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HRP20130458T4 - MALATNA SOL OD N-(4-{[6,7-BIS(METILOKSI)KINOLIN-4-IL]OKSI} FENIL-N'-(4-FLUOROFENIL)CIKLOPROPAN-1,1-DIKARBOKSAMIDA I NJEZINI KRISTALNI OBLICI ZA LIJEČENJE RAKA\n - Google Patents

MALATNA SOL OD N-(4-{[6,7-BIS(METILOKSI)KINOLIN-4-IL]OKSI} FENIL-N'-(4-FLUOROFENIL)CIKLOPROPAN-1,1-DIKARBOKSAMIDA I NJEZINI KRISTALNI OBLICI ZA LIJEČENJE RAKA\n Download PDF

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Publication number
HRP20130458T4
HRP20130458T4 HRP20130458TT HRP20130458T HRP20130458T4 HR P20130458 T4 HRP20130458 T4 HR P20130458T4 HR P20130458T T HRP20130458T T HR P20130458TT HR P20130458 T HRP20130458 T HR P20130458T HR P20130458 T4 HRP20130458 T4 HR P20130458T4
Authority
HR
Croatia
Prior art keywords
salt
dicarboxamide
methyloxy
quinolin
cyclopropane
Prior art date
Application number
HRP20130458TT
Other languages
English (en)
Inventor
Adrian St. Clair BROWN
Peter Lamb
William P. Gallagher
Original Assignee
Exelixis 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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41820137&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20130458(T4) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Exelixis Inc. filed Critical Exelixis Inc.
Publication of HRP20130458T1 publication Critical patent/HRP20130458T1/hr
Publication of HRP20130458T4 publication Critical patent/HRP20130458T4/hr

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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
    • A61K31/47—Quinolines; Isoquinolines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
    • 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
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Claims (14)

1. Malatna sol, naznačena time, da je od N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil)ciklopropan-1,1-dikarboksamida, pri čemu navedena sol je kristalična.
2. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema patentnom zahtjevu 1, naznačena time, da spomenuta sol je (DL)-malatna sol.
3. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema patentnom zahtjevu 1, naznačena time, da spomenuta sol je (L)-malatna sol ili (D)-malatna sol.
4. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema patentnom zahtjevu 3, naznačena time, da spomenuta sol je (L)-malatna sol.
5. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema patentnom zahtjevu 3, naznačena time, da spomenuta sol je (D)-malatna sol.
6. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema bilo kojem patentnom zahtjevu od 3-5, pri čemu navedena sol je u kristalnom Obliku N-1 i navedeni Oblik N-1 je naznačen, najmanje jednim od sljedećih: (i) 13C NMR spektar u krutom stanju sa četiri ili više maksimuma odabranih od 18,1, 42,9, 44,5, 70,4, 123,2, 156,2, 170,8, 175,7 i 182,1 ± 0,2 ppm; (ii) uzorak rendgenske difrakcije na prahu (CuKα λ=1,5418Å) koji uključuje četiri ili više 2θ vrijednosti odabranih između: 12,8 ± 0,2 °2θ, 13,5 ± 0,2 °2θ, 16,9 ± 0,2 °2θ, 19,4 ± 0,2 °2θ, 21,5 ± 0,2 °2θ, 22,8 ± 0,2 °2θ, 25,1 ± 0,2 °2θ, 27,6 ± 0,2 °2θ, pri čemu se mjerenje kristalnog oblika izvodi na sobnoj temperaturi; i/ili (iii) uzorak rendgenske difrakcije na prahu (XRPD) koji je uglavnom u skladu s uzorkom prikazanim na Slici 1.
7. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema patentnom zahtjevu 6, naznačena time, da je navedena sol najmanje 90% po masi Oblik N-1, na bazi mase spomenute soli.
8. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema bilo kojem od patentnih zahtjeva 3-5, pri čemu je spomenuta sol u kristalnom Obliku N-2 i spomenuti Oblik N-2 je naznačen, najmanje jednim od sljedećih: (i) 13C NMR spektar u krutom stanju sa četiri ili više maksimuma odabranih od 23,0, 25,9, 38,0, 41,7, 69,7, 102,0, 122,5, 177,3, 179,3, 180,0 i 180,3 ± 0,2 ppm; (ii) uzorak rendgenske difrakcije na prahu (CuKα λ=1,5418Å) koji uključuje 2θ vrijednosti na 20,9 ± 0,2 °2θ i 21,9 ± 0,2 °2θ, te dvije ili više 2θ vrijednosti odabranih između: 6,4 ± 0,2 °2θ, 9,1 ± 0,2 °2θ, 12,0 ± 0,2 °2θ, 12,8 ± 0,2 °2θ, 13,7 ± 0,2 °2θ, 17,1 ± 0,2 °2θ, 22,6 ± 0,2 °2θ, 23,7 ± 0,2 °2θ, pri čemu se mjerenje kristalnog oblika izvodi na sobnoj temperaturi; i/ili (iii) uzorak rendgenske difrakcije na prahu (XRPD) koji je uglavnom u skladu s uzorkom prikazanim na Slici 8.
9. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema patentnom zahtjevu 8, naznačena time, da je navedena sol najmanje 90% po masi Oblik N-2, na bazi mase spomenute soli.
10. Farmaceutski pripravak, naznačen time, da sadrži malatnu sol, N-(4-{[6,7- bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil)ciklopropan-1,1-dikarboksamida, prema bilo kojem od patentnih zahtjeva 3-9; i farmaceutski prihvatljivo pomoćno sredstvo.
11. Uporaba malatne soli, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil)ciklopropan-1,1-dikarboksamida, prema bilo kojem od patentnih zahtjeva 3-9, naznačena time, da je za proizvodnju lijeka za liječenje raka.
12. Malatna sol, N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil) ciklopropan-1,1-dikarboksamida, prema bilo kojem zahtjevu od 3-9, naznačena time, da je za uporabu u terapijskoj obradi u liječenju raka.
13. Kristalni oblik (L)-malatne soli od N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4- fluorofenil)ciklopropan-1,1-dikarboksamida, prema bilo kojem od patentnih zahtjeva 3, 4 i 6-9, naznačen time, da je za uporabu kao lijek za liječenje tiroidnog raka kod pojedinca.
14. Kristalni oblik (L)-malatne soli od N-(4-{[6,7-bis(metiloksi)kinolin-4-il]oksi}fenil)-N'-(4-fluorofenil)ciklopropan-1,1-dikarboksamida, prema bilo kojem od patentnih zahtjeva 3, 4 i 6-9, naznačen time, da se upotrebljava kao lijek za liječenje glioblastoma kod pojedinca.
HRP20130458TT 2009-01-16 2010-01-15 MALATNA SOL OD N-(4-{[6,7-BIS(METILOKSI)KINOLIN-4-IL]OKSI} FENIL-N'-(4-FLUOROFENIL)CIKLOPROPAN-1,1-DIKARBOKSAMIDA I NJEZINI KRISTALNI OBLICI ZA LIJEČENJE RAKA\n HRP20130458T4 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US14542109P 2009-01-16 2009-01-16
EP10701175.1A EP2387563B2 (en) 2009-01-16 2010-01-15 Malate salt of n- (4- { [ 6, 7-bis (methyloxy) quinolin-4-yl]oxy}phenyl-n' - (4 -fluorophenyl) cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer
PCT/US2010/021194 WO2010083414A1 (en) 2009-01-16 2010-01-15 Malate salt of n- (4- { [ 6, 7-bis (methyloxy) quin0lin-4-yl] oxy}phenyl-n' - (4 -fluorophenyl) cyclopropane-1-dicarboxamide, and crystalline forms therof for the treatment of cancer

Publications (2)

Publication Number Publication Date
HRP20130458T1 HRP20130458T1 (hr) 2013-06-30
HRP20130458T4 true HRP20130458T4 (hr) 2022-08-19

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ID=41820137

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HRP20130458TT HRP20130458T4 (hr) 2009-01-16 2010-01-15 MALATNA SOL OD N-(4-{[6,7-BIS(METILOKSI)KINOLIN-4-IL]OKSI} FENIL-N'-(4-FLUOROFENIL)CIKLOPROPAN-1,1-DIKARBOKSAMIDA I NJEZINI KRISTALNI OBLICI ZA LIJEČENJE RAKA\n

Country Status (24)

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US (14) US8877776B2 (hr)
EP (1) EP2387563B2 (hr)
JP (6) JP5677318B2 (hr)
KR (8) KR20200137052A (hr)
CN (3) CN102388024A (hr)
AR (1) AR075025A1 (hr)
AU (3) AU2010204619B2 (hr)
BR (1) BRPI1006812B8 (hr)
CA (2) CA2995880C (hr)
DK (1) DK2387563T4 (hr)
EA (3) EA019959B1 (hr)
ES (1) ES2402524T5 (hr)
HR (1) HRP20130458T4 (hr)
IL (2) IL214086A (hr)
MX (3) MX350898B (hr)
NZ (3) NZ618004A (hr)
PL (1) PL2387563T5 (hr)
PT (1) PT2387563E (hr)
RS (1) RS52754B2 (hr)
SG (1) SG173014A1 (hr)
SM (1) SMT201300050B (hr)
TW (7) TWI447108B (hr)
WO (1) WO2010083414A1 (hr)
ZA (1) ZA201105167B (hr)

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