Back to results
US 12,636,301 B2Granted
5′-modified carbocyclic ribonucleotide derivatives and methods of use
AssigneeSanegene Bio USA Inc.
InventorsWeimin Wang, Xiaochuan Cai
Life of this patent
Estimating the term…
Abstract
The present disclosure provides phosphate mimic derivatives of Formula (I) or (II): pharmaceutically acceptable salts thereof, and related Nucleic Acid Agents and conjugates. The present disclosure also relates to uses of the phosphate mimic derivatives (e.g., in the Nucleic Acid Agents and conjugates) in treating or preventing diseases.
Claims26
A compound of Formula (I) or (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- B is H or a nucleobase moiety;
- X is halogen or —ORX;
- RX is H, C1-C6 alkyl, or —(C1-C6 alkyl)-(C6-C10 aryl), wherein the C1-C6 alkyl or —(C1-C6 alkyl)-(C6-C10 aryl) is optionally substituted with one or more RXa,
- each RXa independently is halogen, C1-C6 alkyl, or —O—(C1-C6 alkyl), wherein the C1-C6 alkyl or —O—(C1-C6 alkyl) is optionally substituted with one or more halogen;
- Y is H, C1-C6 alkyl optionally substituted with one or more halogen, —P(RY)2, —P(OR)(N(RY)2), —P(═O)(ORY)RY, —P(═S)(OR)RY, —P(═O)(SRY)RY, —P(═S)(SR)RY, —P(═O)(ORY)2, —P(═S)(ORY)2, —P(═O)(SRY)2, —P(═S)(SRY)2, or a hydroxy protecting group;
- each RY independently is H or C1-C6 alkyl optionally substituted with one or more halogen or cyano;
- Z is —P(RZ)2, —P(ORZ)(N(RZ)2), —P(═O)(ORZ)RZ, —P(═S)(ORZ)RZ, —P(═O)(SRZ)RZ, —P(═S)(SRZ)RZ, —P(═O)(ORZ)2, —P(═S)(ORZ)2, —P(═O)(SRZ)2, or —P(═S)(SRZ)2;
- each RZ independently is H or C1-C6 alkyl optionally substituted with one or more halogen or cyano;
- R1 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R2 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R3 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R4 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- indicates a single bond;
- and
- each R6 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen.
13 more elements
A Nucleic Acid Agent, or a pharmaceutically acceptable salt thereof, comprising:
- an oligonucleotide comprising one or two 5′-End Unit, wherein each 5′-End Unit independently is:
- wherein:
- B is H or a nucleobase moiety;
- X is H, halogen, or —ORX;
- RX is H, C1-C6 alkyl, or —(C1-C6 alkyl)-(C6-C10 aryl), wherein the C1-C6 alkyl or —(C1-C6 alkyl)-(C6-C10 aryl) is optionally substituted with one or more RXa;
- each RXa independently is halogen, C1-C6 alkyl, or —O—(C1-C6 alkyl), wherein the C1-C6 alkyl or —O—(C1-C6 alkyl) is optionally substituted with one or more halogen;
- Z is —P(RZ)2, —P(ORZ)(N(RZ)2), —P(═O)(ORZ)RZ, —P(═S)(ORZ)RZ, —P(═O)(SRZ)RZ, —P(═S)(SRZ)RZ, —P(═O)(ORZ)2, —P(═S)(ORZ)2, —P(═O)(SRZ)2, or P(═S)(SRZ)2;
- each RZ independently is H or C1-C6 alkyl optionally substituted with one or more halogen or cyano;
- R1 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R2 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R3 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R4 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- indicates a single bond;
- each R6 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- and
- ## indicates attachment to the rest of the oligonucleotide.
13 more elements
A conjugate, or a pharmaceutically acceptable salt thereof, comprising:
- (i) one or more Nucleic Acid Agent, wherein each Nucleic Acid Agent comprises:
- an oligonucleotide comprising one or two 5′-End Unit being covalently attached to the oligonucleotide, wherein each 5′-End Unit independently is:
- and
- (ii) one or more Ligand being covalently attached to the one or more Nucleic Acid Agent, wherein:
- B is H or a nucleobase moiety;
- X is H, halogen, or —ORX;
- RX is H, C1-C6 alkyl, or —(C1-C6 alkyl)-(C6-C10 aryl), wherein the C1-C6 alkyl or —(C1-C6 alkyl)-(C6-C10 aryl) is optionally substituted with one or more RXa,
- each RXa independently is halogen, C1-C6 alkyl, or —O—(C1-C6 alkyl), wherein the C1-C6 alkyl or —O—(C1-C6 alkyl) is optionally substituted with one or more halogen;
- Z is —P(RZ)2, —P(ORZ)(N(RZ)2), —P(═O)(ORZ)RZ, —P(═S)(ORZ)RZ, —P(═O)(SRZ)RZ, —P(═S)(SRZ)RZ, —P(═O)(ORZ)2, —P(═S)(ORZ)2, —P(═O)(SRZ)2, or —P(═S)(SRZ)2;
- each RZ independently is H or C1-C6 alkyl optionally substituted with one or more halogen or cyano;
- R1 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R2 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R3 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- R4 is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- indicates a single bond;
- each R6 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- and
- ## indicates an attachment to the rest of the oligonucleotide.
15 more elements
Dependencies are inferred from the claim text.