en) 2019-02-13 2022-11-02 Denali Therapeutics Inc. COMPOUNDS, COMPOSITIONS AND METHODS
WO2020181247A1 (en) * 2019-03-06 2020-09-10 Denali Therapeutics Inc. Compounds, compositions and methods
WO2020238791A1 (zh) * 2019-05-24 2020-12-03 江苏恒瑞医药股份有限公司 氢化吡啶并嘧啶类衍生物、其制备方法及其在医药上的应用
WO2021175192A1 (en) * 2020-03-02 2021-09-10 Ascentage Pharma (Suzhou) Co., Ltd. Treatment methods and biomarkers for mdm2 inhibitors
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same

Family Cites Families (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU9307098A (en) * 1997-09-08 1999-03-29 Arqule, Inc. Spiro{pyrrolidine-2,3'-oxindole} compounds and methods of use
US6740495B1 (en) 2000-04-03 2004-05-25 Rigel Pharmaceuticals, Inc. Ubiquitin ligase assay
US6979551B2 (en) 2000-04-03 2005-12-27 Rigel Pharmaceuticals, Inc. Assays for identifying ubiquitin agents and for identifying agents that modify the activity of ubiquitin agents
MXPA04005906A (es) 2001-12-18 2004-09-13 Hoffmann La Roche Cis-2,4,5-trifenil-.imidazolinas y uso de la misma para tratamiento de tumores.
JP4361798B2 (ja) 2001-12-18 2009-11-11 エフ．ホフマン−ラ ロシュ アーゲー Ｍｄｍ２インヒビターとしてのシス−イミダゾリン
US7425638B2 (en) 2003-06-17 2008-09-16 Hoffmann-La Roche Inc. Cis-imidazolines
US7132421B2 (en) 2003-06-17 2006-11-07 Hoffmann-La Roche Inc. CIS-imidazoles
WO2005058892A1 (en) 2003-12-19 2005-06-30 Glaxo Group Limited Pyrazolo [3,4-b] pyridine compounds, and their use as phosphodiesterase inhibitors
ES2314660T3 (es) 2004-05-18 2009-03-16 F. Hoffmann-La Roche Ag Nuevas cis-imidazolinas.
GB0419481D0 (en) 2004-09-02 2004-10-06 Cancer Rec Tech Ltd Isoindolin-1-one derivatives
WO2006032466A2 (en) 2004-09-24 2006-03-30 Actelion Pharmaceuticals Ltd New bicyclic antibiotics
CA2752738C (en) * 2005-02-22 2014-05-27 The Regents Of The University Of Michigan Small molecule inhibitors of mdm2 and uses thereof
US7576082B2 (en) 2005-06-24 2009-08-18 Hoffman-La Roche Inc. Oxindole derivatives
KR100939347B1 (ko) 2005-07-20 2010-01-29 (주)카이로드 광학적으로 순수한 (ｓ)-3-히드록시 피롤리딘의 제조방법
JP2009530236A (ja) 2006-03-13 2009-08-27 エフ．ホフマン−ラ ロシュ アーゲー スピロインドリノン誘導体
US20070213341A1 (en) * 2006-03-13 2007-09-13 Li Chen Spiroindolinone derivatives
ZA200901224B (en) 2006-08-30 2010-05-26 Univ Michigan New small molecule inhibitors of MDM2 the uses thereof
US7737174B2 (en) * 2006-08-30 2010-06-15 The Regents Of The University Of Michigan Indole inhibitors of MDM2 and the uses thereof
KR101109438B1 (ko) 2006-09-21 2012-07-12 에프. 호프만-라 로슈 아게 항암제로서의 옥신돌 유도체
US7638548B2 (en) 2006-11-09 2009-12-29 Hoffmann-La Roche Inc. Spiroindolinone derivatives
RU2493155C2 (ru) 2006-12-08 2013-09-20 Ф.Хоффманн-Ля Рош Аг Замещенные пиримидины и их применение в качестве модуляторов jnk
AU2008234954B9 (en) 2007-03-29 2012-02-02 Novartis Ag 3-imidazolyl-indoles for the treatment of proliferative diseases
US7553833B2 (en) 2007-05-17 2009-06-30 Hoffmann-La Roche Inc. 3,3-spiroindolinone derivatives
US7834179B2 (en) 2007-05-23 2010-11-16 Hoffmann-La Roche Inc. Spiroindolinone derivatives
US8134001B2 (en) 2007-12-14 2012-03-13 Hoffmann-La Roche Inc. Spiroindolinone derivatives
US7776875B2 (en) 2007-12-19 2010-08-17 Hoffman-La Roche Inc. Spiroindolinone derivatives
US7723372B2 (en) 2008-03-19 2010-05-25 Hoffman-La Roche Inc. Spiroindolinone derivatives
AR073578A1 (es) 2008-09-15 2010-11-17 Priaxon Ag Pirrolidin-2-onas
CA2734363C (en) 2008-09-18 2016-10-25 F. Hoffmann-La Roche Ag Substituted pyrrolidine-2-carboxamides
US8354444B2 (en) 2008-09-18 2013-01-15 Hoffmann-La Roche Inc. Substituted pyrrolidine-2-carboxamides
EP2380892B1 (en) 2009-01-16 2014-04-02 Daiichi Sankyo Company, Limited Imidazothiazole derivative having proline ring structure
US20100190814A1 (en) 2009-01-26 2010-07-29 Li Chen Spiroindolinone derivative prodrugs
US7928233B2 (en) 2009-02-10 2011-04-19 Hoffmann-La Roche Inc. Spiroindolinone pyridine derivatives
US8217051B2 (en) 2009-02-17 2012-07-10 Hoffmann-La Roche Inc. Spiroindolinone derivatives
US8076482B2 (en) 2009-04-23 2011-12-13 Hoffmann-La Roche Inc. 3,3′-spiroindolinone derivatives
US8017607B2 (en) 2009-10-14 2011-09-13 Hoffmann-La Roche Inc. N-substituted-pyrrolidines as inhibitors of MDM2-P-53 interactions
MX2012005507A (es) * 2009-11-12 2012-07-03 Univ Michigan Antagonistas de espiro-oxindol de mdm2.
US20110118283A1 (en) 2009-11-17 2011-05-19 Qingjie Ding Substituted Pyrrolidine-2-Carboxamides
US8088815B2 (en) * 2009-12-02 2012-01-03 Hoffman-La Roche Inc. Spiroindolinone pyrrolidines
US8288431B2 (en) 2010-02-17 2012-10-16 Hoffmann-La Roche Inc. Substituted spiroindolinones
KR20130050938A (ko) 2010-04-09 2013-05-16 더 리젠츠 오브 더 유니버시티 오브 미시건 질환 치료시 사용하기 위한 ｍｄｍ2 억제제에 대한 바이오마커
US8217044B2 (en) 2010-04-28 2012-07-10 Hoffmann-La Roche Inc. Spiroindolinone pyrrolidines
US20120010235A1 (en) 2010-07-12 2012-01-12 Xin-Jie Chu N-substituted pyrrolidines
US20120046306A1 (en) 2010-08-18 2012-02-23 David Joseph Bartkovitz Substituted Heteroaryl Spiropyrrolidine MDM2 Antagonists
US20120065210A1 (en) 2010-09-15 2012-03-15 Xin-Jie Chu Substituted hexahydropyrrolo[1,2-c]imidazolones
US20120071499A1 (en) 2010-09-20 2012-03-22 Xin-Jie Chu Substituted Spiro[3H-Indole-3,6'(5'H)-[1H]Pyrrolo[1,2c]Imidazole-1',2(1H,2'H)-diones
AU2011326395B2 (en) 2010-11-12 2016-01-07 Ascenta Licensing Corporation Spiro-oxindole MDM2 antagonists
WO2012076513A1 (en) 2010-12-09 2012-06-14 F. Hoffmann-La Roche Ag 3-cyano-1-hydroxymethyl-2-phenylpyrrolidine derivatives as inhibitors of mdm2-p53 interactions useful for the treatment of cancer
SI2684880T1 (en) * 2011-03-10 2018-08-31 Daiichi Sankyo Company, Limited DERIVAT DISPIROPYROLIDINE
ES2624808T3 (es) * 2011-05-11 2017-07-17 The Regents Of The University Of Michigan Antagonistas de MDM2 espirooxindólicos

Also Published As

Publication number Publication date
ES2666870T3 (es) 2018-05-08
US20220106324A1 (en) 2022-04-07
TW201249842A (en) 2012-12-16
HUE038714T2 (hu) 2018-11-28
SI2684880T1 (en) 2018-08-31
EP2684880A1 (en) 2014-01-15
CN105753872A (zh) 2016-07-13
IL228322A (en) 2017-03-30
PH12015501860B1 (en) 2017-04-17
NZ614218A (en) 2015-08-28
CO6781539A2 (es) 2013-10-31
WO2012121361A1 (ja) 2012-09-13
JPWO2012121361A1 (ja) 2014-07-17
KR20140059161A (ko) 2014-05-15
US20130165424A9 (en) 2013-06-27
CN105753872B (zh) 2017-11-17
CN103635473B (zh) 2016-08-17
CA2829188C (en) 2016-10-18
EP2684880A4 (en) 2014-07-23
US8629133B2 (en) 2014-01-14
US20240246989A1 (en) 2024-07-25
TR201807311T4 (tr) 2018-06-21
SG193002A1 (en) 2013-09-30
BR112013023175A2 (pt) 2016-12-13
NZ710585A (en) 2017-02-24
US20140121196A1 (en) 2014-05-01
LT2684880T (lt) 2018-04-25
PH12015501860A1 (en) 2017-04-17
RU2612534C2 (ru) 2017-03-09
AU2012226890A1 (en) 2013-09-19
BR112013023175B1 (pt) 2022-11-16
CA2829188A1 (en) 2012-09-13
EP2684880B1 (en) 2018-02-28
MX342958B (es) 2016-10-18
PT2684880T (pt) 2018-04-27
ZA201306552B (en) 2016-07-27
MY172862A (en) 2019-12-13
US20120264738A1 (en) 2012-10-18
KR101779644B1 (ko) 2017-09-18
MX2013010334A (es) 2014-03-05
PL2684880T3 (pl) 2018-07-31
JP5792279B2 (ja) 2015-10-07
CN103635473A (zh) 2014-03-12
RU2013145310A (ru) 2015-04-20
SG10201601802YA (en) 2016-04-28
TWI494312B (zh) 2015-08-01
AU2012226890B2 (en) 2016-10-06
IL228322A0 (en) 2013-11-25
HRP20180646T1 (hr) 2018-06-01
RS57158B1 (sr) 2018-07-31

Similar Documents

Publication Publication Date Title
DK2684880T3 (da) Dispiropyrrolidinderivat
AU2019269391B2 (en) MCL-1 inhibitors
TWI789381B (zh) 雜環化合物
JP2022533023A (ja) 統合的ストレス経路の調節剤としての置換シクロアルキル
JP2023052094A (ja) タンパク質チロシンホスファターゼ阻害物質及びその使用方法
EP3243813A1 (en) Tricyclic spiro compound
WO2018066545A1 (ja) 複素環化合物
JP2023548169A (ja) 統合的ストレス経路の調節剤
JP2023542503A (ja) タンパク質チロシンホスファターゼ阻害物質及びその使用方法
WO2018030550A1 (en) Heterocyclic compounds with an ror(gamma)t modulating activity
JP7071400B2 (ja) 免疫プロテアソーム阻害剤
CA3234429A1 (en) Ras inhibitors, compositions and methods of use thereof
NZ614218B2 (en) Dispiropyrrolidine derivatives
CN117580824A (zh) 整合应激通路的调节剂