JP-2025515329-A5 -

Dates

Publication Date

20260508

Application Date

20230425

Description

Various changes and modifications to the disclosed embodiments will be obvious to those skilled in the art and can be made without departing from the spirit and scope thereof. Another aspect of the present invention may be as follows: [1] Compound of formula (I) or a pharmaceutically acceptable salt thereof (In the formula, R1 is hydrogen or a C1 - C6 alkyl group . X is selected from O, NR2 , S, and bond. R2 is hydrogen, C1 - C6 alkyl , C2 - C6 alkenyl, C2 - C6 alkynyl, C3 - C6 cycloalkyl , or halo- C1 - C6 -alkyl. L is selected from C8 - C80 alkyl , C8 - C80 alkenyl , C8 - C80 alkynyl , C8-C80 heteroalkyl, C8 - C80 heteroalkenyl , and C8 - C80 heteroalkynyl , each of which may be substituted with one or more substituents selected from hydroxyl and amino. [2] The compound described in [1] above, or a pharmaceutically acceptable salt thereof, wherein R1 is methyl . [3] The compound described in [1] or [2] above, or a pharmaceutically acceptable salt thereof, wherein L is selected from C12 - C40 alkyl and C12 - C40 alkenyl . [4] L is a compound according to any of [1] to [3] above having formula (A), or a pharmaceutically acceptable salt thereof: (In the formula, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40. R a and R b are each independently selected from C6 - C40 alkyl, C6 - C40 alkenyl, C6 - C40 heteroalkyl , and C6 - C40 heteroalkenyl . [5] The compound described in [4] above, or a pharmaceutically acceptable salt thereof, wherein n is 1, 2, 3, 4, 5, 6, 7, or 8. [6] L is a compound according to any one of the above [1] to [5], having formula (D), (E), or (F), or a pharmaceutically acceptable salt thereof: (In the formula, n, p, and q are independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40. R a1 and R a2 are each independently selected from C6 - C40 alkyl and C6 - C40 alkenyl . [7] The compound described in [6], or a pharmaceutically acceptable salt thereof, wherein n, p, and q are each independently 1, 2, 3, 4, 5, 6, 7, or 8. [8] L is a compound selected from the following, described in any one of the above items [1] to [7], or a pharmaceutically acceptable salt thereof: [9] The compound described in [1] above, wherein the compound is selected from the group consisting of the following: [10] A lipid composition comprising any of the compounds described in [1] to [9] above. [11] The lipid composition according to [10], further comprising one or more cationic and/or ionizable lipids, phospholipids, neutral or non-cationic lipids, or combinations thereof. [12] The lipid composition according to [10] or [11], further comprising structural lipids. [13] The lipid composition according to [12], wherein the structural lipid is selected from the group consisting of cholesterol, fecosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatidine, cholesteryl hemisuccinate, cholesteryl sulfate, ursolic acid, alpha-tocopherol, and mixtures thereof. [14] A lipid composition according to any one of [10] to [13], further comprising polyethylene glycol (PEG)-lipid conjugate. [15] A lipid composition according to any one of [10] to [14], further comprising at least one active agent. [16] The lipid composition according to [15], wherein at least one active agent is encapsulated in liposomes, lipid nanoparticles, or micelles in the lipid composition. [17] The lipid composition according to [15] or [16], wherein the at least one active agent comprises nucleic acid or protein. [18] The lipid composition according to any one of [15] to [17], wherein the at least one active agent comprises RNA. [19] The lipid composition according to [18], wherein the RNA is selected from the group consisting of small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), dicer substrate RNA (dsRNA), small hairpin RNA (shRNA), messenger RNA (mRNA), ribozymes, and mixtures thereof. [20] The lipid composition according to any one of [17] to [19], wherein the nucleic acid encodes an antigen or a functional fragment thereof. [21] The lipid composition according to any one of [10] to [20], wherein the at least one active agent comprises an immunomodulator, a chemotherapeutic agent, a steroid, an analgesic, an antibacterial agent, or a combination thereof. [22] A pharmaceutical composition comprising a lipid composition according to any one of [10] to [21] above and a pharmac