DK2909192T3 - Methylen-forbundne quinolinylmodulatorer af ror-gamma-t - Google Patents

Methylen-forbundne quinolinylmodulatorer af ror-gamma-t Download PDF

Info

Publication number
DK2909192T3
DK2909192T3 DK13786564.8T DK13786564T DK2909192T3 DK 2909192 T3 DK2909192 T3 DK 2909192T3 DK 13786564 T DK13786564 T DK 13786564T DK 2909192 T3 DK2909192 T3 DK 2909192T3
Authority
DK
Denmark
Prior art keywords
alkyl
pyridyl
optionally substituted
methyl
phenyl
Prior art date
Application number
DK13786564.8T
Other languages
English (en)
Inventor
Kristi A Leonard
Kent Barbay
James P Edwards
Kevin D Kreutter
David A Kummer
Umar Maharoof
Rachel Nishimura
Maud Urbanski
Hariharan Venkatesan
Aihua Wang
Ronald L Wolin
Craig R Woods
Joan Pierce
Steven Goldberg
Anne Fourie
Xiaohua Xue
Original Assignee
Janssen Pharmaceutica Nv
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 Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv
Application granted granted Critical
Publication of DK2909192T3 publication Critical patent/DK2909192T3/da

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • 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
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Steroid Compounds (AREA)

Claims (15)

1. Forbindelse med formel I hvor:
R1 er pyrrolyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, pyridyl, pyridyl N-oxid, pyrazinyl, pyrimidinyl, pyridazyl, piperidinyl, quinazolinyl, cinnolinyl, benzothiazolyl, indazolyl, tetrahydropyranyl, tetrahydrofuranyl, furanyl, phenyl, oxazolyl, isoxazolyl, thiophenyl, benzoxazolyl, benzimidazolyl, indolyl, thiadiazolyl, oxadiazolyl eller quinolinyl; hvor pyridyl, pyridyl N-oxid, pyrazinyl, pyrimidinyl, pyridazyl, piperidinyl, quinazolinyl, cinnolinyl, benzothiazolyl, indazolyl, imidazolyl, phenyl, thiophenyl, benzoxazolyl, benzimidazolyl, indolyl, quinolinyl og pyrazolyl eventuelt er substitueret med C(0)C(i-4)alkyl, C(0)NH2, C(0)NHQi-2)alkyl, C(0)N(Qi-2)alkyl)2, NHC(0)C(i-4)alkyl, NHS02C(i-4)alkyl, C(i-4)alkyl, CFa, CH2CF3, Cl, F, -CN, OC(i-4)alkyl, N(C(i-4)alkyl)2, - (O-hJsOCHs, SQi-4)alkyl, OH, CO2H, C02C(i-4)alkyl, C(0)CF3, SO2CF3, OCFa, OCHF2, SO2CH3, SO2NH2, SO2NHQ1-2)alkyl, S02N(Qi-2)alkyl)2, C(0)NHS02CH3 eller OCH2OCH3; og eventuelt substitueret med op til to yderligere substituenter valgt uafhængigt fra gruppen bestående af Cl, Qi-2)alkyl, SCH3, OQi-2)alkyl, CF3, -CN og F; og hvor triazolyl, oxazolyl, isoxazolyl, pyrrolyl og thiazolyl eventuelt er substitueret med op til to substituenter valgt uafhængigt fra gruppen bestående af SO2CH3, SO2NH2, C(0)NH2, -CN, OQi-zjalkyl, (CH2)(2-3)OCH3, SCH3, CF3, F, Cl og C(i-2)alkyl; og thiadiazolyl og oxadiazolyl eventuelt er substitueret med Qi-2)alkyl; og pyridyl, pyridyl-N-oxid, pyrimidinyl, pyridazyl og pyrazinyl eventuelt er substitueret med op til tre yderligere substituenter valgt uafhængigt fra gruppen bestående af C(0)NHQi-2)alkyl, C(0)N(Qi-2)alkyl)2, NHC(0)C(i-4)alkyl, NHS02C(i-4)alkyl, C(0)CF3, SO2CF3, S02NHC(i-2)alkyl, S02N(C(i-2)alkyl)2, C(0)NHS02CH3, SO2CH3, SO2NH2, C(0)NH2, -CN, 0C(i-4)alkyl, (CH2)(2-3)OCH3, SC(i-4)alkyl, CF3, F, Cl og Qi- 4)alkyl; R2 er triazolyl, pyridyl, pyridyl-N-oxid, pyrazolyl, pyrimidinyl, oxazolyl, isoxazolyl, azetidin-3-yl, N-acetyl-azetidin-3-yl, N-methylsulfonyl-azetidin-3-yl, N-Boc-azetidin-3-yl, N-acetyl piperidinyl, 1-H-piperidinyl, N-Boc-piperidinyl, N-C(i-3)alkyl-piperidinyl, thiazolyl, pyridazyl, pyrazinyl, l-(3-methoxypropyl)-imidazolyl, thiadiazolyl, oxadiazolyl eller imidazolyl; hvor imidazolyl eventuelt er substitueret med op til tre yderligere substituenter valgt uafhængigt fra gruppen bestående af Qi-2)alkyl, SCH3, OC(i-2)alkyl, CF3, -CN, F og Cl; og pyridyl, pyridyl-N-oxid, pyrimidinyl, pyridazyl og pyrazinyl, eventuelt er substitueret med op til tre yderligere substituenter valgt uafhængigt fra gruppen bestående af SO2CH3, SO2NH2, C(0)NH2, -CN, OC(i-2)alkyl, (CH2)(2-3)OCH3, SCH3, CF3, F, Cl eller Qi-2)alkyl; og triazolyl, thiazolyl, oxazolyl og isoxazolyl eventuelt er substitueret med op til to substituenter valgt uafhængigt fra gruppen bestående af SO2CH3, SO2NH2, C(0)NH2, -CN, OC(i-2)alkyl, (CH2)(2-3)OCH3, SCH3, CF3, F, Cl og Qi-zjalkyl; og thiadiazolyl og oxadiazolyl eventuelt er substitueret med C(i-2)alkyl; og pyrazolyl eventuelt er substitueret med op til tre Chb-grupper; R3 er H, OH, OCHs eller NH2; R4 er H eller F; R5 er H, Cl, -CN, CF3, SC(i-4)alkyl, OC(i-4)alkyl, OH, C(i-4)alkyl, N(CH3)OCH3, NH(C(i-4)alkyl), N(C(i-4)alkyl)2 eller 4-hydroxy-piperidinyl; R6 er phenyl, pyridyl, benzothiophenyl, thiophenyl, pyrimidinyl, pyridazyl eller pyrazinyl; hvor pyrimidinyl, pyridazyl eller pyrazinyl eventuelt er substitueret med Cl, F, CH3, SCH3, OQi-4)alkyl, -CN, CONH2, SO2NH2 eller SO2CH3; og hvor phenyl eller pyridyl eventuelt er substitueret med op til to gange med OCF3, S02Qi-4)alkyl, CF3, CHF2, pyrazolyl, triazolyl, imidazolyl, tetrazolyl, oxazolyl, thiazolyl, C(i-4)alkyl, C(3-4)cycloalkyl, 0Ca-4)alkyl, N(CH3)2, SO2NH2, SO2NHCH3, S02N(CH3)2, CONH2, CONHCH3, CON(CH3)2, Cl, F, -CN, CO2H, OH, CH2OH, NHCOC(i-2)alkyl, COQi-2)alkyl, SCH3, CO2Q1-4)alkyl, NH2, NHC(i-2)alkyl eller OCH2CF3; hvor valget af hver eventuel substituent er uafhængigt; og hvor pyrazolyl, triazolyl, imidazolyl, tetrazolyl, oxazolyl og thiazolyl eventuelt er substitueret med CH3; R7 er H, Cl, -CN, C(i-4)alkyl, OC(i-4)alkylCF3, OCFs, OCHF2, OCHzCHzOCd-4)alkyl, CF3, SCHa, Cd-^alkyllWA2, CH2OC(2-3)alkylNA1A2, IWA2, QOJlWA2, CH2NHC(2-3)alkylNA1A2, CH2N(CH3)C(2-3)alkylNA1A2, NHQ2-ajalkyllWA2, N(CH3)C(2-4)alkylNA1A2, OQz-^alkylNAW, 0C(i-4)alkyl, OCH2-(l-methyl)-imidazol-2-yl, phenyl, thiophenyl, furyl, pyrazolyl, imidazolyl, pyridyl, pyridazyl, pyrazinyl eller pyrimidinyl; hvor phenyl, thiophenyl, furyl, pyrazolyl, imidazolyl, pyridyl, pyridazyl, pyrazinyl og pyrimidinyl eventuelt er substitueret med op til tre substituenter valgt uafhængigt fra gruppen bestående af F, Cl, CH3, CF3 og OCH3; A1 er H eller C(i-4)alkyl; A2 er H, C(i-4)alkyl, C(i-4)alkylOC(i-4)alkyl, C(i-4)alkylOH, C(0)C(i-4)alkyl eller OC(i-4)alkyl; eller A1 og A2 kan tages sammen med deres forbundne nitrogen til at danne en ring valgt fra gruppen bestående af:
Ra er H, OC(i-4)alkyl, CHzOH, NH(CH3), N(CHa)z, NH2, CHa, F, CF3, SO2CH3 eller OH; Rb er H, C02C(CH3)3, C(i-4)alkyl, C(0)C(i-4)alkyl, S02C(i-4)alkyl, CH2CH2CF3, CH2CF3, CH2-cyclopropyl, phenyl, CH2-phenyl eller C(3-6)Cycloalkyl; R8 er H, Qi-3)alkyl, 0Qi-3)alkyl, CF3, NH2, NHCHs, -CN eller F; R9 er H eller F; og farmaceutisk acceptable salte deraf; forudsat at (4-chlor-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)bis(l,2,5-trimethyl-lH-imidazol-4-yl)methanol, N-(2-((3-(4-(lH-pyrazol-l-yl)benzyl)-6-((4-chlorphenyl)(hydroxy)(l-methyl-lH-imidazol-5-yl)methyl)-4-hydroxyquinolin-2-yl)oxy)ethyl)acetamid og (3-(4-(lH-pyrazol-l-yl)benzyl)-4-chlor-2-(4-methylpiperazin-l-yl)quinolin-6-yl)(l-methyl-lH-imidazol-5-yl)(6-(trifluormethyl)pyridin-3-yl)methanol er undtaget fra kravet.
2. Forbindelse ifølge krav 1 hvor: R1 er pyrrolyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, pyridyl, pyridyl N-oxid, pyrazinyl, pyrimidinyl, pyridazyl, piperidinyl, tetrahydropyranyl, phenyl, oxazolyl, isoxazolyl, thiophenyl, benzoxazolyl eller quinolinyl; hvor piperidinyl, imidazolyl, phenyl, thiophenyl, benzoxazolyl, pyrazolyl, pyridyl, pyridyl N-oxid, pyrazinyl, pyrimidinyl, pyridazyl eller quinolinyl eventuelt er substitueret med C(0)C(i-4)alkyl, C(0)NH2, Qi-4)alkyl, CF3, CH2CF3, Cl, F, -CN, OC(i-4)alkyl, N(Qi-4)alkyl)2, -(CH2)30CH3, SC(i-4)alkyl, OH, CO2H, C02C(i-4)alkyl, OCF3, OCHF2, SO2CH3, SO2NH2 eller OCH2OCH3; og eventuelt substitueret med op til to yderligere substituenter uafhængigt valgt fra gruppen bestående af Cl, Qi-2)alkyl, SCH3, OQi-2)alkyl, CF3, -CN og F; og hvor triazolyl, oxazolyl, isoxazolyl, pyrrolyl og thiazolyl eventuelt er substitueret med op til to substituenter valgt uafhængigt fra gruppen bestående af SO2CH3, SO2NH2, C(0)NH2, -CN, OC(i-2)alkyl, (CH2)(2-3)OCH3, SCH3, CF3, F, Cl, and Qi-2)alkyl; og pyridyl og pyridyl-N-oxid eventuelt er substitueret med op til tre yderligere substituenter valgt uafhængigt fra gruppen bestående af SO2CH3, SO2NH2, C(0)NH2, -CN, OC(i-4)alkyl, (CH2)c2- 3)OCH3, SC(i-4)alkyl, CF3, F, Cl og C(i-4)alkyl; R2 er 1-methyl triazolyl, pyridyl, pyridyl-N-oxid, 1-methyl pyrazolyl, pyrimidinyl, oxazolyl, isoxazolyl, N-acetyl-azetidin-3-yl, N-methylsulfonyl-azetidin-3-yl, N-Boc-azetidin-3-yl, N-acetyl piperidinyl, 1-H-piperidinyl, N-Boc-piperidinyl, N-C(i-3)alkyl-piperidinyl, thiazolyl, pyridazyl, pyrazinyl, l-(3-methoxypropyl)-imidazolyl eller l-C(i-2)alkyl imidazolyl; hvor l-Qi- 2) alkylimidazolyl eventuelt er substituret med op til to yderligere substituenter valgt uafhængigt fra gruppen bestående af Qi-2)alkyl, SCH3, OC(i-2)alkyl, CF3, -CN, F og Cl; og pyridyl og pyridyl-N-oxid eventuelt er substitueret med op til tre yderligere substituenter valgt uafhængigt fra gruppen bestående af SO2CH3, SO2NH2, C(0)NH2, -CN, OC(i-2)alkyl, (CH2)(2- 3) OCH3, SCH3, CF3, F, Cl og C(i-2)alkyl; og thiazolyl, oxazolyl og isoxazolyl eventuelt er substitueret med op til to substituenter valgt uafhængigt fra gruppen bestående af SO2CH3, SO2NH2, C(0)NH2, -CN, OC(i-2)alkyl, (CH2)c2- 3)OCH3, SCH3, CF3, F, Cl og C(i-2)alkyl; og 1-methylpyrazolyl eventuelt er substitueret med op til to yderligere CH3-grupper; R6 er phenyl, pyridyl, benzothiophenyl, thiophenyl, pyrimidinyl, pyridazyl eller pyrazinyl; hvor phenyl eller pyridyl eventuelt er substitueret med OCF3, S02C(i-4)alkyl, CF3, CHF2, pyrazolyl, triazolyl, imidazolyl, tetrazolyl, oxazolyl, thiazolyl, C(i-4)alkyl, C(3-4)Cycloalkyl, OC(i-4)alkyl, N(CH3)2, SO2NH2, SO2NHCH3, S02N(CH3)2, CONH2, CONHCH3, CON(CH3)2, Cl, F,-CN, CO2H, OH, CH2OH, NHCOC(i-2)alkyl, COC(i-2)alkyl eller SCHs; R7 er H, Cl, -CN, C(i-4)alkyl, OC(i-4)alkylCF3, OCH2CH2OC(i-4)alkyl, CF3, SCH3, CH2NA1A2, CH20C(2-3)alkyNA1A2, NAW, C(0)NA1A2, N(CH3)C(2-4)alkylNA1A2, OC^alkylNAW, OQi-4)alkyl, OCH2-(l-methyl)-imidazol-2-yl, furyl, pyrazolyl, imidazolyl, pyridyl, pyridazyl, pyrazinyl eller pyrimidinyl; hvor imidazolyl eller pyrazolyl eventuelt er substitueret med en CH3-gruppe; A1 er, H eller Qi-4)alkyl; A2 er H, C(i-4)alkyl, C(i-4)alkylOC(i-4)alkyl, Qi-4)alkylOH, C(0)C(i-4)alkyl, eller OC(i-4)alkyl; eller A1 og A2 kan tages sammen med deres forbundne nitrogen til at danne en ring valgt fra gruppen bestående af:
Ra er H, 0C(i-4)alkyl, CH2OH, NH(CH3), N(CH3)2, NH2, CH3, F eller OH; Rb er H, C02C(CH3)3, C(i-4)alkyl, C(0)C(i-4)alkyl, S02C(i-4)alkyl, CH2CH2CF3, CH2CF3, CH2-cyclopropyl, phenyl, CH2-phenyl eller C(3-6)Cydoalkyl; R8 er H, CH3, OCH3 eller F; og farmaceutisk acceptable salte deraf.
3. Forbindelse ifølge krav 2 hvor: R1 er pyrrolyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, pyridyl, pyridyl N-oxide, pyrazinyl, pyrimidinyl, pyridazyl, piperidinyl, tetrahydropyranyl, phenyl, oxazolyl, isoxazolyl, thiophenyl, benzoxazolyl eller quinolinyl; hvor piperidinyl, pyridyl, pyridyl N-oxid, imidazolyl, phenyl, thiophenyl, benzoxazolyl og pyrazolyl eventuelt er substitueret med C(0)Qi-4)alkyl, C(0)NH2, C(i-4)alkyl, CF3, CH2CF3, Cl, F, -CN, OC(i-4)alkyl, N(C(i-4)alkyl)2, -(CH2)3OCH3, SC(i-4)alkyl, OH, COzH, C02C(i-4)alkyl, OCF3, OCHF2, S02CH3, S02NH2 eller OCH2OCH3; og eventuelt substitueret med op til to yderligere substituenter valgt uafhængigt fra gruppen bestående af Cl, OCH3 og CH3; og hvor triazolyl, oxazolyl, isoxazolyl og thiazolyl eventuelt er substitueret med en eller to CH3grupper; R2 er 1-methyl triazolyl, pyridyl, pyridyl-N-oxid, 1-methyl pyrazolyl, pyrimidinyl, pyrazinyl, oxazolyl, isoxazolyl, N-acetyl-azetidin-3-yl, N-methylsulfonyl-azetidin-3-yl, N-Boc-azetidin-3-yl, N-acetyl piperidinyl, 1-H-piperidinyl, N-Boc-piperidinyl, N-C(i-2)alkyl-piperidinyl, thiazolyl, pyridazyl, l-(3-methoxypropyl)-imidazolyl, eller l-C(i-2)alkylimidazolyl; hvor l-C(i-2)alkylimidazolyl eventuelt er substituret med op til to yderligere CH3-grupper, eller en substituent valgt fra gruppen bestående af SCH3 og Cl; og pyridyl og pyridyl-N-oxid eventuelt er substitueret med op til to subsitutenter valgt uafhængigt fra gruppen bestående af S02CH3, S02NH2, C(0)NH2, -CN, OCH3, CF3, Cl og CH3; og thiazolyl, oxazolyl og isoxazolyl eventuelt er substitueret med op til to CH3-grupper; og 1-methylpyrazolyl eventuelt er substitueret med op til to yderligere CH3-grupper; R6 er phenyl, pyridyl, benzothiophenyl, thiophenyl, pyrimidinyl, pyridazyl eller pyrazinyl; hvor phenyl eller pyridyl eventuelt er substitueret med OCF3, S02CH3, CF3, CHF2, pyrazolyl, triazolyl, imidazolyl, tetrazolyl, oxazolyl, thiazolyl, CHs, OCH3, N(CH3)2, SO2NH2, CONH2, Cl, F, -CN, CO2H, OH, CH2OH, NHCOCH3 eller COCH3; R7 er H, Cl, -CN, C(i-4)alkyl, 0C(i-4)alkylCF3, 0CH2CH20C(i-4)alkyl, CF3, SCHs, mw, C{0)mw, NiCHsJCc^alkyNAW, OQ^alkylNAW, 0C(i-4)alkyl, OCH2-(l-methyl)-imidazol-2-yl, imidazolyl, furyl, pyrazolyl, pyridyl eller pyrimidinyl; hvor imidazolyl eller pyrazolyl eventuelt er substitueret med en CH3-gruppe; A1 er H, eller C(i-4)alkyl; A2 er H, C(i-4)alkyl, C(i-4)alkylOC(i-4)alkyl, C(i-4)alkylOH, C(0)C(i-4)alkyl eller OC(i-4)alkyl; eller A1 og A2 kan tages sammen med deres forbundne nitrogen til at danne en ring valgt fra gruppen bestående af:
Ra er H, F, 0C(i-4)alkyl eller OH; Rb er C(i-4)alkyl, C(0)CH3 eller phenyl; og farmaceutisk acceptable salte deraf.
4. Forbindelse ifølge krav 3 hvor: R1 er pyrrolyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, pyridyl, pyridyl N-oxid, pyrazinyl, pyrimidinyl, pyridazyl, piperidinyl, tetrahydropyranyl, phenyl, oxazolyl, isoxazolyl, thiophenyl, benzoxazolyl eller quinolinyl; hvor piperidinyl, pyridyl, pyridyl N-oxid, imidazolyl, phenyl, thiophenyl, benzoxazolyl og pyrazolyl eventuelt er substitueret med SO2CH3, C(0)CH3, C(0)NH2, CH3, CH2CH3, CF3, Cl, F, -CN, OCH3, N(CH3)2, -(CH2)3OCH3, SCH3, OH, CO2H, C02C(CH3)3 eller OCH2OCH3; og eventuelt substitueret med op til to yderligere substituenter valgt uafhængigt fra gruppen bestående af Cl, 0CH3 og Chb; og hvor triazolyl, oxazolyl, isoxazolyl og thiazolyl eventuelt er substitueret med en eller to Chb-grupper; R2 er l-methyl-l,2,3-triazolyl, pyridyl, pyridyl-N-oxid, 1-methyl pyrazol-4-yl, pyrimidin-5-yl, pyridazyl, pyrazin-2-yl, isoxazolyl, N-acetyl-azetidin-3-yl, N-methylsulfonyl-azetidin-3-yl, N-Boc-azetidin-3-yl, N-acetyl piperidinyl, 1-H-piperidinyl, N-Boc-piperidinyl, N-C(i-2)alkyl-piperidinyl, thiazol-5-yl, l-(3-methoxypropyl)-imidazol-5-yl, eller l-C(i-2)alkyl imidazol-5-yl; hvor l-C(i-2)alkyl imidazol-5-yl eventuelt er substitueret med op til to yderligere Chb-grupper, eller en substituent valgt fra gruppen bestående af SCH3, og Cl; og pyridyl og pyridyl-N-oxid eventuelt er substitueret med op til to substituenter valgt uafhængigt fra gruppen bestående af C(0)NH2, -CN, OCH3, CF3, Cl og CH3; og thiazol-5-yl, og isoxazolyl eventuelt er substitueret med op til to CH3-grupper; og 1-methyl pyrazol-4-yl eventuelt er substitueret med op til to yderligere Chb-grupper; R5 er H, Cl, -CN, CF3, SChb, OC(i-3)alkyl, OH, C(i-4)alkyl, N(CH3)OCH3, NH(C(i-2)alkyl), N(C(i-2)alkyl)2 eller 4-hydroxy-piperidinyl; R6 er pyridyl, phenyl, benzothiophenyl eller thiophenyl; hvor pyridyl eller phenyl eventuelt er substitueret med OCF3, SO2CH3, CF3, CHF2, imidazol-1-yl, pyrazol-l-yl, 1,2,4-triazol-l-yl, CH3, OCH3, Cl, F eller -CN; R7 er H, Cl, -CN, Qi-4)alkyl, OCH2CF3, OCH2CH2OCH3, CF3, SCH3, NAW, C(0)NHCH3, N(CH3)CH2CH2NA1A2, OCH2CH2NA1A2, OC(i-3)alkyl, OCH2-(l-methyl)-imidazol-2-yl, imidazol-2-yl, fur-2-yl, pyrazol-4-yl, pyrid-3-yl, eller pyrimidin-5-yl; hvor imidazolyl eller pyrazolyl eventuelt er substitueret med en CH3-gruppe; A1 er H, eller C(i-4)alkyl; A2 er H, C(i-4)alkyl, C(i-4)alkylOC(i-4)alkyl, C(i-4)alkylOH, C(0)C(i-2)alkyl, eller OCH3; eller A1 og A2 kan tages sammen med deres forbundne nitrogen til at danne en ring valgt fra gruppen bestående af:
Ra er H, F, OCH3, eller OH; Rb er CH3, eller phenyl; og farmaceutisk acceptable salte deraf.
5. Forbindelse ifølge krav 4 hvor: R1 er imidazolyl, pyrimidinyl, triazolyl, tetrahydropyranyl, thiazolyl, pyridyl, piperidinyl, phenyl eller oxazolyl; hvor piperidinyl, pyridyl, imidazolyl, og phenyl eventuelt er substitueret med SO2CH3, C(0)CH3, CH3, CF3, Cl, F, -CN, OCH3, -CF3 eller N(CH3)2; og eventuelt substitueret med op til en yderligere gruppe valgt uafhængigt fra Cl, OCH3 og CH3; og hvor triazolyl, oxazolyl og thiazolyl eventuelt er substitueret med en eller to CH3-grupper; R2 er l-methyl-l,2-3triazol-5-yl, pyrid-3-yl, 1-methyl pyrazol-4-yl, thiazol-5-yl, N-acetyl-piperidin-4-yl, N-acetyl-azetidin-3-yl, N-methylsulfonyl-azetidin-3-yl, N-Boc-azetidin-3-yl, 1,2-dimethyl imidazol-5-yl eller 1-methyl imidazol-5-yl; R3 er OH, eller NH2; R4 er H; R5 er H, Cl, -CN, CFs, CHs, OH, N(CH3)OCH3 eller OCHs; R6 er pyridyl, phenyl, benzothiophenyl eller thiophenyl; hvor pyridyl eller phenyl eventuelt er substitueret med pyrazol-l-yl, 1,2,4-triazol-l-yl, CF3, OCHs, SO2CH3, Cl, F, eller-CN; R7 er Cl, -CN, CFs, Qi-4)alkyl, NA4A2, C(0)NHCH3, OCH2CH2OCH3, 1-methyl imidazol-2-yl, 1-methyl pyrazol-4-yl eller OC(i-2)alkyl; A1 er C(i-2)alkyl; A2 er Qi-2)alkyl, CH2CH2OCH3 eller OCH3; eller A1 og A2 kan tages sammen med deres forbundne nitrogen til at danne en ring valgt fra gruppen bestående af:
Ra er OH, OCH3, F, eller H; R9 er H; og farmaceutisk acceptable salte deraf
6. Forbindelse ifølge krav 5 hvor: R1 er imidazolyl, triazolyl, thiazolyl, pyridyl, piperidinyl, phenyl eller oxazolyl; hvor piperidinyl, pyridyl, imidazolyl og phenyl eventuelt er substitueret med C(0)CH3, CH3, CF3, Cl, F, -CN, OCH3 eller N(CH3)2; og eventuelt substitueret med op til en yderligere gruppe valgt uafhængigt fra Cl, OCH3 og CH3; og hvor triazolyl, oxazolyl og thiazolyl eventuelt er substitueret med en eller to CH3-grupper; R2 er l-methyl-l,2-3triazol-5-yl, pyrid-3-yl, 1-methyl pyrazol-4-yl, thiazol-5-yl, N-acetyl-piperidin-4-yl, 1,2-dimethyl imidazol-5-yl eller 1-methyl imidazol-5-yl; R3 er OH; R5 er H, Cl, -CN, CF3, CH3 eller OCHs; R6 er phenyl, thiophen-2-yl, benzothiophen-2-yl; hvor phenyl eventuelt er substitueret med pyrazol-l-yl, 1,2,4-triazol-l-yl, OCH3, SO2CH3, Cl, F, CF3 eller -CN; R7 er Cl, -CN, CH3, NAW, C(0)NHCH3 eller OC(i-2)alkyl; A1 er C(i-2)alkyl; A2 er C(i-2)alkyl, eller OCH3; eller A1 og A2 kan tages sammen med deres forbundne nitrogen til at danne en ring der er: iNC>. og farmaceutisk acceptable salte deraf.
7. Forbindelse ifølge krav 1 valgt
fra gruppen bestående af:
og farmaceutisk acceptable salte deraf.
10. Farmaceutisk sammensætning, omfattende en forbindelse ifølge krav 1 og en farmaceutisk acceptabel bærer.
11. Farmaceutisk sammensætning fremstillet ved at blande en forbindelse ifølge krav 1 og en farmaceutisk acceptabel bærer.
12. Fremgangsmåde til fremstilling af en farmaceutisk sammensætning omfattende at blande en forbindelse ifølge krav 1 og en farmaceutisk acceptabel bærer.
13. Forbindelse ifølge krav 1 til anvendelse til at behandle eller forbedre et RORYt-medieret inflammatorisk syndrom, -lidelse eller -sygdom.
14. Forbindelse ifølge krav 1 som anvendt i krav 13, hvor sygdommen er valgt fra gruppen bestående af: rheumatoid artritis, psoriasis, kronisk obstruktiv lungesygdom, psoriasis artritis, Bechterews sygdom, Crohns sygdom, neutrofil astma, steroid-resistent astma, multipel sklerose, systemisk lupus erythematosus og ulcerøs colit.
15. Forbindelse ifølge krav 1 som anvendt ifølge krav 13, hvor sygdommen er psoriasis.
16. Forbindelse ifølge krav 1 som anvendt ifølge krav 13, hvor sygdommen er rheumatoid artritis.
17. Forbindelse ifølge krav 1 eller sammensætning eller medikament deraf til anvendelse i en kombinationsterapi med et eller flere anti-inflammatoriske midler, eller immunosuppressive midler, til at behandle eller forbedre et syndrom, en lidelse eller sygdom valgt fra gruppen bestående af rheumatoid artritis og psoriasis.
DK13786564.8T 2012-10-16 2013-10-15 Methylen-forbundne quinolinylmodulatorer af ror-gamma-t DK2909192T3 (da)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201261714419P 2012-10-16 2012-10-16
US201261725528P 2012-11-13 2012-11-13
US201361782257P 2013-03-14 2013-03-14
PCT/US2013/065013 WO2014062658A1 (en) 2012-10-16 2013-10-15 Methylene linked quinolinyl modulators of ror-gamma-t

Publications (1)

Publication Number Publication Date
DK2909192T3 true DK2909192T3 (da) 2017-08-07

Family

ID=49546611

Family Applications (1)

Application Number Title Priority Date Filing Date
DK13786564.8T DK2909192T3 (da) 2012-10-16 2013-10-15 Methylen-forbundne quinolinylmodulatorer af ror-gamma-t

Country Status (38)

Country Link
US (1) US9290476B2 (da)
EP (1) EP2909192B1 (da)
JP (1) JP6466335B2 (da)
KR (1) KR20150070347A (da)
CN (1) CN105209453B (da)
AR (1) AR093017A1 (da)
AU (1) AU2013331496B2 (da)
BR (1) BR112015008308A2 (da)
CA (1) CA2888210C (da)
CL (1) CL2015000945A1 (da)
CR (1) CR20150193A (da)
CY (1) CY1119234T1 (da)
DK (1) DK2909192T3 (da)
EA (1) EA026415B1 (da)
EC (1) ECSP15015022A (da)
ES (1) ES2632269T3 (da)
GT (1) GT201500093A (da)
HR (1) HRP20171082T1 (da)
HU (1) HUE035335T2 (da)
IL (1) IL237866B (da)
LT (1) LT2909192T (da)
ME (1) ME02794B (da)
MX (1) MX358508B (da)
MY (1) MY189505A (da)
NI (1) NI201500053A (da)
NZ (1) NZ706775A (da)
PE (1) PE20150778A1 (da)
PH (1) PH12015500817B1 (da)
PL (1) PL2909192T3 (da)
PT (1) PT2909192T (da)
RS (1) RS56283B1 (da)
SG (1) SG11201502369XA (da)
SI (1) SI2909192T1 (da)
SM (1) SMT201700347T1 (da)
TW (1) TWI606045B (da)
UY (1) UY35084A (da)
WO (1) WO2014062658A1 (da)
ZA (1) ZA201503418B (da)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013120771A1 (en) * 2012-02-13 2013-08-22 F. Hoffmann-La Roche Ag Imidazolylketone derivatives asd aldosterone synthase inhibitors
AU2013403335B2 (en) * 2012-10-16 2018-11-15 Janssen Pharmaceutica Nv Methylene linked quinolinyl modulators of ROR-gamma-t
US9604982B2 (en) 2013-03-14 2017-03-28 Janssen Pharmaceutica Nv P2X7 modulators
US9040534B2 (en) 2013-03-14 2015-05-26 Janssen Pharmaceutica Nv [1,2,4]triazolo[4,3-a]pyrazines as P2X7 modulators
ES2845473T3 (es) 2013-03-14 2021-07-26 Boehringer Ingelheim Int (Bencil-ciano-metil)-amidas sustituidas de ácido 2-aza-biciclo[2.2.1]heptano-3-carboxílico inhibidores de la catepsina- C
JO3509B1 (ar) 2013-03-14 2020-07-05 Janssen Pharmaceutica Nv معدلات p2x7
TWI644671B (zh) 2013-03-14 2018-12-21 比利時商健生藥品公司 Ｐ２ｘ７調節劑
JP6407285B2 (ja) 2013-09-09 2018-10-17 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ ＲＯＲγ調節因子
US9284308B2 (en) * 2013-10-15 2016-03-15 Janssen Pharmaceutica Nv Methylene linked quinolinyl modulators of RORγt
US10555941B2 (en) * 2013-10-15 2020-02-11 Janssen Pharmaceutica Nv Alkyl linked quinolinyl modulators of RORγt
US9403816B2 (en) 2013-10-15 2016-08-02 Janssen Pharmaceutica Nv Phenyl linked quinolinyl modulators of RORγt
BR112016008215A2 (pt) 2013-10-15 2017-09-26 Janssen Pharmaceutica Nv moduladores de quinolinila ligados por alquila de roryt
BR112016008258A2 (pt) 2013-10-15 2017-10-10 Janssen Pharmaceutica Nv moduladores de ror?t de quinolinila
JP6320523B2 (ja) * 2013-10-15 2018-05-09 ヤンセン ファーマシューティカ エヌ．ベー． ＲＯＲγＴの第二級アルコールキノリニルモジュレータ
ES2716966T3 (es) * 2014-05-28 2019-06-18 Glaxosmithkline Ip Dev Ltd Derivados de piperazina como moduladores de ROR-gamma
EP3180335B1 (en) 2014-08-11 2021-05-05 Angion Biomedica Corporation Cytochrome p450 inhibitors and uses thereof
EP3511331A1 (en) 2014-09-12 2019-07-17 Boehringer Ingelheim International GmbH Spirocyclic inhibitors of cathepsin c
AU2015315693B2 (en) 2014-09-12 2020-01-16 Janssen Pharmaceutica Nv P2X7 modulating n-acyl-triazolopyrazines
WO2016039977A1 (en) 2014-09-12 2016-03-17 Janssen Pharmaceutica Nv P2x7 modulators
CA2970819A1 (en) 2014-12-31 2016-07-07 Angion Biomedica Corp. Methods and agents for treating disease
KR20210069079A (ko) 2018-09-28 2021-06-10 얀센 파마슈티카 엔.브이. 모노아실글리세롤 리파아제 조절제
MY205440A (en) 2018-09-28 2024-10-21 Janssen Pharmaceutica Nv Monoacylglycerol lipase modulators
US10947253B2 (en) 2019-08-05 2021-03-16 Ankh Life Sciences Limited Fused polycyclic dimers
JP7697934B2 (ja) 2019-09-30 2025-06-24 ヤンセン ファーマシューティカ エヌ．ベー． 放射線標識されたｍｇｌ ｐｅｔリガンド
KR20220093340A (ko) * 2019-10-31 2022-07-05 지앙수 헨그루이 메디슨 컴퍼니 리미티드 RORγ 조절제의 산부가염
BR112022019077A2 (pt) 2020-03-26 2022-12-27 Janssen Pharmaceutica Nv Moduladores da monoacilglicerol lipase
AU2021266148A1 (en) 2020-04-30 2023-01-05 Idorsia Pharmaceuticals Ltd Azetidin-3-ylmethanol derivatives as CCR6 receptor modulators
US12129265B2 (en) 2020-07-21 2024-10-29 Ankh Life Sciences Limited Therapeutic agents and uses thereof
CN112939974B (zh) * 2021-03-11 2023-10-20 中山大学 一种氮杂苯并薁衍生物的制备方法
WO2023057548A1 (en) 2021-10-07 2023-04-13 Idorsia Pharmaceuticals Ltd Ccr6 receptor modulators
WO2023072924A1 (en) 2021-10-26 2023-05-04 Idorsia Pharmaceuticals Ltd Ccr6 receptor modulators
TW202325271A (zh) 2021-10-28 2023-07-01 瑞士商愛杜西亞製藥有限公司 Ccr6受體調節劑

Family Cites Families (102)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3472859A (en) 1966-11-01 1969-10-14 Sterling Drug Inc 1-alkyl-1,4-dihydro-4-oxo-3 quinoline-carboxylic acids and esters
JPS4826772Y1 (da) 1969-04-04 1973-08-06
ATE27451T1 (de) 1981-03-24 1987-06-15 Ciba Geigy Ag Acyl-chinolinonderivate, verfahren zu ihrer herstellung, diese enthaltende pharmazeutische praeparate und ihre verwendung.
US4910327A (en) 1982-05-25 1990-03-20 American Cyanamid Company Alkyl esters of substituted 2-methyl-3-quinolinecarboxylic acid and quinoline-2,3-dicarboxylic acid: dialkyl 3-(substituted)phenylaminobut-2-ene-dioates and methods for the preparation thereof
US4656283A (en) 1982-05-25 1987-04-07 American Cyanamid Company Alkyl esters of substituted 2-methyl-3-quinolinecarboxylic acid and quinoline-2,3-dicarboxylic acid
US4710507A (en) 1983-12-22 1987-12-01 Pfizer Inc. Quinolone inotropic agents
FR2634483B2 (fr) 1987-12-29 1994-03-04 Esteve Labor Dr Derives des acides 7-(1-azetidinyl)-1,4-dihydro-4-oxoquinoleine-3-carboxyliques, leur preparation et leur application en tant que medicaments
CA2002864C (en) 1988-11-29 1999-11-16 Eddy J. E. Freyne (1h-azol-1-ylmethyl) substituted quinoline, quinazoline or quinoxaline derivatives
SG64322A1 (en) 1991-05-10 1999-04-27 Rhone Poulenc Rorer Int Bis mono and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase
US5478832A (en) 1992-05-08 1995-12-26 The Green Cross Corporation Quinoline compounds
JPH0826772A (ja) 1994-07-22 1996-01-30 Sony Corp 融着用ガラス、その製造方法及び製造装置、並びに磁気ヘッドの製造方法
DE69512495T2 (de) 1994-10-27 2000-02-03 Asahi Glass Co. Ltd., Tokio/Tokyo Verfahren zur Herstellung von Chinolin-2-yl-benzoesäure
GB9523267D0 (en) 1995-11-14 1996-01-17 Sandoz Ltd Organic compounds
SK283335B6 (sk) 1995-12-08 2003-06-03 Janssen Pharmaceutica N. V. (Imidazol-5-yl)metyl-2-chinolinónové deriváty, spôsob a medziprodukty na ich prípravu, ich použitie a farmaceutické kompozície na ich báze
AU710926B2 (en) 1996-05-20 1999-09-30 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
AU740603B2 (en) * 1997-06-02 2001-11-08 Janssen Pharmaceutica N.V. (imidazol-5-yl)methyl-2-quinolinone derivatives as inhibitors of smooth muscle cell proliferation
PL341364A1 (en) 1997-12-22 2001-04-09 Upjohn Co 4-hydroxyqinoline-3-carboxamides and hydrazides as antiviral agents
FR2776388B1 (fr) 1998-03-20 2006-04-28 Lipha Utilisation de recepteurs de la famille ror pour le criblage de substances utiles pour le traitement de l'atherosclerose
US6399629B1 (en) 1998-06-01 2002-06-04 Microcide Pharmaceuticals, Inc. Efflux pump inhibitors
HRP20000904A2 (en) * 1998-07-06 2001-12-31 Janssen Pharmaceutica Nv Farnesyl protein transferase inhibitors for treating arthropathies
ID26987A (id) 1998-07-06 2001-02-22 Janssen Pharmaceutica Nv Inhibitor-inhibitor transferase protein farnesil dengan sifat-sifat peka terhadap sinar radiasi in vivo
JP2000169451A (ja) 1998-09-30 2000-06-20 Kyorin Pharmaceut Co Ltd ６，７―ジ置換キノリンカルボン酸誘導体とその付加塩及びそれらの製造方法
ID29241A (id) 1998-12-23 2001-08-16 Janssen Pharmaceutica Nv Turunan-turunan kinolin teranelasi-1,2
US6248736B1 (en) 1999-01-08 2001-06-19 Pharmacia & Upjohn Company 4-oxo-1,4-dihydro-3-quinolinecarboxamides as antiviral agents
US6248739B1 (en) 1999-01-08 2001-06-19 Pharmacia & Upjohn Company Quinolinecarboxamides as antiviral agents
PL349839A1 (en) 1999-02-11 2002-09-23 Pfizer Prod Inc Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents
PT1106612E (pt) 1999-11-30 2004-06-30 Pfizer Prod Inc Derivados de quinolina uteis para inibir a farnesil-proteina-transferase
JP5491681B2 (ja) 2000-02-04 2014-05-14 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 乳ガンの治療のためのファルネシルタンパク質トランスフェラーゼ阻害剤
US6838467B2 (en) 2000-02-24 2005-01-04 Janssen Pharmaceutica N. V. Dosing regimen
AU2001244167A1 (en) 2000-02-29 2001-09-12 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibitor combinations with anti-tumor anthracycline derivatives
JP2003525252A (ja) 2000-02-29 2003-08-26 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ Ｈｅｒ２抗体とのファルネシルタンパク質トランスフェラーゼ阻害剤組み合わせ剤
WO2001064196A2 (en) 2000-02-29 2001-09-07 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibitor combinations with vinca alkaloids
AU2001252147A1 (en) 2000-02-29 2001-09-12 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibitor combinations
EP1261343A2 (en) 2000-02-29 2002-12-04 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibitor combinations with anti-tumor nucleoside derivatives
US20030027808A1 (en) 2000-02-29 2003-02-06 Palmer Peter Albert Farnesyl protein transferase inhibitor combinations with platinum compounds
US20030078281A1 (en) 2000-02-29 2003-04-24 Rybak Mary Ellen Margaret Farnesyl protein transferase inhibitor combinations with anti-tumor alkylating agents
JP2003525239A (ja) 2000-02-29 2003-08-26 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ タキサン化合物とのファルネシルタンパク質トランスフェラーゼ阻害剤の組み合わせ剤
CA2397448A1 (en) 2000-02-29 2001-09-07 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibitor combinations with further anti-cancer agents
EP1267871A2 (en) 2000-02-29 2003-01-02 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibitor combinations with anti-tumor podophyllotoxin derivatives
WO2001064194A2 (en) 2000-02-29 2001-09-07 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibitor combinations with camptothecin compounds
US6844357B2 (en) 2000-05-01 2005-01-18 Pfizer Inc. Substituted quinolin-2-one derivatives useful as antiproliferative agents
US6525049B2 (en) 2000-07-05 2003-02-25 Pharmacia & Upjohn Company Pyrroloquinolones as antiviral agents
US6624159B2 (en) 2000-07-12 2003-09-23 Pharmacia & Upjohn Company Heterocycle carboxamides as antiviral agents
ATE276262T1 (de) 2000-07-12 2004-10-15 Upjohn Co Oxazinochinolone für die behandlung viraler infektionen
WO2002024682A1 (en) 2000-09-25 2002-03-28 Janssen Pharmaceutica N.V. Farnesyl transferase inhibiting quinoline and quinazoline derivatives as farnesyl transferase inhibitors
WO2002024686A2 (en) 2000-09-25 2002-03-28 Janssen Pharmaceutica N.V. Farnesyl transferase inhibiting 6-heterocyclylmethyl quinoline and quinazoline derivatives
US7067531B2 (en) 2000-09-25 2006-06-27 Angibaud Patrick Rene Farnesyl transferase inhibiting 6-heterocyclylmethyl quinolinone derivatives
CZ20031145A3 (cs) 2000-10-02 2003-12-17 Janssen Pharmaceutica N.V. Antagonisté metabotropního glutamátového receptoru
DK1339407T3 (da) 2000-11-28 2006-08-14 Janssen Pharmaceutica Nv Farnesylproteintransferaseinhibitorer til behandling af inflammatorisk tarmsygdom
ES2260316T3 (es) 2000-12-27 2006-11-01 Janssen Pharmaceutica N.V. Derivados de quinazolina y quinolina 4-sustituidos que inhiben la farnesil transferasa.
JP4969016B2 (ja) 2001-02-15 2012-07-04 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 抗エストロゲン剤とファルネシルプロテイントランスフェラーゼ阻害剤の組み合わせ物
US6544990B2 (en) 2001-03-01 2003-04-08 Pharmacia & Upjohn Company Substituted quinolinecarboxamides as antiviral agents
EP1390033A1 (en) 2001-04-25 2004-02-25 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibitors for treating cachexia
EP1412367A4 (en) 2001-06-21 2006-05-03 Ariad Pharma Inc NEW CHINOLINE AND ITS USE
EP1456208A1 (en) 2001-12-20 2004-09-15 PHARMACIA & UPJOHN COMPANY Pyridoquinoxaline antivirals
AU2002350244A1 (en) 2001-12-20 2003-07-09 Pharmacia And Upjohn Company Pyridoquinoxaline antivirals
CA2479109C (en) 2002-03-29 2011-08-02 Janssen Pharmaceutica N.V. Radiolabelled quinoline and quinolinone derivatives and their use as metabotropic glutamate receptor ligands
ATE404537T1 (de) 2002-08-13 2008-08-15 Shionogi & Co Heterocyclische verbindungen mit hiv-integrase- hemmender wirkung
AU2003262947A1 (en) 2002-08-30 2004-03-19 Pharmacia And Upjohn Company Method of preventing or treating atherosclerosis or restenosis
GB0222516D0 (en) 2002-09-27 2002-11-06 Karobio Ab Novel compounds
RS20060018A (sr) 2003-07-14 2007-12-31 Arena Pharmaceuticals Inc., Derivati spojenih arila i heteroarila kao modulatori metabolizma u profilaksi i lečenju sa njima povezanih stanja
BRPI0416206A (pt) 2003-11-20 2006-12-26 Janssen Pharmaceutica Nv 2-quinolinonas e 2-quinoxalinonas substituìdas por 6-alquenila e 6-fenilalquila como inibidores de polimerase de poli(adp-ribose)
SG151249A1 (en) 2003-12-05 2009-04-30 Janssen Pharmaceutica Nv 6-substituted 2-quinolinones and 2-quinoxalinones as poly(adp-ribose) polymerase inhibitors
US7652014B2 (en) 2003-12-10 2010-01-26 Janssen Pharmaceutica Substituted 6-cyclohexylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly(ADP-ribose) polymerase inhibitors
AU2004298486A1 (en) 2003-12-12 2005-06-30 Wyeth Quinolines useful in treating cardiovascular disease
EA011277B1 (ru) 2004-01-23 2009-02-27 Янссен Фармацевтика Н.В. Производные хинолина и их применение в качестве ингибиторов микобактерий
EA011572B9 (ru) 2004-01-29 2018-01-31 Янссен Фармацевтика Н.В. Производные хинолина для применения в качестве микобактериальных ингибиторов
JP2005225250A (ja) 2004-02-10 2005-08-25 Murakami Corp 車載用監視装置
ATE540936T1 (de) 2004-06-30 2012-01-15 Janssen Pharmaceutica Nv Substituierte 2-alkyl-chinazolinonderivate als parp-hemmer
ES2407813T3 (es) 2004-08-04 2013-06-14 Meiji Seika Pharma Co., Ltd. Derivados de quinolina e insecticida que contienen los mismos como constituyente activo
KR100686531B1 (ko) 2004-08-31 2007-02-23 한국화학연구원 히스톤 디아세틸라제 저해활성을 갖는 아릴아미노메틸프로페닐 벤즈하이드록시아마이드 유도체 및 그의 제조방법
HRP20130399T1 (hr) 2004-11-05 2013-06-30 Janssen Pharmaceutica Nv Terapeutska upotreba inhibitora farenziltransferaze i postupci praä†enja njihove efikasnosti
JO2855B1 (en) 2005-08-03 2015-03-15 شركة جانسين فارماسوتيكا ان. في Quinoline derivatives acting as antibacterial agents
JO2952B1 (en) 2005-08-03 2016-03-15 جانسين فارماسوتيكا ان. في Quinoline derivatives acting as antibacterial agents
WO2007088978A1 (ja) 2006-02-03 2007-08-09 Meiji Seika Kaisha, Ltd. 新規キノリン誘導体およびこれを有効成分として含有する農園芸用殺菌剤
US8389739B1 (en) 2006-10-05 2013-03-05 Orphagen Pharmaceuticals Modulators of retinoid-related orphan receptor gamma
KR101083177B1 (ko) 2006-10-23 2011-11-11 에스지엑스 파마슈티컬스, 인코포레이티드 트리아졸로-피리다진 단백질 키나제 조정제
JO3271B1 (ar) 2006-12-06 2018-09-16 Janssen Pharmaceutica Nv مشتقات الكوينولين المضادة للجراثيم
AR065093A1 (es) 2007-02-05 2009-05-13 Merck Frosst Canada Ltd Compuestos farmacéuticos inhibidores de la biosintesis de leucotrienos
UY30892A1 (es) 2007-02-07 2008-09-02 Smithkline Beckman Corp Inhibidores de la actividad akt
EP2155197A4 (en) 2007-03-09 2011-10-12 Link Medicine Corp TREATMENT OF LYSOSOMAL STORAGE DISEASES
EP2162132A4 (en) 2007-05-21 2013-01-16 Sgx Pharmaceuticals Inc Heterocyclic kinase modulators
CN101143845B (zh) 2007-10-15 2010-08-25 中国药科大学 取代喹啉甲酰胍衍生物、其制备方法及其医药用途
AU2009205539B2 (en) 2008-01-18 2013-12-05 Allergan.Inc Substitued-aryl-(imidazole)-methyl)-phenyl compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors
JP2011511056A (ja) 2008-02-05 2011-04-07 ファイザー・インク Ｃｎｓ障害および代謝障害治療のためのピリジニルアミド
BRPI0912604A2 (pt) 2008-05-13 2019-09-10 Allergan Inc quinolinilmetilimidazóis como agentes terapêuticos
WO2010068296A1 (en) 2008-12-11 2010-06-17 Stiefel Laboratories, Inc. Piperazine carboxamidines as antimicrobial agents
WO2010127208A1 (en) 2009-04-30 2010-11-04 Forest Laboratories Holdings Limited Inhibitors of acetyl-coa carboxylase
CN101899011B (zh) 2009-05-26 2013-01-16 北京大学 氨基二硫代甲酸酯类化合物、其制备方法和应用
AR077004A1 (es) 2009-06-09 2011-07-27 Hoffmann La Roche Compuestos heterociclicos antivirales
SG176986A1 (en) 2009-06-25 2012-02-28 Amgen Inc Polycyclic derivatives of pyridine and their use in the treatment of (inter alia) rheumatoid arthritis and similar diseases
CA2771432A1 (en) 2009-08-20 2011-02-24 Novartis Ag Heterocyclic oxime compounds
EP2368886A1 (en) 2010-03-01 2011-09-28 Phenex Pharmaceuticals AG Novel compounds for modulation of orphan nuclear receptor RAR-related orphan receptor-gamma (ROR gamma, NR1F3) activity and for the treatment of chronic inflammatory and autoimmune desease
US9101600B2 (en) 2010-03-11 2015-08-11 New York University Compounds as RORγt modulators and uses thereof
CN105962259A (zh) 2010-04-15 2016-09-28 卓莫赛尔公司 用于减小或消除苦味的化合物、组合物和方法
WO2012064744A2 (en) * 2010-11-08 2012-05-18 Lycera Corporation Tetrahydroquinoline and related bicyclic compounds for inhibition of rorϒ activity and the treatment of disease
US11179500B2 (en) 2011-02-24 2021-11-23 Emory University JAB1 inhibitory compositions for ossification and methods related thereto
PE20141637A1 (es) 2011-04-28 2014-11-20 Japan Tobacco Inc Compuesto de amida y aplicacion farmaceutica para el mismo
WO2012158784A2 (en) 2011-05-16 2012-11-22 Theodore Mark Kamenecka Modulators of the nuclear hormone receptor ror
GB201118652D0 (en) 2011-10-28 2011-12-07 Astex Therapeutics Ltd New compounds
WO2013064231A1 (en) 2011-10-31 2013-05-10 Phenex Pharmaceuticals Ag SEVEN-MEMBERED SULFONAMIDES AS MODULATORS OF RAR-RELATED ORPHAN RECEPTOR-GAMMA (RORγ, NR1F3)
EP2800745B1 (en) 2011-12-02 2020-02-12 Phenex Pharmaceuticals AG Pyrrolo carboxamides as modulators of orphan nuclear receptor rar-related orphan receptor-gamma (rory, nr1f3) activity and for the treatment of chronic inflammatory and autoimmune diseases

Also Published As

Publication number Publication date
MY189505A (en) 2022-02-16
CN105209453A (zh) 2015-12-30
US9290476B2 (en) 2016-03-22
EA026415B1 (ru) 2017-04-28
WO2014062658A1 (en) 2014-04-24
CR20150193A (es) 2015-05-18
NZ706775A (en) 2018-10-26
MX2015004783A (es) 2015-08-14
EP2909192B1 (en) 2017-05-17
SI2909192T1 (sl) 2017-08-31
CN105209453B (zh) 2017-06-20
JP6466335B2 (ja) 2019-02-06
AU2013331496B2 (en) 2017-07-27
ES2632269T3 (es) 2017-09-12
HRP20171082T1 (hr) 2017-10-06
ECSP15015022A (es) 2016-01-29
RS56283B1 (sr) 2017-12-29
TWI606045B (zh) 2017-11-21
LT2909192T (lt) 2017-07-10
CL2015000945A1 (es) 2015-08-28
AR093017A1 (es) 2015-05-13
PH12015500817A1 (en) 2015-06-08
CA2888210C (en) 2021-02-09
PL2909192T3 (pl) 2017-09-29
ME02794B (me) 2018-01-20
HUE035335T2 (en) 2018-05-02
HK1213248A1 (en) 2016-06-30
PT2909192T (pt) 2017-08-04
AU2013331496A1 (en) 2015-04-09
CY1119234T1 (el) 2018-02-14
TW201427969A (zh) 2014-07-16
PE20150778A1 (es) 2015-05-23
BR112015008308A2 (pt) 2017-12-05
CA2888210A1 (en) 2014-04-24
US20140107094A1 (en) 2014-04-17
SG11201502369XA (en) 2015-05-28
NI201500053A (es) 2020-03-18
EA201590736A1 (ru) 2015-09-30
JP2015536320A (ja) 2015-12-21
UY35084A (es) 2014-04-30
SMT201700347T1 (it) 2017-09-07
GT201500093A (es) 2017-09-26
IL237866B (en) 2018-05-31
EP2909192A1 (en) 2015-08-26
WO2014062658A8 (en) 2014-07-10
ZA201503418B (en) 2017-11-29
PH12015500817B1 (en) 2015-06-08
KR20150070347A (ko) 2015-06-24
MX358508B (es) 2018-08-22

Similar Documents

Publication Publication Date Title
DK2909192T3 (da) Methylen-forbundne quinolinylmodulatorer af ror-gamma-t
EP2909193B1 (en) Phenyl linked quinolinyl modulators of ror-gamma-t
US9284308B2 (en) Methylene linked quinolinyl modulators of RORγt
AU2013403335B2 (en) Methylene linked quinolinyl modulators of ROR-gamma-t
WO2015057626A1 (en) QUINOLINYL MODULATORS OF RORyT
KR20160070823A (ko) RORγt의 헤테로아릴 결합 퀴놀리닐 조절제
JP6377152B2 (ja) ＲＯＲγｔのフェニル結合キノリニルモジュレータ
HK1213248B (en) Methylene linked quinolinyl modulators of ror-gamma-t
HK1227855A1 (en) Methylene linked quinolinyl modulators of ror-gamma-t
HK1227855B (en) Methylene linked quinolinyl modulators of ror-gamma-t