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AR119784A1 - Agentes antipalúdicos - Google Patents

Agentes antipalúdicos

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Publication number
AR119784A1
AR119784A1 ARP200102325A ARP200102325A AR119784A1 AR 119784 A1 AR119784 A1 AR 119784A1 AR P200102325 A ARP200102325 A AR P200102325A AR P200102325 A ARP200102325 A AR P200102325A AR 119784 A1 AR119784 A1 AR 119784A1
Authority
AR
Argentina
Prior art keywords
6alkyl
6alkylcooh
haloc1
cooh
hydrogen
Prior art date
Application number
ARP200102325A
Other languages
English (en)
Inventor
John A Mcauley
Alan F Cowman
Lera Ruiz Manuel De
Paola Favuzza
Zhuyan Guo
Bin Hu
Iii Michael J Kelly
Zhiyu Lei
David B Olsen
Jennifer K Thompson
Tony Triglia
Dongmei Zhan
Cailing Zhang
Lianyun Zhao
Brad Sleebs
Original Assignee
Merck Sharp & Dohme
Walter & Eliza Hall Inst Medical Res
Msd R&D China Co Ltd
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 Merck Sharp & Dohme, Walter & Eliza Hall Inst Medical Res, Msd R&D China Co Ltd filed Critical Merck Sharp & Dohme
Publication of AR119784A1 publication Critical patent/AR119784A1/es

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • A61P33/02Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06Antimalarials
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/20Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D239/22Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic 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
    • C07D491/02Heterocyclic 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
    • C07D491/04Ortho-condensed systems
    • C07D491/044Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10Spiro-condensed systems
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La presente proporciona métodos para el tratamiento contra la malaria que comprende la administración de compuesto de la fórmula (1) o una sal de este farmacéuticamente aceptable, a un sujeto que lo necesite, en donde las variables son como se definen en la presente. La presente también proporciona usos de los compuestos de la fórmula (1), como se define en la presente, para inhibir la actividad de plasmepsina X, plasmepsina IX o plasmepsina X y IX, para el tratamiento contra la infección de Pasmodium, y para el tratamiento contra la malaria. También se proporcionan métodos de tratamiento que comprenden además la administración de uno o más compuestos antipalúdicos. Reivindicación 1: Un compuesto que tiene la fórmula estructural (1) o una sal de este farmacéuticamente aceptable, en donde: X es un enlace, C(R¹⁴)₂, O, S, SO, SO₂ o NH; Y es CR⁹ o N, en donde cuando Y es N, Z es CR¹¹ y V es CR¹⁰; V es CR¹⁰ o N, en donde cuando V es N, Z es CR¹¹ y Y es CR⁹; Z es CR¹¹ o N, en donde cuando Z es N, V es CR¹⁰ y Y es CR⁹; R¹ es un heterocicloalquilo, C₃₋₁₂cicloalquilo, arilo, C₁₋₆alquilarilo o cuando se toma con R², y el nitrógeno al cual están unidos, forma un anillo que contiene nitrógeno, en donde el heterocicloalquilo, C₃₋₁₂cicloalquilo, arilo, C₁₋₆alquilarilo o anillo que contiene nitrógeno está sustituido o no sustituido con 1 a 5 sustituyentes seleccionados independientemente del grupo que consiste en halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquiloOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, oxo, COOC₁₋₆alquilo, C₁₋₆alquilCOOC₁₋₆alquilo, C₃₋₆cicloalquilo, C₁₋₆alquilC₃₋₆cicloalquilo, arilo, C₁₋₆alquilo, C₁₋₆alquilOhaloC₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) y C₁₋₆-alquilN(R⁷)(R⁸); R² es hidrógeno, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo o C₁₋₆alquilOH o cuando se toma con R¹, y el nitrógeno al cual están unidos, forma un anillo que contiene nitrógeno, en donde el anillo que contiene nitrógeno está sustituido o no sustituido con 1 a 5 sustituyentes seleccionados independientemente del grupo que consiste en halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, oxo, COOC₁₋₆alquilo, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) y C₁₋₆alquilN(R⁷)(R⁸); R³ es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸), C₁₋₆alquilN(R⁷)(R⁸), C₁₋₆alquil(OCH₂CH₂)ₙN(R⁷)(R⁸) o C₁₋₆alquilOhaloC₁₋₆alquil o cuando se toma con R⁴ forma un C₃₋₆cicloalquilo o C₃₋₆heterocicloalquilo; R⁴ es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸), C₁₋₆alquilN(R⁷)(R⁸), C₁₋₆alquil(OCH₂CH₂)ₙN(R⁷)(R⁸) o C₁₋₆alquilOhaloC₁₋₆alquil o cuando se toma con R³ forma un C₃₋₆cicloalquilo o C₃₋₆heterocicloalquilo; R⁵ es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquiloOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) o C₁₋₆alquilN(R⁷)(R⁸) o cuando se toma con R⁶ forma un C₃₋₆cicloalquilo o C₃₋₆heterocicloalquilo; R⁶ es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) o C₁₋₆alquilN(R⁷)(R⁸) o cuando se toma con R⁵ forma un C₃₋₆cicloalquilo o C₃₋₆heterocicloalquilo; R⁷ es hidrógeno, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, COC₁₋₆alquilo o COOC₁₋₆alquilo; R⁸ es hidrógeno, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, COC₁₋₆alquilo o COOC₁₋₆alquilo; R⁹ es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) o C₁₋₆alquilN(R⁷)(R⁸); R¹⁰ es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) o C₁₋₆alquilN(R⁷)(R⁸); R¹¹ es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalqquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) o C₁₋₆alquilN(R⁷)(R⁸); R¹² es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) o C₁₋₆alquilN(R⁷)(R⁸); R¹³ es hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) o C₁₋₆alquilN(R⁷)(R⁸); cada caso de R¹⁴ se selecciona independientemente del grupo que consiste en hidrógeno, halógeno, CN, OH, C₁₋₆alcoxi, C₁₋₆alquilOC₁₋₆alquilo, C₁₋₆alquilCOOH, COOH, C₃₋₆cicloalquilo, C₁₋₆alquilo, haloC₁₋₆alquilo, C₁₋₆alquilOH, CON(R⁷)(R⁸), N(R⁷)(R⁸) y C₁₋₆alquil(R⁷)(R⁸); n es 1, 2, 3 ó 4; y m es 0, 1 ó 2.
ARP200102325A 2019-08-15 2020-08-14 Agentes antipalúdicos AR119784A1 (es)

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WO2023102747A1 (en) * 2021-12-07 2023-06-15 Merck Sharp & Dohme Llc Antimalarial agents
WO2022066545A1 (en) * 2020-09-23 2022-03-31 Merck Sharp & Dohme Corp. Methods of chemovaccination against plasmodium infections
WO2022169790A1 (en) * 2021-02-05 2022-08-11 Merck Sharp & Dohme Llc Chemovaccination against plasmodium infection with selective plasmepsin x inhibitors
WO2024254795A1 (en) * 2023-06-14 2024-12-19 Merck Sharp & Dohme Llc Antimalaria agents

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