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US 2025/0092083 A1Published application
Sterol based ionizable lipids and lipid nanoparticles comprising the same
AssigneesAdvanced RNA Vaccine (ARV) Technologies, Inc., Suzhou Vencubio Ltd.
InventorsJiangsheng XU, Jiayi ZHENG, Ju Hyeong JEON, Renhuan XU
Life of this patent
Estimating the term…
Abstract
Described are compounds, compositions, and methods for delivery of therapeutic, diagnostic, or prophylactic agents (for example, a nucleic acid).
Claims7
A compound of Formula Y:
- or pharmaceutically acceptable salts thereof, wherein:
- R is H or —CH3;
- denotes carbon-carbon bond or carbon-carbon double bond;
- R7 is H or OR16;
- R8a and R8b are each independently, H or OR16, or R8a and R8b, together with the atom to which each is attached, combine to form a cycloalkyl, aryl, heterocycloalkyl, or heteroaryl;
- R9 is H, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
- W is CR4a or CR4aR4b, where if a double bond is present between W and the adjacent carbon, then W is CR4a;
- and if a single bond is present between W and the adjacent carbon, then W is CR4aR4b;
- each of R4a and R4b is, independently, H, halogen, or C1-C6 alkyl;
- A is
- X is O or S;
- L1 is —O(C═O)—, —C(═O)—, —S(O)x—, —C(═O)RaC(═O)—, —NRaC(═O)—, —NC(═O)RaC(═O)—, or —C(═O)NRaC(═O)—;
- L2 is —O(C═O)—, —(C═O)O—, —O(C═O)O—, —C(═O)—, —O—, —S(O)x—, —S—S—, —NRaC(═O)—, or —C(═O)RaN—;
- L3 is absent, —O(C═O)—, —(C═O)O—, —O(C═O)O—, —C(═O)—, —O—, —NRaC(═O)—, or —C(═O)RaN—;
- Ra is
- wherein n is an integer from 0 to 12;
- x is 0, 1, or 2;
- M is CH,
- G1, G2 and G3 are each independently selected from C1-C12 alkyl or C1-C12 alkenyl;
- G4 is absent or selected from C1-C12 alkyl or C1-C12 alkenyl;
- R2 is —CRbRc, C6-C24 alkyl or C6-C24 alkenyl;
- R3 is
- R6 is H, ORb, CN, —C(═O)ORb, —NC(═O)Rb, —C(═O)NRb,
- Rb and Rc are independently H, C1-C12 alkyl or C1-C12 alkenyl;
- p and q are independently 0, 1, 2, 3 or 4;
- R35 is
- L4 is absent,
- R10 is absent or C1-C6 alkyl;
- L5 is absent, or
- m is an integer 1, 2, or 3;
- L6 is absent,
- R4 is a C3-C10 alkyl, C3-C10 cycloalkyl, C3-C10 alkenyl, C3-C10 cycloalkenyl, C3-C10 alkynyl, C3-C10 aryl, C2-C9 heterocyclyl, or C2-C9 heteroaryl;
- L7 is C1-C6 alkylene;
- R13a, R13b, and R13c are each independently C1-C6 alkyl or C6-C10 aryl;
- R14, R16, R19, R21, R22, R24, R28, R29, and R31 are each independently H or C1-C6 alkyl;
- R15 is —OR16, —NR17R17, or
- R17 are each independently H, —OR16, C6-C10 aryl, or C1-C6 alkyl;
- R18 are each independently halogen or C1-C6 alkyl;
- o1 is an integer from 0 to 8;
- p1 and p2 are each independently an integer from 0 to 2;
- Z is CH2, O, S, or NR16;
- s and t are each independently 0 or 1;
- R23 is halo, hydroxyl, C1-C6 alkyl, or C1-C6 heteroalkyl;
- R20, R25a and R25b, R30a, R30b, R30c, R32a, R32b, and R34 are each independently C1-C6 alkyl;
- R26a and R26b are each independently H, C1-C6 alkyl, or R26a and R26b, together with the atom to which each is attached combine to form
- were R26c and R26d are each independently H or substituted C1-C6 alkyl;
- R27a and R26b are each independently H, hydroxyl, or C1-C6 alkyl;
- u is 1, 2, or 3;
- R33a and R33b are each independently C1-C6 alkyl, C1-C6 heteroalkyl, halogen, or hydroxyl;
- Q is O, S, or NR16;
- and
- or a pharmaceutically acceptable salt thereof.
49 more elements
A compound of Formula I:
- or pharmaceutically acceptable salts thereof, wherein:
- R1 is H or —CH3;
- denotes carbon-carbon bond or carbon-carbon double bond;
- L4 is absent,
- R10 is absent or C1-C6 alkyl;
- L5 is absent, or
- m is an integer 1, 2, or 3;
- L6 is absent,
- R4 is a C3-C10 alkyl, C3-C10 cycloalkyl, C3-C10 alkenyl, C3-C10 cycloalkenyl, C3-C10 alkynyl, C3-C10 aryl, C2-C9 heterocyclyl, C2-C9 heteroaryl;
- R7 is H or OR16;
- R8a and R8b are each independently, H or OR16, or R8a and R8b, together with the atom to which each is attached, combine to form a cycloalkyl, aryl, heterocycloalkyl, or heteroaryl;
- R16 is H or C1-C6 alkyl;
- R9 is H, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
- W is CR4a or CR4aR4b, where if a double bond is present between W and the adjacent carbon, then W is CR4a;
- and if a single bond is present between W and the adjacent carbon, then W is CR4aR4b;
- each of R4a and R4b is, independently, H, halogen, or C1-C6 alkyl;
- A is
- X is O or S;
- L1 is —O(C═O)—, —C(═O)—, —S(O)x—, —C(═O)RaC(═O)—, —NRaC(═O)—, —NC(═O)RaC(═O)—, or —C(═O)NRaC(═O)—;
- L2 is —O(C═O)—, —(C═O)O—, —O(C═O)O—, —C(═O)—, —O—, —S(O)x—, —S—S—, —NRaC(═O)—, or —C(═O)RaN—;
- L3 is absent, —O(C═O)—, —(C═O)O—, —O(C═O)O—, —C(═O)—, —O—, —NRaC(═O)—, or —C(═O)RaN—;
- Ra is
- wherein n is an integer from 0 to 12;
- x is 0, 1, or 2;
- M is CH,
- G1, G2 and G3 are each independently selected from C1-C12 alkyl or C1-C12 alkenyl;
- G4 is absent or selected from C1-C12 alkyl or C1-C12 alkenyl;
- R2 is —CRbRc, C6-C24 alkyl or C6-C24 alkenyl;
- R3 is
- R6 is H, ORb, CN, —C(═O)ORb, —NC(═O)Rb, —C(═O)NRb,
- Rb and Rc are independently H, C1-C12 alkyl or C1-C12 alkenyl;
- and
- p and q are independently 0, 1, 2, 3 or 4;
- or a pharmaceutically acceptable salt thereof.
31 more elements
A compound of Formula Ia:
- or pharmaceutically acceptable salts thereof, wherein:
- R1 is H or —CH3;
- denotes carbon-carbon bond or carbon-carbon double bond;
- L4 is absent,
- L5 is absent, or
- wherein m is an integer 1, 2, or 3;
- L6 is absent,
- R4 is a C3-C10 alkyl, C3-C10 cycloalkyl, C3-C10 alkenyl, C3-C10 cycloalkenyl, C3-C10 alkynyl, C3-C10 aryl, C2-C9 heterocyclyl, C2-C9 heteroaryl;
- R10 is absent or C1-C6 alkyl;
- A is
- X is O or S;
- L1 is —O(C═O)—, —C(═O)—, —S(O)x—, —C(═O)RaC(═O)—, —NRaC(═O)—, —NC(═O)RaC(═O)—, or —C(═O)NRaC(═O)—;
- L2 is —O(C═O)—, —(C═O)O—, —O(C═O)O—, —C(═O)—, —O—, —S(O)x—, —S—S—, —NRaC(═O)—, or —C(═O)RaN—;
- L3 is absent, —O(C═O)—, —(C═O)O—, —O(C═O)O—, —C(═O)—, —O—, —NRaC(═O)—, or —C(═O)RaN—;
- Ra is
- wherein n is an integer from 0 to 12;
- x is 0, 1, or 2;
- M is CH,
- G1, G2 and G3 are each independently selected from C1-C12 alkyl or C1-C12 alkenyl;
- G4 is absent or selected from C1-C12 alkyl or C1-C12 alkenyl;
- R2 is —CRbRc, C6-C24 alkyl or C6-C24 alkenyl;
- R3 is
- R6 is H ORb, CN, —C(═O)ORb, —NC(O)Rb, —C(═O)NRb,
- Rb and Rc are independently H, C1-C12 alkyl or C1-C12 alkenyl;
- and
- p and q are independently 0, 1, 2, 3 or 4;
- or a pharmaceutically acceptable salt thereof.
24 more elements
5-7. (canceled)
A compound of Formula II or Formula III:
- or pharmaceutically acceptable salts thereof, wherein:
- R is H or —CH3;
- X is O or S;
- denotes carbon-carbon bond or carbon-carbon double bond;
- L4 is absent,
- R10 is absent or C1-C6 alkyl;
- L5 is absent, or
- m is an integer 1, 2, or 3;
- L6 is absent,
- R4 is a C3-C10 alkyl, C3-C10 cycloalkyl, C3-C10 alkenyl, C3-C10 cycloalkenyl, C3-C10 alkynyl, or a derivative thereof;
- L1 is —O(C═O)—, —C(═O)—, —S(O)x—, —C(═O)RaC(═O)—, —NRaC(═O)—, —NC(═O)RaC(═O)—, or —C(═O)NRaC(═O)—;
- L2 is —O(C═O)—, —(C═O)O—, —O(C═O)O—, —C(═O)—, —O—, —S(O)x—, —S—S—, —NRaC(═O)—, or —C(═O)RaN—;
- L3 is absent, —O(C═O)—, —(C═O)O—, —O(C═O)O—, —C(═O)—, —O—, —NRaC(═O)—, or —C(═O)RaN—;
- Ra is
- wherein n is an integer from 0 to 12;
- x is 0, 1, or 2;
- M is CH,
- G1, G2 and G3 are each independently selected from C1-C12 alkyl or C1-C12 alkenyl;
- G4 is absent or selected from C1-C12 alkyl or C1-C12 alkenyl;
- R2 is —CRbRc, C6-C24 alkyl or C6-C24 alkenyl;
- R3 is
- R6 is H, ORb, CN, —C(═O)ORb, —N(═O)Rb, —C(═O)NRb,
- Rb and Rc are independently H, C1-C12 alkyl or C1-C12 alkenyl;
- and
- p and q are independently 0, 1, 2, 3 or 4;
- or a pharmaceutically acceptable salt thereof.
23 more elements
9-85. (canceled)
Dependencies are inferred from the claim text.