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WO2009069132A3 - Nouveaux inhibiteurs de transcriptase inverse - Google Patents

Nouveaux inhibiteurs de transcriptase inverse Download PDF

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Publication number
WO2009069132A3
WO2009069132A3 PCT/IL2008/001555 IL2008001555W WO2009069132A3 WO 2009069132 A3 WO2009069132 A3 WO 2009069132A3 IL 2008001555 W IL2008001555 W IL 2008001555W WO 2009069132 A3 WO2009069132 A3 WO 2009069132A3
Authority
WO
WIPO (PCT)
Prior art keywords
reverse transcriptase
compounds
inhibiting
activity
disclosed
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.)
Ceased
Application number
PCT/IL2008/001555
Other languages
English (en)
Other versions
WO2009069132A2 (fr
Inventor
Amnon Hizi
Alon Herschhorn
Abraham Nudelman
Michal Weitman
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.)
Ramot at Tel Aviv University Ltd
Bar Ilan University
Original Assignee
Ramot at Tel Aviv University Ltd
Bar Ilan University
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 Ramot at Tel Aviv University Ltd, Bar Ilan University filed Critical Ramot at Tel Aviv University Ltd
Publication of WO2009069132A2 publication Critical patent/WO2009069132A2/fr
Publication of WO2009069132A3 publication Critical patent/WO2009069132A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
    • C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/04—Derivatives of thiourea
    • C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/04—Derivatives of thiourea
    • C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C335/18—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/04—Derivatives of thiourea
    • C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C335/20—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/04—Derivatives of thiourea
    • C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C335/22—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/30—Isothioureas
    • C07C335/36—Isothioureas having sulfur atoms of isothiourea groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G01N2333/91205—Phosphotransferases in general
    • G01N2333/91245—Nucleotidyltransferases (2.7.7)
    • G01N2333/9125—Nucleotidyltransferases (2.7.7) with a definite EC number (2.7.7.-)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Virology (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Microbiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne des composés qui sont capables d'inhiber une activité d'une transcriptase inverse. Elle concerne en outre des compositions pharmaceutiques contenant ces composés, et des procédés d'inhibition d'une activité de transcriptase inverse et/ou d'un mutant de celle-ci et de traitement d'une infection provoquée par un rétrovirus, au moyen de ces composés. Les composés décrits sont identifiés par le calcul ou sont conçus et nouvellement préparés en se basant sur des caractéristiques structurales identifiées, au moins en partie, par le calcul. Ainsi, l'invention concerne en outre un procédé d'identification de composés candidats pour inhiber une activité de transcriptase inverse de type sauvage et/ou traiter une infection virale provoquée par un rétrovirus.
PCT/IL2008/001555 2007-11-29 2008-11-27 Nouveaux inhibiteurs de transcriptase inverse Ceased WO2009069132A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US99667407P 2007-11-29 2007-11-29
US60/996,674 2007-11-29

Publications (2)

Publication Number Publication Date
WO2009069132A2 WO2009069132A2 (fr) 2009-06-04
WO2009069132A3 true WO2009069132A3 (fr) 2009-11-12

Family

ID=40456859

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL2008/001555 Ceased WO2009069132A2 (fr) 2007-11-29 2008-11-27 Nouveaux inhibiteurs de transcriptase inverse

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WO (1) WO2009069132A2 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR104388A1 (es) * 2015-04-23 2017-07-19 Bristol Myers Squibb Co Inhibidores de la replicación del virus de la inmunodeficiencia humana
CN109761974B (zh) * 2019-01-21 2021-05-14 河南大学 1,2,3,4-四氢-9H-吡啶并[3,4-b]吲哚类TRPV1拮抗剂及其应用
JOP20220130A1 (ar) 2019-12-06 2023-01-30 Vertex Pharma مجموعات تترا هيدروفيوران بها استبدال في صورة عوامل تعديل لقنوات الصوديوم
JP2024508789A (ja) 2021-02-19 2024-02-28 スドー バイオサイエンシーズ リミテッド Ｔｙｋ２阻害剤およびその使用
AU2022222472A1 (en) 2021-02-19 2023-09-28 Sudo Biosciences Limited Tyk2 inhibitors and uses thereof
WO2022256622A1 (fr) 2021-06-04 2022-12-08 Vertex Pharmaceuticals Incorporated N-(hydroxyalkyl (hétéro)aryl) tétrahydrofuran carboxamides utilisés en tant que modulateurs de canaux sodiques

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1111554A (en) * 1964-12-12 1968-05-01 Ferrania Spa Process for producing photographic coloured images and colour couplers for use therein
WO2000056736A2 (fr) * 1999-03-20 2000-09-28 Parker Hughes Institute Nni (inhibiteurs non nucleosidiques de la transcriptase inverse) pour le traitement de vih rebelles a la multitherapie
US20030228573A1 (en) * 2002-04-22 2003-12-11 Summers Michael F. Antiviral inhibition of capsid proteins

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1111554A (en) * 1964-12-12 1968-05-01 Ferrania Spa Process for producing photographic coloured images and colour couplers for use therein
WO2000056736A2 (fr) * 1999-03-20 2000-09-28 Parker Hughes Institute Nni (inhibiteurs non nucleosidiques de la transcriptase inverse) pour le traitement de vih rebelles a la multitherapie
US20030228573A1 (en) * 2002-04-22 2003-12-11 Summers Michael F. Antiviral inhibition of capsid proteins

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
BELL, CANTRELL, HÖGBERG ET AL.: "Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. !. Synthesis and basic structure-activity relationship studies of PETT analogs", JOURNAL OF MEDICINAL CHEMISTRY, vol. 38, 1995, pages 4929 - 4936, XP002521387 *
BERGEY, SULKOWSKI, MUCH, WENDT: "Antiarrhythmic, hemodynamic and cardiac electrophysiological evaluation of N-(2,6-dimethylphenyl)-N'-[3-(1-methylethylamino)-propyl]urea.", ARZNEIMITTEL FORSCHUNG, vol. 33, 1983, pages 1258 - 1268, XP001539416 *
BERNTSSON P ET AL: "Gastric acid secretion inhibitors. I. Compounds chemically related to lidocaine", ACTA PHARMACEUTICA SUECICA,, vol. 13, no. 5-6, 1 January 1976 (1976-01-01), pages 385 - 390, XP009114493, ISSN: 0001-6675 *
CAUJOLLE, AMAROUCH, PAYARD, LOISEAU, BORIES, GRAYRAL, LINAS, SEGUELA: "Synthesis, antifungal and nematocidal activities of thioureines with an aminoester sequence", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 30, 1995, pages 801 - 807, XP002521392 *
CHITI W: "Rapporti fra struttura chimica ed azione anestetica locale. Potenziamento, mediante transformazione in derivati barbiturici, dell'azione anestetica locale di alcune aril-uree basiche", FARMACO, EDIZIONE SCIENTIFICA, SOCIETA CHIMICA ITALIANA, PAVIA, vol. 15, no. 2, 1 January 1960 (1960-01-01), pages 114 - 125, XP009114492, ISSN: 0430-0920 *
DERZAJ-BIZJAK, OBLAK, TISLER: "Reaction of aryl isothiocyanates with ethyl-3-aminopropionate and synthesis of 3-substituted 2-thio-4-oxohexahydro-1,3-diazines", JOURNAL OF ORGANIC CHEMISTRY, vol. 27, 1962, pages 1343 - 1346, XP002521388 *
HERSCHHORN ALON ET AL: "Virtual Screening, Identification, and Biochemical Characterization of Novel Inhibitors of the Reverse Transcriptase of Human Immunodeficiency Virus Type-1", JOURNAL OF MEDICINAL CHEMISTRY, vol. 51, no. 18, 23 August 2008 (2008-08-23), pages 5702 - 5713, XP009114558, ISSN: 0022-2623, [retrieved on 20080823] *
KIM, HEIRTZLER, MORISSEAU, NISHI, TSAI, HAMMOCK: "Optimization of amide-based inhibitors of soluble epoxide hydrolase with improved water solubility", JOURNAL OF MEDICINAL CHEMISTRY, vol. 48, 2005, pages 3621 - 3629, XP002521393 *
KIMURA, WATANABE, MATSUI, HAYASHI, TANAKA, OHTSUKA, SAEKI, KOGUSHI, KABAYASHI, AKASAKA, YAMATISHI, SAITOU, YAMATSU: "Structure-activity relationship of a series of phenylureas linked to 4-phenylimidazole. Novel potent inhibitors of Acyl-CoA:Cholesterol O-Acyltransferase with antiatherosclerotic activity", JOURNAL OF MEDICINAL CHEMISTRY, vol. 36, 1993, pages 1641 - 1653, XP002521389 *
ROARK, ROTH, HOLMES, TRIVEDI, KIEFT, ESSENBURG, KRAUSE, STANFIELD: "Inhibitors of Acyl-CoA:Cholesterol Acyltransferase (ACAT). 2. Modification of fatty acid anylide ACAT inhibitors: Bioisosteric replacement of the amide bond.", JOURNAL OF MEDICINAL CHEMISTRY, vol. 36, 1993, pages 1662 - 1668, XP002521390 *
ROBERT FERGUS HUNTER ET AL: "Aminobenzthiazoles. Part X. The Mobility of the 1-Amino-3-methylbenzthiazole System", JOURNAL OF THE CHEMICAL SOCIETY, CHEMICAL SOCIETY, LETCHWORTH., GB, 1 January 1928 (1928-01-01), pages 3020 - 3027, XP009114495, ISSN: 0368-1769 *
TILLEY, LEVITAN, KIERSTEAD: "Antihypertensive (2-aminoethyl)thiourea derivatives. 1.", JOURNAL OF MEDICINAL CHEMISTRY, vol. 23, 1980, pages 1387 - 1392, XP002521391 *

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