AR119030A1 - 5H-THIOCHROME[4,3-b]PYRIDIN-2-OXO-3-CARBOXYLATES OR THEIR DIOXO OR TRIOXO DERIVATIVES AND THEIR USE IN THE TREATMENT OR PROPHYLAXIS OF HEPATITIS B - Google Patents

5H-THIOCHROME[4,3-b]PYRIDIN-2-OXO-3-CARBOXYLATES OR THEIR DIOXO OR TRIOXO DERIVATIVES AND THEIR USE IN THE TREATMENT OR PROPHYLAXIS OF HEPATITIS B

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Publication number
AR119030A1
AR119030A1 ARP200101509A ARP200101509A AR119030A1 AR 119030 A1 AR119030 A1 AR 119030A1 AR P200101509 A ARP200101509 A AR P200101509A AR P200101509 A ARP200101509 A AR P200101509A AR 119030 A1 AR119030 A1 AR 119030A1
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AR
Argentina
Prior art keywords
independently selected
substituted
unsubstituted
alkyl
halo
Prior art date
Application number
ARP200101509A
Other languages
Spanish (es)
Inventor
Jacques Huck
Oscar Mammoliti
Adeline Marie Elise Palisse
Sbastien Richard
Pascal Pierre Alexandre Savy
Original Assignee
Galapagos Nv
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 Galapagos Nv filed Critical Galapagos Nv
Publication of AR119030A1 publication Critical patent/AR119030A1/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

Compuestos 5H-tiocromeno[4,3-b]piridin-2-oxo-3-carboxilato o sus dioxo o trioxo derivados, composiciones farmacéuticas que los comprenden y su uso en el tratamiento o prevención de la Hepatitis B. Reivindicación 1: Un compuesto de acuerdo con la fórmula (1), en donde X es -S-, -S(=O)- o -S(=O)₂-; G es -OH o alcoxi C₁₋₄; R¹ es cicloalquilo C₃₋₆ monocíclico no sustituido o sustituido con uno o más, seleccionados independientemente, halo o alquilo C₁₋₄, o cicloalquilo C₆₋₁₀ espirocíclico no sustituido o sustituido con uno o más, seleccionados independientemente, halo o alquilo C₁₋₄; cada R²ᵃ y R²ᵇ se selecciona independientemente de: H, alquilo C₁₋₄, cicloalquilo C₃₋₇ no sustituido o sustituido con uno o más, seleccionados independientemente: alquilo C₁₋₄ no sustituido o sustituido con uno o más, seleccionados independientemente, halo, o alcoxi C₁₋₄ no sustituido o sustituido con uno o más, seleccionados independientemente, halo; y heterocicloalquilo monocíclico de 4 a 7 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S, no sustituido o sustituido con uno o más, seleccionados independientemente: alquilo C₁₋₄ no sustituido o sustituido con uno o más, seleccionados independientemente, halo, o alcoxi C₁₋₄ no sustituido o sustituido con uno o más, seleccionados independientemente, halo; o R²ᵃ y R²ᵇ junto con el átomo al que están unidos pueden formar un anillo espirocíclico de cicloalquilo C₃₋₇; R³ es halo, -OH, -CN, alquilo C₁₋₄ no sustituido o sustituido con uno o más, seleccionados independientemente, grupos Rᵃ¹, alcoxi C₁₋₆ no sustituido o sustituido con uno o más, seleccionados independientemente, grupos Rᵃ¹, fenilo no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ¹, heteroarilo monocíclico de 5 ó 6 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S, donde el heteroarilo está no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ¹, cicloalquilo C₃₋₇, donde el cicloalquilo está no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ¹, -O-cicloalquilo C₃₋₇, donde el cicloalquilo está no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ¹, heterocicloalquilo monocíclico de 4 a 7 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S, donde el heterocicloalquilo está no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ¹, -O-(heterocicloalquilo monocíclico de 4 a 7 miembros), donde el heterocicloalquilo comprende uno o más heteroátomos seleccionados independientemente de O, N o S, y donde el heterocicloalquilo está no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ¹, -C(=O)NR⁶ᵃR⁶ᵇ, -NR⁶ᶜ-C(=O)-alquilo C₁₋₄, -S(=O)₂NR⁶ᵈR⁶ᵉ, -NR⁶ᶠ-C(=O)O-alquilo C₁₋₄, o -NR⁶ᵍR⁶ʰ; R⁴ es H, -SO₂-alquilo C₁₋₄, halo, CN, alquilo C₁₋₄ no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵃ², fenilo no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ², heteroarilo monocíclico de 5 ó 6 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S, donde el heteroarilo está no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ², cicloalquilo C₃₋₇, donde el cicloalquilo está no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ², heterocicloalquilo monocíclico de 4 a 7 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S, donde el heterocicloalquilo está no sustituido o sustituido con uno o más, seleccionados independientemente, Rᵇ², -C(=O)NR⁷ᵃR⁷ᵇ, -NR⁷ᶜ-C(=O)-alquilo C₁₋₄, -S(=O)₂NR⁷ᵈR⁷ᵉ, -NR⁷ᶠ-C(=O)O-alquilo C₁₋₄, o -NR⁷ᵍR⁷ʰ; R⁵ es H, -N, halo o alquilo C₁₋₄ no sustituido o sustituido con uno o más, seleccionados independientemente, halo; cada R⁶ᵃ, R⁶ᵇ, R⁶ᶜ, R⁶ᵈ, R⁶ᵉ, R⁶ᶠ, R⁶ᵍ y R⁶ʰ es independientemente H o alquilo C₁₋₄; cada R⁷ᵃ, R⁷ᵇ, R⁷ᶜ, R⁷ᵈ, R⁷ᵉ, R⁷ᶠ, R⁷ᵍ y R⁷ʰ es independientemente H o alquilo C₁₋₄ no sustituido o sustituido con un -C(=O)OH; cada Rᵃ¹ y Rᵃ² es independientemente: halo, -CN, -OH, -SO₂-alquilo C₁₋₄, alcoxi C₁₋₄, fenilo, heteroarilo monocíclico de 5 ó 6 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S, cicloalquilo C₃₋₇ no sustituido o sustituido con uno o más, seleccionados independientemente, R⁹ᵃ, heterocicloalquilo monocíclico de 4 a 7 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S, no sustituido o sustituido con uno o más, seleccionados independientemente, R⁹ᵇ, y heterocicloalquilo fusionado / espiro / puenteado de 4 a 10 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S, no sustituido o sustituido con uno o más, seleccionados independientemente, R⁹ᶜ; cada R⁹ᵃ, R⁹ᵇ y R⁹ᶜ se selecciona independientemente de: halo, -CN, -SO₂-alquilo C₁₋₄, oxo, alquilo no sustituido o sustituido con uno o más, seleccionados independientemente, halo, -alcoxi C₁₋₄ u -OH, -C(=O)NR¹⁰ᵃR¹⁰ᵇ, -alcoxi C₁₋₄, o -C(=O)alquilo C₁₋₄; cada Rᵇ¹ y Rᵇ² se selecciona independientemente de: halo, oxo, alquilo C₁₋₄ no sustituido o sustituido con un alcoxi C₁₋₄ o -C(=O)OH; alcoxi C₁₋₄, y heterocicloalquilo monocíclico de 4 a 7 miembros que comprende uno o más heteroátomos seleccionados independientemente de O, N o S; y cada R¹⁰ᵃ y R¹⁰ᵇ es independientemente H o alquilo C₁₋₄; o una sal farmacéuticamente aceptable del mismo, solvato o sal farmacéuticamente aceptable del solvato.5H-thiochromene[4,3-b]pyridine-2-oxo-3-carboxylate compounds or their dioxo or trioxo derivatives, pharmaceutical compositions comprising them and their use in the treatment or prevention of Hepatitis B. Claim 1: A compound according to formula (1), wherein X is -S-, -S(=O)- or -S(=O)₂-; G is -OH or C₁₋₄ alkoxy; R¹ is monocyclic C₃₋₆ cycloalkyl unsubstituted or substituted with one or more independently selected halo or C₁₋₄ alkyl, or spirocyclic C₆₋₁₀ cycloalkyl unsubstituted or substituted with one or more independently selected halo or C₁₋₄ alkyl ; each R²ᵃ and R²ᵇ is independently selected from: H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl unsubstituted or substituted with one or more, independently selected: C₁₋₄ alkyl unsubstituted or substituted with one or more, independently selected, halo, or C₁₋₄ alkoxy unsubstituted or substituted with one or more independently selected halo; and 4 to 7 membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from O, N or S, unsubstituted or substituted by one or more, independently selected: C₁₋₄ alkyl unsubstituted or substituted by one or more, independently selected , halo, or C₁₋₄ alkoxy unsubstituted or substituted with one or more independently selected halo; or R²ᵃ and R²ᵇ together with the atom to which they are attached can form a C₃₋₇ cycloalkyl spirocyclic ring; R³ is halo, -OH, -CN, C₁₋₄ alkyl unsubstituted or substituted with one or more independently selected Rᵃ¹ groups, C₁₋₆ alkoxy unsubstituted or substituted with one or more independently selected Rᵃ¹ groups, non-phenyl substituted or substituted with one or more, independently selected, Rᵇ¹, 5- or 6-membered monocyclic heteroaryl comprising one or more heteroatoms independently selected from O, N, or S, where heteroaryl is unsubstituted or substituted with one or more, independently selected , Rᵇ¹, C₃₋₇ cycloalkyl, where cycloalkyl is unsubstituted or substituted by one or more, independently selected, Rᵇ¹, -O-C₃₋₇ cycloalkyl, where cycloalkyl is unsubstituted or substituted by one or more, independently selected, Rᵇ¹, 4 to 7 membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from O, N or S, where heterocycloalkyl is unsubstituted or substituted with one or more, independently selected, Rᵇ¹, -O-(4- to 7-membered monocyclic heterocycloalkyl), where heterocycloalkyl comprises one or more heteroatoms independently selected from O, N, or S, and where heterocycloalkyl is unsubstituted or substituted with one or plus, independently selected, Rᵇ¹, -C(=O)NR⁶ᵃR⁶ᵇ, -NR⁶ᶜ-C(=O)-C₁₋₄-alkyl, -S(=O)₂NR⁶ᵈR⁶ᵉ, -NR⁶ᶠ-C(=O)O-C₁₋-alkyl ₄, or -NR⁶ᵍR⁶ʰ; R⁴ is H, -SO₂-C₁₋₄ alkyl, halo, CN, C₁₋₄ alkyl unsubstituted or substituted by one or more, independently selected, Rᵃ², phenyl unsubstituted or substituted by one or more, independently selected, Rᵇ², heteroaryl 5- or 6-membered monocyclic comprising one or more heteroatoms independently selected from O, N or S, where heteroaryl is unsubstituted or substituted with one or more independently selected Rᵇ², C₃₋₇ cycloalkyl, where cycloalkyl is unsubstituted or substituted with one or more, independently selected, Rᵇ², 4- to 7-membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from O, N, or S, where heterocycloalkyl is unsubstituted or substituted with one or more, independently selected, Rᵇ², -C(=O)NR⁷ᵃR⁷ᵇ, -NR⁷ᶜ-C(=O)-C₁₋₄-alkyl, -S(=O)₂NR⁷ᵈR⁷ᵉ, -NR⁷ᶠ-C(=O)O-C₁₋₄-alkyl, or -NR⁷ᵍR⁷ʰ ; R⁵ is H, -N, halo, or C₁₋₄ alkyl unsubstituted or substituted with one or more independently selected halo; each R⁶ᵃ, R⁶ᵇ, R⁶ᶜ, R⁶ᵈ, R⁶ᵉ, R⁶ᶠ, R⁶ᵍ and R⁶ʰ is independently H or C₁₋₄ alkyl; each R⁷ᵃ, R⁷ᵇ, R⁷ᶜ, R⁷ᵈ, R⁷ᵉ, R⁷ᶠ, R⁷ᵍ and R⁷ʰ is independently H or C₁₋₄ alkyl unsubstituted or substituted with one -C(=O)OH; each Rᵃ¹ and Rᵃ² is independently: halo, -CN, -OH, -SO₂-C₁₋₄ alkyl, C₁₋₄ alkoxy, phenyl, 5- or 6-membered monocyclic heteroaryl comprising one or more heteroatoms independently selected from O, N or S, C₃₋₇ cycloalkyl unsubstituted or substituted with one or more, independently selected, R⁹ᵃ, 4- to 7-membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from O, N or S, unsubstituted or substituted with one or more , independently selected, R⁹ᵇ, and 4 to 10 membered fused/spiro/bridged heterocycloalkyl comprising one or more heteroatoms independently selected from O, N, or S, unsubstituted or substituted by one or more, independently selected, R⁹ᶜ; each R⁹ᵃ, R⁹ᵇ and R⁹ᶜ is independently selected from: halo, -CN, -SO₂-C₁₋₄ alkyl, oxo, alkyl unsubstituted or substituted with one or more independently selected halo, -C₁₋₄ alkoxy or -OH, -C(=O)NR¹⁰ᵃR¹⁰ᵇ, -C₁₋₄ alkoxy, or -C(=O)C₁₋₄ alkyl; each Rᵇ¹ and Rᵇ² is independently selected from: halo, oxo, C₁₋₄ alkyl unsubstituted or substituted with a C₁₋₄ alkoxy or -C(=O)OH; C₁₋₄ alkoxy, and 4 to 7 membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from O, N or S; and each R¹⁰ᵃ and R¹⁰ᵇ is independently H or C₁₋₄ alkyl; or a pharmaceutically acceptable salt thereof, solvate or pharmaceutically acceptable salt of solvate.

ARP200101509A 2019-05-29 2020-05-28 5H-THIOCHROME[4,3-b]PYRIDIN-2-OXO-3-CARBOXYLATES OR THEIR DIOXO OR TRIOXO DERIVATIVES AND THEIR USE IN THE TREATMENT OR PROPHYLAXIS OF HEPATITIS B AR119030A1 (en)

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GBGB1907547.2A GB201907547D0 (en) 2019-05-29 2019-05-29 Novel compounds and pharmaceutical compositions thereof for the treatment of hepatitis B

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AR (1) AR119030A1 (en)
GB (1) GB201907547D0 (en)
TW (1) TW202110855A (en)
WO (1) WO2020239656A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3031063A1 (en) * 2016-07-29 2018-02-01 Newave Pharmaceutical Inc. Benzo-quinolizin-2oxo carboxylic acid derivatives for the treatment of hbv infection
GB201720163D0 (en) * 2017-12-04 2018-01-17 Galapagos Nv Novel compounds and pharmaceutical compositions thereof for the treatment of hepatitis B

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GB201907547D0 (en) 2019-07-10
WO2020239656A1 (en) 2020-12-03

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