Back to results
US 2018/0002367 A1Published application
Phosphorodiamidate Backbone Linkage for Oligonucleotides
AssigneeGeron Corporation
InventorsKrisztina PONGRACZ, Mahesh Ramaseshan
Life of this patent
Estimating the term…
Abstract
This invention relates to antisense oligonucleotides comprising at least one N3′→P5′ phosphorodiamidate linkage (NPN) in the backbone as well as methods for using the same. The antisense oligonucleotides can effectively prevent or decrease protein expression.
Claims24
-14. (canceled)
A compound of formula (II):
- wherein
- R1 is an acid labile amino protecting group;
- R3 is independently selected from hydrogen, hydroxyl, and —O—R3a;
- wherein R3a is C1-6 alkyl or C1-6 alkyl substituted with —NR3bR3c, imidazolyl, —(CH2)aO(CH2)bNR3bR3c, or —(CH2)aONR3d(CH2)bNR3bR3c;
- wherein R3b is hydrogen or C1-2 alkyl;
- R3c is hydrogen or C1-2 alkyl;
- R3d is hydrogen or C1-2 alkyl;
- a is an integer selected from one to 4;
- b is an integer selected from one to 4;
- R4 is C1-6 alkyl or C1-6 alkyl substituted with —NR4aR4b;
- wherein R4a is hydrogen or C1-2 alkyl and R4b is hydrogen or C1-2 alkyl;
- R5 is C1-6 alkyl or C1-6 alkyl substituted with —NR5aR5b;
- wherein R5a is hydrogen or C1-2 alkyl and R5b is hydrogen or C1-2 alkyl;
- or
- R4 and R5 taken together with the nitrogen to which they are attached form a monocyclic heterocyclyl or a monocyclic heterocyclyl substituted with C1-6 alkyl, sperminyl or spermidinyl;
- R6 is a leaving group;
- W is independently selected from O, S, and Se;
- and
- B1 is a heterocyclic base moiety or a protected heterocyclic base moiety;
- or a salt thereof.
17 more elements
-40. (canceled)
-60. (canceled)
A method of preparing a compound of formula (II):
- wherein
- R1 is an acid labile amino protecting group;
- R3 is independently selected from hydrogen, hydroxyl, and —O—R3a;
- wherein R3a is C1-6 alkyl or C1-6 alkyl substituted with —NR3bR3c, imidazolyl, —(CH2)aO(CH2)bNR3bR3c, or —(CH2)aONR3d(CH2)bNR3bR3c;
- wherein R3b is hydrogen or C1-2 alkyl;
- R3c is hydrogen or C1-2 alkyl;
- R3d is hydrogen or C1-2 alkyl;
- a is an integer selected from one to 4;
- b is an integer selected from one to 4;
- R4 is C1-6 alkyl or C1-6 alkyl substituted with —NR4aR4b;
- wherein R4a is hydrogen or C1-2 alkyl and R4b is hydrogen or C1-2 alkyl;
- R5 is C1-6 alkyl or C1-6 alkyl substituted with —NR5aR5b;
- wherein R5a is hydrogen or C1-2 alkyl and R5b is hydrogen or C1-2 alkyl;
- or
- R4 and R5 taken together with the nitrogen to which they are attached form a monocyclic heterocyclyl or a monocyclic heterocyclyl substituted with C1-6 alkyl, sperminyl, or spermidinyl;
- R6 is a leaving group;
- W is independently selected from O, S, and Se;
- and
- B1 is a heterocyclic base moiety or a protected heterocyclic base moiety;
- or a salt thereof;
- wherein the method comprises:
- a) contacting a compound of formula (A)
- with a phosphorylating reagent having the formula:
20 more elements
-68. (canceled)
Dependencies are inferred from the claim text.