CA2087818A1 - Oligonucleotide analogs, their preparation and use - Google Patents

Oligonucleotide analogs, their preparation and use

Info

Publication number
CA2087818A1
CA2087818A1 CA002087818A CA2087818A CA2087818A1 CA 2087818 A1 CA2087818 A1 CA 2087818A1 CA 002087818 A CA002087818 A CA 002087818A CA 2087818 A CA2087818 A CA 2087818A CA 2087818 A1 CA2087818 A1 CA 2087818A1
Authority
CA
Canada
Prior art keywords
aryl
alkyl
preparation
seh
alkoxy
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.)
Granted
Application number
CA002087818A
Other languages
French (fr)
Other versions
CA2087818C (en
Inventor
Eugen Uhlmann
Anuschirwan Peyman
Gerard O'malley
Matthias Helsberg
Irvin Winkler
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.)
Hoechst AG
Original Assignee
Eugen Uhlmann
Anuschirwan Peyman
Gerard O'malley
Matthias Helsberg
Irvin Winkler
Hoechst Aktiengesellschaft
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 Eugen Uhlmann, Anuschirwan Peyman, Gerard O'malley, Matthias Helsberg, Irvin Winkler, Hoechst Aktiengesellschaft filed Critical Eugen Uhlmann
Publication of CA2087818A1 publication Critical patent/CA2087818A1/en
Application granted granted Critical
Publication of CA2087818C publication Critical patent/CA2087818C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • 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
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/11—Compounds covalently bound to a solid support

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Epidemiology (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Steroid Compounds (AREA)

Abstract

The invention relates to compounds of the formula I (see formula I) where R1 is H, alkyl, acyl, aryl or a phosphate residue; R2 is H, OH, alkoxy, NH2 or halogen; B is a base customary in nucleotide chemistry; a is O or CH2; n is an integer from 1 to 100; W = O, S or Se; V = O, S or NH; Y = O, S, NH or CH2; Y' = O, S, NH or alkylene; X = OH or SH; U = OH, SH, SeH, alkyl, aryl or amine and Z = OH, SH, SeH, an optionally substituted radical from the group comprising alkyl, aryl, heteroaryl, alkoxy or amino, or a group which favors intracellular uptake or serves as the label of a DNA probe or attacks the target nucleic acid during hybridization, where if Z = OH, SH, CH3 or OC2H5, at least one of the groups X, Y, Y', V or W is not OH or O or R1 is not H; a process for their preparation and their use as inhibitors of gene expression, as probes for detecting nucleic acids and as aids in molecular biology.
CA002087818A 1992-01-22 1993-01-21 Oligonucleotide analogs, their preparation and use Expired - Lifetime CA2087818C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4201662.2 1992-01-22
DE4201662 1992-01-22

Publications (2)

Publication Number Publication Date
CA2087818A1 true CA2087818A1 (en) 1993-07-23
CA2087818C CA2087818C (en) 2007-07-10

Family

ID=6450030

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002087818A Expired - Lifetime CA2087818C (en) 1992-01-22 1993-01-21 Oligonucleotide analogs, their preparation and use

Country Status (17)

Country Link
EP (1) EP0552766B1 (en)
JP (1) JP3717081B2 (en)
KR (1) KR930016437A (en)
AT (1) ATE217880T1 (en)
AU (1) AU661365B2 (en)
CA (1) CA2087818C (en)
DE (1) DE59310285D1 (en)
DK (1) DK0552766T3 (en)
ES (1) ES2177532T3 (en)
FI (1) FI115214B (en)
HU (1) HU227794B1 (en)
IL (1) IL104461A (en)
NO (1) NO308215B1 (en)
NZ (1) NZ245720A (en)
PL (1) PL172257B1 (en)
PT (1) PT552766E (en)
ZA (1) ZA93422B (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5674856A (en) * 1993-01-29 1997-10-07 Sankyo Company, Limited Modified oligodeoxyribonucleoditides
US5874553A (en) * 1995-03-13 1999-02-23 Hoechst Aktiengesellschaft Phosphonomonoester nucleic acids, process for their preparation, and their use
US6087490A (en) * 1996-03-23 2000-07-11 Novartis Ag Dinucleotide and oligonucleotide analogues
US6723706B2 (en) 1997-05-05 2004-04-20 Aventis Pharma Deutschland Gmbh Modified antisense nucleotides complementary to a section of the human Ha-ras gene
US7635769B2 (en) 2001-07-12 2009-12-22 Sanofi-Aventis Drutschland Oligoribonucleotide derivatives for specific inhibition of gene expression

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5378825A (en) * 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5646261A (en) * 1992-01-22 1997-07-08 Hoechst Aktiengesellschaft 3'-derivatized oligonucleotide analogs with non-nucleotidic groupings, their preparation and use
DE59306170D1 (en) 1992-09-24 1997-05-22 Hoechst Ag Oligoribonucleotide and ribozyme analogs with terminal 3'-3 'and 5'-5' linkages
EP0602524A1 (en) * 1992-12-15 1994-06-22 Hoechst Aktiengesellschaft Chemiluminescence marked sequences and their use in sequence testing
US6087491A (en) 1993-01-08 2000-07-11 Hybridon, Inc. Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks
CN1122137A (en) * 1993-01-08 1996-05-08 海布里顿公司 Synthesis of dimmer blocks and their use in assembling oligonucleotides
DK0677056T3 (en) * 1993-01-25 1996-08-05 Hybridon Inc Oligonucleotide alkyl phosphonates and alkyl phosphonothioates
US5532130A (en) * 1993-07-20 1996-07-02 Dyad Pharmaceutical Corporation Methods and compositions for sequence-specific hybridization of RNA by 2'-5' oligonucleotides
DE4331670A1 (en) * 1993-09-17 1995-03-23 Hoechst Ag Antisense oligonucleotides against HSV-1 and the preparation thereof
DE4338704A1 (en) 1993-11-12 1995-05-18 Hoechst Ag Stabilized oligonucleotides and their use
DE4408528A1 (en) * 1994-03-14 1995-09-28 Hoechst Ag Peptide oligonucleotide derivatives, their preparation and use
US6919441B2 (en) 1994-03-14 2005-07-19 Aventis Pharma Deutschland Gmbh Polyamide-oligonucleotide derivatives, their preparation and use
US5599922A (en) * 1994-03-18 1997-02-04 Lynx Therapeutics, Inc. Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties
CA2184375C (en) * 1994-03-18 2006-05-02 Sergei M. Gryaznov Oligonucleotide n3'-p5' phosphoramidates: synthesis and compounds; hybridization and nuclease resistance properties
US5726297A (en) * 1994-03-18 1998-03-10 Lynx Therapeutics, Inc. Oligodeoxyribonucleotide N3' P5' phosphoramidates
DE4415370A1 (en) * 1994-05-02 1995-11-09 Hoechst Ag Modified oligonucleotides, their preparation and their use
US5986076A (en) * 1994-05-11 1999-11-16 Trustees Of Boston University Photocleavable agents and conjugates for the detection and isolation of biomolecules
US5696248A (en) * 1994-06-15 1997-12-09 Hoechst Aktiengesellschaft 3'-modified oligonucleotide derivatives
DE4438918A1 (en) * 1994-11-04 1996-05-09 Hoechst Ag Modified oligonucleotides, their preparation and their use
US6150510A (en) 1995-11-06 2000-11-21 Aventis Pharma Deutschland Gmbh Modified oligonucleotides, their preparation and their use
DE19502912A1 (en) * 1995-01-31 1996-08-01 Hoechst Ag G-Cap Stabilized Oligonucleotides
US6326487B1 (en) 1995-06-05 2001-12-04 Aventis Pharma Deutschland Gmbh 3 modified oligonucleotide derivatives
US5684143A (en) * 1996-02-21 1997-11-04 Lynx Therapeutics, Inc. Oligo-2'-fluoronucleotide N3'->P5' phosphoramidates
US5859233A (en) * 1996-02-21 1999-01-12 Lynx Therapeutics, Inc. Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates
DK0808898T3 (en) * 1996-05-24 2004-09-27 Aventis Pharma Gmbh Reagent and method for inhibiting N-ras expression
DE19627898A1 (en) * 1996-07-11 1998-01-15 Hoechst Ag Solid phase synthesis of oligonucleotides
WO1999019474A1 (en) * 1997-10-14 1999-04-22 Sankyo Company, Limited Modified oligodeoxyribonucleotides having tggg sequence
EP1004661A1 (en) 1998-11-11 2000-05-31 DALLI-WERKE WÄSCHE- und KÖRPERPFLEGE GmbH & Co. KG High density granule, method for production thereof, and its use as disintegrant in tablets
DE19935302A1 (en) 1999-07-28 2001-02-08 Aventis Pharma Gmbh Conjugates and processes for their preparation and their use for the transport of molecules across biological membranes
DE19935303A1 (en) 1999-07-28 2001-02-08 Aventis Pharma Gmbh Oligonucleotides to inhibit the expression of human eg5
AU2004269150C1 (en) 2003-08-28 2010-11-18 Novartis Ag Interfering RNA duplex having blunt-ends and 3'-modifications
GB0608838D0 (en) 2006-05-04 2006-06-14 Novartis Ag Organic compounds
EP2247729B1 (en) 2008-02-11 2019-05-01 Phio Pharmaceuticals Corp. Modified rnai polynucleotides and uses thereof
US8815818B2 (en) 2008-07-18 2014-08-26 Rxi Pharmaceuticals Corporation Phagocytic cell delivery of RNAI
US8796443B2 (en) 2008-09-22 2014-08-05 Rxi Pharmaceuticals Corporation Reduced size self-delivering RNAi compounds
WO2010059226A2 (en) 2008-11-19 2010-05-27 Rxi Pharmaceuticals Corporation Inhibition of map4k4 through rnai
WO2010090762A1 (en) 2009-02-04 2010-08-12 Rxi Pharmaceuticals Corporation Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
EP2550000A4 (en) 2010-03-24 2014-03-26 Advirna Inc Reduced size self-delivering rnai compounds
WO2011119871A1 (en) 2010-03-24 2011-09-29 Rxi Phrmaceuticals Corporation Rna interference in ocular indications
KR102453078B1 (en) 2010-03-24 2022-10-11 피오 파마슈티칼스 코프. Rna interference in dermal and fibrotic indications
RU2744194C2 (en) 2013-12-02 2021-03-03 Фио Фармасьютикалс Корп Cancer immunotherapy
WO2015125845A1 (en) * 2014-02-20 2015-08-27 塩野義製薬株式会社 Phosphate site modification of nucleic acid containing nitrogen-containing non-aromatic heterocycle
EP3137119B1 (en) 2014-04-28 2020-07-01 Phio Pharmaceuticals Corp. Methods for treating cancer using a nucleic acid targeting mdm2
US10900039B2 (en) 2014-09-05 2021-01-26 Phio Pharmaceuticals Corp. Methods for treating aging and skin disorders using nucleic acids targeting Tyr or MMP1
US10808247B2 (en) 2015-07-06 2020-10-20 Phio Pharmaceuticals Corp. Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
US11001845B2 (en) 2015-07-06 2021-05-11 Phio Pharmaceuticals Corp. Nucleic acid molecules targeting superoxide dismutase 1 (SOD1)
CA3002744A1 (en) 2015-10-19 2017-04-27 Rxi Pharmaceuticals Corporation Reduced size self-delivering nucleic acid compounds targeting long non-coding rna

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3239888A1 (en) * 1982-10-28 1984-05-03 Hubert Prof. Dr. 2000 Hamburg Köster METHOD FOR PRODUCING OLIGONUCLEOSIDE PHOSPHONATES
US4739044A (en) * 1985-06-13 1988-04-19 Amgen Method for derivitization of polynucleotides
DE3751468T2 (en) * 1986-10-30 1996-02-29 Daicel Chem METHOD FOR PRODUCING OLIGONUCLEOTIDES AND COMPOUNDS FOR FORMING HIGH-MOLECULAR PROTECTION GROUPS.
US4816571A (en) * 1987-06-04 1989-03-28 Applied Biosystems, Inc. Chemical capping by phosphitylation during oligonucleotide synthesis
DE69034150T2 (en) * 1989-10-24 2005-08-25 Isis Pharmaceuticals, Inc., Carlsbad 2'-modified oligonucleotides
US5210015A (en) * 1990-08-06 1993-05-11 Hoffman-La Roche Inc. Homogeneous assay system using the nuclease activity of a nucleic acid polymerase
GB9021625D0 (en) * 1990-10-04 1990-11-21 Ici Plc Synthesis of oligonucleotides

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5674856A (en) * 1993-01-29 1997-10-07 Sankyo Company, Limited Modified oligodeoxyribonucleoditides
US5807837A (en) * 1993-01-29 1998-09-15 Sankyo Company, Limited Composition and method for the treatment or prophylaxis of viral infections using modified oligodeoxyribonucleotides
US5874553A (en) * 1995-03-13 1999-02-23 Hoechst Aktiengesellschaft Phosphonomonoester nucleic acids, process for their preparation, and their use
US6127346A (en) * 1995-03-13 2000-10-03 Hoechst Aktiengesellschaft Phosphonomonoester nucleic acids process for their preparation and their use
US6087490A (en) * 1996-03-23 2000-07-11 Novartis Ag Dinucleotide and oligonucleotide analogues
US6723706B2 (en) 1997-05-05 2004-04-20 Aventis Pharma Deutschland Gmbh Modified antisense nucleotides complementary to a section of the human Ha-ras gene
US7635769B2 (en) 2001-07-12 2009-12-22 Sanofi-Aventis Drutschland Oligoribonucleotide derivatives for specific inhibition of gene expression

Also Published As

Publication number Publication date
PL297515A1 (en) 1993-09-06
NO930199D0 (en) 1993-01-21
CA2087818C (en) 2007-07-10
JP3717081B2 (en) 2005-11-16
IL104461A0 (en) 1993-05-13
ZA93422B (en) 1993-09-16
AU661365B2 (en) 1995-07-20
AU3191093A (en) 1993-07-29
FI115214B (en) 2005-03-31
IL104461A (en) 2001-05-20
PL172257B1 (en) 1997-08-29
DE59310285D1 (en) 2002-06-27
HUT63173A (en) 1993-07-28
ES2177532T3 (en) 2002-12-16
JPH05310779A (en) 1993-11-22
NZ245720A (en) 1995-12-21
NO930199L (en) 1993-07-23
EP0552766B1 (en) 2002-05-22
PT552766E (en) 2002-10-31
FI930220A (en) 1993-07-23
HU227794B1 (en) 2012-03-28
ATE217880T1 (en) 2002-06-15
NO308215B1 (en) 2000-08-14
DK0552766T3 (en) 2002-08-19
HU9300162D0 (en) 1993-04-28
EP0552766A3 (en) 1994-09-07
KR930016437A (en) 1993-08-26
EP0552766A2 (en) 1993-07-28
FI930220A0 (en) 1993-01-20

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Legal Events

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Effective date: 20130121