AR088989A1 - Derivados biciclicos de dihidroisoquinolin-1-ona - Google Patents

Derivados biciclicos de dihidroisoquinolin-1-ona

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Publication number
AR088989A1
AR088989A1 ARP120104439A ARP120104439A AR088989A1 AR 088989 A1 AR088989 A1 AR 088989A1 AR P120104439 A ARP120104439 A AR P120104439A AR P120104439 A ARP120104439 A AR P120104439A AR 088989 A1 AR088989 A1 AR 088989A1
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Argentina
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substituted
heterocycloalkyl
cycloalkyl
alkyl
heteroaryl
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ARP120104439A
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English (en)
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Aebi Johannes
Amrein Kurt
Chen Wenming
Hornsperger Benoit
Kuhn Bernd
Liu Yongfu
P Maerki Hans
V Mayweg Alexander
Mohr Peter
Tan Xuefei
Wang Zhanguo
Zhou Mingwei
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Hoffmann La Roche
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Publication of AR088989A1 publication Critical patent/AR088989A1/es

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    • 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
    • C07D401/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • 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
    • A61P5/00Drugs for disorders of the endocrine system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/38Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/42Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D217/00Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • CCHEMISTRY; METALLURGY
    • 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • 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
    • C07D405/14Heterocyclic 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 three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10Spiro-condensed systems
    • C07D491/107Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10Spiro-condensed systems
    • C07D491/113Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Los compuestos son útiles para tratar enfermedades renales crónicas hipertensión, aldosterismo primario y síndrome de Cushing. Reivindicación 1: Compuestos de la fórmula (1) en la que: R¹, R², R³ y R⁴ se eligen con independencia entre H, alquilo, cicloalquilo, cicloalquilalquilo, haloalquilo, halocicloalquilo, hidroxialquilo, alcoxialquilo, haloalcoxialquilo, halocicloalquilalquilo, heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, arilalquilo sustituido y heteroarilalquilo sustituido, dichos heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, arilalquilo sustituido y heteroarilalquilo sustituido están sustituidos por R¹², R¹³ y R¹⁴; o R² y R⁴ juntos forman un doble enlace, pero en el caso de que R² y R⁴ juntos formen un doble enlace, entonces R⁵ es H; o R¹ y R² junto con el átomo de carbono al que están unidos forman un cicloalquilo sustituido o un heterocicloalquilo sustituido, dichos cicloalquilo sustituido y heterocicloalquilo sustituido están sustituidos por R²², R²³ y R²⁴; o R³ y R⁴ junto con el átomo de carbono al que están unidos forman un cicloalquilo sustituido o un heterocicloalquilo sustituido, dichos cicloalquilo sustituido y heterocicloalquilo sustituido están sustituidos por R²⁹, R³⁰ y R³¹; o R¹ y R³ junto con el átomo de carbono al que están unidos forman un cicloalquilo sustituido o un heterocicloalquilo sustituido, dichos cicloalquilo sustituido y heterocicloalquilo sustituido están sustituidos por R⁴⁴, R⁴⁵ y R⁴⁶; A¹ es CR⁸ o N; A² es CR⁹ o N; A³ es CR¹⁰ o N; A⁴ es CR¹¹ o N; A⁵ es CR⁶ o N; uno de R⁵, R⁶, R⁷ y R⁸ se elige entre halógeno, ciano, alcoxi, hidroxialcoxi, haloalquilo, haloalcoxi e hidroxi y los demás se eligen con independencia entre sí entre H, halógeno, ciano, alcoxi, hidroxialcoxi, haloalcoxi e hidroxi; R⁹ es H, halógeno, hidroxi, ciano, alquilo, hidroxialquilo, haloalquilo, cicloalquilo, cicloalquilalquilo, alquilcicloalquilo, halocicloalquilo, alquilcicloalquilalquilo, alcoxicicloalquilalquilo, halocicloalquilalquilo, cicloalquilalcoxi, cicloalquilalcoxialquilo, cicloalcoxi, cicloalcoxialquilo, halocicloalcoxi, halocicloalcoxialquilo, alquilcicloalcoxi, alquilcicloalcoxialquilo, alcoxi, alcoxialquilo, alcoxicicloalquilalquilo, dialcoxialquilo, haloalcoxi, haloalcoxialquilo, alcoxialcoxi, alcoxialcoxialquilo, haloalcoxialcoxi, haloalcoxialcoxialquilo, arilalquilo sustituido, arilhidroxialquilo sustituido, heterocicloalquilalquilo sustituido o heteroarilalquilo sustituido, dichos arilalquilo sustituido, arilhidroxialquilo sustituido, heterocicloalquilalquilo sustituido y heteroarilalquilo sustituido están sustituidos por R³², R³³ y R³⁴; R¹⁰ es -Oₘ-(CR¹⁵R¹⁶)ₚ-(CR¹⁷R¹⁸)q-(CR¹⁹R²⁰)ʳ-R²¹; o R⁹ y R¹⁰ junto con los átomos de carbono a los que están unidos forman un cicloalquilo sustituido, un heterocicloalquilo sustituido, un arilo sustituido o un heteroarilo sustituido, dichos cicloalquilo sustituido, heterocicloalquilo sustituido, arilo sustituido y heteroarilo sustituido están sustituidos por R³⁵, R³⁶ y R³⁷; R¹¹ es H; R¹⁵, R¹⁷ y R¹⁹ se eligen con independencia entre H, alquilo, cicloalquilo, haloalquilo y halocicloalquilo; R¹⁶, R¹⁸ y R²⁰ se eligen con independencia entre H, hidroxi, halógeno y alquilo; o R¹⁵ y R¹⁶ junto con el átomo de carbono al que están unidos forman un cicloalquilo; o R¹⁷ y R¹⁸ junto con el átomo de carbono al que están unidos forman un cicloalquilo; o R¹⁹ y R²⁰ junto con el átomo de carbono al que están unidos forman un cicloalquilo; o R¹⁵ y R¹⁷ juntos forman un -(CH₂)ᵛ-; o R¹⁵ y R¹⁹ juntos forman un -(CH₂)ʷ-; o R¹⁷ y R¹⁹ juntos forman un -(CH₂)ˣ-; R²¹ es H, halógeno, ciano, -OR²⁵, -SR²⁵, -S(O)R²⁵, -S(O)₂R²⁵, -NR²⁵R²⁶, -NR²⁶SO₂R²⁵, -NR²⁶SO₂NR²⁵R²⁷, -NR²⁶C(O)R²⁵, -NR²⁶C(O)-NR²⁵R²⁷, -C(O)R²⁸, -C(O)NR²⁵R²⁶, cicloalquilo, heterociclo-alquilo sustituido, heteroarilo sustituido o arilo sustituido, dichos heterocicloalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido y arilo sustituido están sustituidos por R³⁸, R³⁹ y R⁴⁰; R²⁵ es H, alquilo, hidroxialquilo, carboxialquilo, haloalquilo, cicloalquilo, cicloalquilalquilo, alquilcicloalquilo, halocicloalquilo, alquilcicloalquilalquilo, alcoxicicloalquilalquilo, halocicloalquilalquilo, cicloalquilalcoxi-alquilo, cicloalcoxialquilo, halocicloalcoxialquilo, alquilcicloalcoxialquilo, alcoxialquilo, haloalcoxialquilo, alcoxialcoxialquilo, haloalcoxialcoxialquilo, heterociclo-alquilo sustituido, heterocicloalquilalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido, arilo sustituido o arilalquilo sustituido, dichos heterocicloalquil sustituido, heterocicloalquilalquilo sustituido, heteroarilo, heteroarilalquilo sustituido, arilo sustituido y arilalquilo sustituido están sustituidos por R⁴¹, R⁴² y R⁴³; R²⁶ y R²⁷ se eligen con independencia entre H, alquilo, cicloalquilo, haloalquilo y halocicloalquilo; o R¹⁵ y R²⁶ junto con el átomo de nitrógeno y el átomo de carbono al que están unidos forman un heterocicloalquilo sustituido o un heteroarilo sustituido, dichos heterocicloalquilo sustituido y heteroarilo sustituido están sustituidos por R⁴⁷, R⁴⁸ y R⁴⁹; o R¹⁷ y R²⁶ junto con el átomo de nitrógeno y el átomo de carbono al que están unidos forman un heterocicloalquilo sustituido o un heteroarilo sustituido, dichos heterocicloalquilo sustituido y heteroarilo sustituido están sustituidos por R⁴⁷, R⁴⁸ y R⁴⁹; o R¹⁹ y R²⁶ junto con el átomo de nitrógeno y el átomo de carbono al que están unidos forman un heterocicloalquilo sustituido o un heteroarilo sustituido, dichos heterocicloalquilo sustituido y heteroarilo sustituido están sustituidos por R⁴⁷, R⁴⁸ y R⁴⁹; R²⁸ es H, hidroxi, alquilo, hidroxialquilo, haloalquilo, cicloalquilo, cicloalquilalquilo, alquilcicloalquilo, halocicloalquilo, alquilcicloalquilalquilo, alcoxicicloalquil, halocicloalquilalquilo, cicloalquilalcoxi, cicloalquilalcoxialquilo, cicloalcoxi, cicloalcoxialquilo, halocicloalcoxi, halocicloalcoxialquilo, alquilcicloalcoxi, alquilcicloalcoxialquilo, alcoxi, alcoxialquilo, haloalcoxi, haloalcoxialquilo, alcoxialcoxi, alcoxialcoxi-alquilo, haloalcoxialcoxi, haloalcoxialcoxialquilo, heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, heteroarilo sustituido, heteroarilalquilo sustituido, arilo sustituido o arilalquilo sustituido, dichos heterocicloalquilo sustituido, heterocicloalquilalquilo sustituido, heteroarilo sustituido heteroarilalquilo sustituido, arilo sustituido y arilalquilo sustituido están sustituidos por R⁵⁰, R⁵¹ y R⁵²; R¹², R¹³, R¹⁴, R²², R²³, R²⁴, R²⁹, R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, R³⁸, R³⁹, R⁴⁰, R⁴¹, R⁴², R⁴³, R⁴⁴, R⁴⁵, R⁴⁶, R⁴⁷, R⁴⁸, R⁴⁹, R⁵⁰, R⁵¹ y R⁵² se eligen con independencia entre H, halógeno, hidroxi, amino, nitro, ciano, oxo, alquilo, alquilcarbonilo, alquilsulfonilo, hidroxialquilo, haloalquilo, cicloalquilo, cicloalquilalquilo, alquilcicloalquilo, halocicloalquilo, alquilcicloalquilalquilo, alquilcarbonil-amino, alquilsulfonilo, alquilsulfonilamino, alcoxicicloalquilalquilo, halocicloalquilalquilo, cicloalquilalcoxi, cicloalquilalcoxialquilo, cicloalcoxi, cicloalcoxialquilo, halocicloalcoxi, halocicloalcoxialquilo, alquilcicloalcoxi, alquilcicloalcoxialquilo, alcoxi, alcoxicarbonilo, alcoxialquilo, haloalcoxi, haloalcoxialquilo, alcoxialcoxi, alcoxialcoxialquilo, haloalcoxialcoxi, halo-alcoxialcoxialquilo, cloropiridinilcarbonilo y heterocicloalquilo; n es el número cero ó 1; m es el número cero ó 1; p, q y r se eligen con independencia entre cero y 1; v y x se eligen con independencia entre 1, 2, 3 y 4; w es el número cero, 1, 2 ó 3; con la condición de que no más de dos de A², A³ y A⁴ sean N; y las sales farmacéuticamente aceptables de los mismos.
ARP120104439A 2011-11-30 2012-11-27 Derivados biciclicos de dihidroisoquinolin-1-ona AR088989A1 (es)

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EP (2) EP3587401A1 (es)
JP (1) JP6382108B2 (es)
KR (1) KR102089927B1 (es)
AR (1) AR088989A1 (es)
AU (1) AU2012344041B2 (es)
BR (1) BR112014013136B1 (es)
CA (1) CA2850700C (es)
CL (1) CL2014001389A1 (es)
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