AR116913A1 - Inhibidores de apol1 y sus métodos de uso - Google Patents

Inhibidores de apol1 y sus métodos de uso

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Publication number
AR116913A1
AR116913A1 ARP190103717A ARP190103717A AR116913A1 AR 116913 A1 AR116913 A1 AR 116913A1 AR P190103717 A ARP190103717 A AR P190103717A AR P190103717 A ARP190103717 A AR P190103717A AR 116913 A1 AR116913 A1 AR 116913A1
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Argentina
Prior art keywords
groups
branched
linear
cyclic
nhc
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ARP190103717A
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English (en)
Inventor
Faith Witkos
Tiansheng Wang
Muna Shrestha
Yi Shi
Timothy J Senter
Camil Sayegh
Peter Rose
Oliver Nicolas
Suganthini S Nanthakumar
Ales Medek
Brian Ledford
Elaine B Krueger
Kan Hu
- Hamel Martine Nian
Kevin Gagnon
Anne Fortier
Warren Dorsch
Francois Denis
Leslie A Dakin
Jon H Come
Jingrong Cao
Michael Brodney
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Vertex Pharma
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Publication of AR116913A1 publication Critical patent/AR116913A1/es

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    • 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
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • A61K31/69—Boron compounds
    • 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
    • A61K31/695—Silicon compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C07F7/0814—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring is substituted at a C ring atom by Si
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C07F7/0816—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring comprising Si as a ring atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/46—Phosphinous acids R2=P—OH; Thiophosphinous acids; Aminophosphines R2-P-NH2 including R2P(=O)H; derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Urology & Nephrology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Reivindicación 1: Al menos una entidad seleccionada de compuestos de la formula (1), sus sales farmacéuticamente aceptables, solvatos de cualquiera de los anteriores y derivados deuterados de cualquiera de los anteriores, en donde: (i) cada R¹ se selecciona, de modo independiente, de grupos halógeno, hidroxi, tiol, amino, ciano, grupos alquilo -OC(O)C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -C(O)C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -NHC(O)C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -C(O)NHC₁₋₆ lineales, ramificados y cíclicos, grupos -NHC(O)arilo, grupos -C(O)NH-arilo, grupos -NHC(O)heteroarilo, grupos -C(O)NH-heteroarilo, grupos alquilo -NHS(O)₂C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -S(O)₂NHC₁₋₆ lineales, ramificados y cíclicos, grupos -NHS(O)₂arilo, grupos -S(O)₂NH-arilo, grupos -NHS(O)₂heteroarilo, grupos -S(O)₂NH-heteroarilo, grupos alquilo -NHC(O)NHC₁₋₆ lineales, ramificados y cíclicos, grupos -NHC(O)NH-arilo, grupos -NHC(O)NH-heteroarilo, grupos alquilo C₁₋₆ lineales, ramificados y cíclicos, grupos alquenilo C₂₋₆ lineales, ramificados y cíclicos, grupos hidroxialquilo C₁₋₆ lineales, ramificados y cíclicos, grupos alcoxi C₁₋₆ lineales, ramificados y cíclicos, grupos tioalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloaminoalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos halotioalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloalcoxi C₁₋₆ lineales, ramificados y cíclicos, grupos benciloxi, bencilamino o benciltio, grupos heterocicloalquenilo de 3 a 6 miembros, grupos heterocicloalquilo de 3 a 6 miembros y grupos heteroarilo de 5 y 6 miembros; o dos grupos R¹, junto con los átomos de carbono a los que están unidos, forman un grupo cicloalquilo C₄₋₈, un grupo arilo o un grupo heteroarilo; (ii) cada R² se selecciona, de modo independiente, de grupos halógeno, hidroxi, tiol, amino, ciano, grupos alquilo -NHC(O)C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -C(O)NHC₁₋₆ lineales, ramificados y cíclicos, grupos -NHC(O)arilo, grupos -C(O)NH-arilo, grupos -NHC(O)heteroarilo, grupos -C(O)NH-heteroarilo, grupos alquilo -NHS(O)₂C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -S(O)₂NHC₁₋₆ lineales, ramificados y cíclicos, grupos -NHS(O)₂arilo, grupos -S(O)₂NH-arilo, grupos -NHS(O)₂heteroarilo, grupos -S(O)₂NH-heteroarilo, grupos alquilo -NHC(O)NHC₁₋₄ lineales, ramificados y cíclicos, grupos -NHC(O)NH-arilo, grupos -NHC(O)NH-heteroarilo, grupos alquilo C₁₋₄ lineales, ramificados y cíclicos, grupos alquenilo C₂₋₄ lineales, ramificados y cíclicos, grupos hidroxialquilo C₁₋₄ lineales, ramificados y cíclicos, grupos alcoxi C₁₋₄ lineales, ramificados y cíclicos, grupos tioalquilo C₁₋₄ lineales, ramificados y cíclicos, grupos haloalquilo C₁₋₄ lineales, ramificados y cíclicos, grupos haloaminoalquilo C₁₋₄ lineales, ramificados y cíclicos, grupos halotioalquilo C₁₋₄ lineales, ramificados y cíclicos y grupos haloalcoxi C₁₋₄ lineales, ramificados y cíclicos; (iii) m se selecciona de 0, 1, 2, 3 y 4; (iv) n se selecciona de 0, 1, 2, 3, 4 y 5; (v) Y se selecciona de grupos alquilo divalentes C₁₋₈ lineales y ramificados cíclicos, grupos alcoxi divalentes C₁₋₈ lineales y ramificados, grupos aminoalquilo divalentes C₁₋₈ lineales y ramificados y grupos tioalquilo divalentes C₁₋₈ lineales y ramificados, en donde los grupos alquilo divalentes, grupos alcoxi divalentes, grupos aminoalquilo divalentes y grupos tioalquilo divalentes están opcionalmente sustituidos con al menos un grupo seleccionado de grupos alquilo C₁₋₆, grupos arilo, grupos heteroarilo, grupos halógeno, hidroxi, y amino; (vi) cada de R³ y R⁴ se selecciona, de modo independiente, de hidrógeno, hidroxi, tiol, amino, grupos halógeno, grupos hidroxialquilo C₁₋₆ lineales, ramificados y cíclicos, grupos alcoxi C₁₋₆ lineales, ramificados y cíclicos, grupos tioalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloaminoalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos halotioalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloalcoxi C₁₋₆ lineales, ramificados y cíclicos o R³ y R⁴, junto con el átomo de carbono al que están unidos, forman un grupo cicloalquilo C₃₋₆ o grupo carbonilo; (vii) cada de R⁵ y R⁶ se selecciona, de modo independiente, de hidrógeno, tiol, amino, grupos halógeno, hidroxi, grupos hidroxialquilo C₁₋₆ lineales, ramificados y cíclicos, grupos alcoxi C₁₋₆ lineales, ramificados y cíclicos, grupos tioalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloaminoalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos halotioalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloalcoxi C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -OC(O)C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -C(O)C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -NHC(O)C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -C(O)NHC₁₋₆ lineales, ramificados y cíclicos, grupos -NHC(O)arilo, grupos -C(O)NH-arilo, grupos -NHC(O)heteroarilo, grupos -C(O)NH-heteroarilo, grupos alquilo -NHS(O)₂C₁₋₆ lineales, ramificados y cíclicos, grupos alquilo -S(O)₂NHC₁₋₆ lineales, ramificados y cíclicos, grupos -NHS(O)₂arilo, grupos -S(O)₂NH-arilo, grupos -NHS(O)₂heteroarilo, grupos -S(O)₂NH-heteroarilo, grupos alquilo -NHC(O)NHC₁₋₆ lineales, ramificados y cíclicos, grupos -NHC(O)NH-arilo y grupos -NHC(O)NH-heteroarilo; y (viii) cada de R⁷, R⁸ y R⁹ se selecciona, de modo independiente, de hidrógeno, grupos alquilo C₁₋₆ lineales, ramificados y cíclicos, grupos hidroxialquilo C₁₋₆ lineales, ramificados y cíclicos, grupos alcoxi C₁₋₆ lineales, ramificados y cíclicos, grupos tioalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos haloaminoalquilo C₁₋₆ lineales, ramificados y cíclicos, grupos halotioalquilo C₁₋₆ lineales, ramificados y cíclicos y grupos haloalcoxi C₁₋₆ lineales, ramificados y cíclicos.
ARP190103717A 2018-12-17 2019-12-17 Inhibidores de apol1 y sus métodos de uso AR116913A1 (es)

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JP (1) JP2022515369A (es)
KR (1) KR20210116483A (es)
CN (1) CN113453760A (es)
AR (1) AR116913A1 (es)
AU (1) AU2019405477A1 (es)
BR (1) BR112021011564A2 (es)
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MA54538A (fr) 2018-12-17 2021-10-27 Vertex Pharma Inhibiteurs d'apol1 et leurs procédés d'utilisation
AU2021213758A1 (en) 2020-01-29 2022-09-01 Vertex Pharmaceuticals Incorporated Inhibitors of APOL1 and methods of using same
WO2021158666A1 (en) 2020-02-04 2021-08-12 Vertex Pharmaceuticals Incorporated Solid forms of apol1 inhibitor and methods of using same
IL296035A (en) * 2020-03-06 2022-10-01 Vertex Pharma Treatment methods for apol-1 dependent focal segmental tuberous sclerosis
EP4165022A1 (en) 2020-06-12 2023-04-19 Vertex Pharmaceuticals Incorporated Inhibitors of apol1 and use of the same
WO2021252863A1 (en) 2020-06-12 2021-12-16 Vertex Pharmaceuticals Incorporated Solid forms of apol1 inhibitor and using the same
WO2021252849A1 (en) 2020-06-12 2021-12-16 Vertex Pharmaceuticals Incorporated Inhibitors of apol1 and use of the same
CR20230132A (es) 2020-08-26 2023-06-27 Vertex Pharma Inhibidores de apol1 y métodos para usar los mismos

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IL283592A (en) 2021-07-29
CN113453760A (zh) 2021-09-28
EP3897833A1 (en) 2021-10-27
PE20212302A1 (es) 2021-12-10
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JOP20210129A1 (ar) 2023-01-30
CR20210383A (es) 2021-09-22
KR20210116483A (ko) 2021-09-27
JOP20210131A1 (ar) 2023-01-30
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ECSP21052184A (es) 2021-08-31
UY38514A (es) 2020-07-31
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DOP2021000116A (es) 2021-09-30
MA54538A (fr) 2021-10-27
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CA3121910A1 (en) 2020-06-25
SG11202105769XA (en) 2021-07-29
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BR112021011564A2 (pt) 2021-08-31

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