Polynucleotide phosphorodithioate compounds

• US 5,602,244 A
• Filed: 05/08/1995
• Issued: 02/11/1997
• Est. Priority Date: 05/26/1988
• Status: Expired due to Fees

• Current Assignee: Competitive Technologies Incorporated
• Original Assignee: Competitive Technologies Incorporated
• Inventors: Nielsen, John, Caruthers, Marvin H., Ma, Michael, Yau, Eric, Brill, Wolfgang K.-D.
• Primary Examiner(s): Kunz, Gary L.
• Application Number:
  US08/436,714
• Time in Patent Office: 645 Days
• Field of Search: 536/25.6, 536/24.5
• US Class Current: 536/25.6
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 21/02 with ribosyl as saccharide radical
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical

Abstract

Dinucleoside phosphorodithioate phosphoramidite precursors useful in the synthesis of oligonucleotide phosphorodithioate which can be used as antisense inhibitors of translation.

Claims

1. A compound according to the general formula:

##STR41## wherein A which may be the same or different is --OH, --H, --halogen, --SH, --NH₂, azide, --OR₄, --SR₄ or --NR₄ wherein R₄ is a heteroatom substituted or unsubstituted blocking group;

wherein B which may be the same or different is a nucleoside or deoxynucleoside base;

wherein R₁ and R₃ which may be the same or different are --H or a blocking group; and

wherein R₂ is selected from the group consisting of

(1) S-R₅ where R₅ is a heteroatom substituted or unsubstituted alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, alkenyl, cycloalkenyl, aralkenyl, alkynyl, aralkynyl or cycloalkynyl;

(2) NHR₆ and NR₆ R₇

(a) wherein R₆ and R₇ taken together with the nitrogen atom to which they are attached is a heterocyclic containing up to 5 carbon atoms in the cyclic structure which structure may contain up to an additional 5 carbon atoms pendant thereon,

(b) wherein R₆ and R₇ each taken separately is a heteroatom substituted or unsubstituted alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, alkenyl, cycloalkenyl, aralkenyl, alkynyl, aralkynyl, or cycloalkynyl group,

(c) wherein R₆ and R₇ when taken together with the nitrogen atom to which they are attached is a saturated or unsaturated nitrogen heterocycle including at least one additional heteroatom from the group consisting of nitrogen, oxygen and sulfur;

(3) sulfur double-bonded to the phosphorous atom; and

(4) oxygen double-bonded to the phosphorous atom.

2. The compound according to claim 1 wherein B is selected from the group consisting of purines and pyrimidines.

3. The compound according to claim 2 wherein each B is independently selected form the group consisting of adenine, hypoxanthine, guanine, cytosine, uracil, and thymine.

4. The compound according to claim 1 wherein R₁ and R₃ are selected from the group consisting of trityl, methoxytrityl, dimethoxytrityl, pivalyl, acetyl tetrahydropyranyl, methoxytetrahydropyranyl, phenoxyacetyl, isobutyloxycarbonyl, t-butyldimethylsilyl, triisopropylsilyl, alkylcaronyl, and arylcarbonoyl.

5. A compound according to claim 1 wherein the amines NHR₆ and NR₆ R₇ are selected from the group consisting of methylamine, ethylamine, propylamine, isopropylamine, aniline, cyclohexylamine, benzylamine, polycyclic amines, heteroatom substituted aryl and alkylamines, dimethylamine, diethylamine, diisopropylamine, dibutylamine, methylpropylamine, methylhexylamlne, methylcyclopropylamine, ethylcylohexylamine, methylbenzylamine, methylcyclohexylmethylamine, butylcyclohexylamine, morpholine, thiomorpholine, pyrrolidine, piperidine, 2,6-dimethylpiperidine, piperazine, and heteroatom substituted alkyl and aryl amines.