HRP20151162T1 - Derivati indolizina, postupak za njihovo pripremanje i terapijska primjena - Google Patents

Derivati indolizina, postupak za njihovo pripremanje i terapijska primjena Download PDF

Info

Publication number
HRP20151162T1
HRP20151162T1 HRP20151162TT HRP20151162T HRP20151162T1 HR P20151162 T1 HRP20151162 T1 HR P20151162T1 HR P20151162T T HRP20151162T T HR P20151162TT HR P20151162 T HRP20151162 T HR P20151162T HR P20151162 T1 HRP20151162 T1 HR P20151162T1
Authority
HR
Croatia
Prior art keywords
alk
formula
compound
group
image
Prior art date
Application number
HRP20151162TT
Other languages
English (en)
Inventor
Chantal Alcouffe
Corentin Herbert
Gilbert Lassalle
Original Assignee
Sanofi
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=43382527&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20151162(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Sanofi filed Critical Sanofi
Publication of HRP20151162T1 publication Critical patent/HRP20151162T1/hr

Links

Classifications

    • 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
    • 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
    • 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
    • A61K31/4709—Non-condensed quinolines 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
    • A61K31/495—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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • 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
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • 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
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/36—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D211/82—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Urology & Nephrology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biomedical Technology (AREA)
  • Emergency Medicine (AREA)
  • Neurology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Reproductive Health (AREA)
  • Ophthalmology & Optometry (AREA)
  • Child & Adolescent Psychology (AREA)

Claims (18)

1. Spoj s formulom (I): [image] naznačen time da: - R1 predstavlja . vodik ili atom halogena, . alkil skupinu proizvoljno supstituiranu s -COOR5, . alkenil skupinu proizvoljno supstituiranu s --COOR5, . -COOR5 ili -CONR5R6 skupinu, . -NR5COR6 ili -NR5-SO2R6 skupinu, . -OR5, -O-Alk-OR5, -O-Alk-COOR5, -O-Alk-OR5, -O-Alk-NR5R6 ili -O-Alk-NR7R8 skupinu ili . aril skupinu, naročito fenil, ili heteroaril skupinu, navedena arilna ili heteroarilna skupina je proizvoljno supstituirana s jednom ili više skupina odabranih od: atoma halogena, alkil skupinama, cikloalkil skupinama, -COOR5, -CF3, -OCF3, -CN, -C(NH2)NOH, -OR5, -O-Alk-COOR5, -O-Alk-NR5R6, -O-Alk-NR7R8, -Alk-OR5, -Alk-COOR5, -CONR5R6, -CO-NR5-OR6, -CO-NR5-SO2R7, -CONR5-Alk-NR5R6, -CONR5-Alk-NR7R8, -Alk-NR5R6, -NR5R6, -NC(O)N(CH3)2, -CO-Alk, -CO(OAlk)nOH, -COO-Alk-NR5R6, -COO-Alk-NR7R8 i 5-članim heteroarilnim skupinama, navedene heteroarilne skupine su proizvoljno supstituirane s jednom ili više skupina odabranih od atoma halogena i alkila, -CF3, -CN, -COOR5, -Alk-OR5, -Alk-COOR5, -CONR5R6, -CONR7R8, -CO-NR5-OR6, -CO-NR5-SO2R6, -NR5R6 i -Alk-NR5R6 skupinama, ili s hidroksilom skupinom ili s atomom kisika, - n je cijeli broj u rasponu od 1 do 3, - R2 predstavlja: . vodikov atom, . alkilnu skupinu, . fenilnu skupina proizvoljno supstituiranu s jednom ili više alkilnih skupina, - R3 i R4 tvore zajedno, s ugljikovim atomima fenilne jezgre na koju su spojeni, 6-člani dušikov heterocikal koji odgovara jednoj od formula (A), (B) ili (C) niže: [image] u kojima valovite linije predstavljaju fenilnu jezgru na koju su spojeni R3 i R4 i: . Ra predstavlja vodikov atom ili alkil, haloalkil, -Alk-CF3, -Alk-COOR5, -Alk'-COOR5 , -Alk-CONR5R6, -Alk'-CONR5R6, -Alk-CONR7R8, -Alk-NR5R6, -AlkCONR5-OR6, -Alk-NR7R8, -Alk-cikloalkil, -Alk-O-R5, -Alk-S-R5, -Alk-CN, -OR5, -OAlkCOOR5, -NR5R6, -NR5-COOR6, -Alk-aril, -Alk-O-aril, -Alk-O-heteroaril, -Alk-heteroaril ili heteroaril skupina, gdje su arilna ili heteroarilna skupina proizvoljno supstituirane s jednim ili više atoma halogena i/ili alkilom, cikloalkilom, -CF3, -OCF3, -O-R5 ili -S-R5 skupinama, . Ra' predstavlja vodikov atom ili linearnu, razgranatu, cikličku ili djelomično cikličku alkil skupinu, ili -Alk-OR5, -Alk-NR5R6 ili -Alk-NR7R8 skupinu, Ra' je proizvoljno supstituiran s jednim ili više atoma halogena, . Rb predstavlja vodikov atom ili alkil ili -Alk-COOR5 skupinu, . Rb' predstavlja vodikov atom ili alkil, haloalkil, cikloalkil, fenil ili -Alk-COOR5 skupinu, . RC predstavlja vodikov atom ili alkil, -CN, -COOR5, -CO-NR5R6, -CONR7R8, -CO-NR5-Alk-NR5R6, -CONR5-Alk-OR5, -CONR5SO2R5, -Alk-aril ili -Alk-heteroaril skupinu, gdje je arilna ili heteroarilna skupina proizvoljno supstituirana s jednim ili više atoma halogena i/ili alkil, cikloalkil, -CF3, -OCF3, -O-alkil ili -S-alkil skupinama, . RC' predstavlja vodikov atom ili alkil skupinu, . RC" predstavlja vodikov atom ili alkil, alkenil, haloalkil, cikloalkil, -Alk-NR5R6, -Alk-NR7R8, -Alk-OR5 ili -Alk-SR5 skupinu, - R5 i R6, koji mogu biti isti ili različiti, predstavljaju vodikove atome, haloalkil skupine ili alkil skupine, cikloalkil skupine ili Ms skupinu, - R7 i R8, koji mogu biti isti ili različiti, predstavljaju vodikove atome ili alkil ili fenil skupine, ili drugačije R7 i R8 zajedno tvore 3- do 8-člani zasićeni prsten koji proizvoljno može sadržavati heteroatom, - Alk predstavlja linearni ili razgranati alkilenski lanac, i - Alk' predstavlja linearni, razgranati, ciklički ili djelomično ciklički alkilenski lanac, proizvoljno u obliku njegove farmaceutski prihvatljive soli.
2. Spoj prema zahtjevu 1, naznačen time da R1 predstavlja -OR5, - O-Alk-OR5, -COOR5 ili -O-Alk-COOR5 skupinu ili fenilnu skupinu proizvoljno supstituiranu s jednom ili više alkil ili -COOR5 skupina, gdje R5 predstavlja vodikov atom ili alkil skupinu koja sadrži od 1 do 4 ugljikova atoma, i Alk predstavlja alkilenski lanac koji sadrži 1 ili 2 ugljikova atoma, ili heteroarilnu skupinu, poželjno piridinil skupinu.
3. Spojevi prema zahtjevu 1 ili 2, naznačeni time da R1 predstavlja -OR5, -O-Alk-OR5 ili -O-Alk-COOR5 skupinu ili fenilnu skupinu proizvoljno supstituiranu s jednom ili više alkil ili -COOR5 skupina, gdje R5 predstavlja vodikov atom ili metil skupina, i Alk predstavlja alkilenski lanac koji sadrži 1 ili 2 ugljikova atoma, ili heteroarilnu skupinu, poželjno piridinil skupinu.
4. Spojevi s formulom (I) prema zahtjevima 1 do 3, naznačeni time da R2 predstavlja alkilnu skupinu koja sadrži od 1 do 4 ugljikova atoma ili fenilnu skupinu.
5. Spojevi s formulom (I) prema bilo kojem od zahtjeva 1 do 4, naznačeni time da R3 i R4 tvore zajedno, s ugljikovim atomima fenilne jezgre na koju su spojeni, 6-člani dušikov heterocikal koji odgovara jednoj od formula (A), (B) ili (C) definiranim gore i u kojima: . Ra predstavlja vodikov atom ili alkil ili haloalkil, -OR5, -Alk-OR5, -Alk'-COOR5, -NR5R6, -Alk-NR7R8, -Alk-CN, -NR5-COOR6, -Alk'-CO-NR5R6, -Alk-CO-NR5-OR6 ili -O-Alk-COOR5 skupinu, ili heteroaril, -Alk-heteroaril ili -Alk-aril skupinu u kojima je arilna ili heteroarilna skupina proizvoljno supstituirana s alkilnom skupinom ili s atomom halogena, . Ra' predstavlja vodikov atom ili alkilnu ili -Alk-OR5 skupinu, . Rb predstavlja vodikov atom ili alkilnu ili -Alk-COOR5 skupinu, . Rb' predstavlja vodikov atom ili alkilnu, haloalkil ili -Alk-COOR5 skupinu, . RC predstavlja vodikov atom ili alkil, -COOR5, CN, -CO-NR5R6 ili -CO-NR7R8 skupinu, heteroaril ili Alk-heteroaril, . RC' predstavlja vodikov atom ili alkilnu skupinu, . RC" predstavlja vodikov atom ili alkilnu ili alkenil skupinu, . gore navedene alkilne ili alkenilne skupine sadrže od 1 do 4 ugljikova atoma, . R5 i R6 predstavljaju vodikove atome ili alkil ili haloalkil skupine, te navedene alkil i haloalkil skupine sadrže od 1 do 4 ugljikova atoma, . R7 i R8 predstavljaju vodikove atome ili alkil skupine koje sadrže od 1 do 4 ugljikova atoma, ili tvore zajedno 5- ili 6-člani zasićeni prsten, . Alk predstavlja linearni ili razgranati alkilenski lanac koji sadrži od 1 do 4 ugljikova atoma, i . Alk' predstavlja linearni, razgranati, ciklički ili djelomično ciklički alkilenski lanac koji sadrži od 1 do 4 ugljikova atoma.
6. Spojevi s formulom (I) prema zahtjevu 5, naznačeni time da R3 i R4 tvore zajedno, s ugljikovim atomima fenilne jezgre na koju su spojeni, 6-člani dušikov heterocikal koji odgovara bilo kojoj od formula (A) i (C), a radikali Ra, Ra', Rc, Rc' i Rc" su kako je definirano u zahtjevu 1.
7. Spoj s formulom (I) prema zahtjevu 5, naznačen time da R3 i R4 tvore zajedno, s ugljikovim atomima fenilne jezgre na koju su spojeni, 6-člani dušikov heterocikal koji odgovara formuli (C), te su Rc, Rc' i Rc" kako je definirano u zahtjevu 1.
8. Spojevi s formulom (I) prema bilo kojem od zahtjeva 1 do 5, naznačeni time da su odabrani od slijedećih spojeva: 2-{6-[(1-metoksi-2-metilindolizin-3-il)karbonil]-2,4-diokso-1,4-dihidrokinazolin-3(2H)-il}-N,N'-dimetilacetamida, 2-{6-[(1-metoksi-2-metilindolizin-3-il)karbonil]-1-metil-2,4-diokso-1,4-dihidrokinazolin-3(2H)-il}-N,N'-dimetilacetamida, 6-[(1-metoksi-2-metilindolizin-3-il)karbonil]-3-[(3-metil-1,2,4-oksadiazol-5-il)metil]kinazolin-2,4(1H,3H)-diona, 3-{3-(2,4-diokso-3-propil-1,2,3,4-tetrahidrokinazolin-6-il)karbonil}-2-metilindolizin-1-il}benzojeve kiseline, {6-[(1-metoksi-2-fenilindolizin-3-il)karbonil]-2,4-diokso-1,4-dihidrokinazolin-3(2H)-il}octena kiseline, etil ({6-[(1-metoksi-2-metilindolizin-3-il)karbonil]-2,4-diokso-1,4-dihidrokinazolin-3(2H)-il}oksi)acetata, 3-amino-6-[(1-metoksi-2-metilindolizin-3il)karbonil]kinazolin-2,4(1H,3H)-diona, 6-[(1-metoksi-2-metilindolizin-3-il)karbonil]-2-metilkinazolin-4(3H)-ona, 3-{2-metil-3-[(2-metil-4-okso-3,4-dihidrokinazolin-6-il)karbonil]indolizin-1-il}-benzojeve kiseline, 6-{[1(2-metoksietoksi)-2-metilindolizin-3-il]karbonil}-3-propilkinazolin-2,4(1H,3H)-diona, 6-[(1-metoksi-2-metilindolizin-3-il)karbonil]-1-metil-4-okso-1,4-dihidrokinolin-3-karboksilne kiseline, 6-[(1-metoksi-2-metilindolizin-3-il)karbonil]-2-metil-4-okso-1,4-dihidrokinolin-3-karboksilne kiseline, 6-[(1-metoksi-2-metilindolizin-3-il)karbonil]-N-metil-4-okso-1,4-dihidrokinolin-3-karboksamida, N-1-dimetil-6-[(2-metilindolizin-3-il)karbonil]-4-okso-1,4-dihidrokinolin-3-karboksamida, N-1-dimetil-6-{[2-metil-1-(piridin-4-il)indolizin-3-il]karbonil}-4-okso-1,4-dihidrokinolin-3-karboksamid hidroklorida.
9. Postupak za pripremanje spojeva s formulom (I) prema bilo kojem od zahtjeva 1 do 7 u kojima R3 i R4 tvore zajedno, s ugljikovim atomima fenilne jezgre na koju su spojeni, 6-člani dušikov heterocikal koji odgovara formuli (A), R1 predstavlja -OR5, -O-Alk-OR5, -COOR5, -O-Alk-COOR5, -O-Alk-OR5, O-Alk-NR5R6 ili -O-Alk-NR7R8 skupinu, i R2 je kako je definirano u zahtjevu 1, naznačen time da: - spoj s formulom (II) [image] je kondenziran sa spojem s formulom (III) [image] kako bi se dobio spoj s formulom (IV) [image] - spoj s formulom (IV) se podvrgava bazičnoj reakciji hidrolize kako bi se dobio spoj s formulom (V): [image] - provodi se esterifikacija spoja s formulom (V) i dobiven je spoj s formulom (VI): [image] - spoj s formulom (VI) se podvrgava djelovanju trifosgena tako da se stvori izocijanat koji odgovara spoju s formulom (VI), te se zatim ovaj izocijanat kondenzira sa aminom s formulom RaNH2, te je Ra kako je definirano u zahtjevu 1, kako bi se dobila urea s formulom (VII), [image] - spoj s formulom (VII) se podvrgava reakciji ciklizacije u bazičnom mediju, kako bi se dobio spoj s formulom (VIII): [image] - spoj s formulom (VIII) se podvrgava reakciji alkilacije u prisutnosti baze i halogeniranog derivata Ra'X, te je Ra' kako je definirano u zahtjevu 1 i X je halogen.
10. Postupak za pripremanje spojeva s formulom (I) prema bilo kojem od zahtjeva 1 do 7 u kojem R3 i R4 tvore zajedno dušikov heterocikal s formulom (A) i u kojem R1 je kako je definirano u zahtjevu 1, uz uvjet da R1 ne predstavlja jednu od slijedećih skupina: -OR5, -O-Alk-OR5, -COOR5, -O-Alk-COOR5, -O-Alk-OR5, O-Alk-NR5R6 i -O-Alk-NR7R8, te je R2 kako je definirano u zahtjevu 1, naznačen time da: - spoj s formulom (IX) [image] se kondenzira sa spojem s formulom (III) [image] kako bi se dobio spoj s formulom (X) [image] - spoj s formulom (X) se podvrgava bazičnoj reakciji hidrolize kako bi se dobio spoj s formulom (XI): [image] - provodi se esterifikacija spoja s formulom (XI) i dobiven je spoj s formulom (XII): [image] - spoj s formulom (XII) je dobiven s N-bromosukcinimidom i dobiven je spoj s formulom (XIII): [image] - spoj s formulom (XIII) se podvrgava djelovanju trifosgena i dobiven je izocijanat koji odgovara spoju s formulom (XIII), koji se kondenzira sa aminom s formulom RaNH2, te je Ra kako je definirano u zahtjevu 1, kako bi se dobila urea s formulom (XIV): [image] - spoj s formulom (XIV) se podvrgava reakciji ciklizacije u bazičnom mediju kako bi se dobio spoj s formulom (XV): [image] - spoj s formulom (XV) se podvrgava, u prisutnosti paladijevog katalizatora, liganda i baze: . reakciji sa fenilboratnim ili heteroarilboratnim ili fenilboronatnim esterom ili derivatima heteroarilboronatnog estera u skladu sa Suzuki spajanjem, . ili reakciji cijanacije s cinkovim cijanidom, nakon čega slijedi kisela hidroliza, kako bi se dobio spoj s formulom (XVI): [image] - spoj s formulom (XVI) se podvrgava reakciji alkilacije u prisutnosti baze i halogeniranog derivata Ra'X, te je Ra' kako je definirano u zahtjevu 1 i X je halogen.
11. Postupak za pripremanje spojeva s formulom (I) prema bilo kojem od zahtjeva 1 do 8 u kojem R3 i R4 tvore zajedno dušikov heterocikal s formulom (C), u kojoj R1 predstavlja -OR5, -O-Alk-OR5, -COOR5, -O-Alk-COOR5, -O-Alk-OR5, O-Alk-NR5R6 ili -O-Alk-NR7R8 skupinu, i R5, R6 i R2 su kako je definirano u zahtjevu 1, naznačen time da: - spoj s formulom (II): [image] se kondenzira sa spojem s formulom (III): [image] kako bi se dobio spoj s formulom (IV): [image] - spoj s formulom (IV) se podvrgava bazičnoj reakciji hidrolize kako bi se dobio spoj s formulom (V): [image] spoj (V) se podvrgava reakciji kondenzacije kako bi se dobio spoj (XXI): [image] - spoj (XXI) se podvrgava reakciji alkilacije u prisutnosti baze i halogeniranog derivata Rc"X, te je Rc" kako je definirano u zahtjevu 1 i X je halogen, ili zaštitnoj skupini, te je dobiven spoj s formulom (XXII): [image] - spoj (XXII) se podvrgava reakciji kondenzacije s derivatom malonske kiseline kako bi se dobio spoj s formulom (XXIII): [image] u kojoj su Rc' i Rc definirani u zahtjevu 1, - spoj s formulom (XXIII) se podvrgava reakciji deprotekcije.
12. Postupak za pripremanje spojeva s formulom (I) prema bilo kojem od zahtjeva 1 do 8 u kojem R3 i R4 tvore zajedno dušikov heterocikal s formulom (C), R1 predstavlja aril ili heteroaril skupinu, proizvoljno supstituiranu s jednom ili više alkil, -OR5, NR5R6 ili -COOR5 skupina, Rc' poželjno predstavlja alkil, Rc" R5, R6 i R2 su definirani u zahtjevu 1, naznačen time da: - spoj s formulom (IX): [image] se kondenzira sa spojem s formulom (III): [image] kako bi se dobio spoj s formulom (X): [image] - spoj s formulom (X) se podvrgava bazičnoj reakciji hidrolize kako bi se dobio spoj s formulom (XI): [image] - provodi se esterifikacija spoja s formulom (XI) i dobiven je spoj s formulom (XII): [image] - spoj s formulom (XII) reagira sa N-bromosukcinimidom i dobiven je spoj s formulom (XIII): [image] - spoj s formulom (XIII) se podvrgava reakciji saponifikacije u bazičnom mediju kako bi se dobio spoj (XVIII): [image] - spoj (XVIII) se podvrgava reakciji kondenzacije kako bi se dobio spoj (XXIV): [image] - spoj s formulom (XXIV) se podvrgava reakciji alkilacije u prisutnosti baze i halogeniranog derivata RC"X, te je RC" kako je definirano u zahtjevu 1 i X je halogen, ili zaštitne skupine, kako bi se dobio spoj s formulom (XXV): [image] - spoj s formulom (XXV) se podvrgava reakciji kondenzacije s derivatom malonske kiseline kako bi se dobio spoj s formulom (XXVI): [image] u kojoj su RC' i RC kako je definirano u zahtjevu 1, - spoj s formulom (XXVI) se podvrgava, u prisutnosti paladijevog katalizatora, liganda i baze, reakciji sa fenilboratnim ili heteroarilboratnim ili fenilboronatnim esterom ili derivatima heteroarilboronatnog estera u skladu sa Suzuki spajanjem, kako bi se dobio spoj s formulom (XXVII): [image] - spoj s formulom (XXVII) se podvrgava reakciji deprotekcije.
13. Postupak za pripremanje spojeva s formulom (I) prema bilo kojem od zahtjeva 1 do 7, u kojem R3 i R4 tvore zajedno dušikov heterocikal s formulom (C), gdje Rc' predstavlja vodik, Rc i Rc" su kako je definirano u zahtjevu 1, te R1 predstavlja vodik ili -OR5, -O-Alk-OR5, -COOR5, -O-Alk-COOR5, -O-Alk-OR5, O-Alk-NR5R6 ili -O-Alk-NR7R8 skupinu su kako je definirano u zahtjevu 1, naznačen time da: - spoj s formulom (II): [image] kondenzira s kloridom 4-nitrobenzojeve kiseline i dobiven je spoj s formulom (XXVIII): [image] - spoj s formulom (XXVIII) se podvrgava reakciji u prisutnosti željeza i octene kiseline i dobiven je spoj s formulom (XXIX): [image] - spoj s formulom (XXIX) se podvrgava kondenzacijskoj redukciji i dobiven je spoj s formulom (XXX): [image] - spoj s formulom (XXX) se podvrgava reakciji alkilacije u prisutnosti halogenida Rc"X, te je Rc" kako je definirano u zahtjevu 1 i X je halogen, te u prisutnosti baze.
14. Farmaceutski pripravak naznačen time da sadrži, kao aktivnu tvar, spoj s formulom (I) prema bilo kojem od zahtjeva 1 do 8, proizvoljno u kombinaciji s jednim ili više pogodnih inertnih pomoćnih sredstava.
15. Spoj prema bilo kojem od zahtjeva 1 do 8, naznačen time da je za primjenu za liječenje i sprječavanje bolesti koje zahtijevaju modulaciju b-FGF-ova.
16. Spoj prema bilo kojem od zahtjeva 1 do 8, naznačen time da je za primjenu za liječenje i sprječavanje karcinoma, naročito karcinoma koji imaju visok stupanj vaskularizacije, kao što su rak pluća, rak dojke, rak prostate, rak gušterače, rak debelog crijeva, rak bubrega i ezofagealni karcinomi, te karcinomi koji induciraju metastaze, kao što su rak debelog crijeva, rak jetre i rak želuca, melanomi, gliomi, limfomi, leukemije, te također trombopenije.
17. Spoj prema zahtjevu 16, naznačen time da je za primjenu u kombinaciji s jednim ili više antikancerogenih aktivnih sastojaka i/ili s radioterapijom i/ili s bilo kojim anti-VEGF tretmanom.
18. Spoj prema bilo kojem od zahtjeva 1 do 8, naznačen time da je za primjenu za liječenje i sprječavanje kardiovaskularnih bolesti, poput ateroskleroze ili postangioplastične restenoze, bolesti povezanih s komplikacijama koje se javljaju nakon implantacije endovaskularnih stentova i/ili aortokoronarnih premosnica ili drugih vaskularnih transplantata, srčane hipertrofije, vaskularnih komplikacija dijabetesa, kao što je dijabetička retinopatija, fibroza jetre, fibroza bubrega i fibroza pluća, neuropatska bol, kroničnih upalnih bolesti kao što je reumatoidni artritis ili IBD, hiperplazije prostate, psorijaze, akantoma svijetlih stanica, osteoartritisa, ahondroplazija (ACH), hipohondroplazija (HCH), TD (tanatoforičnih displazija), pretilosti, te makularne degeneracije, kao što je makularna degeneracija povezana sa starenjem (ARMD).
HRP20151162TT 2010-07-06 2015-11-02 Derivati indolizina, postupak za njihovo pripremanje i terapijska primjena HRP20151162T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR1055477A FR2962438B1 (fr) 2010-07-06 2010-07-06 Derives d'indolizines, procedes de preparation et application en therapeutique
PCT/IB2011/052953 WO2012004731A1 (en) 2010-07-06 2011-07-04 Indolizine derivatives, process for the preparation thereof and therapeutic use thereof
EP11743363.1A EP2590975B1 (en) 2010-07-06 2011-07-04 Indolizine derivatives, process for the preparation thereof and therapeutic use thereof

Publications (1)

Publication Number Publication Date
HRP20151162T1 true HRP20151162T1 (hr) 2015-12-04

Family

ID=43382527

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20151162TT HRP20151162T1 (hr) 2010-07-06 2015-11-02 Derivati indolizina, postupak za njihovo pripremanje i terapijska primjena

Country Status (38)

Country Link
US (1) US8859544B2 (hr)
EP (1) EP2590975B1 (hr)
JP (1) JP5863788B2 (hr)
KR (1) KR101797795B1 (hr)
CN (1) CN103080112B (hr)
AR (1) AR082768A1 (hr)
AU (1) AU2011275426B2 (hr)
BR (1) BR112013000306A2 (hr)
CA (1) CA2805065C (hr)
CL (1) CL2013000018A1 (hr)
CO (1) CO6650361A2 (hr)
CR (1) CR20130001A (hr)
CY (1) CY1116945T1 (hr)
DK (1) DK2590975T3 (hr)
DO (1) DOP2012000321A (hr)
EA (1) EA024160B1 (hr)
EC (1) ECSP13012362A (hr)
ES (1) ES2552850T3 (hr)
FR (1) FR2962438B1 (hr)
GT (1) GT201300001A (hr)
HR (1) HRP20151162T1 (hr)
HU (1) HUE026067T2 (hr)
IL (1) IL223844A (hr)
MA (1) MA34451B1 (hr)
MX (1) MX2012015306A (hr)
MY (1) MY163202A (hr)
NI (1) NI201200191A (hr)
PE (1) PE20130386A1 (hr)
PL (1) PL2590975T3 (hr)
PT (1) PT2590975E (hr)
SG (2) SG186436A1 (hr)
SI (1) SI2590975T1 (hr)
TN (1) TN2012000609A1 (hr)
TW (1) TWI494310B (hr)
UA (1) UA109013C2 (hr)
UY (1) UY33489A (hr)
WO (1) WO2012004731A1 (hr)
ZA (1) ZA201300100B (hr)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8754114B2 (en) 2010-12-22 2014-06-17 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
FR2985258A1 (fr) * 2011-12-28 2013-07-05 Sanofi Sa Composes dimeres agonistes des recepteurs des fgfs (fgfrs), leur procede de preparation et leur application en therapeutique
CN107383009B (zh) 2012-06-13 2020-06-09 因塞特控股公司 作为fgfr抑制剂的取代的三环化合物
US9388185B2 (en) 2012-08-10 2016-07-12 Incyte Holdings Corporation Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors
US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
CN105263931B (zh) 2013-04-19 2019-01-25 因赛特公司 作为fgfr抑制剂的双环杂环
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
BR112017014770A2 (pt) * 2015-01-08 2018-01-16 Advinus Therapeutics Ltd compostos bicíclicos, composições e aplicações médicas dos mesmos
WO2016134294A1 (en) 2015-02-20 2016-08-25 Incyte Corporation Bicyclic heterocycles as fgfr4 inhibitors
EP3617205B1 (en) 2015-02-20 2021-08-04 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
MA41551A (fr) 2015-02-20 2017-12-26 Incyte Corp Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
US11253521B2 (en) 2015-09-25 2022-02-22 Ludwig Institute For Cancer Research Ltd 3-hydroxy-quinazoline-2,4-dione derivatives and their use as nuclease modulators
CN106045994A (zh) * 2016-06-12 2016-10-26 上海大学 全氟烷基吲嗪衍生物及其合成方法
AR111960A1 (es) 2017-05-26 2019-09-04 Incyte Corp Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
US11466004B2 (en) 2018-05-04 2022-10-11 Incyte Corporation Solid forms of an FGFR inhibitor and processes for preparing the same
JP2021523118A (ja) 2018-05-04 2021-09-02 インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ Ｆｇｆｒ阻害剤の塩
WO2020185532A1 (en) 2019-03-08 2020-09-17 Incyte Corporation Methods of treating cancer with an fgfr inhibitor
US11591329B2 (en) 2019-07-09 2023-02-28 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
AU2020366006A1 (en) 2019-10-14 2022-04-21 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
US11566028B2 (en) 2019-10-16 2023-01-31 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
BR112022010664A2 (pt) 2019-12-04 2022-08-16 Incyte Corp Derivados de um inibidor de fgfr
EP4069696A1 (en) 2019-12-04 2022-10-12 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
WO2021146424A1 (en) 2020-01-15 2021-07-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
JP2024522189A (ja) 2021-06-09 2024-06-11 インサイト・コーポレイション Ｆｇｆｒ阻害剤としての三環式ヘテロ環

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040116462A1 (en) 2002-12-12 2004-06-17 Mitsunori Ono Indolizine compounds
ES2291628T3 (es) 2002-04-03 2008-03-01 Bristol-Myers Squibb Company Compuestos triciclicos a base de tiofeno y composiciones farmaceuticas que comprenden dichos compuestos.
FR2838123B1 (fr) * 2002-04-04 2005-06-10 Sanofi Synthelabo Nouveaux derives d'indolozine-1,2,3 substituee, inhibiteurs selectifs du b-fgf
FR2859997B1 (fr) 2003-09-18 2006-02-03 Sanofi Synthelabo Nouveaux derives d'indolizine 1,2,3,6,7,8 substituee, inhibiteurs des fgfs, leur procede de preparation et les compositions pharmaceutiques les contenant.
ATE500254T1 (de) 2003-09-25 2011-03-15 Janssen Pharmaceutica Nv Die replikation von hiv hemmende purinderivate
FR2865934B1 (fr) 2004-02-05 2006-05-05 Sanofi Synthelabo Utilisation de derives d'indolizine 1,2,3 substitues, inhibiteurs des fgfs, pour la preparation de medicaments utiles pour le traitement de maladies liees a une angiogenese pathologique choroidienne
FR2883286B1 (fr) 2005-03-16 2008-10-03 Sanofi Aventis Sa NOUVEAUX DERIVES D'IMIDAZO[1,5-a]PYRIDINES, INHIBITEURS DE FGFs, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
FR2893616B1 (fr) 2005-11-23 2008-01-04 Sanofi Aventis Sa Nouveaux derives d'indolizine, leur procede de preparation et les compositions therapeutiques les comprenant
FR2896247B1 (fr) * 2006-01-13 2008-02-29 Sanofi Aventis Sa Composes dimeres agonistes des recepteurs des fgfs (fgfrs), leur procede de preparation et leur application en therapeutique
EP1891955A1 (en) * 2006-07-24 2008-02-27 Sanofi-Aventis Use of 1,2,3-substituted indolizine derivatives, inhibitors of FGFs, for the preparation of a medicament intended for the treatment of degenerative joint diseases

Also Published As

Publication number Publication date
MY163202A (en) 2017-08-15
BR112013000306A2 (pt) 2020-08-04
US8859544B2 (en) 2014-10-14
JP5863788B2 (ja) 2016-02-17
FR2962438A1 (fr) 2012-01-13
SI2590975T1 (sl) 2015-12-31
EP2590975B1 (en) 2015-08-19
CA2805065A1 (en) 2012-01-12
CN103080112A (zh) 2013-05-01
AU2011275426B2 (en) 2016-05-12
SG186436A1 (en) 2013-01-30
CO6650361A2 (es) 2013-04-15
IL223844A (en) 2016-03-31
UA109013C2 (en) 2015-07-10
GT201300001A (es) 2014-04-29
TWI494310B (zh) 2015-08-01
CY1116945T1 (el) 2017-04-05
AU2011275426A1 (en) 2013-01-24
CR20130001A (es) 2013-02-05
TW201206931A (en) 2012-02-16
HUE026067T2 (en) 2016-05-30
MA34451B1 (fr) 2013-08-01
MX2012015306A (es) 2013-04-29
AR082768A1 (es) 2013-01-09
ECSP13012362A (es) 2013-01-31
DK2590975T3 (en) 2015-12-07
EA201291409A1 (ru) 2013-05-30
PE20130386A1 (es) 2013-04-11
DOP2012000321A (es) 2013-04-15
PT2590975E (pt) 2015-11-24
WO2012004731A1 (en) 2012-01-12
US20130116249A1 (en) 2013-05-09
SG10201505282YA (en) 2015-08-28
KR20130128362A (ko) 2013-11-26
CA2805065C (en) 2018-07-03
EA024160B1 (ru) 2016-08-31
PL2590975T3 (pl) 2016-01-29
UY33489A (es) 2012-01-31
EP2590975A1 (en) 2013-05-15
NI201200191A (es) 2013-05-13
KR101797795B1 (ko) 2017-11-15
JP2013530210A (ja) 2013-07-25
FR2962438B1 (fr) 2012-08-17
CL2013000018A1 (es) 2013-05-10
ZA201300100B (en) 2014-03-26
ES2552850T3 (es) 2015-12-02
TN2012000609A1 (en) 2014-04-01
CN103080112B (zh) 2016-04-20

Similar Documents

Publication Publication Date Title
HRP20151162T1 (hr) Derivati indolizina, postupak za njihovo pripremanje i terapijska primjena
HRP20151309T1 (hr) Derivati imidazopiridina, postupak za njihovu pripravu i njihova terapeutska upotreba
KR102189066B1 (ko) Dna 알킬화제
JP2013544261A5 (hr)
KR101687082B1 (ko) 폐동맥 고혈압의 치료를 위한 비시클릭 헤테로사이클 유도체
JP5343072B2 (ja) ７−アルキニル−１，８−ナフチリドン（ｎａｐｈｔｈｙｒｉｄｏｎｅ）の誘導体、それらの調製方法および治療におけるそれらの使用
CN108290867B (zh) 一种制备酪氨酸激酶抑制剂及其衍生物的方法
WO2016033169A1 (en) Compounds and methods for inhibiting histone demethylases
US20190071434A1 (en) Mutant idh1 inhibitors useful for treating cancer
US8889719B2 (en) Phenylamino isonicotinamide compounds
SK109999A3 (en) Compounds for inhibition of gastric acid secretion
JP2014504286A (ja) 置換イミダゾキノリン誘導体
JP5346337B2 (ja) ７−アルキニル−１，８−ナフチリドンの誘導体、これらの調製方法および治療におけるこれらの使用
JP2022551093A (ja) 四環系ピリミジノン類化合物、その製造方法、その組成物及び使用
JPS58189179A (ja) イミダゾピリジン誘導体
TW202220993A (zh) Atr抑制劑及其用途
EP2760864B1 (en) 5-BENZYLAMINOMETHYL-6-AMINOPYRAZOLO[3,4-b]PYRIDINE DERIVATIVES AS CHOLESTERYL ESTER-TRANSFER PROTEIN (CETP) INHIBITORS USEFUL FOR THE TREATMENT OF ATHEROSCLEROSIS
ES2676396T3 (es) Moduladores alostéricos positivos del receptor de acetilcolina nicotínico
JP2004523509A (ja) ベンゾ〔ｇ〕キノリン−３−カルボニトリルの置換体およびベンゾ〔ｇ〕キナゾリンの置換体の位置選択的調製方法
WO2013024358A2 (en) Substituted heterocyclic amine compounds as cholestryl ester-transfer protein (cetp) inhibitors
AU2021302146A1 (en) ATR inhibitors and uses thereof
CN115043841B (zh) 一种作为btk抑制剂杂环类化合物的制备及其应用
US20230339889A1 (en) Derivatives of 2-oxo-n-(4-(pyrimidin-4-yloxy/thio)phenyl)-1,2-dihydropyridine-3-carboxamide for use as protein kinase inhibitors for therapy
KR101662597B1 (ko) 아자인돌 유도체 화합물, 이를 포함하는 c-KIT 저해제 조성물 및 c-KIT와 관련된 질환의 치료용 약학 조성물
PL242403B1 (pl) Sposób wytwarzania estru