ME01478B - Uracil spirooksetanski nukleozidi - Google Patents

Uracil spirooksetanski nukleozidi

Info

Publication number
ME01478B
ME01478B MEP-2013-47A MEP4713A ME01478B ME 01478 B ME01478 B ME 01478B ME P4713 A MEP4713 A ME P4713A ME 01478 B ME01478 B ME 01478B
Authority
ME
Montenegro
Prior art keywords
phenyl
substituted
alkyl
formula
phosphate
Prior art date
Application number
MEP-2013-47A
Other languages
English (en)
Inventor
Tim Hugo Maria Jonckers
Koen Vandyck
Hoof Steven Maurice Paula Van
Abdellah Tahri
Pierre Jean-Marie Bernard Raboisson
Lili Hu
Original Assignee
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
Application filed by Medivir Ab, Janssen Products Lp filed Critical Medivir Ab
Publication of ME01478B publication Critical patent/ME01478B/me

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Classifications

    • 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
    • C07H19/067—Pyrimidine radicals with ribosyl as the saccharide radical
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/503—Pyridazines; Hydrogenated pyridazines spiro-condensed
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings
    • 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
    • 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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

Jedinjenja   sa  formul om  (I)  uključujući sve njihove moguće  stereoi z omer e ,  gde : R 4   je  mono fosfat , di fosfat   ili  tri fosfat  ester;  ili  R 4   je  formula (II)  ili  formula (III),  R 7   je   ponekad   supstituisan i   fenil ,  ponekad   supstituisan i   naftil  ili  ponekad   supstituisan i  indol il ; R 8   i  R 8 ’   su vodonik , C 1 -C 6 alk il , benz il  ili   fenil ;  ili   R 8   i  R 8 ’  form iraju  C 3 -C 7 ciklo alk il ; R 9   je  C 1 -C 10 alk il , C 3 -C 7 ciklo alk il ,  fenil   ili   fenil -C 1 -C 6 alk il ,  gde   pomenuti  fenil ni   ostatak   u   fenil u ili  fenil -C 1 -C 6 alk il u je   ponekad   supstituisan ;  ili   njihova farmaceutski prihvatljiva so  solvat;  farmaceutske formulacije i upotreba  jedinjenja  I  kao  HCV inhibitor e .
MEP-2013-47A 2009-05-14 2010-05-11 Uracil spirooksetanski nukleozidi ME01478B (me)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP09160215 2009-05-14
EP10718207A EP2430035B1 (en) 2009-05-14 2010-05-11 Uracyl spirooxetane nucleosides
PCT/EP2010/056438 WO2010130726A1 (en) 2009-05-14 2010-05-11 Uracyl spirooxetane nucleosides

Publications (1)

Publication Number Publication Date
ME01478B true ME01478B (me) 2014-04-20

Family

ID=40823307

Family Applications (1)

Application Number Title Priority Date Filing Date
MEP-2013-47A ME01478B (me) 2009-05-14 2010-05-11 Uracil spirooksetanski nukleozidi

Country Status (39)

Country Link
US (2) US8481510B2 (me)
EP (2) EP2430035B1 (me)
JP (2) JP5778135B2 (me)
KR (1) KR101806837B1 (me)
CN (1) CN102439024B (me)
AP (1) AP2783A (me)
AR (1) AR076579A1 (me)
AU (1) AU2010247439B2 (me)
BR (1) BRPI1010579A2 (me)
CA (1) CA2760329C (me)
CL (1) CL2011002859A1 (me)
CO (1) CO6440533A2 (me)
CR (1) CR20120297A (me)
CY (2) CY1114081T1 (me)
DK (2) DK2511282T3 (me)
EA (1) EA022084B1 (me)
EC (1) ECSP11011461A (me)
ES (2) ES2477598T3 (me)
HK (1) HK1166326A1 (me)
HN (1) HN2011003014A (me)
HR (2) HRP20130554T1 (me)
IL (1) IL215955A (me)
JO (1) JO3027B1 (me)
ME (1) ME01478B (me)
MX (1) MX2011012027A (me)
MY (1) MY157018A (me)
NI (1) NI201100197A (me)
NZ (1) NZ596073A (me)
PL (2) PL2430035T3 (me)
PT (2) PT2511282E (me)
RS (1) RS52822B (me)
SG (1) SG175981A1 (me)
SI (2) SI2430035T1 (me)
SM (2) SMT201300078B (me)
TW (1) TWI461432B (me)
UA (1) UA105790C2 (me)
UY (1) UY32642A (me)
WO (1) WO2010130726A1 (me)
ZA (1) ZA201108309B (me)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8173621B2 (en) 2008-06-11 2012-05-08 Gilead Pharmasset Llc Nucleoside cyclicphosphates
KR20110104074A (ko) 2008-12-23 2011-09-21 파마셋 인코포레이티드 퓨린 뉴클레오시드의 합성
JO3027B1 (ar) 2009-05-14 2016-09-05 Janssen Products Lp نيوكليوسيدات يوراسيل سبيرواوكسيتان
WO2012062869A1 (en) * 2010-11-10 2012-05-18 Janssen Products, Lp Uracyl spirooxetane nucleoside phosphoramidates
PT2638054E (pt) 2010-11-10 2015-03-02 Medivir Ab Fosforamidatos de nucleósidos de uracilo espirooxetano
WO2012075140A1 (en) * 2010-11-30 2012-06-07 Pharmasset, Inc. Compounds
AU2015252113B2 (en) * 2010-11-30 2017-05-04 Gilead Pharmasset Llc Compounds
US8877733B2 (en) * 2011-04-13 2014-11-04 Gilead Sciences, Inc. 1′-substituted pyrimidine N-nucleoside analogs for antiviral treatment
EP2794630A4 (en) * 2011-12-22 2015-04-01 Alios Biopharma Inc SUBSTITUTED PHOSPHORTHIOAT NUCLEOTIDE ANALOGUE
AR091156A1 (es) 2012-05-25 2015-01-14 Jansen R & D Ireland Nucleosidos de espirooxetano de uracilo
AU2014225052B2 (en) * 2013-03-08 2016-11-10 Nanjing Sanhome Pharmaceutical Co., Ltd. Novel nucleoside phosphoramidate compound and use thereof
BR112015025766A2 (pt) 2013-04-12 2017-10-17 Achillion Pharmaceuticals Inc derivado de nucleosídeo altamente ativo para o tratamento de hcv
CN104231023B (zh) * 2013-06-06 2019-02-05 南京汇诚制药有限公司 三环稠杂环类核苷氨基磷酸酯化合物、其制备方法及应用
US20170165287A1 (en) * 2013-11-28 2017-06-15 Janssen Sciences Ireland Uc Crystal form of a nucleoside inhibitor of hcv
KR102363946B1 (ko) 2015-03-06 2022-02-17 아테아 파마슈티컬즈, 인크. HCV 치료를 위한 β-D-2'-데옥시-2'-α-플루오로-2'-β-C-치환된-2-변형된-N6-치환된 퓨린 뉴클레오티드
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
EP4088725A1 (en) 2016-09-07 2022-11-16 ATEA Pharmaceuticals, Inc. 2'-substituted-n6-substituted purine nucleotides for the treatment of a virus from the picornaviridae family
UA127407C2 (uk) 2017-02-01 2023-08-16 Атеа Фармасеутікалс, Інк. Гемісульфатна сіль нуклеотиду для лікування спричиненого вірусом гепатиту с захворювання
JP2021521118A (ja) 2018-04-10 2021-08-26 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 肝硬変を伴うｈｃｖ感染患者の治療
US10874687B1 (en) 2020-02-27 2020-12-29 Atea Pharmaceuticals, Inc. Highly active compounds against COVID-19
EP4135716A1 (en) * 2020-04-14 2023-02-22 Janssen Pharmaceuticals, Inc. Spirocyclic nucleoside analogues for the treatment of hepatitis e

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUP0400726A3 (en) * 2001-01-22 2007-05-29 Merck & Co Inc Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
EP1773355B1 (en) * 2004-06-24 2014-06-25 Merck Sharp & Dohme Corp. Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection
WO2007020193A2 (en) * 2005-08-15 2007-02-22 F. Hoffmann-La Roche Ag Antiviral phosphoramidates of 4 ' -substituted pronucleotides
US7879815B2 (en) * 2006-02-14 2011-02-01 Merck Sharp & Dohme Corp. Nucleoside aryl phosphoramidates for the treatment of RNA-dependent RNA viral infection
PA8852101A1 (es) * 2008-12-08 2010-07-27 Medivir Ab Nucleótidos uracil ciclopropílicos
JO3027B1 (ar) 2009-05-14 2016-09-05 Janssen Products Lp نيوكليوسيدات يوراسيل سبيرواوكسيتان

Also Published As

Publication number Publication date
AP2011005958A0 (en) 2011-10-31
AP2783A (en) 2013-10-31
PT2430035E (pt) 2013-05-22
JP2012526764A (ja) 2012-11-01
DK2430035T3 (da) 2013-05-27
SMT201400085B (it) 2014-09-08
ECSP11011461A (es) 2012-02-29
JO3027B1 (ar) 2016-09-05
US8933052B2 (en) 2015-01-13
CN102439024A (zh) 2012-05-02
CA2760329C (en) 2017-10-31
IL215955A0 (en) 2012-01-31
JP5778135B2 (ja) 2015-09-16
UA105790C2 (uk) 2014-06-25
US8481510B2 (en) 2013-07-09
HRP20130554T1 (en) 2013-07-31
AU2010247439A1 (en) 2011-12-01
CA2760329A1 (en) 2010-11-18
AR076579A1 (es) 2011-06-22
KR101806837B1 (ko) 2017-12-08
RS52822B (en) 2013-10-31
HN2011003014A (es) 2014-06-30
NI201100197A (es) 2012-05-28
US20120065156A1 (en) 2012-03-15
UY32642A (es) 2010-11-30
KR20120018355A (ko) 2012-03-02
EP2430035A1 (en) 2012-03-21
MY157018A (en) 2016-04-15
SMT201300078B (it) 2013-09-06
MX2011012027A (es) 2012-02-28
WO2010130726A1 (en) 2010-11-18
ES2411086T3 (es) 2013-07-04
NZ596073A (en) 2013-02-22
TWI461432B (zh) 2014-11-21
CN102439024B (zh) 2014-09-17
CY1115383T1 (el) 2017-01-04
EA201171406A1 (ru) 2012-05-30
IL215955A (en) 2015-03-31
HRP20140605T1 (hr) 2014-09-26
JP2015180692A (ja) 2015-10-15
SG175981A1 (en) 2011-12-29
SI2511282T1 (sl) 2014-09-30
EA022084B1 (ru) 2015-10-30
EP2511282A1 (en) 2012-10-17
DK2511282T3 (da) 2014-07-07
US20130217648A1 (en) 2013-08-22
CO6440533A2 (es) 2012-05-15
ES2477598T3 (es) 2014-07-17
ZA201108309B (en) 2013-04-24
TW201100442A (en) 2011-01-01
BRPI1010579A2 (pt) 2016-03-15
PL2511282T3 (pl) 2014-09-30
PT2511282E (pt) 2014-07-11
PL2430035T3 (pl) 2013-08-30
AU2010247439B2 (en) 2014-09-25
EP2430035B1 (en) 2013-04-03
EP2511282B1 (en) 2014-04-02
CL2011002859A1 (es) 2012-07-20
HK1166326A1 (en) 2012-10-26
SI2430035T1 (sl) 2013-08-30
CY1114081T1 (el) 2016-07-27
CR20120297A (es) 2012-10-25

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