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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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
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Medivir AB
Janssen Products LP
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Medivir AB
Janssen Products LP
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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)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Bioinformatics & Cheminformatics (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
US9676797B2 (en) 2015-09-02 2017-06-13 Abbvie Inc. Anti-viral compounds
PL2861611T3 (pl) 2012-05-25 2017-08-31 Janssen Sciences Ireland Uc Nukleozydy uracylowe spirooksetanu
JP2016506371A (ja) * 2012-11-16 2016-03-03 ユニバーシティ カレッジ カーディフ コンサルタンツ リミテッド ヌクレオシドプロドラッグを調製する方法
RU2621709C2 (ru) * 2013-03-08 2017-06-07 Наньцзин Саньхоме Фармасьютикал Ко., Лтд. Новое фосфорамидатное производное нуклеозида и его применение
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
RU2015148006A (ru) 2013-04-12 2017-05-18 Ачиллион Фармасютикалз, Инк. Дейтерированные нуклеозидные пролекарства, применимые для лечения 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
CA3182565A1 (en) 2015-03-06 2016-09-15 Atea Pharmaceuticals, Inc. .beta.-d-2'-deoxy-2'-.alpha.-fluoro-2'-.beta.-c-substituted-2-modified-n6-substituted purine nucleotides for hcv treatment
LU100724B1 (en) 2016-07-14 2018-07-31 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
EP3865136A1 (en) 2016-09-07 2021-08-18 ATEA Pharmaceuticals, Inc. 2'-substituted-n6-substituted purine nucleotides for corona virus treatment
FI3577124T3 (fi) 2017-02-01 2025-02-13 Atea Pharmaceuticals Inc Nukleotidihemisulfaattisuola hepatiitti C -viruksen hoitoon
KR20200140865A (ko) 2018-04-10 2020-12-16 아테아 파마슈티컬즈, 인크. 간경변증을 갖는 hcv 감염 환자의 치료
US10874687B1 (en) 2020-02-27 2020-12-29 Atea Pharmaceuticals, Inc. Highly active compounds against COVID-19
MX2023014898A (es) 2021-06-17 2024-04-29 Atea Pharmaceuticals Inc Terapia combinada anti-vhc ventajosa.

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
KR100187613B1 (ko) 1992-12-29 1999-06-01 스티븐 에프. 웨인스톡 레트로바이러스성 프로테이제 억제 화합물, 이의 제조방법 및 이를 함유하는 약제학적 조성물
US20010021509A1 (en) * 1997-10-23 2001-09-13 Sathe Ganesh Madhusudan cDNA clone HNEAA81 that encodes a human 7-transmembrane receptor
RS114004A (sr) * 2002-06-28 2007-02-05 Idenix (Cayman) Limited, Modifikovani 2'i 3'-nukleozid prolekovi za lečenje flaviridae infekcija
US7589078B2 (en) * 2003-02-19 2009-09-15 Yale University Anti-viral nucleoside analogs and methods for treating viral infections, especially HIV infections
DK1628685T3 (da) * 2003-04-25 2011-03-21 Gilead Sciences Inc Antivirale phosphonatanaloge
JP2008532950A (ja) * 2005-03-08 2008-08-21 バイオタ サイエンティフィック マネージメント ピーティーワイ リミテッド 治療薬としての二環式ヌクレオシドおよび二環式ヌクレオチド
WO2008043704A1 (en) 2006-10-10 2008-04-17 Medivir Ab Hcv nucleoside inhibitor

Also Published As

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

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