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US 2023/0227480 A1Published application
Polyhydroxylated cyclopentane 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 linker compounds of Formula (I) or (II): pharmaceutically acceptable salts thereof, and related scaffolds and conjugates. The present disclosure also relates to uses of the linker compounds, scaffolds, and conjugates, e.g., in delivering nucleic acid and/or treating or preventing diseases.
Claims28
A compound of Formula (I) or (II):
- or a pharmaceutically acceptable salt thereof, wherein:
- W is H, C1-C6 alkyl optionally substituted with one or more halogen, or an amino substitution group;
- 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;
- Y is H, C1-C6 alkyl optionally substituted with one or more halogen, —P(RY)2, —P(ORY)(N(RY)2), —P(═O)(ORY)RY, —P(═S)(ORY)RY, —P(═O)(SRY)RY, —P(═S)(SRY)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 H, or C1-C6 alkyl optionally substituted with one or more halogen, —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, —P(═S)(SRZ)2, or a hydroxy protecting group;
- each Rz independently is H or C1-C6 alkyl optionally substituted with one or more halogen or cyano;
- or Y and Z in Formula (I), together form —Si(RL)2—O—Si(RL)2—, wherein each RL independently is H or C1-C6 alkyl;
- 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;
- and
- each R5 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- and
- each R6 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen.
15 more elements
A scaffold or a pharmaceutically acceptable salt thereof, wherein the scaffold comprises:
- (i) one or more Ligands, or one or more Nucleic Acid Agents;
- and
- (ii) one or more Linker Units, wherein each Linker Unit independently is:
- wherein:
- W is H, C1-C6 alkyl optionally substituted with one or more halogen, or an amino substitution group;
- 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;
- Y is H, C1-C6 alkyl optionally substituted with one or more halogen, —P(RY)2, —P(ORY)(N(RY)2), —P(═O)(ORY)RY, —P(═S)(ORY)RY, —P(═O)(SRY)RY, —P(═S)(SRY)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 H, or C1-C6 alkyl optionally substituted with one or more halogen, —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, —P(═S)(SRZ)2, or a hydroxy protecting group;
- each RZ independently is H or C1-C6 alkyl optionally substituted with one or more halogen or cyano;
- or Y and Z in Formula (I), together form —Si(RL)2—O—Si(RL)2—, wherein each RL independently is H or C1-C6 alkyl;
- 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;and
- each R5 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- each R6 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- # indicates an attachment to the Ligand, and ## indicates an attachment to the Nucleic Acid Agent.
17 more elements
(canceled)
A conjugate or a pharmaceutically acceptable salt thereof, wherein the conjugate comprises:
- (i) one or more Nucleic Acid Agent;
- (ii) one or more Ligand;
- and
- (iii) one or more Linker Unit, wherein each Linker Unit independently is:
- wherein:
- 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;
- Y is H, C1-C6 alkyl optionally substituted with one or more halogen, —P(RY)2, —P(ORY)(N(RY)2), —P(═O)(ORY)RY, —P(═S)(ORY)RY, —P(═O)(SRY)RY, —P(═S)(SRY)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 H, or C1-C6 alkyl optionally substituted with one or more halogen, —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, —P(═S)(SRZ)2, or a hydroxy protecting group;
- each RZ independently is H or C1-C6 alkyl optionally substituted with one or more halogen or cyano;
- or Y and Z in Formula (I), together form —Si(RL)2—O—Si(RL)2—, wherein each RL independently is H or C1-C6 alkyl;
- 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;and
- each R5 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- each R6 independently is H, halogen, or C1-C6 alkyl optionally substituted with one or more halogen;
- # indicates an attachment to the Ligand, and ## indicates an attachment to the Nucleic Acid Agent.
17 more elements
5-8. (canceled)
23-34. (canceled)
(canceled)
42-43. (canceled)
Dependencies are inferred from the claim text.