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AR116800A1 - 5-MEMBER HETEROARYL CARBOXAMIDE COMPOUNDS FOR THE TREATMENT OF HBV - Google Patents

5-MEMBER HETEROARYL CARBOXAMIDE COMPOUNDS FOR THE TREATMENT OF HBV

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Publication number
AR116800A1
AR116800A1 ARP190103019A ARP190103019A AR116800A1 AR 116800 A1 AR116800 A1 AR 116800A1 AR P190103019 A ARP190103019 A AR P190103019A AR P190103019 A ARP190103019 A AR P190103019A AR 116800 A1 AR116800 A1 AR 116800A1
Authority
AR
Argentina
Prior art keywords
alkyl
group
hydrogen
haloc1
monocycloalkyl
Prior art date
Application number
ARP190103019A
Other languages
Spanish (es)
Inventor
Michael Walker
Lynne Bannen
Roopa Rai
Mark G Bures
Leping Li
Simon Nicolas Haydar
Original Assignee
Assembly Biosciences Inc
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 Assembly Biosciences Inc filed Critical Assembly Biosciences Inc
Publication of AR116800A1 publication Critical patent/AR116800A1/en

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Abstract

Esta divulgación proporciona, en parte, compuestos de heteroaril carboxamida de 5 miembros y composiciones farmacéuticas de esto, que son útiles para interrumpir el ensamblaje de la proteína central del VHB, así como métodos para tratar la infección por hepatitis B (VHB). Reivindicación 1: En un aspecto, se indica en la presente un compuesto de fórmula (1), una sal de este aceptable en términos farmacéuticos, donde: X¹ es NRˣ¹, O ó S; X² es N o CRˣ²; X³ es O, NR⁷, CR⁴R⁸, C(O), S(O)ₜ, C=CR⁴R⁰ o C=NR⁴; X⁴ y X⁶ son independientemente O ó S; X⁵ es O, S o NR⁰; L es un enlace o C₁₋₆ alquileno; L¹ es un enlace, C₁₋₆ alquileno, O, NRᶜ, C(O), C(O)NRᶜ, S(O)ₜ o S(O)ₜNRᶜ; Rˣ¹ y Rˣ² están seleccionados de manera independiente del grupo que consiste en hidrógeno, C₁₋₆ alquilo, haloC₁₋₆ alquilo y C₃₋₆ monocicloalquilo; Rᵃ, Rᵇ y Rᶜ están seleccionados de manera independiente para cada surgimiento del grupo que consiste en hidrógeno, C₁₋₆ alquilo, haloC₁₋₆ alquilo y C₃₋₆ monocicloalquilo; Rᵈ es hidrógeno, OH, C₁₋₆ alquilo o C₁₋₆ alcoxi; R⁰, R⁶, R⁸ y R¹¹ se seleccionan independientemente para cada ocurrencia a partir del grupo que consta de hidrógeno, halógeno, OH, CN, NO₂, oxo, RᵈN=, hidrazino, formilo, azida, silil, siloxi, HOC(O)-, RᵃRᵇN-, RᵃRᵇNS(O)ₜ-, C₁₋₆ alquilo, C₂₋₆ alquenil, C₂₋₆ alquinil, C₃₋₆ monocicloalquilo, haloC₁₋₆ alquilo, hidroxiC₁₋₆ alquilo-, RᵃRᵇNC₁₋₆ alquilo-, HOC(O)C₁₋₆ alquilo-, RᵃRᵇNC₁₋₆ alquiloNRᶜ-, C₁₋₆ alquiloNRᵃC₁₋₆ alquiloNRᶜ-, C₁₋₆ alcoxi, haloC₁₋₆ alcoxi, hidroxiC₁₋₆ alcoxi-, RᵃRᵇNC₁₋₆ alcoxi-, C₁₋₆ alcoxiC₁₋₆ alquilo-, haloC₁₋₆ alcoxiC₁₋₆ alquilo-, RᵃRᵇNC(O)-, C₁₋₆ alquiloC(O)-, C₁₋₆ alcoxiC(O)-, C₁₋₆ alquiloC(O)O-, C₁₋₆ alquiloS(O)q-, C₁₋₆ alquiloS(O)ₜNRᶜ-, C₁₋₆ alquiloS(O)ₜC₁₋₆ alquilo-, C₁₋₆ alquiloS(O)ₜNRᵃC₁₋₆ alquilo-, C₃₋₆ cicloalquiloS(O)ₜC₁₋₆ alquilo-, C₁₋₆ alquiloC(O)C₁₋₆ alquilo-, y C₁₋₆ alquiloC(O)OC₁₋₆ alquilo-; R⁰ᵃ está seleccionado de manera independiente para cada surgimiento del grupo que consiste en hidrógeno, halógeno, OH, CN, NO₂, RᵃRᵇN-, C₁₋₆ alquilo y haloC₁₋₆ alquilo; R¹ es un fenilo, naftilo, C₃₋₆ monocicloalquilo, C₃₋₆ monoheterocicloalquilo o heteroarilo monocíclico de 5 - 6 miembros, donde: el fenilo, C₃₋₆ monocicloalquilo, C₃₋₆ monoheterocicloalquilo o heteroarilo monocíclico de 5 - 6 miembros se sustituye opcionalmente por uno, dos o tres grupos R¹¹ seleccionados de manera independiente; R² es hidrógeno, halógeno, RᵃRᵇN, C₁₋₆ alquilo, haloC₁₋₆ alquilo, C₃₋₆ monocicloalquilo o C₁₋₆ alcoxi; R³ se selecciona a partir del grupo que consiste en los compuestos del grupo de fórmulas (2); R⁴ es R⁵, R⁶ o R⁵-L¹-; R⁴ y R⁸ juntos con el átomo de carbono al que están unidos forman un grupo de fórmula (3) ó (4); R⁴ᵃ es hidrógeno o C₁₋₆ alquilo; R⁴ᵇ es R⁵, R⁵ᵃ, R⁶ o R⁵-L¹-; R⁵ se selecciona del grupo que consiste en los compuestos del grupo de fórmulas (5); R⁵ᵃ es un resto de fórmula (6); R⁵ᵇ es un compuesto seleccionado del grupo de fórmulas (7); R⁶ᵃ es hidrógeno o C₁₋₆ alquilo; R⁷ es hidrógeno, C₁₋₆ alquilo, C₁₋₆ haloalquilo, C₁₋₆ alcoxiC₁₋₆ alquilo-, NRᵃRᵇC(O)-, R⁷ᵃC(O)-, C₁₋₆ alquiloxiC(O)-, C₁₋₆ alquiloS(O)q- o C₁₋₆ haloalquiloS(O)q-; R⁷ᵃ es C₁₋₆ alquilo o C₃₋₆ monocicloalquilo; q, r, t y w se seleccionan de manera independiente para cada surgimiento de 0, 1 y 2; y v se selecciona de manera independiente para cada surgimiento de 0, 1, 2 y 3.This disclosure provides, in part, 5-membered heteroaryl carboxamide compounds and pharmaceutical compositions thereof, which are useful for disrupting HBV core protein assembly, as well as methods for treating hepatitis B (HBV) infection. Claim 1: In one aspect, there is indicated herein a compound of formula (1), a pharmaceutically acceptable salt thereof, where: X¹ is NRˣ¹, O or S; X² is N or CRˣ²; X³ is O, NR⁷, CR⁴R⁸, C (O), S (O) ₜ, C = CR⁴R⁰ or C = NR⁴; X⁴ and X⁶ are independently O or S; X⁵ is O, S, or NR⁰; L is a bond or C₁₋₆ alkylene; L¹ is a bond, C₁₋₆ alkylene, O, NRᶜ, C (O), C (O) NRᶜ, S (O) ₜ or S (O) ₜNRᶜ; Rˣ¹ and Rˣ² are independently selected from the group consisting of hydrogen, C₁₋₆ alkyl, haloC₁₋₆ alkyl, and C₃₋₆ monocycloalkyl; Rᵃ, Rᵇ, and Rᶜ are independently selected for each occurrence from the group consisting of hydrogen, C₁₋₆ alkyl, haloC₁₋₆ alkyl, and C₃₋₆ monocycloalkyl; Rᵈ is hydrogen, OH, C₁₋₆ alkyl or C₁₋₆ alkoxy; R⁰, R⁶, R⁸, and R¹¹ are independently selected for each occurrence from the group consisting of hydrogen, halogen, OH, CN, NO₂, oxo, RᵈN =, hydrazino, formyl, azide, silyl, siloxy, HOC (O) - , RᵃRᵇN-, RᵃRᵇNS (O) ₜ-, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₆ monocycloalkyl, haloC₁₋₆ alkyl, hydroxyC₁₋₆ alkyl-, RᵃRᵇNC₁₋₆ alkyl-, HOC ( O) C₁₋₆ alkyl-, RᵃRᵇNC₁₋₆ alkylNRᶜ-, C₁₋₆ alkylNRᵃC₁₋₆ alkylNRᶜ-, C₁₋₆ alkoxy, haloC₁₋₆ alkoxy, hydroxyC₁₋₆ alkoxy-, RᵃRᵇNC₁₋₆ alkoxy-, C₁₋₆ alkoxyC₁₋ ₆ alkyl-, haloC₁₋₆ alkoxyC₁₋₆ alkyl-, RᵃRᵇNC (O) -, C₁₋₆ alkylC (O) -, C₁₋₆ alkoxyC (O) -, C₁₋₆ alkylC (O) O-, C₁₋₆ alkylS (O) q-, C₁₋₆ alkylS (O) ₜNRᶜ-, C₁₋₆ alkylS (O) ₜC₁₋₆ alkyl-, C₁₋₆ alkylS (O) ₜNRᵃC₁₋₆ alkyl-, C₃₋₆ cycloalkylS (O) ₜC₁₋₆ alkyl-, C₁₋₆ alkylC (O) C₁₋₆ alkyl-, and C₁₋₆ alkylC (O) OC₁₋₆ alkyl-; R⁰ᵃ is independently selected for each occurrence from the group consisting of hydrogen, halogen, OH, CN, NO₂, RᵃRᵇN-, C₁₋₆ alkyl, and haloC₁₋₆ alkyl; R¹ is a 5-6 membered phenyl, naphthyl, C₃₋₆ monocycloalkyl, C₃₋₆ monoheterocycloalkyl or monocyclic 5-6 membered heteroaryl, where: phenyl, C₃₋₆ monocycloalkyl, C₃₋₆ monoheterocycloalkyl or 5-6 membered monocyclic heteroaryl is optionally substituted by one, two or three independently selected R¹¹ groups; R² is hydrogen, halogen, RᵃRᵇN, C₁₋₆ alkyl, haloC₁₋₆ alkyl, C₃₋₆ monocycloalkyl or C₁₋₆ alkoxy; R³ is selected from the group consisting of the compounds of the group of formulas (2); R⁴ is R⁵, R⁶ or R⁵-L¹-; R⁴ and R⁸ together with the carbon atom to which they are attached form a group of formula (3) or (4); R⁴ᵃ is hydrogen or C₁₋₆ alkyl; R⁴ᵇ is R⁵, R⁵ᵃ, R⁶, or R⁵-L¹-; R⁵ is selected from the group consisting of the compounds of the group of formulas (5); R⁵ᵃ is a residue of formula (6); R⁵ᵇ is a compound selected from the group of formulas (7); R⁶ᵃ is hydrogen or C₁₋₆ alkyl; R⁷ is hydrogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxyC₁₋₆ alkyl-, NRᵃRᵇC (O) -, R⁷ᵃC (O) -, C₁₋₆ alkyloxyC (O) -, C₁₋₆ alkylS (O ) q- or C₁₋₆ haloalkylS (O) q-; R⁷ᵃ is C₁₋₆ alkyl or C₃₋₆ monocycloalkyl; q, r, t, and w are selected independently for each occurrence of 0, 1, and 2; and v is independently selected for each occurrence of 0, 1, 2, and 3.

ARP190103019A 2018-10-22 2019-10-22 5-MEMBER HETEROARYL CARBOXAMIDE COMPOUNDS FOR THE TREATMENT OF HBV AR116800A1 (en)

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US201862748906P 2018-10-22 2018-10-22

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AR116800A1 true AR116800A1 (en) 2021-06-16

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