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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
Individual
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 Individual filed Critical Individual
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)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Genetics & Genomics (AREA)
  • Communicable Diseases (AREA)
  • Virology (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
DE4201662 1992-01-22
DEP4201662.2 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 (48)

* Cited by examiner, † Cited by third party
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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
ES2103408T3 (en) 1992-09-24 1997-09-16 Hoechst Ag ANALOGS OF OLIGORRIBONUCLEOTIDES AND RIBOZYMES WITH TERMINAL JOINTS IN 3'-3 'OR 5'-5' RESPECTIVELY.
EP0602524A1 (en) * 1992-12-15 1994-06-22 Hoechst Aktiengesellschaft Chemiluminescence marked sequences and their use in sequence testing
ES2100051T3 (en) * 1993-01-08 1997-06-01 Hybridon Inc SYNTHESIS OF DIMER BLOCKS AND THEIR USE IN THE ASSEMBLY OF OLIGONUCLEOTIDES.
US6087491A (en) 1993-01-08 2000-07-11 Hybridon, Inc. Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks
CN1121721A (en) * 1993-01-25 1996-05-01 海布里顿公司 Oligonucleotido alky phosphate and alky substituted phosphate
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
PL316434A1 (en) * 1994-03-18 1997-01-06 Lynx Therapeutics Oligonucleotidic phosphoramides n3'-p5', their compositions, synthesising and hydridising methods as well as immunological properties in respect to nuclease
US5726297A (en) * 1994-03-18 1998-03-10 Lynx Therapeutics, Inc. Oligodeoxyribonucleotide N3' P5' phosphoramidates
US5599922A (en) * 1994-03-18 1997-02-04 Lynx Therapeutics, Inc. Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties
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
US5859233A (en) * 1996-02-21 1999-01-12 Lynx Therapeutics, Inc. Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates
US5684143A (en) * 1996-02-21 1997-11-04 Lynx Therapeutics, Inc. Oligo-2'-fluoronucleotide N3'->P5' phosphoramidates
PT808898E (en) * 1996-05-24 2004-10-29 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
DE19935303A1 (en) 1999-07-28 2001-02-08 Aventis Pharma Gmbh Oligonucleotides to inhibit the expression of human eg5
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
CN101914533B (en) 2003-08-28 2013-06-19 诺瓦提斯公司 Interfering RNA duplexes with blunt ends and 3' modifications
GB0608838D0 (en) 2006-05-04 2006-06-14 Novartis Ag Organic compounds
US10131904B2 (en) 2008-02-11 2018-11-20 Rxi Pharmaceuticals Corporation Modified RNAi polynucleotides and uses thereof
WO2010008582A2 (en) 2008-07-18 2010-01-21 Rxi Pharmaceuticals Corporation Phagocytic cell drug delivery system
CA2753338A1 (en) 2008-09-22 2010-03-25 Rxi Pharmaceuticals Corporation Neutral nanotransporters
WO2010059226A2 (en) 2008-11-19 2010-05-27 Rxi Pharmaceuticals Corporation Inhibition of map4k4 through rnai
US9745574B2 (en) 2009-02-04 2017-08-29 Rxi Pharmaceuticals Corporation RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
US9095504B2 (en) 2010-03-24 2015-08-04 Rxi Pharmaceuticals Corporation RNA interference in ocular indications
CN110042099A (en) 2010-03-24 2019-07-23 菲奥医药公司 RNA in skin and fibrotic conditions is interfered
WO2011119852A1 (en) 2010-03-24 2011-09-29 Rxi Pharmaceuticals Corporation Reduced size self-delivering rnai compounds
JP6772062B2 (en) 2013-12-02 2020-10-21 フィオ ファーマシューティカルズ コーポレーションＰｈｉｏ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｃｏｒｐ． 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
US11279934B2 (en) 2014-04-28 2022-03-22 Phio Pharmaceuticals Corp. Methods for treating cancer using nucleic acids targeting MDM2 or MYCN
EP3188799B1 (en) 2014-09-05 2022-07-06 Phio Pharmaceuticals Corp. Methods for treating aging and skin disorders using nucleic acids targeting tyr or mmp1
WO2017007825A1 (en) 2015-07-06 2017-01-12 Rxi Pharmaceuticals Corporation Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
WO2017007813A1 (en) 2015-07-06 2017-01-12 Rxi Pharmaceuticals Corporation Nucleic acid molecules targeting superoxide dismutase 1 (sod1)
US11021707B2 (en) 2015-10-19 2021-06-01 Phio Pharmaceuticals Corp. Reduced size self-delivering nucleic acid compounds targeting long non-coding RNA
EP3790970A1 (en) 2018-05-07 2021-03-17 Alnylam Pharmaceuticals Inc. Extrahepatic delivery

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
CA2071510C (en) * 1989-10-24 2004-07-06 Chris A. Buhr 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
PL172257B1 (en) 1997-08-29
DE59310285D1 (en) 2002-06-27
AU3191093A (en) 1993-07-29
NO930199L (en) 1993-07-23
CA2087818C (en) 2007-07-10
NZ245720A (en) 1995-12-21
HUT63173A (en) 1993-07-28
IL104461A0 (en) 1993-05-13
KR930016437A (en) 1993-08-26
ES2177532T3 (en) 2002-12-16
ZA93422B (en) 1993-09-16
EP0552766A3 (en) 1994-09-07
IL104461A (en) 2001-05-20
FI930220A (en) 1993-07-23
PT552766E (en) 2002-10-31
EP0552766A2 (en) 1993-07-28
JP3717081B2 (en) 2005-11-16
ATE217880T1 (en) 2002-06-15
AU661365B2 (en) 1995-07-20
EP0552766B1 (en) 2002-05-22
NO308215B1 (en) 2000-08-14
HU227794B1 (en) 2012-03-28
JPH05310779A (en) 1993-11-22
FI930220A0 (en) 1993-01-20
HU9300162D0 (en) 1993-04-28
NO930199D0 (en) 1993-01-21
FI115214B (en) 2005-03-31
DK0552766T3 (en) 2002-08-19

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Effective date: 20130121