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DK3060547T3 - Carboxamidderivater og anvendelse deraf som lægemidler ved behandling af hepatits b - Google Patents

Carboxamidderivater og anvendelse deraf som lægemidler ved behandling af hepatits b Download PDF

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Publication number
DK3060547T3
DK3060547T3 DK14793047.3T DK14793047T DK3060547T3 DK 3060547 T3 DK3060547 T3 DK 3060547T3 DK 14793047 T DK14793047 T DK 14793047T DK 3060547 T3 DK3060547 T3 DK 3060547T3
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compound
methyl
mmol
fluoro
mixture
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DK14793047.3T
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English (en)
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Koen Vandyck
Geerwin Yvonne Paul Haché
Bart Rudolf Romanie Kesteleyn
Pierre Jean-Marie Bernard Raboisson
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Janssen Sciences Ireland Uc
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    • 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
    • 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
    • A61K31/4025—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 not condensed and containing further heterocyclic rings, e.g. cromakalim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • 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
    • 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
    • C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • 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
    • C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—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 no 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—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 no 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
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Claims (13)

1. Forbindelse med formlen (I)
eller en stereoisomer eller tautomer form deraf, hvor:
hpfpansr ^
5 hver af Ra, Rb, Rc, Rd, Re, Rf og Rg er uafhængigt valgt fra gruppen bestående af hydrogen og methyl; Rh er hydrogen; Ri er hydrogen; R1, R2 og R3 er uafhængigt valgt fra gruppen bestående af hydrogen, fluor, chlor, brom, -CHF2, -CH2F, -CF3, -CN og methyl; R6 er valgt fra gruppen bestående af (C1-C6) -alkyl og en 3-7-leddet mættet ring, der eventuelt indeholder et eller flere heteroatomer, som hvert er uafhængigt valgt fra gruppen bestående af 0, S og N, hvor en sådan (C1-C6)-alkyl eller 3-7-leddet mættet ring eventuelt er substitueret med en eller flere substituenter valgt fra gruppen bestående af fluor, (Ci-C3) -alkyl eventuelt substitueret med en eller flere fluor, CN, OH; R7 betegner hydrogen; eller et farmaceutisk acceptabelt salt eller et solvat deraf.
2. Forbindelse ifølge krav 1 med formlen (II)
eller en stereoisomer eller tautomer form deraf, hvor: n betegner et heltal på 1 eller 2; R1, R2 og R3 er uafhængigt valgt fra gruppen bestående af hydrogen, fluor, chlor, brom, -CHF2, -CH2F, -CF3, -CN og methyl; R4 og R5 er uafhængigt valgt blandt hydrogen eller methyl; R6 er valgt fra gruppen bestående af (C1-C6) -alkyl og en 3-7-leddet mættet ring, der eventuelt indeholder et eller flere heteroatomer, som hvert er uafhængigt valgt fra gruppen bestående af 0, S og N, hvor en sådan (C1-C6)-alkyl eller 3-7-leddet mættet ring eventuelt er substitueret med en eller flere substituenter valgt fra gruppen bestående af fluor, (Ci-C3) -alkyl eventuelt substitueret med en eller flere af fluor, CN, OH; R7 betegner hydrogen; eller et farmaceutisk acceptabelt salt eller et solvat deraf.
3. Forbindelse ifølge krav 1 eller 2, hvor R1 er valgt blandt hydrogen, fluor, chlor, -CHF2, -CN, -CF3 og methyl.
4. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor mindst to af R1, R2 og R3 er fluor, chlor eller brom.
5. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R4 er methyl.
6. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R6 indeholder en 3-7-leddet mættet ring, der eventuelt indeholder et oxygenatom, hvor en sådan 3-7-leddet mættet ring eventuelt er substitueret med methyl.
7. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R6 er en 4- eller 5-leddet mættet ring, der eventuelt indeholder et oxygenatom, hvor en sådan 4- eller 5-leddet mættet ring eventuelt er substitueret med methyl.
8. Forbindelse ifølge et hvilket som helst af kravene 1 til 5, hvor R6 er en forgrenet (Οι-Οε) -alkyl, der eventuelt er substitueret med et eller flere fluoratomer.
9. Forbindelse ifølge et hvilket som helst af de foregående krav mpri fnrml pn < T T T )
hvor R1 ikke er hydrogen.
10. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor den stereokemiske konfiguration af atomet (*) er som følger
11. Forbindelse ifølge et hvilket som helst af de foregående krav til anvendelse til forebyggelse eller behandling af en HBV-infektion hos et pattedyr.
12. Farmaceutisk sammensætning, som omfatter en forbindelse ifølge et hvilket som helst af kravene 1 til 10 og en farmaceutisk acceptabel bærer.
13. Forbindelse ifølge et hvilket som helst af kravene 1 til 10 eller farmaceutisk sammensætning ifølge krav 12 til anvendelse i kombination med mindst et andet anti-HBV-middel.
DK14793047.3T 2013-10-23 2014-10-22 Carboxamidderivater og anvendelse deraf som lægemidler ved behandling af hepatits b DK3060547T3 (da)

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EP13189880 2013-10-23
PCT/EP2014/072690 WO2015059212A1 (en) 2013-10-23 2014-10-22 Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b

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EP (1) EP3060547B1 (da)
JP (1) JP6452119B2 (da)
KR (1) KR102290189B1 (da)
CN (1) CN105658624B (da)
AP (1) AP2016009122A0 (da)
AU (2) AU2014338947B2 (da)
CA (1) CA2923712C (da)
CL (1) CL2016000952A1 (da)
CR (1) CR20160237A (da)
DK (1) DK3060547T3 (da)
EA (1) EA034448B1 (da)
ES (1) ES2655518T3 (da)
GT (1) GT201600070A (da)
IL (1) IL244486A0 (da)
MX (1) MX368158B (da)
NZ (1) NZ717629A (da)
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