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AR103574A1 - Compuestos tricíclicos y usos de lo mismos en medicina - Google Patents

Compuestos tricíclicos y usos de lo mismos en medicina

Info

Publication number
AR103574A1
AR103574A1 ARP160100271A ARP160100271A AR103574A1 AR 103574 A1 AR103574 A1 AR 103574A1 AR P160100271 A ARP160100271 A AR P160100271A AR P160100271 A ARP160100271 A AR P160100271A AR 103574 A1 AR103574 A1 AR 103574A1
Authority
AR
Argentina
Prior art keywords
independently
heterocyclyl
aryl
cycloalkyl
alkyl
Prior art date
Application number
ARP160100271A
Other languages
English (en)
Original Assignee
Sunshine Lake Pharma Co Ltd
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 Sunshine Lake Pharma Co Ltd filed Critical Sunshine Lake Pharma Co Ltd
Publication of AR103574A1 publication Critical patent/AR103574A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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    • A61K31/4192—1,2,3-Triazoles
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    • A61K31/42—Oxazoles
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    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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Abstract

Un método para el tratamiento de enfermedades y/o estados mediados por FXR que comprende administrar el compuesto o la composición farmacéutica. Reivindicación 1: Un compuesto caracterizado porque presenta la fórmula (1) o un estereoisómero, un isómero geométrico, un tautómero, un N-óxido, un hidrato, un solvato, un metabolito, una sal aceptable para uso farmacéutico o un profármaco del mismo, en la que: X es N, CH o ÅN-O&#⁹²⁰;; el anillo D es un anillo heteroaromático de cinco miembros o un heterociclo de cinco miembros; L es un enlace, -(CR³R⁴)ᶠ-, -(CR³R⁴)ᶠ-O-, -(CR³R⁴)ᶠ-NH- o -(CR³R⁴)ᶠ-S(=O)ₜ-; R es un triciclilo fusionado o un heterotriclililo fusionado, en el que R está sustituido opcionalmente con uno, dos, tres, cuatro o cinco R⁸; cada R¹ es de modo independiente H, deuterio, F, Cl, Br, l, hidroxi, amino, nitro, ciano, alquilo, haloalquilo, haloalcoxi, cicloalquilo, heterociclilo, alquenilo, alquinilo, alquilamino, alcoxi, arilo o heteroarilo; R² es H, deuterio, F, Cl, Br, I, hidroxi, amino, nitro, ciano, alquilo, haloalquilo, haloalcoxi, alcoxialquilo, cicloalquilo, hidroxialquilo, heterociclilo, alquilamino o alcoxi; cada uno de R³ y R⁴ es de modo independiente H, deuterio, alquilo C₁₋₄, F, Cₗ, Bʳ, ₗₒ ₕₐₗₒₐₗqᵘⁱₗₒ C₁₋₄; cada R⁸ es de modo independiente H, deuterio, F, Cl, Br, I, hidroxi, nitro, amino, aminoalquilo, alquilamino, alquilo, hidroxialquilo, alcoxi, haloalquilo, haloalcoxi, cicloalquilo, cicloalcoxi, alquenilo, alquinilo, arilo, arilo halo sustituido, arilalquilo, oxo (=O), -L¹-C(=O)OR¹⁵, -L¹-S(=O)ₜR¹⁶, -O-L²-C(=O)OR¹⁵, -O-L²-S(=O)ₜR¹⁶, -C(=O)NR¹⁷R¹⁸, -C(=O)N(R¹⁷)S(=O)₂R¹⁶, -C(=NR¹⁷)NR¹⁷R¹⁸, -C(=O)N(R¹⁷)-L³-S(=O)₂OR¹⁵, -C(=O)N(R¹⁷)C(=O)OR¹⁵, -C(=O)N(R¹⁷)-L³-C(=O)OR¹⁵, ciano, heterociclilo o heteroarilo; o dos R⁸, junto con el mismo átomo C al que están unidos, de modo independiente y opcional forman cicloalquilo o heterociclilo; o dos R⁸, junto con los átomos C adyacentes al que están unidos, de modo independiente y opcional forman cicloalquilo, heterociclilo, arilo o heteroarilo; en la que R⁸ está sustituido de modo independiente y opcional con uno o más R¹⁹; cada R¹⁵ es de modo independiente H, deuterio, alquilo, aminoalquilo, alquenilo, alquinilo, haloalquilo, cicloalquilo, heterociclilo o arilo; cada R¹⁶ es de modo independiente H, deuterio, hidroxi, amino, alquilo, aminoalquilo, alquenilo, alquinilo, haloalquilo, cicloalquilo, heterociclilo, arilo o -NR¹⁷R¹⁸; cada uno de R¹⁷ y R¹⁸ es de modo independiente H, deuterio, alquilo, aminoalquilo, alquenilo, alquinilo, haloalquilo, cicloalquilo, heterociclilo o arilo; o R¹⁷ y R¹⁸, junto con el átomo N al que están unidos, de modo independiente, y opcional forman heterociclilo o heteroarilo; cada L¹ es de modo independiente un enlace, -C(=O)-, alquileno C₁₋₆, alquenileno C₂₋₆ o alquinileno C₂₋₆; cada L² es de modo independiente alquileno C₁₋₆, alquenileno C₂₋₆ o alquinileno C₂₋₆; cada L³ es de modo independiente un enlace o alquileno C₁₋₄; n es 0, 1, 2, 3 ó 4; cada f es de modo independiente 0, 1 ó 2; cada t es de modo independiente 0, 1, ó 2; donde cada uno de dicho hidroxi, amino, alquilo, hidroxialquilo, aminoalquilo, alquenilo, alquinilo, cicloalquilo, haloalquilo, alquilamino, alcoxi, alcoxialquilo, cicloalquiloxi, haloalcoxi, heterociclilo, arilo, heteroarilo, arilo halosustituido, arilalquilo, haloalquilo C₁₋₄, alquileno C₁₋₆, alquenileno C₂₋₆, alquinileno C₂₋₆ y alquileno C₁₋₄ de R¹, R², R³, R⁴, R⁸, R¹⁵, R¹⁶, R¹⁷, R¹⁸, L¹, L² y L³ está sustituido de modo independiente y opcional con uno o más R⁹; y cada uno de R⁹ y R¹⁹ es de modo independiente H, deuterio, F, Cl, Br, l, ciano, oxo (=O), hidroxi, alquilo, alquilamino, amino, arilo, heterociclilo, heteroarilo, alquenilo, alquinilo, cicloalquilo, alcoxi o haloalquilo.
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