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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Spain
Prior art keywords
alkyl
formula
amino
hydrogen
benzyl
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Active
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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
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Publication of ES2525007T3 publication Critical patent/ES2525007T3/es
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds 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
    • A61K31/7064—Compounds 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
    • A61K31/7068—Compounds 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
    • A61K31/7072—Compounds 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs 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)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • AIDS & HIV (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pulmonology (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

imagen1
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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
SG11201407336PA (en) 2012-05-25 2015-03-30 Janssen Sciences Ireland Uc Uracyl spirooxetane nucleosides
PT3235824T (pt) * 2012-11-16 2019-05-30 NuCana plc Mistura de rp/sp gencitabina-[fenil-(benziloxi-l-alaninil)]-fosfato
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
JP2016522172A (ja) 2013-04-12 2016-07-28 アキリオン ファーマシューティカルズ，インコーポレーテッド Ｈｃｖを治療するのに有用な重水素化されたヌクレオシドプロドラッグ
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
US9718851B2 (en) * 2014-11-06 2017-08-01 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
AU2016229966B2 (en) 2015-03-06 2018-09-27 Atea Pharmaceuticals, Inc. Beta-D-2'-deoxy-2'alpha-fluoro-2'-beta-C-substituted-2-modified-N6-substituted purine nucleotides for HCV treatment
CA2997170A1 (en) 2015-09-02 2017-03-09 Abbvie Inc. Anti-viral tetrahydrofurane derivatives
WO2018013937A1 (en) 2016-07-14 2018-01-18 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
ES2907874T3 (es) 2016-09-07 2022-04-26 Atea Pharmaceuticals Inc Nucleótidos de purina 2'-sustituidos-N6-sustituidos para el tratamiento de virus de ARN
JP7066728B2 (ja) 2017-02-01 2022-05-13 アテア ファーマシューティカルズ， インコーポレイテッド Ｃ型肝炎ウイルスの治療のためのヌクレオチドヘミ硫酸塩
WO2019200005A1 (en) 2018-04-10 2019-10-17 Atea Pharmaceuticals, Inc. Treatment of hcv infected patients with cirrhosis
US10874687B1 (en) 2020-02-27 2020-12-29 Atea Pharmaceuticals, Inc. Highly active compounds against COVID-19
JP2024525164A (ja) 2021-06-17 2024-07-10 アテア ファーマシューティカルズ， インコーポレイテッド 有利な抗ｈｃｖ併用療法

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
EP0674513B1 (en) 1992-12-29 1996-09-25 Abbott Laboratories 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
MY140819A (en) * 2002-06-28 2010-01-29 Idenix Caymans Ltd Modified 2' and 3'-nucleoside prodrugs for treating flaviviridae
CN1777432B (zh) * 2003-02-19 2011-06-08 耶鲁大学 用于hiv感染的抗病毒核苷类似物
US7429565B2 (en) * 2003-04-25 2008-09-30 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
MX2009003452A (es) 2006-10-10 2009-04-14 Medivir Ab Inhibidores nucleosidicos del vhc.

Also Published As

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

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