AR123583A1 - COMPOSITIONS AND METHODS FOR THE TREATMENT OF CORONAVIRUS INFECTION - Google Patents

COMPOSITIONS AND METHODS FOR THE TREATMENT OF CORONAVIRUS INFECTION

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Publication number
AR123583A1
AR123583A1 ARP210102643A ARP210102643A AR123583A1 AR 123583 A1 AR123583 A1 AR 123583A1 AR P210102643 A ARP210102643 A AR P210102643A AR P210102643 A ARP210102643 A AR P210102643A AR 123583 A1 AR123583 A1 AR 123583A1
Authority
AR
Argentina
Prior art keywords
alkyl
aryl
group
optionally substituted
substituted
Prior art date
Application number
ARP210102643A
Other languages
Spanish (es)
Inventor
Casey C Lynch
Joseph VACCA
Stephen S Dominy
Leslie J Holsinger
Florian Ermini
Original Assignee
Cortexyme 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 Cortexyme Inc filed Critical Cortexyme Inc
Publication of AR123583A1 publication Critical patent/AR123583A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • C07D401/02—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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Se divulgan compuestos y métodos para el tratamiento de infecciones por coronavirus. Los compuestos de acuerdo con la fórmula (1) aquí descritos, que contienen grupos funcionales reactivos para el enlace covalente a residuos de sitio activo en proteasas diana, se pueden usar para el tratamiento de la infección por el SARS-CoV-2 y otros coronavirus. Reivindicación 1: Un compuesto de acuerdo con la fórmula (1), o una sal farmacéuticamente aceptable de este, en donde: R¹ se selecciona del grupo que consiste en fenilo sustituido, fenilo insustituido, otro arilo C₆₋₁₀, heteroarilo de 5 a 12 miembros y haloalquilo C₁₋₆, en donde: el fenilo está sustituido con 4, 3, 2 ó 1 R¹ᵃ, el arilo C₆₋₁₀ está sustituido con uno o más R¹ᵃ, y el heteroarilo de 5 a 12 miembros está opcionalmente sustituido con uno o más R¹ᵇ; cada R¹ᵃ es independientemente halógeno; cada R¹ᵇ se selecciona independientemente del grupo que consiste en halógeno, alquilo C₁₋₃ y haloalquilo C₁₋₃; R² se selecciona del grupo que consiste en oxopirrolidinilo, dioxopirrolidinilo, pirrolidinilo, piperidinilo, azepanilo y -CH₂C(O)NH₂, en donde el piperidinilo y azepanilo están opcionalmente sustituidos con uno o más restos oxo; R³ se selecciona del grupo que consiste en H y alquilo C₁₋₆; R⁴ se selecciona del grupo que consiste en propilo sustituido con uno o más R⁴ᵃ, propilo insustituido, alquilo C₁₋₂, alquilo C₄₋₆ y arilo C₆₋₁₀, en donde el alquilo C₁₋₂, alquilo C₄₋₆ y arilo C₆₋₁₀ están opcionalmente sustituidos con uno o más R⁴ᵃ; cada R⁴ᵃ se selecciona independientemente del grupo que consiste en alquilo C₁₋₆, cicloalquilo C₃₋₈ y arilo C₆₋₁₀, cada uno de los cuales está opcionalmente sustituido con uno o más R⁴ᵇ; cada R⁴ᵇ es un halógeno independientemente seleccionado; R⁵ se selecciona del grupo que consiste en H y alquilo C₁₋₆; o R⁴ y R⁵ se toman juntos para formar un heterociclilo de 5 a 12 miembros monocíclico o bicíclico, que está opcionalmente sustituido con uno o más R⁴ᵃ; R⁶ se selecciona del grupo que consiste en indolilo sustituido con R⁶ᵃ, otro heteroarilo de 5 a 12 miembros, arilo C₆₋₁₀, -OR⁷, -NHR⁷, -NHC(O)OR⁷ y -CHR⁷NHC(O)R⁷, en donde el arilo C₆₋₁₀ y heteroarilo de 5 a 12 miembros están opcionalmente sustituidos con uno o más R⁶ᵃ; cada R⁶ᵃ se selecciona independientemente del grupo que consiste en alcoxi C₁₋₆, alquilo C₁₋₆, hidroxi, cicloalquilo C₃₋₈ y arilo C₆₋₁₀; o R⁵ y R⁶ se toman junto con los átomos con los cuales están unidos para formar un heterociclilo de 5 a 12 miembros, que está opcionalmente sustituido con -NHR⁷ o -NHC(O)OR⁷; R⁷ se selecciona del grupo que consiste en alquilo C₁₋₆, cicloalquilo C₃₋₈ y arilo C₆₋₁₀, cada uno de los cuales está opcionalmente sustituido con uno o más R⁷ᵃ; cada R⁷ᵃ se selecciona independientemente del grupo que consiste en halógeno, alquilo C₁₋₆, arilo C₆₋₁₀ y cicloalquilo C₃₋₈, en donde el alquilo C₁₋₆, arilo C₆₋₁₀ y cicloalquilo C₃₋₈ están opcionalmente sustituidos con uno o más R⁷ᵇ; y cada R⁷ᵇ es un halógeno independientemente seleccionado.Compounds and methods for the treatment of coronavirus infections are disclosed. Compounds according to formula (1) described herein, which contain reactive functional groups for covalent linkage to active site residues in target proteases, can be used for the treatment of infection by SARS-CoV-2 and other coronaviruses. . Claim 1: A compound according to formula (1), or a pharmaceutically acceptable salt thereof, wherein: R¹ is selected from the group consisting of substituted phenyl, unsubstituted phenyl, other C₆₋₁₀ aryl, 5 to 12 heteroaryl and C₁₋₆ haloalkyl, wherein: phenyl is substituted with 4, 3, 2, or 1 R¹ᵃ, C₆₋₁₀ aryl is substituted with one or more R¹ᵃ, and 5- to 12-membered heteroaryl is optionally substituted with one or more R¹ᵇ; each R¹ᵃ is independently halogen; each R¹ᵇ is independently selected from the group consisting of halogen, C₁₋₃ alkyl, and C₁₋₃ haloalkyl; R² is selected from the group consisting of oxopyrrolidinyl, dioxopyrrolidinyl, pyrrolidinyl, piperidinyl, azepanyl, and -CH₂C(O)NH₂, wherein the piperidinyl and azepanyl are optionally substituted with one or more oxo moieties; R³ is selected from the group consisting of H and C₁₋₆ alkyl; R⁴ is selected from the group consisting of propyl substituted with one or more R⁴ᵃ, unsubstituted propyl, C₁₋₂ alkyl, C₄₋₆ alkyl, and C₆₋₁₀ aryl, wherein C₁₋₂ alkyl, C₄₋₆ alkyl, and C₆₋ aryl ₁₀ are optionally substituted with one or more R⁴ᵃ; each R⁴ᵃ is independently selected from the group consisting of C₁₋₆ alkyl, C₃₋₈ cycloalkyl, and C₆₋₁₀ aryl, each of which is optionally substituted with one or more R⁴ᵇ; each R⁴ᵇ is an independently selected halogen; R⁵ is selected from the group consisting of H and C₁₋₆ alkyl; or R⁴ and R⁵ are taken together to form a 5- to 12-membered monocyclic or bicyclic heterocyclyl, which is optionally substituted with one or more R⁴ᵃ; R⁶ is selected from the group consisting of indolyl substituted with R⁶ᵃ, other 5 to 12 membered heteroaryl, C₆₋₁₀ aryl, -OR⁷, -NHR⁷, -NHC(O)OR⁷ and -CHR⁷NHC(O)R⁷, wherein the aryl C₆₋₁₀ and 5- to 12-membered heteroaryl are optionally substituted with one or more R⁶ᵃ; each R⁶ᵃ is independently selected from the group consisting of C₁₋₆ alkoxy, C₁₋₆ alkyl, hydroxy, C₃₋₈ cycloalkyl, and C₆₋₁₀ aryl; or R⁵ and R⁶ are taken together with the atoms to which they are attached to form a 5 to 12 membered heterocyclyl, which is optionally substituted with -NHR⁷ or -NHC(O)OR⁷; R⁷ is selected from the group consisting of C₁₋₆ alkyl, C₃₋₈ cycloalkyl, and C₆₋₁₀ aryl, each of which is optionally substituted with one or more R⁷ᵃ; each R⁷ᵃ is independently selected from the group consisting of halogen, C₁₋₆ alkyl, C₆₋₁₀ aryl, and C₃₋₈ cycloalkyl, wherein C₁₋₆ alkyl, C₆₋₁₀ aryl, and C₃₋₈ cycloalkyl are optionally substituted with one or plus R⁷ᵇ; and each R⁷ᵇ is an independently selected halogen.

ARP210102643A 2020-09-23 2021-09-23 COMPOSITIONS AND METHODS FOR THE TREATMENT OF CORONAVIRUS INFECTION AR123583A1 (en)

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US202063082305P 2020-09-23 2020-09-23

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EP (1) EP4216961A1 (en)
AR (1) AR123583A1 (en)
TW (1) TW202229309A (en)
WO (1) WO2022066776A1 (en)

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Publication number Priority date Publication date Assignee Title
WO2022208262A1 (en) * 2021-03-30 2022-10-06 Pfizer Inc. Ether-linked antiviral compounds
CA3228146A1 (en) 2021-06-11 2022-12-15 The Scripps Research Institute Protease inhibitors for the treatment of coronavirus infections
CN114989045B (en) * 2022-06-14 2023-09-08 斯坦德药典标准物质研发(湖北)有限公司 Intermediate for synthesizing Namactetvir and preparation method thereof and method for synthesizing Namactetvir

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JP2003506457A (en) * 1999-08-04 2003-02-18 アグロン・ファーマシュウティカルズ・インコーポレーテッド Anti-picornavirus compounds and compositions, their pharmaceutical use, and substances for their synthesis
US20040235952A1 (en) * 2003-05-05 2004-11-25 Agouron Pharmaceuticals, Inc. Inhibitors of severe acute respiratory syndrome (SARS) 3C-like proteinase
WO2005113580A1 (en) * 2004-05-21 2005-12-01 Pfizer Inc. Anticoronviral compounds and compositions, their pharmaceutical uses and materials for their synthesis

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