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
Prior art date
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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
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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)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (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

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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
HUE029038T2 (en) 2012-05-25 2017-01-30 Janssen Sciences Ireland Uc Uracil spirooxetan nucleosides
HUE044605T2 (hu) * 2012-11-16 2019-11-28 Univ College Cardiff Consultants Ltd RP/SP gemcitabin-[fenil-(benziloxi-L-alaninil)]-foszfát keveréke
EP2940031B1 (en) 2013-03-08 2017-09-27 Nanjing Sanhome Pharmaceutical Co., Ltd. Nucleoside phosphoramidate compounds for use in the treatment of hcv
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
BR112015025766A2 (pt) 2013-04-12 2017-10-17 Achillion Pharmaceuticals Inc derivado de nucleosídeo altamente ativo para o tratamento de hcv
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
GEP20217282B (en) 2015-03-06 2021-08-10 Atea Pharmaceuticals Inc β-D-2'-DEOXY-2'α-FLUORO-2'-β-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT
MX2018002707A (es) 2015-09-02 2018-08-01 Abbvie Inc Derivados de tetrahidrofurano antivirales.
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
PT3512863T (pt) 2016-09-07 2022-03-09 Atea Pharmaceuticals Inc Nucleótidos de purina 2'-substituídos-n6-substituídos para tratamento de vírus de rna
CN110248951B (zh) 2017-02-01 2022-10-28 阿堤亚制药公司 用于治疗丙型肝炎病毒的核苷酸半硫酸盐
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
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4916122A (en) * 1987-01-28 1990-04-10 University Of Georgia Research Foundation, Inc. 3'-Azido-2',3'-dideoxyuridine anti-retroviral composition
DE69305093T2 (de) 1992-12-29 1997-04-17 Abbott Lab Inhibitoren der retroviralen protease
US20010021509A1 (en) * 1997-10-23 2001-09-13 Sathe Ganesh Madhusudan cDNA clone HNEAA81 that encodes a human 7-transmembrane receptor
PT1523489E (pt) * 2002-06-28 2014-06-24 Centre Nat Rech Scient Profármacos de nucleósido modificado em 2' e 3' para tratamento de infecções por flaviridae
BRPI0407374A (pt) * 2003-02-19 2006-01-10 Univ Yale Análogos de nucleosìdeo antiviral e métodos para tratar infecções virais, especialmente infecções de hiv
PL1628685T3 (pl) * 2003-04-25 2011-05-31 Gilead Sciences Inc Przeciwwirusowe analogi fosfonianowe
EP1858889A1 (en) * 2005-03-08 2007-11-28 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
JP5683480B2 (ja) 2015-03-11
IL212897A0 (en) 2011-07-31
EP2373671A1 (en) 2011-10-12
PA8852101A1 (es) 2010-07-27
TW201036989A (en) 2010-10-16
US20110230436A1 (en) 2011-09-22
JP2012510980A (ja) 2012-05-17
KR20110104000A (ko) 2011-09-21
CN102256991B (zh) 2015-08-12
AU2009326125B2 (en) 2015-03-12
SG171973A1 (en) 2011-07-28
BRPI0922681A2 (pt) 2016-01-05
CA2745523C (en) 2017-07-04
EP2373671B1 (en) 2014-09-10
CA2745523A1 (en) 2010-06-17
AP2011005717A0 (en) 2011-06-30
CN102256991A (zh) 2011-11-23
WO2010066699A1 (en) 2010-06-17
UY32308A (es) 2010-06-30
EA020244B1 (ru) 2014-09-30
MX2011006023A (es) 2011-06-28
US8399429B2 (en) 2013-03-19
ZA201104231B (en) 2012-11-28
CL2011001364A1 (es) 2011-09-23
IL212897A (en) 2013-12-31
AU2009326125A1 (en) 2010-06-17
AR074504A1 (es) 2011-01-19
EA201170780A1 (ru) 2011-12-30

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