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ES2525007T3 - Nucleósidos ciclopropílicos de uracilo - Google Patents

Nucleósidos ciclopropílicos de uracilo Download PDF

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Publication number
ES2525007T3
ES2525007T3 ES09764845.5T ES09764845T ES2525007T3 ES 2525007 T3 ES2525007 T3 ES 2525007T3 ES 09764845 T ES09764845 T ES 09764845T ES 2525007 T3 ES2525007 T3 ES 2525007T3
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ES
Spain
Prior art keywords
alkyl
formula
amino
hydrogen
benzyl
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Active
Application number
ES09764845.5T
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English (en)
Inventor
Tim Hugo Maria Jonckers
Pierre Jean-Marie Bernard Raboisson
Steven Maurice Paula Van Hoof
Leen Anna Maria Vandekerckhove
Koen Vandyck
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medivir AB
Janssen Products LP
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Medivir AB
Janssen Products LP
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
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Publication of ES2525007T3 publication Critical patent/ES2525007T3/es
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06Pyrimidine radicals
    • C07H19/10Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • 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
    • 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
    • A61P31/16Antivirals for RNA viruses for influenza or rhinoviruses
    • 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
    • A61P31/18Antivirals for RNA viruses for HIV
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Virology (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Pulmonology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Un compuesto de fórmula I:**Fórmula** incluyendo cualesquiera estereoisómeros posibles del mismo, en el que: R1 es hidrógeno o halo; R4 es un éster de monofosfato, difosfato o trifosfato; o R4 es un grupo de fórmula**Fórmula** R7 es fenilo, opcionalmente sustituido con 1, 2 o con 3 sustituyentes, cada uno seleccionado independientemente de halo, alquilo de C1-C6, alquenilo de C3-C6, alcoxi de C1-C6, alcoxicarbonilo de C1-C6, hidroxi y amino; o R7 es naftilo; o R7 es indolilo, o N-alquil C1-C6-oxi-carbonilindolilo; R8 es hidrógeno, alquilo de C1-C6, bencilo; R8' es hidrógeno, alquilo de C1-C6, bencilo; o R8 y R8', junto con el átomo de carbono al que están unidos, forman cicloalquilo de C3-C7; R9 es alquilo de C1-C10, cicloalquilo de C3-C7, alquenilo de bencilo, o fenilo, fenilo el cual puede estar opcionalmente sustituido con 1, 2 ó 3 sustituyentes, cada uno seleccionado independientemente de hidroxi, alcoxi de C1-C6, amino, mono- y di-alquil C1-C6-amino; o su sal farmacéuticamente aceptable o solvato.

Description

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E09764845
27-11-2014
Número de compuesto
EC50 (M) replicón CC50 (M) (Huh-7) EC50 VIH (M) CC50 (M) (MT-4)
4
23,9 >98 >98 >98
9,2
>98 >90 >98
6
16,5 >98 >90 >98
7
6,1 >90 >90 >64
7a
10,9 58,4 >60 >50
7b
3,4 >98 >98 >90
8
5,9 >98 >98 >98
9
2,9 >98 >85 >98
2,8
>32 >60 29
11
2,8 >98 >98 >98
12
3,1 >98 >98 >98
13
3,2 >98 >98 >98
14
3,3 >98 >98 >98
3,6
>98 >60 >60
16
4,2 >32 >98 >32
17
4,4 >98 >98 >98
18
5,1 >98 >98 >64
19
7,2 >32 >32 >32
7,6
>32 >98 >98
21
7,8 >98 >98 >80
22
9,2 >32 1,65 2,1
23
11,2 >32 >98 >30
24
12,4 >98 >98 >98
23,1
>32 >98 23
26
73,7 >98 >98 >98
27
91,4 >98 >98 >98
28
>98 >98 >98 >98
29
>98 >98 >98 >98
>98
>98
>98
>98
31
>98 >98 >95 >98
32
>98 >98 >98 >98
33
>98 >98 >98 >98
34
11,0 >98 - -
“-” significa que el resultado del ensayo no está disponible
26

Claims (1)

  1. imagen1
    imagen2
ES09764845.5T 2008-12-08 2009-12-08 Nucleósidos ciclopropílicos de uracilo Active ES2525007T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP08171006 2008-12-08
EP08171006 2008-12-08
PCT/EP2009/066562 WO2010066699A1 (en) 2008-12-08 2009-12-08 Uracyl cyclopropyl nucleotides

Publications (1)

Publication Number Publication Date
ES2525007T3 true ES2525007T3 (es) 2014-12-17

Family

ID=40852521

Family Applications (1)

Application Number Title Priority Date Filing Date
ES09764845.5T Active ES2525007T3 (es) 2008-12-08 2009-12-08 Nucleósidos ciclopropílicos de uracilo

Country Status (21)

Country Link
US (1) US8399429B2 (es)
EP (1) EP2373671B1 (es)
JP (1) JP5683480B2 (es)
KR (1) KR20110104000A (es)
CN (1) CN102256991B (es)
AP (1) AP2011005717A0 (es)
AR (1) AR074504A1 (es)
AU (1) AU2009326125B2 (es)
BR (1) BRPI0922681A2 (es)
CA (1) CA2745523C (es)
CL (1) CL2011001364A1 (es)
EA (1) EA020244B1 (es)
ES (1) ES2525007T3 (es)
IL (1) IL212897A (es)
MX (1) MX2011006023A (es)
PA (1) PA8852101A1 (es)
SG (1) SG171973A1 (es)
TW (1) TW201036989A (es)
UY (1) UY32308A (es)
WO (1) WO2010066699A1 (es)
ZA (1) ZA201104231B (es)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JO3027B1 (ar) * 2009-05-14 2016-09-05 Janssen Products Lp نيوكليوسيدات يوراسيل سبيرواوكسيتان
US9676797B2 (en) 2015-09-02 2017-06-13 Abbvie Inc. Anti-viral compounds
MX2014014323A (es) 2012-05-25 2015-02-12 Janssen R & D Ireland Nucleosidos de espirooxetano de uracilo.
CN104903339A (zh) * 2012-11-16 2015-09-09 卡迪夫大学学院顾问有限公司 用于制备核苷前体药物的方法
MX374244B (es) 2013-03-08 2025-03-05 Nanjing Sanhome Pharmaceutical Co Ltd Compuesto de fosforamidato de nucleosido novedoso y su uso.
CN103848876B (zh) * 2013-03-25 2016-05-11 安徽贝克联合制药有限公司 一种核苷磷酰胺前药及其制备方法和其应用
CN105705511A (zh) 2013-04-12 2016-06-22 艾其林医药公司 用于治疗hcv的氘化核苷前药
CN105348342B (zh) * 2014-09-30 2018-09-21 南京正大天晴制药有限公司 核苷氨基磷酸酯化合物及药物组合物和用途
WO2016073756A1 (en) * 2014-11-06 2016-05-12 Enanta Pharmaceuticals, Inc. Deuterated nucleoside/tide derivatives
CN105801646B (zh) * 2014-12-31 2019-08-16 浙江大德药业集团有限公司 炔基取代的核苷氨基磷酸酯
WO2016134053A1 (en) * 2015-02-18 2016-08-25 Abbvie Inc. Anti-viral compounds
MY190867A (en) 2015-03-06 2022-05-13 Atea Pharmaceuticals Inc ? -d-2'-deoxy-2'-?-fluoro-2'- ? -c-substituted-2-modified-n6-substituted purine nucleotides for hcv treatment
US10711029B2 (en) 2016-07-14 2020-07-14 Atea Pharmaceuticals, Inc. Beta-d-2′-deoxy-2′-alpha-fluoro-2′-beta-c-substituted-4′fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection
PL3512863T3 (pl) 2016-09-07 2022-04-04 Atea Pharmaceuticals, Inc. 2'-Podstawione-N6-podstawione nukleotydy purynowe do leczenia zakażeń wirusem RNA
IL295609B2 (en) 2017-02-01 2023-11-01 Atea Pharmaceuticals Inc Nucleotide hemisulfate salt for the treatment of hepatitis C virus
CN112351799A (zh) 2018-04-10 2021-02-09 阿堤亚制药公司 具有硬化的hcv感染患者的治疗
US10874687B1 (en) 2020-02-27 2020-12-29 Atea Pharmaceuticals, Inc. Highly active compounds against COVID-19
BR112023026356A2 (pt) 2021-06-17 2024-03-05 Atea Pharmaceuticals Inc Método para tratar vírus da hepatite c ou uma condição resultante de uma infecção por hepatite c, combinação, uso da combinação, composição farmacêutica, e, kit para o tratamento de vírus da hepatite c

Family Cites Families (8)

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US4916122A (en) * 1987-01-28 1990-04-10 University Of Georgia Research Foundation, Inc. 3'-Azido-2',3'-dideoxyuridine anti-retroviral composition
EP1302468B1 (en) 1992-12-29 2008-12-17 Abbott Laboratories Processes and intermediates for manufacturing retroviral protease inhibiting compounds
US20010021509A1 (en) * 1997-10-23 2001-09-13 Sathe Ganesh Madhusudan cDNA clone HNEAA81 that encodes a human 7-transmembrane receptor
TW200500375A (en) * 2002-06-28 2005-01-01 Idenix Cayman Ltd Modified 2' and 3'-nucleoside prodrugs for treating flaviviridae
PL219609B1 (pl) * 2003-02-19 2015-06-30 Masanori Baba Analogi nukleozydów przeciwwirusowych, zawierająca je kompozycja farmaceutyczna i ich zastosowania
AU2004233898B2 (en) * 2003-04-25 2010-12-23 Gilead Sciences, Inc. Antiviral phosphonate analogs
AU2006222563A1 (en) * 2005-03-08 2006-09-14 Biota Scientific Management Pty Ltd. Bicyclic nucleosides and nucleotides as therapeutic agents
EP2084175B1 (en) 2006-10-10 2010-12-29 Medivir AB Hcv nucleoside inhibitor

Also Published As

Publication number Publication date
EP2373671B1 (en) 2014-09-10
SG171973A1 (en) 2011-07-28
CA2745523C (en) 2017-07-04
US8399429B2 (en) 2013-03-19
AU2009326125B2 (en) 2015-03-12
PA8852101A1 (es) 2010-07-27
AR074504A1 (es) 2011-01-19
CN102256991B (zh) 2015-08-12
CN102256991A (zh) 2011-11-23
US20110230436A1 (en) 2011-09-22
EA201170780A1 (ru) 2011-12-30
IL212897A0 (en) 2011-07-31
ZA201104231B (en) 2012-11-28
WO2010066699A1 (en) 2010-06-17
BRPI0922681A2 (pt) 2016-01-05
KR20110104000A (ko) 2011-09-21
AP2011005717A0 (en) 2011-06-30
JP5683480B2 (ja) 2015-03-11
JP2012510980A (ja) 2012-05-17
MX2011006023A (es) 2011-06-28
TW201036989A (en) 2010-10-16
IL212897A (en) 2013-12-31
CL2011001364A1 (es) 2011-09-23
AU2009326125A1 (en) 2010-06-17
EA020244B1 (ru) 2014-09-30
EP2373671A1 (en) 2011-10-12
UY32308A (es) 2010-06-30
CA2745523A1 (en) 2010-06-17

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