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AR109950A1 - INHIBIDORES DE LA ÁCIDO a-AMINO-b-CARBOXIMUCÓNICO SEMIALDEHÍDO DESCARBOXILASA - Google Patents

INHIBIDORES DE LA ÁCIDO a-AMINO-b-CARBOXIMUCÓNICO SEMIALDEHÍDO DESCARBOXILASA

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Publication number
AR109950A1
AR109950A1 ARP170102868A ARP170102868A AR109950A1 AR 109950 A1 AR109950 A1 AR 109950A1 AR P170102868 A ARP170102868 A AR P170102868A AR P170102868 A ARP170102868 A AR P170102868A AR 109950 A1 AR109950 A1 AR 109950A1
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AR
Argentina
Prior art keywords
alkyl
aryl
halogen
independently
heteroaryl
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ARP170102868A
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English (en)
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Roberto Pellicciari
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Tes Pharma S R L
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Publication of AR109950A1 publication Critical patent/AR109950A1/es

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    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
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    • C07D233/04Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
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    • 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]
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    • A61P3/00Drugs for disorders of the metabolism
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P31/04Antibacterial agents
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    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07D233/04Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
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    • C07D233/04Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
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    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
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    • C07D233/96Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
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    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52Two oxygen atoms
    • C07D239/54Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/557Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
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Abstract

Compuestos capaces de modular la actividad de la ácido a-amino-b-carboximucónico semialdehido descarboxilasa (ACMSD), que son útiles en la prevención y/o el tratamiento de enfermedades y desórdenes asociados con defectos en la biosíntesis de NAD⁺, por ejemplo, desórdenes metabólicos, enfermedades neurodegenerativas, enfermedades inflamatorias crónicas, enfermedades renales, y enfermedades asociadas con el envejecimiento. También, composiciones farmacéuticas que comprenden dichos compuestos y el uso de dichos compuestos como medicamentos. Reivindicación 1: Un compuesto caracterizado porque está representado por la fórmula (1), o una sal farmacéuticamente aceptable o tautómero del mismo, donde: X¹ es O, S, OR², SH, NH, NH₂, o halógeno; X² es O, S, OR², SR², NH, NHR², o halógeno; L es -(CH₂)ₘCH=CH(CH₂)ₚ-, -(CH₂)ₒ-, -(CH₂)ₘY¹(CH₂)ₚ-, un resto de fórmula (2), -(CH₂)ₘY¹CH=CH-, -(CH₂)ₘC=(O)(CH₂)ₚ-, -(CH₂)ₘC=(O)O(CH₂)ₚ-, -(CH₂)ₘC=(O)NR³(CH₂)ₚ-, -(CH₂)ₘNR³C=(O)(CH₂)ₚ-, fenilo, piridinilo, o tiofenilo; Y¹ es O, NR⁴, o S(O)q; Y² es O, NH o S; R¹ es C₆₋₁₀ arilo o heteroarilo, donde el heteroarilo comprende uno o dos anillos de 5 a 7 miembros y 1 - 4 heteroátomos seleccionados entre N, O y S, y donde el arilo y el heteroarilo están sustituidos con Rᵃ y Rᵇ, y opcionalmente sustituidos con uno o dos Rᵉ; R² es H o C₁₋₄ alquilo; R³ es H o C₁₋₄ alquilo; R⁴ es H o C₁₋₄ alquilo; Rᵃ es H, C₁₋₄ alquilo, -(C(Rᶠ)₂)ʳCO₂Rˣ, -Y²(C(Rᶠ)₂)ʳCO₂Rˣ, -O(C(Rᶠ)₂)ʳC(O)NHRᵍ, halógeno, -(C(Rᶠ)₂)ʳC₆₋₁₀ arilo, -(C(Rᶠ)₂)ʳS-C₆₋₁₀ arilo, -(C(Rᶠ)₂)ʳheteroarilo, -O(C(Rᶠ)₂)ʳheteroarilo, -O(C(Rᶠ)₂)ʳheterocicloalquilo, -O(C(Rᶠ)₂)ʳC₃₋₇ cicloalquilo, -(C(Rᶠ)₂)ʳP(O)(OH)ORˣ, -O(C(Rᶠ)₂)ʳP(O)(OH)ORˣ, -(C(Rᶠ)₂)ʳS(O)₂OH, -O(C(Rᶠ)₂)ʳS(O)₂OH, -(C(Rᶠ)₂)ʳP(O)₂OH, -O(C(Rᶠ)₂)ʳP(O)₂OH, -O(C(Rᶠ)₂)ʳOH, -ORʸ, -(C(Rᶠ)₂)ʳC(O)NHCN, -CH=CHCO₂Rˣ, o -(C(Rᶠ)₂)ʳC(O)NHS(O)₂alquilo, donde el arilo y el heteroarilo están opcionalmente sustituidos con entre uno y tres sustituyentes seleccionados en forma independiente en cada caso entre halógeno y OH, y donde el heterocicloalquilo está sustituido con uno o dos =O ó =S; Rᵇ es C₁₋₄ alquilo, -(C(Rᶠ)₂)ʳCO₂Rˣ, -Y²(C(Rᶠ)₂)ʳCO₂Rˣ, -O(C(Rᶠ)₂)ʳC(O)NHRᵍ, halógeno, -(C(Rᶠ)₂)ʳC₆₋₁₀ arilo, -(C(Rᶠ)₂)ʳS-C₆₋₁₀ arilo, -(C(Rᶠ)₂)ʳheteroarilo, -O(C(Rᶠ)₂)ʳheteroarilo, -O(C(Rᶠ)₂)ʳheterocicloalquilo, -(C(Rᶠ)₂)ʳP(O)(OH)ORˣ, -O(C(Rᶠ)₂)ʳP(O)(OH)ORˣ, -(C(Rᶠ)₂)ʳS(O)₂OH, -O(C(Rᶠ)₂)ʳS(O)₂OH, -(C(Rᶠ)₂)ʳP(O)₂OH, -O(C(Rᶠ)₂)ʳP(O)₂OH, -O(C(Rᶠ)₂)ʳOH, -ORʸ, -(C(Rᶠ)₂)ʳC(O)NHCN, -CH=CHCO₂Rˣ, o -(C(Rᶠ)₂)ʳC(O)NHS(O)₂alquilo, donde el arilo y el heteroarilo están sustituidos con entre uno y tres sustituyentes seleccionados entre halógeno y OH, y donde el heterocicloalquilo está sustituido con uno o dos =O ó =S; o Rᵃ y Rᵇ cuando se encuentran sobre átomos adyacentes junto con los átomos a los cuales están unidos forman un anillo C₆₋₁₀ arilo opcionalmente sustituido con uno o más -CO₂H; Rᵃ y Rᵇ cuando se encuentran sobre átomos adyacentes junto con los átomos a los cuales están unidos forman un anillo heteroarilo de 5 ó 6 miembros opcionalmente sustituido con uno o más -CO₂H; Rᶜ es C₁₋₆ alquilo, C₁₋₆ haloalquilo, halógeno, -CN, -ORˣ, o -CO₂Rˣ; cada Rᵈ en forma independiente en cada caso está ausente o es H o metilo; cada Rᵉ es en forma independiente en cada caso C₁₋₆ alquilo, C₂₋₆ alquenilo, C₂₋₆ alquinilo, halógeno, C₁₋₆ haloalquilo, -NHRᶻ, -OH, o -CN; cada Rᶠ es en forma independiente H o C₁₋₆ alquilo; Rᵍ es H, C₁₋₆ alquilo, OH, -S(O)₂(C₁₋₆ alquilo), o -S(O)₂N(C₁₋₆ alquilo)₂; Rˣ es H o C₁₋₆ alquilo; cada Rʸ y Rᶻ es en forma independiente H, C₁₋₆ alquilo, o C₁₋₆ haloalquilo; cada m, p, q, y r es en forma independiente 0, 1 ó 2; n es 0 ó 1; o es 0, 1, 2, 3, o 4; y la línea punteada es un enlace doble opcional.
ARP170102868A 2016-10-14 2017-10-13 INHIBIDORES DE LA ÁCIDO a-AMINO-b-CARBOXIMUCÓNICO SEMIALDEHÍDO DESCARBOXILASA AR109950A1 (es)

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WO2019055832A1 (en) * 2017-09-15 2019-03-21 The Regents Of The University Of California COMPOSITIONS AND METHODS FOR INHIBITING N-SMASE2
MX2021005904A (es) * 2018-11-20 2021-09-08 Tes Pharma S R L Inhibidores de la ácido alfa-amino-beta-carboximucónico semialdehído descarboxilasa.
EP3980027A1 (en) * 2019-06-05 2022-04-13 Société des Produits Nestlé S.A. Reduced nicotinamideribosides for the treatment/prevention of liver disease
EP3822268A1 (en) 2019-11-15 2021-05-19 Bayer Aktiengesellschaft Substituted hydantoinamides as adamts7 antagonists
EP3822265A1 (en) 2019-11-15 2021-05-19 Bayer AG Substituted hydantoinamides as adamts7 antagonists
CN111773224B (zh) * 2020-08-31 2022-06-21 重庆医科大学 一种化合物在癌症治疗药物中的应用

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