AR109295A1 - Compuestos tricíclicos que contienen nitrógeno y usos de los mismos en medicina - Google Patents

Compuestos tricíclicos que contienen nitrógeno y usos de los mismos en medicina

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Publication number
AR109295A1
AR109295A1 ARP170102212A ARP170102212A AR109295A1 AR 109295 A1 AR109295 A1 AR 109295A1 AR P170102212 A ARP170102212 A AR P170102212A AR P170102212 A ARP170102212 A AR P170102212A AR 109295 A1 AR109295 A1 AR 109295A1
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Argentina
Prior art keywords
independently
alkyl
deuterium
hydroxy
amino
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ARP170102212A
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English (en)
Inventor
Yingjun Zhang
Shengtian Cao
Shengqiang Pan
Shaohui Xiong
Junwen Wu
Xinye Yang
Xiaojun Wang
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Sunshine Lake Pharma Co Ltd
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Publication of AR109295A1 publication Critical patent/AR109295A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic 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
    • C07D491/02—Heterocyclic 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
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • A61K31/4164—1,3-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/4353—Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic 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
    • C07D491/02—Heterocyclic 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
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic 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
    • C07D491/02—Heterocyclic 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
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Abstract

Compuestos tricíclicos que contienen nitrógeno que actúan como moduladores del FXR, 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, y el uso del compuesto para el tratamiento de enfermedades y/o condiciones mediadas por FXR. Además una composición farmacéutica que contiene el compuesto descripto en la presente y un método para el tratamiento de enfermedades y/o condiciones mediadas por FXR que comprende la administración del compuesto o la composición farmacéutica del mismo. Reivindicación 1: Un compuesto que presenta la fórmula (1), o un esteroisómero, 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, donde: T es -NH-, -O-, -S-, -C(=O)- o -CH₂-; cada uno de X e Y es de modo independiente un enlace, -O-, -S(=O)ₜ, -NRˣ-, -CRʸRᶻ- o -C(=O)-, o -X-Y- es -CHRʰ-CHRᵏ- o -CRʸ=CRᶻ-; cada Rˣ es de modo independiente hidrógeno, deuterio, alquilo, aminoalquilo, haloalquilo, cicloalquilo, heterociclilo, arilo, arilo halo sustituido o arilalquilo; cada uno de Rʸ y Rᶻ es de modo independiente hidrógeno, deuterio, F, Cl, Br, I, hidroxi, amino, nitro, ciano, alquilo, haloalquilo, hidroxialquilo, aminoalquilo, alcoxi, alquilamino, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo, arilo halo sustituido o arilalquilo; o Rʸ y Rᶻ junto con el átomo de carbono adyacente al que están unidos, de modo independiente y opcional forma un anillo de cicloalcano o un anillo heterocíclico, y donde el anillo de cicloalcano y anillo heterocíclico es de modo independiente y opcionalmente sustituido con sustituyentes seleccionados de F, Cl, Br, I, hidroxi, amino, nitro, ciano, metilo, etilo, isopropilo y trifluorometilo; cada Rʰ y Rᵏ es de modo independiente hidrógeno, deuterio, F, Cl, Br, I, hidroxi, amino, nitro, ciano, metilo, etilo, isopropilo o trifluorometilo; o Rʰ y Rᵏ, junto con el átomo de carbón al cual están unido, forman un anillo de cicloalcano o un anillo heterocíclico, donde el anillo cicloalcano y anillo heterocíclico es de modo independiente y opcionalmente sustituido por sustituyentes seleccionados de F, Cl, Br, I, hidroxi, amino, nitro, ciano, metilo, etilo, isopropilo y trifluorometilo; cada Rᵃ y Rᵇ es de modo independiente hidrógeno, deuterio o C₁₋₃ alquilo; cada Rᶜ es de modo independiente hidrógeno, deuterio, F, Cl, Br, I, oxo, hidroxi, amino, nitro, ciano, metilo, etilo, n-propilo, isopropilo, difluorometilo, trifluorometilo, difluorometoxi, trifluorometoxi, hidroximetilo, aminometilo, metilamino, dimetilamino, metoximetilo, isopropoximetilo, vinilo, etinilo, ciclopropilo, ciclobutilo, ciclopentilo, ciclohexilo, azetidinilo, tetrahidrofuranilo, pirrolidinilo, piperidinilo, piperazinilo, tetrahidropiranilo, morfolinilo, tiomorfolinilo, fenilo, tiazolilo, tienilo, oxazolilo, triazolilo, tetrazolilo, piridinilo, pirimidinilo, -COOH, -C(=O)O-C₁₋₃ alquilo, -C(=O)NHS(=O)₂-C₁₋₃ alquilo, -C(=O)NHS(=O)₂-fenilo, -C(=O)NH-C₁₋₃ alquilen-S(=O)₂OH, -C(=O)NH-C₁₋₃ alquilen-C(=O)OH, -S(=O)₂NH₂, -S(=O)₂OH, -S(=O)₂-C₁₋₃ alquilo, -C(=O)NH₂ o -C(=O)N(CH₃)₂; cada R¹ es de modo independiente hidrógeno, deuterio, F, Cl, Br, I, hidroxi, amino, nitro, ciano, alquilo, haloalquilo, hidroxialquilo, aminoalquilo, alcoxi, alquilamino, haloalcoxi, alcoxialquilo, alquenilo, alquinilo, cicloalquilo, cicloalcoxi, cicloalquilalquilo, heterociclilo, heterociclilalquilo, arilo, arilo halo sustituido, arilalquilo, heteroarilo, -L¹-C(=O)OR⁸, -L¹-S(=O)ₜR⁹, -O-L²-C(=O)OR⁸, -O-L²-S(=O)ₜR⁹, -C(=O)NR¹⁰R¹¹, -C(=O)N(R¹⁰)S(=O)₂R⁹, -C(=NR¹⁰)NR¹⁰R¹¹, -C(=O)N(R¹⁰)-L³-S(=O)₂OR⁸, -C(=O)N(R¹⁰)C(=O)OR⁸ o -C(=O)N(R¹⁰)-L³-C(=O)OR⁸; o dos R¹ adyacentes, junto con los átomos del anillo al cual están unidos, de modo independiente y opcional forman un anillo carbocíclico, anillo heterocíclico, anillo aromático o anillo heteroaromático, y donde cada R¹ está de modo independiente y opcionalmente sustituido por uno o más R¹²; cada R⁸ es de modo independiente hidrógeno, deuterio, alquilo, aminoalquilo, alquenilo, alquinilo, haloalquilo, cicloalquilo, heterociclilo o arilo; cada R⁹ es de modo independiente hidrógeno, deuterio, hidroxi, amino, alquilo, aminoalquilo, alquenilo, alquinilo, haloalquilo, cicloalquilo, heterociclilo, arilo o -NR¹⁰R¹¹; cada R¹⁰ y R¹¹ es de modo independiente hidrógeno, deuterio, alquilo, aminoalquilo, alquenilo, alquinilo, haloalquilo, cicloalquilo, heterociclilo o arilo; o R¹⁰ y R¹¹, junto con el átomo de nitrógeno al cual están unido, de modo independiente y opcional forman un anillo heterocíclico o anillo heteroaromático; cada R¹² es de modo independiente hidrógeno, deuterio, F, Cl, Br, I, oxo, hidroxi, amino, nitro, ciano, alquilo, haloalquilo, alcoxi, alquilamino, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo o heteroarilo; cada L¹ es de modo independiente un enlace, -NH-, -C(=O)-, C₁₋₃ alquileno, C₂₋₄ alquenileno o C₂₋₄ alquinileno; cada L² es de modo independiente C₁₋₃ alquileno, C₂₋₄ alquenileno o C₂₋₄ alquinileno; cada L³ es de modo independiente un enlace o C₁₋₃ alquileno; Z es un compuesto seleccionado del grupo de fórmulas (2); cada L es de modo independiente un enlace, -O-, -S-, -NH-, -CH₂-, -CH₂-CH₂-, -O-CH₂-, -O-CH₂-CH₂- o -CH₂-O-CH₂-; cada R², R³, R⁴, R⁵ y R⁶ es de modo independiente hidrógeno, deuterio, F, Cl, Br, I, hidroxi, amino, nitro, ciano, C₁₋₃ alquilo, C₁₋₃ haloalquilo, C₁₋₃ alcoxi or C₁₋₃ haloalcoxi; cada R⁷ es de modo independiente hidrógeno, deuterio, F, Cl, Br, I, hidroxi, amino, nitro, ciano, C₁₋₆ alquilo, C₁₋₆ hidroxialquilo, C₁₋₆ haloalquilo, C₁₋₆ alcoxi, C₁₋₆ alquilamino, C₁₋₆ alcoxi-C₁₋₆ alquilo, C₃₋₆ cicloalquilo o C₂₋₆ heterociclilo, y donde el C₃₋₆ cicloalquilo y C₂₋₆ heterociclilo está de modo independiente y opcionalmente sustituido por sustituyentes seleccionados de F, Cl, Br, I, hidroxi, amino, nitro y ciano; m es 0, 1, 2, 3 ó 4; n es 0, 1 ó 2; y cada t es de modo independiente 0, 1 ó 2; con la condición que un compuesto que tiene la fórmula (I) no sea un compuesto seleccionado del grupo de fórmulas (3).
ARP170102212A 2016-08-05 2017-08-04 Compuestos tricíclicos que contienen nitrógeno y usos de los mismos en medicina AR109295A1 (es)

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US (1) US10562910B2 (es)
EP (1) EP3494118B1 (es)
JP (1) JP6983225B2 (es)
KR (1) KR102368298B1 (es)
CN (1) CN107686486B (es)
AR (1) AR109295A1 (es)
AU (1) AU2017306605B2 (es)
CA (1) CA3030377C (es)
ES (1) ES2950412T3 (es)
TW (1) TW201808283A (es)
WO (1) WO2018024224A1 (es)

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