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AR091416A1 - Diazaespirocicloalcanos y azaespirocicloalcanos como inhibidores de atx y de lpa - Google Patents

Diazaespirocicloalcanos y azaespirocicloalcanos como inhibidores de atx y de lpa

Info

Publication number
AR091416A1
AR091416A1 ARP130102060A AR091416A1 AR 091416 A1 AR091416 A1 AR 091416A1 AR P130102060 A ARP130102060 A AR P130102060A AR 091416 A1 AR091416 A1 AR 091416A1
Authority
AR
Argentina
Prior art keywords
substituted
haloalkoxyalkyl
alkyl
formula
thiophenyl
Prior art date
Application number
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English (en)
Inventor
Hunziker Daniel
Mattei Patrizio
Mauser Harald
Prunotto Marco
Ullmer Christoph
Original Assignee
Hoffmann La Roche
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Filing date
Publication date
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of AR091416A1 publication Critical patent/AR091416A1/es

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    • C07ORGANIC CHEMISTRY
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    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/10Spiro-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D205/00Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/12Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/397Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41921,2,3-Triazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/438The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D249/00Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/16Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • C07D249/18Benzotriazoles
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/10Heterocyclic 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 aromatic rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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 chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/06Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
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    • C07ORGANIC CHEMISTRY
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    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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
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    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10Spiro-condensed systems
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  • Chemical & Material Sciences (AREA)
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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Epidemiology (AREA)
  • Rheumatology (AREA)
  • Transplantation (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Pain & Pain Management (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Composiciones que contienen dichos compuestos y uso de los compuestos para el tratamiento de enfermedades mediadas por la inhibición de ATX y LPA. Reivindicación 1: Compuestos de la fórmula (1) en la que: R¹ es alquilo, haloalquilo, cicloalquilo, fenilo sustituido, fenilalquilo sustituido, fenoxialquilo sustituido, fenilcicloalquilo sustituido, fenilalquenilo sustituido, fenilalquinilo sustituido, piridinilo sustituido, piridinilalquilo sustituido, piridinilalquenilo sustituido, piridinilalquinilo sustituido, tiofenilo sustituido, tiofenilalquilo sustituido, tiofenilalquenilo sustituido, tiofenilalquinilo sustituido, 2,3-dihidro-1H-iso-indol-2-ilo sustituido, 1H-indol-2-ilo sustituido o benzofuran-2-ilo sustituido, dichos fenilo sustituido, fenilalquilo sustituido, fenoxialquilo sustituido, fenilcicloalquilo sustituido, fenilalquenilo sustituido, fenilalquinilo sustituido, piridinilo sustituido, piridinilalquilo sustituido, piridinilalquenilo sustituido, piridinilalquinilo sustituido, tiofenilo sustituido, tiofenilalquilo sustituido, tiofenilalquenilo sustituido, tiofenilalquinilo sustituido, 2,3-dihidro-1H-iso-indol-2-ilo sustituido, 1H-indol-2-ilo sustituido y benzofuran-2-ilo sustituido están sustituidos por R⁸, R⁹ y R¹⁰, pero en el caso de que R¹ sea alquilo e Y sea -C(O)-, entonces R³ se elige entre los grupos de fórmula (22) a (39); R² es -(CR⁴R⁵)ₙ-R³, -C(O)-R³, -S(O)₂-R³ o -C(O)-NR⁶R³; Y es -OC(O)-, -NR¹⁴C(O)-, -C(O)-, -S(O)₂-, o un resto de fórmula (2) ó (3), pero en el caso de que R¹ sea fenilalquenilo sustituido, piridinilalquenilo sustituido o tiofenilalquenilo sustituido, entonces Y no es -OC(O)-; W se elige entre los sistemas de anillo de fórmula (4) a (21); pero en el caso de que W sea uno de los sistemas de anillo de fórmula (16) ó (17), entonces R³ se elige entre los grupos de fórmula (22) a (39) y en el caso de que W sea el sistema de anillo de fórmula (18), entonces R² es -C(O)-NR⁶R³; R³ se elige entre los grupos de fórmula (22) a (39); o R³ es fenilo sustituido, piridinilo sustituido o tiofenilo sustituido, dichos fenilo sustituido, piridinilo sustituido y tiofenilo sustituido están sustituidos por R¹¹, R¹² y R¹³; R⁴ y R⁵ se eligen con independencia entre H, halógeno, alquilo y cicloalquilo; R⁶, R⁷ y R¹⁴ se eligen con independencia entre H, alquilo y cicloalquilo; R⁸, R⁹, R¹⁰, R¹¹, R¹² y R¹³ se eligen con independencia entre H, alquilo, hidroxialquilo, haloalquilo, cicloalquilo, cicloalquilalquilo, cicloalquilalcoxi, cicloalcoxi, cicloalcoxialquilo, cicloalquilalcoxialquilo, alcoxi, alcoxi-alquilo, haloalcoxi, haloalcoxialquilo, alcoxialcoxi, alcoxialcoxialquilo, halógeno, hidroxi, ciano, alquilsulfonilo, cicloalquilsulfonilo, aminosulfonilo sustituido, amino sustituido y aminoalquilo sustituido, dichos aminosulfonilo sustituido, amino sustituido y aminoalquilo sustituido están sustituidos en el átomo de nitrógeno por uno o dos sustituyentes elegidos con independencia entre hidrógeno, alquilo, cicloalquilo, cicloalquilalquilo, hidroxialquilo, alcoxialquilo, alquilcarbonilo y cicloalquilcarbonilo; n es el número cero, 1, 2 ó 3; o sus sales farmacéuticamente aceptables.
ARP130102060 2012-06-13 2013-06-12 Diazaespirocicloalcanos y azaespirocicloalcanos como inhibidores de atx y de lpa AR091416A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP12171839 2012-06-13

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AR091416A1 true AR091416A1 (es) 2015-02-04

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US (3) US9493486B2 (es)
EP (1) EP2861566B1 (es)
JP (1) JP6258928B2 (es)
KR (1) KR20150023373A (es)
CN (1) CN104364239B (es)
AR (1) AR091416A1 (es)
AU (1) AU2013276617B9 (es)
BR (1) BR112014030473A2 (es)
CA (1) CA2872213A1 (es)
CL (1) CL2014003136A1 (es)
CO (1) CO7121325A2 (es)
CR (1) CR20140501A (es)
CY (1) CY1118860T1 (es)
DK (1) DK2861566T3 (es)
EA (1) EA201492223A1 (es)
ES (1) ES2618703T3 (es)
HR (1) HRP20161774T1 (es)
HU (1) HUE030526T2 (es)
IL (1) IL235826A (es)
IN (1) IN2014DN09346A (es)
LT (1) LT2861566T (es)
MA (1) MA37756B1 (es)
MX (1) MX358310B (es)
MY (1) MY180688A (es)
NZ (1) NZ702334A (es)
PE (1) PE20150230A1 (es)
PH (1) PH12014502697B1 (es)
PL (1) PL2861566T3 (es)
PT (1) PT2861566T (es)
RS (1) RS55717B1 (es)
SG (1) SG11201407534PA (es)
SI (1) SI2861566T1 (es)
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ES2618703T3 (es) 2017-06-22

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