PE20221579A1 - Derivados de indol mono o disustituidos como inhibidores de la replicacion viral del dengue - Google Patents

Derivados de indol mono o disustituidos como inhibidores de la replicacion viral del dengue

Info

Publication number
PE20221579A1
PE20221579A1 PE2021001440A PE2021001440A PE20221579A1 PE 20221579 A1 PE20221579 A1 PE 20221579A1 PE 2021001440 A PE2021001440 A PE 2021001440A PE 2021001440 A PE2021001440 A PE 2021001440A PE 20221579 A1 PE20221579 A1 PE 20221579A1
Authority
PE
Peru
Prior art keywords
general formula
compounds
reagent
synthesis
dengue
Prior art date
Application number
PE2021001440A
Other languages
English (en)
Inventor
Bart Rudolf Romanie Kesteleyn
Jean-François Bonfanti
Tim Hugo Maria Jonckers
Pierre Jean-Marie Bernard Raboisson
Dorothee Alice Marie-Eve Bardiot
Arnaud Didier M Marchand
Original Assignee
Janssen Pharmaceuticals Inc
Univ Leuven Kath
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 Janssen Pharmaceuticals Inc, Univ Leuven Kath filed Critical Janssen Pharmaceuticals Inc
Publication of PE20221579A1 publication Critical patent/PE20221579A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • 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
    • A61K31/40Heterocyclic 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
    • A61K31/403Heterocyclic 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
    • A61K31/404Indoles, e.g. pindolol
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • 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
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12Radicals substituted by oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/08Bridged 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)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La presente invencion se refiere a metodos para la sintesis del compuesto de formula I o una forma estereoisomerica, una sal, solvato o polimorfo farmaceuticamente aceptable del mismo, donde R1 es H, F, CH3, CF3 u OCF3; R2 es F, OCH3, H; y R3 es H o CH3. El metodo de sintesis comprende las siguientes etapas: a) conversion del acido 2-(4-cloro-2-metoxifenil)acetico (II) en el correspondiente cloruro de 2-(4-cloro-2-metoxifenil)acetilo (III) con un reactivo de cloracion; b) reaccion de Friedel-Crafts del indol sustituido de formula general (IV) con un cloruro de acido (III) realizada utilizando un reactivo de acido de Lewis en un disolvente y en condiciones de reaccion adecuadas, para proporcionar el indol 3-acilado de formula general (V); c) bromacion de (V) con un reactivo en un disolvente adecuado, para proporcionar compuestos de formula general (VI); d) reaccion de los compuestos de formula general (VI) con 3-metoxi-5- (metilsulfonil)-anilina (VII) en un disolvente adecuado y usando una base para proporcionar los compuestos de formula general I como mezclas racemicas; e) separacion quiral de los compuestos de formula general I para proporcionar los enantiomeros A y B de formula general I. Tambien se refiere a metodos de sintesis de sus compuestos intermedios IV y V.
PE2021001440A 2015-05-08 2016-05-04 Derivados de indol mono o disustituidos como inhibidores de la replicacion viral del dengue PE20221579A1 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP15166900 2015-05-08
EP16163342 2016-03-31
PCT/EP2016/059975 WO2016180696A1 (en) 2015-05-08 2016-05-04 Mono- or di-substituted indole derivatives as dengue viral replication inhibitors

Publications (1)

Publication Number Publication Date
PE20221579A1 true PE20221579A1 (es) 2022-10-06

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Family Applications (2)

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PE2017002377A PE20180232A1 (es) 2015-05-08 2016-05-04 Derivados de indol mono o disustituidos como inhibidores de la replicacion viral del dengue
PE2021001440A PE20221579A1 (es) 2015-05-08 2016-05-04 Derivados de indol mono o disustituidos como inhibidores de la replicacion viral del dengue

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US (3) US10696632B2 (es)
EP (2) EP3294738B1 (es)
JP (4) JP6752821B2 (es)
KR (2) KR102610493B1 (es)
CN (3) CN113045476A (es)
AU (2) AU2016259677B2 (es)
BR (1) BR112017023904A2 (es)
CA (1) CA2981845C (es)
CL (1) CL2017002817A1 (es)
CO (1) CO2017012381A2 (es)
CR (2) CR20200152A (es)
CY (1) CY1124548T1 (es)
DK (1) DK3294738T3 (es)
EA (1) EA034978B1 (es)
EC (2) ECSP17073878A (es)
ES (2) ES2877404T3 (es)
GT (1) GT201700234A (es)
HK (2) HK1252446A1 (es)
HR (1) HRP20210675T1 (es)
HU (1) HUE054724T2 (es)
IL (2) IL255430B (es)
JO (2) JOP20160086B1 (es)
LT (1) LT3294738T (es)
MD (1) MD3294738T2 (es)
MX (2) MX2017014293A (es)
NI (1) NI201700137A (es)
PE (2) PE20180232A1 (es)
PH (1) PH12017502000B1 (es)
PL (1) PL3294738T3 (es)
RS (1) RS62029B1 (es)
SG (1) SG10201900315SA (es)
SI (1) SI3294738T1 (es)
SV (1) SV2017005557A (es)
TW (2) TWI744963B (es)
UA (1) UA121332C2 (es)
UY (2) UY36674A (es)
WO (1) WO2016180696A1 (es)
ZA (1) ZA202002435B (es)

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ECSP22023220A (es) 2022-05-31
CR20200152A (es) 2020-09-08
HRP20210675T1 (hr) 2021-06-25
KR102610493B1 (ko) 2023-12-05
SG10201900315SA (en) 2019-02-27
US20210171462A1 (en) 2021-06-10
AU2016259677A1 (en) 2017-10-26
CN107873022B (zh) 2021-03-12
ZA202002435B (en) 2023-03-29
UY39706A (es) 2022-05-31
SI3294738T1 (sl) 2021-08-31
IL272814B (en) 2021-02-28
GT201700234A (es) 2018-11-26
CN111303000A (zh) 2020-06-19
KR102610491B1 (ko) 2023-12-06
EA201792429A1 (ru) 2018-02-28
BR112017023904A2 (pt) 2018-07-17
DK3294738T3 (da) 2021-06-28
AU2016259677B2 (en) 2020-10-01
JP2018515495A (ja) 2018-06-14
NI201700137A (es) 2019-05-07
JOP20210109A1 (ar) 2023-01-30
CL2017002817A1 (es) 2018-05-11
CA2981845C (en) 2022-03-08
KR20180002644A (ko) 2018-01-08
CN113045476A (zh) 2021-06-29
WO2016180696A1 (en) 2016-11-17
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PH12017502000A1 (en) 2018-03-26
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US20180346419A1 (en) 2018-12-06
IL255430B (en) 2020-03-31
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ES2941674T3 (es) 2023-05-24
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PE20180232A1 (es) 2018-01-31
LT3294738T (lt) 2021-08-25
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JP7132399B2 (ja) 2022-09-06
CA2981845A1 (en) 2016-11-17
UY36674A (es) 2016-11-30
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PH12017502000B1 (en) 2018-03-26
ECSP17073878A (es) 2018-02-28
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JP7451626B2 (ja) 2024-03-18
EP3294738A1 (en) 2018-03-21
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US10919854B2 (en) 2021-02-16
HK1252496A1 (zh) 2019-05-31
PL3294738T3 (pl) 2021-12-13
EA034978B1 (ru) 2020-04-14
CN107873022A (zh) 2018-04-03
IL272814A (en) 2020-04-30
US11827602B2 (en) 2023-11-28
MD3294738T2 (ro) 2021-08-31
CO2017012381A2 (es) 2018-03-28
JP2022166289A (ja) 2022-11-01
AU2020273314B2 (en) 2021-10-21
SV2017005557A (es) 2018-06-26
CN111303000B (zh) 2023-11-28
US20200270209A1 (en) 2020-08-27
CY1124548T1 (el) 2022-07-22
JP6898493B2 (ja) 2021-07-07
US10696632B2 (en) 2020-06-30
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JP6752821B2 (ja) 2020-09-09
TWI744963B (zh) 2021-11-01
JP2020125316A (ja) 2020-08-20
UA121332C2 (uk) 2020-05-12
RS62029B1 (sr) 2021-07-30

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