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AR092108A1 - Piridazina 1,4 disustituida, analogos de la misma y metodos para tratar las enfermedades relacionadas con deficiencia del smn - Google Patents

Piridazina 1,4 disustituida, analogos de la misma y metodos para tratar las enfermedades relacionadas con deficiencia del smn

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Publication number
AR092108A1
AR092108A1 ARP130102863A ARP130102863A AR092108A1 AR 092108 A1 AR092108 A1 AR 092108A1 AR P130102863 A ARP130102863 A AR P130102863A AR P130102863 A ARP130102863 A AR P130102863A AR 092108 A1 AR092108 A1 AR 092108A1
Authority
AR
Argentina
Prior art keywords
alkyl
substituted
independently selected
alkoxy
mono
Prior art date
Application number
ARP130102863A
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English (en)
Inventor
Noel Chin Donovan
Dales Natalie
Fazal Aleem
Brian Hurley Timothy
Kerrigan John
Obrien Gary
Shu Lei
Sung Moo
Kim Cheung Atwood
Sun Robert
Original Assignee
Novartis Ag
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=49029227&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR092108(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of AR092108A1 publication Critical patent/AR092108A1/es

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    • A61K31/41—Heterocyclic 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
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    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
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    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine 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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    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three 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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    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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Abstract

El presente proporciona una combinación de agentes farmacológicamente activos y una composición farmacéutica. Reivindicación 1: Un compuesto o sal del mismo según la fórmula (1), A es 2-hidroxi-fenilo que se sustituye por 0, 1, 2, ó 3 sustituyentes seleccionados independientemente a partir de alquilo C₁₋₄, en donde 2 grupos alquilo C₁₋₄ pueden combinarse con los átomos a los que están unidos para formar un anillo de 5 - 6 miembros y se sustituye por 0 ó 1 sustituyentes seleccionados a partir de oxo, oxima e hidroxilo, haloalquilo C₁₋₄, dihaloalquilo C₁₋₄, trihaloalquilo C₁₋₄, alcoxilo C₁₋₄, alcoxi C₁₋₄-cicloalquilo C₃₋₇, haloalcoxilo C₁₋₄, dihaloalcoxilo C₁₋₄, trihaloalcoxilo C₁₋₄, hidroxilo, ciano, halógeno, amino, mono- y di-alquil C₁₋₄amino, heteroarilo, alquilo C₁₋₄ sustituido por hidroxilo, alcoxilo C₁₋₄ sustituido por arilo, amino, -C(O)NH-alquilo C₁₋₄-heteroarilo, -NHC(O)-heteroarilo-alquilo C₁₋₄-, alquilo C₁₋₄C₍O₎NH₋ₕₑₜₑʳₒₐʳⁱₗₒ, ₐₗqᵘⁱₗₒ C₁₋₄NHC(O)-heteroarilo, cicloalquilo de 3 - 7 miembros, cicloalquenilo de 5 - 7 miembros o heterociclo de 5, 6 ó 9 miembros que contiene 1 ó 2 heteroátomos independientemente seleccionados a partir de S, O y N, en donde heteroarilo tiene 5, 6 ó 9 átomos de anillo, 1, 2 ó 3 heteroátomos de anillo seleccionados a partir de N, O y S y sustituido por 0, 1, ó 2 sustituyentes seleccionados independientemente a partir de oxo, hidroxilo, nitro, halógeno, alquilo C₁₋₄, alquenilo C₁₋₄, alcoxilo C₁₋₄, cicloalquilo C₃₋₇, alquil C₁₋₄-OH, trihaloalquilo C₁₋₄, mono- y di-alquil C₁₋₄amino, -C(O)NH₂, -NH₂, -NO₂, hidroxi-alquil C₁₋₄amino, hidroxialquilo C₁₋₄, heterocicloalquilo C₁₋₄ de 4 - 7 miembros, aminoalquilo C₁₋₄ y mono- y di-alquil C₁₋₄aminoalquilo C₁₋₄; o A es 2-naftilo opcionalmente sustituido en la posición 3 por hidroxilo y adicionalmente sustituido por 0, 1, ó 2 sustituyentes seleccionados a partir de hidroxilo, ciano, halógeno, alquilo C₁₋₄, alquenilo C₂₋₄, alcoxilo C₁₋₅, en donde el alcoxilo no es sustituido o se sustituye por hidroxilo, alcoxilo C₁₋₄, amino, N(H)C(O)alquilo C₁₋₄, N(H)C(O)₂alquilo C₁₋₄, alquileno heterociclo de 4 a 7 miembros, heterociclo de 4 a 7 miembros y mono- y di-alquil C₁₋₄amino; o A es heteroarilo de 6 miembros que tiene 1 - 3 átomos de nitrógeno de anillo, tal heteroarilo de 6 miembros es sustituido por fenilo o un heteroarilo que tiene 5 ó 6 átomos de anillo, 1 ó 2 heteroátomos de anillo seleccionados independientemente a partir de N, O y S y sustituido por 0, 1, ó 2 sustituyentes seleccionados independientemente a partir de alquilo C₁₋₄, mono- y di-alquil C₁₋₄amino, hidroxi-alquil C₁₋₄amino, hidroxialquilo C₁₋₄, aminoalquilo C₁₋₄ y mono- y di-alquil C₁₋₄amino-alquilo C₁₋₄; o A es heteroarilo bicíclico que tiene 9 a 10 átomos de anillo, y 1, 2, ó 3 heteroátomos de anillo seleccionados independientemente a partir de N, O ó S, tal heteroarilo bicíclico se sustituye por 0, 1, ó 2 sustituyentes seleccionados independientemente a partir de ciano, halógeno, hidroxilo, alquilo C₁₋₄, alquenilo C₂₋₄, alquinilo C₂₋₄, alcoxilo C₁₋₄ y alcoxilo C₁₋₄ sustituido por hidroxilo, alcoxilo C₁₋₄, amino y mono- y di-alquil C₁₋₄amino; o A es heteroarilo tricíclico que tiene 12 ó 13 átomos de anillo, y 1, 2, ó 3 heteroátomos de anillo seleccionados independientemente a partir de N, O ó S, tal heteroarilo tricíclico se sustituye por 0, 1, ó 2 sustituyentes seleccionados independientemente a partir de ciano, halógeno, hidroxilo, alquilo C₁₋₄, alquenilo C₂₋₄, alquinilo C₂₋₄, alcoxilo C₁₋₄, alcoxilo C₁₋₄ sustituido por hidroxilo, alcoxilo C₁₋₄, amino, mono- y di-alquil C₁₋₄amino y heteroarilo, en donde dicho heteroarilo tiene 5, 6 ó 9 átomos de anillo, 1, 2 ó 3 heteroátomos de anillo seleccionados a partir de N, O y S y sustituido por 0, 1, ó 2 sustituyentes seleccionados independientemente a partir de oxo, hidroxilo, nitro, halógeno, alquilo C₁₋₄, alquenilo C₁₋₄, alcoxilo C₁₋₄, cicloalquilo C₃₋₇, alquil C₁₋₄-OH, trihaloalquilo C₁₋₄, mono- y di-alquil C₁₋₄amino, -C(O)NH₂, -NH₂, -NO₂, hidroxi-alquil C₁₋₄amino, hidroxialquilo C₁₋₄, heterocicloalquilo C₁₋₄ de 4 - 7 miembros, aminoalquilo C₁₋₄ y mono- y di-alquil C₁₋₄aminoalquilo C₁₋₄; B es un grupo de la fórmula (2), en donde m, n y p son independientemente seleccionados a partir de 0 ó 1; R, R¹, R², R³, y R⁴ son independientemente seleccionados a partir del grupo que consta de hidrógeno, alquilo C₁₋₄, tal alquilo se sustituye opcionalmente por hidroxilo, amino o mono- y di-alquil C₁₋₄amino; R⁵ y R⁶ son independientemente seleccionados a partir de hidrógeno y flúor; o R y R³, tomados en combinación forman un anillo heterocíclico condensado de 5 ó 6 miembros que tiene 0 ó 1 heteroátomos adicionales de anillo seleccionados a partir de N, O ó S; R¹ y R³, tomados en combinación forman un grupo alquileno C₁₋₃; R¹ y R⁵, tomados en combinación forman un grupo alquileno C₁₋₃; R³ y R⁴, tomados en combinación con el átomo de carbono al que están unidos, forman un cicloalquilo C₃₋₆ espirocíclico; X es CRARB, O, NR⁷ o un enlace; R⁷ es hidrógeno, o alquilo C₁₋₄; RA y RB son independientemente seleccionados a partir de hidrógeno y alquilo C₁₋₄, o RA y RB, tomados en combinación, forman un grupo alquileno C₂₋₅ divalente; Z es CR⁸ o N; cuando Z es N, X es un enlace; R⁸ es hidrógeno o tomados en combinación con R⁶ forman un enlace doble; o B es un grupo de la fórmula (3), en donde p y q son independientemente seleccionados a partir del grupo que consta de 0, 1, y 2; R⁹ y R¹³ son independientemente seleccionados a partir de hidrógeno y alquilo C₁₋₄; R¹⁰ y R¹⁴ son independientemente seleccionados a partir de hidrógeno, amino, mono- y di-alquil C₁₋₄amino y alquilo C₁₋₄, tal alquilo se sustituye opcionalmente por hidroxilo, amino o mono- y di-alquil C₁₋₄amino; R¹¹ es hidrógeno, alquilo C₁₋₄, amino o mono- y di-alquil C₁₋₄amino; R¹² es hidrógeno o alquilo C₁₋₄; o R⁹ y R¹¹, tomados en combinación forman un azaciclo saturado que tiene 4 a 7 átomos de anillo, el cual es opcionalmente sustituido por 1 - 3 grupos alquilo C₁₋₄; o R¹¹ y R¹², tomados en combinación forman un azaciclo saturado que tiene 4 a 7 átomos de anillo, el cual es opcionalmente sustituido por 1 - 3 grupos alquilo C₁₋₄.
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