Back to results
US 2003/0069412 A1Published application
Synthesis of oligonucleotides
AssigneeIsis Pharmaceuticals, Inc.
InventorsVasulinga Ravikumar, Douglas L. Cole
Life of this patent
Estimating the term…
Abstract
Synthetic processes are provided for the solution phase synthesis of oligonucleotides, especially phosphorothioate oligonucleotides, and intermediate compounds useful in the processes. Intermediates having structure 1 are prepared in accord with preferred embodiments.
Claims18
A method for the solution phase preparation of an oligonucleotide comprising reacting, in solution, a first synthon having the structure
- 20
- with a second synthon having the structure
- 21
- to form a moiety having the structure
- 22
- where each Q is independently O, S, CH2, CHF or CF2;
- each Bx is independently a nucleosidic base;
- each X is independently, OH, SH, SCH3, F, OCN, O(CH2)nNH2, O(CH2)nCH3 where n is from 1 to about 10;
- C1 to C10 lower alkyl, substituted lower alkyl, alkaryl or aralkyl;
- Cl, Br, CN, CF3, OCF3, O—, S—, or N-alkyl;
- O—, S—, or N-alkenyl;
- SOCH3, SO2CH3;
- ONO2;
- NO2;
- N3;
- NH2;
- heterocycloalkyl;
- heterocycloalkaryl;
- aminoalkylamino;
- polyalkylamino;
- substituted silyl;
- an RNA cleaving group;
- a conjugate;
- a reporter group;
- an intercalator;
- a group for improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide;
- each Y is independently a 5′ hydroxyl protecting group;
- W is a 3′ hydroxyl protecting group;
- each Z is independently O or S;
- each T is independently a phosphorous blocking group;
- U is a phosphite activating group;
- and
- n is an integer from 0 to 50.
30 more elements
A method for preparing an oligomer comprising reacting together, in solution,
- a first synthon comprising at least two nucleoside units and having a 5′ location protected with a 5′ hydroxylic blocking group and a 3′ location substituted with a function having the formula
- U—P—T
- wherein U is a phosphite activating group and T is a phosphorous blocking group,
- with a second synthon comprising a nucleoside unit having a 3′ location protected with a 3′ hydroxylic blocking group and a 5′ location capable of reacting with the U—P—T function.
1 more element
A compound having one of the formulas
- 23
- where each Q is independently O. S, CH2, CHF or CF2;
- each Bx is independently a nucleosidic base;
- each X is independently, OH, SH, SCH3, F, OCN, O(CH2)nNH2, O(CH2)2CH3 where n is from 1 to about 10;
- C1 to C10 lower alkyl, substituted lower alkyl, alkaryl or aralkyl;
- Cl, Br, CN, CF3, OCF3, O—, S—, or N-alkyl;
- O—, S—, or N-alkenyl;
- SOCH3, SO2CH3;
- ONO2;
- NO2;
- N3;
- NH2;
- heterocycloalkyl;
- heterocycloalkaryl;
- aminoalkylamino;
- polyalkylamino;
- substituted silyl;
- an RNA cleaving group;
- a conjugate;
- a reporter group;
- an intercalator;
- a group for improving the pharmacokinetic properties of an oligonucleotide;
- or a group for improving the pharmacodynamic properties of an oligonucleotide;
- each Z is independently O or S;
- Y is H or a hydroxyl protecting group;
- U is a phosphite activating group;
- each T is independently a phosphorous blocking group;
- and
- n is an integer from 1 to 200.
26 more elements
Dependencies are inferred from the claim text.