ES2542326T3 - Inhibidores de la replicación del VIH - Google Patents

Inhibidores de la replicación del VIH Download PDF

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Publication number
ES2542326T3
ES2542326T3 ES01929616.9T ES01929616T ES2542326T3 ES 2542326 T3 ES2542326 T3 ES 2542326T3 ES 01929616 T ES01929616 T ES 01929616T ES 2542326 T3 ES2542326 T3 ES 2542326T3
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ES
Spain
Prior art keywords
alkyl
formula
compound
cyano
amino
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
ES01929616.9T
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English (en)
Spanish (es)
Inventor
Michael Joseph Kukla
Donald W. Ludovici
Robert W. Kavash
Bart L. D. De Corte
Jan Heeres
Paul A. J. Janssen
Lucien M. H. Koymans
Marc René de Jonge
Koen J. A. Van Aken
Alain Krief
Ruben Gerardus George Leenders
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.)
Janssen Pharmaceutica NV
Original Assignee
Janssen Pharmaceutica NV
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 Janssen Pharmaceutica NV filed Critical Janssen Pharmaceutica NV
Application granted granted Critical
Publication of ES2542326T3 publication Critical patent/ES2542326T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
    • C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • C07D251/40—Nitrogen atoms
    • C07D251/48—Two nitrogen atoms
    • C07D251/50—Two nitrogen atoms with a halogen atom attached to the third ring carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • AIDS & HIV (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
ES01929616.9T 2000-05-08 2001-05-03 Inhibidores de la replicación del VIH Expired - Lifetime ES2542326T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US20247200P 2000-05-08 2000-05-08
US202472P 2000-05-08
PCT/EP2001/004991 WO2001085700A2 (en) 2000-05-08 2001-05-03 Hiv replication inhibiting pyrimidines and triazines

Publications (1)

Publication Number Publication Date
ES2542326T3 true ES2542326T3 (es) 2015-08-04

Family

ID=22750002

Family Applications (1)

Application Number Title Priority Date Filing Date
ES01929616.9T Expired - Lifetime ES2542326T3 (es) 2000-05-08 2001-05-03 Inhibidores de la replicación del VIH

Country Status (10)

Country Link
US (1) US7276510B2 (https=)
EP (1) EP1282606B1 (https=)
JP (1) JP5230050B2 (https=)
AR (1) AR028423A1 (https=)
AU (1) AU783981C (https=)
CA (1) CA2406562C (https=)
ES (1) ES2542326T3 (https=)
MY (1) MY139506A (https=)
PA (1) PA8516401A1 (https=)
WO (1) WO2001085700A2 (https=)

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003011836A1 (en) * 2001-08-01 2003-02-13 Merck & Co., Inc. Tyrosine kinase inhibitors
JO3429B1 (ar) 2001-08-13 2019-10-20 Janssen Pharmaceutica Nv مشتقات برميدينات مثبطة فيروس الايدز
US8101629B2 (en) 2001-08-13 2012-01-24 Janssen Pharmaceutica N.V. Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile
US7638522B2 (en) 2001-08-13 2009-12-29 Janssen Pharmaceutica N.V. Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile
US7115617B2 (en) 2001-08-22 2006-10-03 Amgen Inc. Amino-substituted pyrimidinyl derivatives and methods of use
US6939874B2 (en) 2001-08-22 2005-09-06 Amgen Inc. Substituted pyrimidinyl derivatives and methods of use
NZ533057A (en) 2001-10-26 2005-11-25 Angeletti P Ist Richerche Bio N-substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase
EP1441734B1 (en) 2001-10-26 2007-02-28 Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A. Dihydroxypyrimidine carboxamide inhibitors of hiv integrase
TWI329105B (en) 2002-02-01 2010-08-21 Rigel Pharmaceuticals Inc 2,4-pyrimidinediamine compounds and their uses
AR039540A1 (es) * 2002-05-13 2005-02-23 Tibotec Pharm Ltd Compuestos microbicidas con contenido de pirimidina o triazina
SE0201976D0 (sv) * 2002-06-24 2002-06-24 Astrazeneca Ab Novel compounds
GB0215844D0 (en) 2002-07-09 2002-08-14 Novartis Ag Organic compounds
ES2445208T3 (es) 2002-07-29 2014-02-28 Rigel Pharmaceuticals, Inc. Compuestos de 2,4-pirimidindiamina para uso en métodos para tratar o prevenir enfermedades autoinmunitarias
KR101140785B1 (ko) 2002-08-09 2012-05-03 얀센 파마슈티카 엔.브이. 4-〔〔4-〔〔4-（2-시아노에테닐）-2,6-디메틸페닐〕아미노〕-2-피리미디닐〕아미노〕벤조니트릴의 제조방법
AP2005003365A0 (en) 2003-02-07 2005-09-30 Janssen Pharmaceutica Nv Hiv inhibiting 1, 2, 4-triazines.
BRPI0407329A (pt) 2003-02-07 2006-01-10 Janssen Pharmaceutica Nv Derivados de pirimidina para a prevenção de infecção de hiv
CL2004000303A1 (es) 2003-02-20 2005-04-08 Tibotec Pharm Ltd Compuestos derivados de pirimidinas y triazinas; proceso de preparacion; composicion farmaceutica; y su uso para inhibir la replicacion del vih.
WO2004087679A1 (en) * 2003-04-01 2004-10-14 Aponetics Ag 2, 4, 6-trisubstituted pyrimidine derivatives useful for the treatment of neoplastic and autoimmune diseases
BRPI0413018B8 (pt) 2003-07-30 2021-05-25 Rigel Pharmaceuticals Inc composto, e, uso de um composto
EP1730163A4 (en) * 2004-03-17 2009-12-30 Panacos Pharmaceuticals Inc Pharmaceutical salts of 3-O- (3,3-dimethylsuccinyl) betulinic acid
ES2442857T3 (es) 2004-08-10 2014-02-13 Janssen Pharmaceutica Nv Derivados de 1,2,4-triazin-6-ona inhibidores de VIH
RU2405778C2 (ru) * 2004-09-30 2010-12-10 Тиботек Фармасьютикалз Лтд. 5-гетероциклилпиримидины, ингибирующие вич
ATE542802T1 (de) 2004-09-30 2012-02-15 Tibotec Pharm Ltd Hiv-inhibierende 5-substituierte pyrimidine
CN101031550B (zh) 2004-09-30 2015-05-27 泰博特克药品有限公司 抑制hiv的5-碳环-或杂环取代的嘧啶类
AU2005298637B8 (en) 2004-10-29 2012-12-06 Janssen Sciences Ireland Uc HIV inhibiting bicyclic pyrimidine derivatives
EP1814878B1 (en) 2004-11-24 2012-01-04 Rigel Pharmaceuticals, Inc. Spiro-2, 4-pyrimidinediamine compounds and their uses
EP1819323B2 (en) * 2004-12-03 2023-03-22 Merck Sharp & Dohme Corp. Pharmaceutical composition containing an anti-nucleating agent
DE602006010979D1 (de) 2005-01-19 2010-01-21 Rigel Pharmaceuticals Inc Prodrugs aus 2,4-pyrimidindiamin-verbindungen und ihre verwendungen
EP1868613B1 (en) * 2005-04-12 2012-03-07 Myrexis, Inc. Polymorphs of 3-o-(3',3'-dimethylsuccinyl) betulinic acid di-n-methyl-d-glucamine
WO2006133426A2 (en) 2005-06-08 2006-12-14 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US20070203161A1 (en) 2006-02-24 2007-08-30 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
MX2008012577A (es) * 2006-03-30 2008-10-10 Tibotec Pharm Ltd Pirimidinas sustituidas con 5-(hidroximetileno y aminometileno) que inhiben el virus de inmunodeficiencia humana.
WO2007113254A1 (en) 2006-03-30 2007-10-11 Tibotec Pharmaceuticals Ltd. Hiv inhibiting 5-amido substituted pyrimidines
EP2311807B1 (en) 2006-12-08 2015-11-11 Novartis AG Compounds and composition as protein kinase inhibitors
JP5185283B2 (ja) * 2006-12-29 2013-04-17 テイボテク・フアーマシユーチカルズ Ｈｉｖ阻害６−置換ピリミジン
EP2114902B1 (en) * 2006-12-29 2014-09-17 Janssen R&D Ireland Hiv inhibiting 5,6-substituted pyrimidines
BRPI0810411B8 (pt) 2007-04-18 2021-05-25 Pfizer Prod Inc derivados de sulfonil amida para o tratamento de crescimento celular anormal, seu sos, bem como composição farmacêutica
US8138339B2 (en) 2008-04-16 2012-03-20 Portola Pharmaceuticals, Inc. Inhibitors of protein kinases
MX2010011463A (es) 2008-04-16 2011-06-03 Portola Pharm Inc 2,6-diamino-pirimidin-5-il-carboxamidas como inhibidores de syk o jak quinasas.
PT2300013T (pt) 2008-05-21 2017-10-31 Ariad Pharma Inc Derivados de fósforo como inibidores de cinases
US9273077B2 (en) 2008-05-21 2016-03-01 Ariad Pharmaceuticals, Inc. Phosphorus derivatives as kinase inhibitors
US8153790B2 (en) * 2009-07-27 2012-04-10 Krizmanic Irena Process for the preparation and purification of etravirine and intermediates thereof
GR1007010B (el) 2009-10-08 2010-10-07 Χημικα Και Βιοφαρμακευτικα Εργαστηρια Πατρων Αε (Cbl-Patras), Ινσουλινοειδη πεπτιδια
PT2576541T (pt) 2010-06-04 2016-07-08 Hoffmann La Roche Derivados de aminopirimidina como moduladores de lrrk2
HRP20172006T1 (hr) 2010-11-10 2018-02-09 Genentech, Inc. Derivati pirazol-aminopiridina kao lrrk2-modulatori
US9834518B2 (en) 2011-05-04 2017-12-05 Ariad Pharmaceuticals, Inc. Compounds for inhibiting cell proliferation in EGFR-driven cancers
CN102260215A (zh) * 2011-05-13 2011-11-30 复旦大学 一种二芳基嘧啶类衍生物及其制备方法和用途
WO2013047411A1 (ja) * 2011-09-29 2013-04-04 富士フイルム株式会社 新規なトリアジン誘導体、紫外線吸収剤
WO2013059572A1 (en) 2011-10-19 2013-04-25 Assia Chemical Industries Ltd. Process for the preparation of etravirine and intermediates in the synthesis thereof
GB201119358D0 (en) 2011-11-10 2011-12-21 Lewi Paulus J Disubstituted triazine dimers for treatment and/or prevention of infectious diseases
CA3094793A1 (en) 2011-11-23 2013-05-30 Portola Pharmaceuticals, Inc. Pyrazine kinase inhibitors
GB201204756D0 (en) 2012-03-19 2012-05-02 Lewi Paulus J Triazines with suitable spacers for treatment and/or prevention of HIV infections
US20150166591A1 (en) 2012-05-05 2015-06-18 Ariad Pharmaceuticals, Inc. Methods and compositions for raf kinase mediated diseases
WO2014072419A1 (en) 2012-11-08 2014-05-15 Universiteit Antwerpen Novel anti-hiv compounds
AU2014214846A1 (en) 2013-02-08 2015-07-23 Celgene Avilomics Research, Inc. ERK inhibitors and uses thereof
US9611283B1 (en) 2013-04-10 2017-04-04 Ariad Pharmaceuticals, Inc. Methods for inhibiting cell proliferation in ALK-driven cancers
WO2015138919A1 (en) * 2014-03-14 2015-09-17 The University Of North Carolina At Chapel Hill Small molecules for inhibiting male fertility
US10005760B2 (en) 2014-08-13 2018-06-26 Celgene Car Llc Forms and compositions of an ERK inhibitor
MX2021013662A (es) 2019-05-10 2022-03-11 Deciphera Pharmaceuticals Llc Inhibidores de la autofagia de heteroarilaminopirimidina amida y metodos de uso de estos.
EP3966207B1 (en) 2019-05-10 2023-11-01 Deciphera Pharmaceuticals, LLC Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereof
IL325201A (en) 2019-06-17 2026-02-01 Deciphera Pharmaceuticals Llc Aminopyrimidine amide autophagy inhibitors and methods of using them
EP4335847A1 (en) * 2021-05-07 2024-03-13 Voronoi Inc. Heteroaryl derivative, method for preparing same, and pharmaceutical composition comprising same as active ingredient

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2433439A (en) * 1947-12-30 Pyrimidine compounds
GB854011A (en) * 1958-09-10 1960-11-16 Ici Ltd New pyrimidines
NL129020C (https=) * 1964-12-15
US3459731A (en) 1966-12-16 1969-08-05 Corn Products Co Cyclodextrin polyethers and their production
US4659363A (en) * 1983-07-25 1987-04-21 Ciba-Geigy Corporation N-(2-nitrophenyl)-2-aminopyrimidine derivatives, the preparation and use thereof
JPH0784445B2 (ja) 1986-12-03 1995-09-13 クミアイ化学工業株式会社 ピリミジン誘導体および農園芸用殺菌剤
GB9012592D0 (en) 1990-06-06 1990-07-25 Smithkline Beecham Intercredit Compounds
GB9016800D0 (en) * 1990-07-31 1990-09-12 Shell Int Research Tetrahydropyrimidine derivatives
US5516775A (en) 1992-08-31 1996-05-14 Ciba-Geigy Corporation Further use of pyrimidine derivatives
RU2153494C2 (ru) 1993-10-12 2000-07-27 Дзе Дюпон Мерк Фармасьютикал Компани 1-n-алкил-n-арилпиримидинамины, способ лечения заболеваний, фармацевтическая композиция
GB9523675D0 (en) * 1995-11-20 1996-01-24 Celltech Therapeutics Ltd Chemical compounds
CN1198655C (zh) 1995-11-23 2005-04-27 詹森药业有限公司 通过熔体挤出法制备的环糊精固体混合物
CN1163401A (zh) * 1996-02-13 1997-10-29 李占元 全自动血球计数仪试剂及配制方法
NO311614B1 (no) 1996-10-01 2001-12-17 Janssen Pharmaceutica Nv Substituerte diamino-1,3,5-triazinderivater
GB9705361D0 (en) * 1997-03-14 1997-04-30 Celltech Therapeutics Ltd Chemical compounds
AU1507199A (en) * 1997-12-15 1999-07-05 Yamanouchi Pharmaceutical Co., Ltd. Novel pyrimidine-5-carboxamide derivatives
BR9908004A (pt) * 1998-02-17 2001-12-18 Tularik Inc Composto, composição e método para prevençãoou supressão de uma infecção viral
CZ299380B6 (cs) 1998-03-27 2008-07-09 Janssen Pharmaceutica N. V. Pyrimidinová sloucenina, použití této slouceniny pro prípravu léciva, farmaceutický prostredek tutoslouceninu obsahující, zpusob prípravy tohoto prostredku a uvedené slouceniny a kombinace a produktuvedenou slouceninu obsahující
EP0945447A1 (en) 1998-03-27 1999-09-29 Janssen Pharmaceutica N.V. Trisubstituted 1,3,5-triazine derivatives for treatment of HIV infections
AU764472B2 (en) 1998-11-10 2003-08-21 Janssen Pharmaceutica N.V. 2,4-disubstituted triazine derivatives
HRP20080359B1 (hr) * 1998-11-10 2016-01-01 Janssen Pharmaceutica N.V. PIRIMIDINI KOJI INHIBIRAJU REPLIKACIJU HIV-a
GB9828511D0 (en) 1998-12-24 1999-02-17 Zeneca Ltd Chemical compounds

Also Published As

Publication number Publication date
CA2406562A1 (en) 2001-11-15
US20030171374A1 (en) 2003-09-11
AU5633301A (en) 2001-11-20
WO2001085700A2 (en) 2001-11-15
AU783981C (en) 2007-05-03
AR028423A1 (es) 2003-05-07
US7276510B2 (en) 2007-10-02
MY139506A (en) 2009-10-30
AU783981B2 (en) 2006-01-12
PA8516401A1 (es) 2002-02-21
CA2406562C (en) 2009-09-15
JP2003535828A (ja) 2003-12-02
EP1282606B1 (en) 2015-04-22
WO2001085700A3 (en) 2002-02-07
EP1282606A2 (en) 2003-02-12
JP5230050B2 (ja) 2013-07-10

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