Una amidites and uses thereof
Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a disease which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.
1. A compound, or a pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (II):
wherein:
Ring G is
X is O, NH, or C(═O);
R 1 is hydrogen, deuterium, halogen, substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 2 -C 10 alkenyl, substituted or unsubstituted C 2 -C 10 alkynyl, substituted or unsubstituted C 1 -C 10 fluoroalkyl, substituted or unsubstituted C 1 -C 20 heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted —O-aryl, —OR 6 , —C(═O)R 6 , —C(═O)OR 6 , —C(═O)NR 7 R 7 , —OCH 2 C(═O)R 6 , —OCH 2 C(═O)OR 6 , or —OCH 2 C(═O)NR 7 R 7 ;
each R 2 is independently hydrogen, deuterium, or substituted or unsubstituted C 1 -C 10 alkyl;
or two R 2 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted C 3 -C 10 heterocycloalkyl;
R 3 is hydrogen, 4,4′-dimethoxytrityl (DMT), —R 6 , —OR 6 , or —NR 7 R 7 ;
each R 4 is independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted benzoyl;
R 5 is —C(═O)R 6 ;
each R 6 and R 7 are independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.
2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate, thereof, wherein: R 1 is
n is 0, 1, 2, 3, 4, or 5; and
R 5 is hydrogen or substituted or unsubstituted C 1 -C 3 alkyl.
3. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate, thereof, wherein: R 1 is —OCH 2 C(═O)NR 7 R 7 ; wherein each R 7 is independently hydrogen or substituted or unsubstituted C 1 -C 3 alkyl.
4. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
Ring G is
wherein each R 4 is independently hydrogen, or substituted or unsubstituted benzoyl.
5. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein:
Ring G is
wherein each R 4 is independently hydrogen or substituted or unsubstituted benzoyl; and R 5 is —C(═O)R 6 .
6. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein each R 2 is independently isopropyl.
7. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein two R 2 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted C 3 -C 10 heterocycloalkyl.
8. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein X is O; and R 3 is 4,4′-dimethoxytrityl (DMT).