JPWO2020081938A5 - - Google Patents

Claims (48)

Structure (I) below:

[In the formula,
G ¹ is -N(R ³ )R ⁴ or -OR ⁵ ;
R ¹ is optionally substituted branched saturated or unsaturated C ₁₂ -C ₃₆ alkyl;
R ² is optionally substituted branched or unbranched saturated or unsaturated C ₁₂ -C ₃₆ alkyl when L is —C( ⁼ O)—; , L is C ₆ -C ₁₂ alkylene, C ₆ -C ₁₂ alkenylene, or C ₂ -C ₆ alkynylene, optionally substituted branched or unbranched saturated or unsaturated C ₄ - is _C36 alkyl;
R ³ and R ⁴ are ^each independently H or optionally substituted branched or ^unbranched saturated or unsaturated C ₁ -C ₆ alkyl; , L is C ₆ -C ₁₂ alkylene, C ₆ -C ₁₂ alkenylene, or C ₂ -C ₆ alkynylene, each independently optionally substituted branched or unbranched saturated or unsaturated saturated C ₁ -C ₆ alkyl; or R ³ and R ⁴ together with the nitrogen to which they are attached form a heterocyclyl;
R ⁵ is H or optionally substituted C ₁ -C ₆ alkyl;
L is -C(=O)-, C6 _{- C12} alkylene, C6 _- C12 alkenylene, or _{C2 -} C6 _alkynylene ; and
n is an integer from 1 to 12; ]
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof. G ¹ is -N(R ³ )R ⁴ or -OR ⁵ ;
R ¹ is optionally substituted branched saturated or unsaturated C ₁₂ -C ₃₆ alkyl;
R ² is optionally substituted branched or unbranched saturated or unsaturated C ₁₂ -C ₃₆ alkyl;
R ³ and R ⁴ are ^each independently H or optionally substituted branched or ^unbranched saturated or unsaturated C ₁ -C ₆ alkyl; with the nitrogen to which is attached forms a heterocyclyl;
R ⁵ is H or optionally substituted C ₁ -C ₆ alkyl;
L is -C(=O)-; and
n is an integer from 1 to 12;
3. A compound of claim 1, or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof. G ¹ is -N(R ³ )R ⁴ or -OR ⁵ ;
R ¹ is optionally substituted branched saturated or unsaturated C ₁₂ -C ₃₆ alkyl;
R ² is optionally substituted branched or unbranched saturated or unsaturated C ₄ -C ₃₆ alkyl;
R ³ and R ⁴ are ^each independently optionally substituted branched or ^unbranched saturated or unsaturated C ₁ -C ₆ alkyl; together with the attached nitrogen to form a heterocyclyl;
R ⁵ is H or optionally substituted C ₁ -C ₆ alkyl;
L is a C ₆ -C ₁₂ alkylene linker, a C ₆ -C ₁₂ alkenylene linker, or a C ₂ -C ₆ alkynylene linker; and
n is an integer from 1 to 12;
3. A compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof. The following structure (IA):

[In the formula,
R ⁸ and R ⁹ are each independently H or optionally substituted branched or ^unbranched saturated or unsaturated C ₂ -C ₁₂ alkyl ^; , R ¹ are each independently selected to be an optionally substituted branched saturated or unsaturated C ₁₂ -C ₃₆ alkyl; and
R ¹⁰ and R ¹¹ are each independently H or optionally substituted branched or unbranched saturated or unsaturated C ₂ -C ₁₂ alkyl; provided that L is —C (= O)—, then R ² is optionally substituted branched or unbranched saturated or unsaturated C ₁₂ -C ₃₆ alkyl; and L is C ₆ -C ₁₂ alkylene, C ₆ —C ₁₂ alkenylene, or C ₂ -C ₆ alkynylene, such that R ² is an optionally substituted branched or unbranched saturated or unsaturated C ₄ -C ₃₆ alkyl ¹⁰ and R ¹¹ are each independently selected. ]
The compound according to any one of claims 1 to 3, represented by 5. The compound of claim 4, wherein R ⁸ and R ⁹ are each independently optionally substituted branched or unbranched saturated or unsaturated C ₂ -C ₁₂ alkyl. _6. A compound according to any one of claims ₄ or ⁵ , wherein R8 is optionally substituted: _C2 alkyl, _C4 alkyl, C6 alkyl, C8 alkyl, or _C10 alkyl. . A compound according to any one of claims 4 to 6, wherein R ⁸ is optionally substituted: C ₄ alkyl, C ₆ alkyl, or C ₈ alkyl. A compound according to any one of claims 4 to 7, wherein R ⁹ is optionally substituted: C ₄ alkyl, C ₆ alkyl, C ₈ alkyl, C ₁₀ alkyl, or C ₁₂ alkyl. . A compound according to any one of claims 4 to 8, wherein R ⁹ is optionally substituted: C ₆ alkyl, C ₈ alkyl, or C ₁₀ alkyl. 10. Any one of claims 4 to 9, wherein R ¹⁰ and R ¹¹ are each independently optionally substituted branched or unbranched saturated or unsaturated C ₂ -C ₁₂ alkyl Compound as described. A compound according to any one of claims 4 to 10, wherein R ¹⁰ is optionally substituted: C ₂ alkyl, C ₄ alkyl, C ₆ alkyl, C ₈ alkyl, or C ₁₀ alkyl. . A compound according to any one of claims 4 to 11, wherein R ¹⁰ is optionally substituted: C ₄ alkyl, C ₆ alkyl, or C ₈ alkyl. A compound according to any one of claims 3 to 12, wherein R ¹¹ is optionally substituted unbranched C ₂ alkyl, C ₆ alkyl, or C ₁₀ alkyl. 14. The compound of claim ¹³ , wherein R11 is optionally substituted _C2 alkyl. _14. The compound of claim ¹³ , wherein R11 is optionally substituted C6 alkyl. 14. The compound of claim ¹³ , wherein R11 is optionally substituted _C10 alkyl. A compound according to any one of claims 4 to 12, wherein R ¹¹ is optionally substituted: C ₄ alkyl, C ₆ alkyl, C ₈ alkyl, C ₁₀ alkyl, or C ₁₂ alkyl. . A compound according to any one of claims 4 to 12, wherein R ¹¹ is optionally substituted: C ₆ alkyl, C ₈ alkyl, or C ₁₀ alkyl. 5. The method of claim 4, wherein R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ are each independently optionally substituted branched or unbranched saturated or unsaturated C ₆ -C ₁₀ alkyl. Compound as described. 5. The method of claim 4, wherein R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ are each independently optionally substituted branched or unbranched saturated or unsaturated C ₈ -C ₁₂ alkyl. Compound as described. 5. The compound of claim 4, wherein R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ are each independently branched or unbranched saturated or unsaturated C ₂ -C ₆ alkyl. 5. The method of claim 4, wherein R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ are each independently optionally substituted branched or unbranched saturated or unsaturated C ₆ -C ₁₂ alkyl. Compound as described. 2. The compound of claim 1, wherein R ¹ and R ² are each independently an optionally substituted branched saturated or unsaturated C ₁₂ -C ₃₀ alkyl. 2. The compound of claim 1, wherein R ¹ and R ² are each independently optionally substituted branched saturated or unsaturated C ₁₂ -C ₂₀ alkyl. 2. The compound of claim 1, wherein R ¹ and R ² are each independently optionally substituted branched saturated or unsaturated C ₁₅ -C ₂₀ alkyl. 26. The compound of any one of claims 1 or 23-25, wherein R ¹ and R ² are each saturated. 26. The compound of any one of claims 1 or 23-25, wherein at least one of R ¹ and R ² is unsaturated. A compound according to any one of claims 1 to 27, wherein both R ¹ and R ² are unsubstituted. wherein R ¹ and R ² each have the following structure:

2. The compound of claim 1, which is wherein R ¹ and R ² each have the following structure:

2. The compound of claim 1, which is one of R ² has the following structure:

A compound according to any one of claims 1 or 3-29, which is one of R ² has the following structure:

A compound according to any one of claims 1 or 3-29, which is one of R ¹ has the following structure:

33. The compound of any one of claims 31 or 32, which is 34. The compound of any one of claims ₁ or 3-33, wherein L is C6 _- C12 alkylene. A compound according to any one of claims 1 to 34, wherein G ¹ is -N(R ³ )R ⁴ . 36. The compound of claim 35, wherein G ¹ is -NH ₂ , -NHCH ₃ , or -N(CH ₃ ) ₂ . 36. The compound of Claim ³⁵ , wherein R3 and ^R4 together with the nitrogen to which they are attached form a heterocyclyl. G ¹ has the following structure:

38. The compound of claim 37, which is one of G ¹ has the following structure:

36. The compound of claim 35, which is: 40. The compound of any one of claims 1-39, wherein n is 1, 2, 3, 4, 5, or 6. 40. The compound of any one of claims 1-39, wherein n is 7, 8, 9, 10, 11, or 12. The structure below:

2. The compound of claim 1, which is one of The structure below:

2. The compound of claim 1, which is one of 44. A composition comprising a compound of any one of claims 1-43 and a therapeutic agent. 44. A lipid nanoparticle comprising a compound of any one of claims 1-43 and a therapeutic agent. 46. The composition or lipid nanoparticle of any one of Claims 44 or 45, wherein the therapeutic agent comprises a nucleic acid. 47. The composition or lipid nanoparticle of Claim 46, wherein the nucleic acid is selected from antisense RNA and messenger RNA (mRNA). 46. Use of the composition according to claim 44 or lipid nanoparticles according to claim 45 in the manufacture of a medicament for the delivery of therapeutic agents.