Ionic lipids

Abstract

The present invention generally relates to the field of ionic (also referred to as cationic) lipids, and in particular provides a novel type of such lipid represented by formula (I). The present invention further provides methods for producing such lipids and their use, in particular in the preparation of nanoparticle compositions, more specifically in the preparation of nanoparticle compositions containing nucleic acids. The present invention further provides pharmaceutical formulations comprising nanoparticle compositions based on the ionic lipids disclosed herein.

Description

[Technical Field]

[0001] The present invention generally relates to the field of lipids, particularly ionic (also referred to as cationic) lipids, and in particular provides novel types of such lipids represented by any of the formulas disclosed herein. The present invention further provides methods for producing such lipids and their use, in particular in the preparation of nanoparticle compositions, more specifically in nanoparticle compositions containing nucleic acids. The present invention further provides pharmaceutical formulations comprising nanoparticle compositions based on the ionic lipids disclosed herein. [Background technology]

[0002] Nanoparticles, such as liposomes and lipid nanoparticles, are increasingly being used in the therapeutic field to deliver active drugs, such as small molecules, proteins, and nucleic acids, to cells. One of the main requirements for the medical use of nanoparticles is that they must combine efficient and stable encapsulation of active drugs during storage and in the extracellular environment with maximum cellular uptake and efficient release of the payload into the cell.

[0003] Lipid nanoparticles, including combinations of cationic lipids and other lipid components, have been used to facilitate such cellular uptake of active drugs. For example, lipid-based nanoparticles, typically composed of cationic or ionic lipids that can be protonated at acidic pH, helper lipids (e.g., phospholipids), stabilizing lipids (e.g., PEGylated lipids), and sterols, have been used for nucleic acid delivery.

[0004] Each component of nanoparticles possesses a unique function in terms of nanoparticle stability and activity. Therefore, further improvements in the chemical properties of cationic or ionic lipids are necessary to improve the efficacy and safety of nanoparticle-delivered active agents.

[0005] Accordingly, the present invention relates to a new class of ionic lipids, as defined by the set of claims, having improved properties compared to the currently available classes of ionic lipids.

Summary of the Invention

[0006] In a first aspect, the present invention provides a compound of formula (I):

Chemical formula

[0007] In a more specific embodiment, the present invention relates to formula (I): [Chemical formula] (wherein n is an integer selected from 1, 2, and 3, m is an integer selected from 0, 1, 2, 3, and 4, the sum of n and m is at least 4, R1 in each case independently is -H, -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl, and the -C 1-20 alkyl, -C 2-20 ​​Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independently selected from direct bonds and -CH2- in each case. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NRa C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR4R 4’ Cy1, -C(O)-C 1-6 Alkilen-NR4R 4’ , -C(O)-C 1-6 Alkylene-Cy1,-C(O)OC 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkylene-Cy1,-OC(O)-C 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Substituting with one to three substituents independently selected from alkylene-Cy1, R4 extends to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group may be optionally and independently substituted with one to three substituents independently selected from Het1 and Ar1, or R4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5- to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy1 is independently a 5- to 10-membered aromatic or non-aromatic ring in each case, and optionally and independently contains 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b'Substituted with 1 to 5 substituents independently selected from, the above Cy1 contains at least one N atom, Het1 is, independently in each case, a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, and optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, Ar1 is independently a 5-membered or 6-membered aromatic ring in each case, and optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally a -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 The present invention provides lipids, particularly ionic lipids, that are represented by (substituted with one to three substituents independently selected from the alkyl-OH group).

[0008] In a more specific embodiment, the present invention relates to formula (I): [ka] (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is optionally and independently substituted with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -OC(O)-, -NR a C(O)-, -NR a C(O)O- and -OC(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR4R 4’ Cy1, -C(O)-C 1-6 Alkilen-NR4R 4’ , -C(O)-C 1-6 Alkylene-Cy1,-C(O)OC 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkylene-Cy1,-OC(O)-C 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Substituting with one to three substituents independently selected from alkylene-Cy1, R4 extends to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group may be optionally and independently substituted with one to three substituents independently selected from Het1 and Ar1, or R4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5- to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy1 is independently a 5- to 10-membered aromatic or non-aromatic ring in each case, and optionally and independently contains 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, the above Cy1 contains at least one N atom, Het1 is, independently in each case, a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, and optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, Ar1 is independently a 5-membered or 6-membered aromatic ring in each case, and optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally a -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6The present invention provides lipids, particularly ionic lipids, that are represented by (substituted with one to three substituents independently selected from the alkyl-OH group).

[0009] In a more specific embodiment, the present invention relates to formula (I): [ka] (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is optionally and independently substituted with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R3 is independently -CH3, -OH, -CH2-OH, -CH2-SH, and -CH2-NR4R in each case. 4’ Selected from , and -C(O)H, R4 extends to each case and R 4' These are -H and -C, respectively, independently in each case. 1-6 We provide lipids represented by alkyl groups, particularly ionic lipids.

[0010] In a more specific embodiment, the present invention relates to formula (I): [ka] (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is optionally and independently substituted with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, and -C 1-12 Selected from alkylene, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR4R 4’ Cy1, -C(O)-C 1-6 Alkilen-NR4R 4’ , -C(O)-C 1-6 Alkylene-Cy1,-C(O)OC 1-6 Alkilen-NR4R 4’ -C(O)OC1-6 Alkylene-Cy1,-OC(O)-C 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Substituting with one to three substituents independently selected from alkylene-Cy1, R4 extends to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group may be optionally and independently substituted with one to three substituents independently selected from Het1 and Ar1, or R4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5- to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy1 is independently a 5- to 10-membered aromatic or non-aromatic ring in each case, and optionally and independently contains 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, the above Cy1 contains at least one N atom, Het1 is, independently in each case, a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, and optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -C 1-6 Alkyl and -C 1-6Substituted with one to three substituents independently selected from the alkyl-OH group, Ar1 is independently a 5-membered or 6-membered aromatic ring in each case, and optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally a -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 The present invention provides lipids, particularly ionic lipids, that are represented by (substituted with one to three substituents independently selected from the alkyl-OH group).

[0011] In a particular embodiment, the present invention relates to formula (Ia): [ka] (In the formula, m is an integer selected from 3 and 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independently selected in each case from direct bonds and -CH2- bonds. FG is independent in each case, -O-, -NR a -, -OC(O)-, -NR a C(O)-, -NR a C(O)O- and -OC(O)NR a- Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R3 is independently -CH3, -OH, -CH2-OH, -CH2-SH, and -CH2-NR4R in each case. 4’ Selected from , and -C(O)H, R4 extends to each case and R 4' These are -H and -C, respectively, independently in each case. 1-6 We provide lipids represented by alkyl groups, particularly ionic lipids.

[0012] In more specific embodiments, the present invention is defined herein by formula (IIa) or formula (IIb): [ka] (In the formula, X1 is directly joined in each case, X2 in each case, and X3 in each case independently, -C 1-6 Alkylene-,-C2-6 Alkenylene-, and -C 2-6 Selected from alkynylene, R5 extends to each case and R 5' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, X1, X2, X3, R5 and R 5' In each of these cases, X1, X2, X3, R5 and R, which are associated with the N atom to which they are bonded. 5' The total number of C atoms is at least 5. Y, FG, Z, R3, R4, R 4’ Cy1, Het1, Ar1, R a , R b , R b’ The present invention provides lipids, particularly ionic lipids, represented by (where n and m are as defined herein).

[0013] In another specific embodiment, the present invention is defined herein by formula (IIIa) or formula (IIIb): [ka] (In the formula, X4 is independent in each case and X5 is independent in each case, -C 1-12 Selected from alkylene, R6 extends to each case and R 6' In each case, -C 1-20 Alkyl, -C 2-20Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, X4, X5, R6 and R 6' In each of these cases, X4, X5, R6 and R, which are associated with the N atom to which they are bonded. 6' The total number of C atoms is at least 6. Y, FG, Z, R3, R4, R 4’ Cy1, Het1, Ar1, R a , R b , R b’ The present invention provides lipids, particularly ionic lipids, represented by (where n and m are as defined herein).

[0014] In more specific embodiments, the present invention is defined herein by formula (IIIb): [ka] (In the formula, n is 1, m is 3, X4 is independent in each case and X5 is independent in each case, -C 1-12 Selected from alkylene, R6 extends to each case and R 6' In each case, -C 8-20 Alkyl, -C 8-20 Alkenyl and -C 8-20 Selected from Alkinil, Y, FG, Z, R3, R4, R 4’ Cy1, Het1, Ar1, R a , Rb , and R b' The present invention provides lipids, particularly ionic lipids, represented as (as defined herein).

[0015] In more specific embodiments, the present invention is defined herein by formulas (Va), (VaN), (Va'), (Va'N), (Vb), (VbN), (Vb'), (Vb'N), (Vc), (VcN), (Vd), (VdN), (Vd'), (Vd'N), (Ve), or (VeN): [ka] [ka] [ka] The present invention provides lipids represented by the formula (wherein Z, R1, R2, and R7 are as defined herein), particularly ionic lipids.

[0016] In particular, the present invention relates to formula (VII): [ka] (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. R1 is -H, -C in each case and R2 is -H, -C in each case independently. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl optionally further contains one or more heteroatoms and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, the total number of C atoms in R1 and R2 is at least 8. Y1 is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, Y2 is independently selected from -O- and -NR4- in each case. B1 is independently selected from =O and =S in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6Alkilen-NR4R 4’ Substituted with one to three substituents independently selected from, R4 extends to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional N atoms and / or optionally -C 1-6 Alkyl and -C 1-6 The present invention provides ionic lipids represented by (substituted with one to three substituents selected from alkyl-OH groups).

[0017] In particular, the present invention relates to formula (VIIIa) or formula (VIIIb): [ka] (In the formula, X1 is directly joined in each case, X2 in each case, and X3 in each case independently, -C 1-6 Alkylene-,-C 2-6 Alkenylene-, and -C 2-6 Selected from alkynylene, R5 extends to each case and R 5' In each case, -C 1-20 Alkyl, -C2-20 Alkenyl and -C 2-20 Selected from alkinyl, X1, X2, X3, R5 and R 5' The total number of C atoms in is at least 5. Y1, Y2, Z, B1, R3, R4, R 4’ The present invention provides an ionic lipid represented as follows (where n and m are as defined in any one embodiment of the present invention).

[0018] In particular, the present invention relates to formula (IXa) or formula (IXb): [ka] (In the formula, X4 is independent in each case and X5 is independent in each case, -C 1-20 Alkylene-,-C 2-20 Alkenylene-, and -C 2-20 Selected from alkynylene, R6 extends to each case and R 6' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from Alkinyl, X4, X5, R6 and R 6' The total number of C atoms in is at least 6. Y1, Y2, Z, B1, R3, R4, R 4' The present invention provides an ionic lipid represented as follows (where n and m are as defined in any one embodiment of the present invention).

[0019] In particular, the present invention, formula (Xa), formula (Xb), formula (Xc), formula (Xd), or formula (Xe): [ka] (In the formula, Y1, Y2, Z, B1, R1, R2, R3, R4, R 4’ The present invention provides an ionic lipid represented by (where m is as defined in any one embodiment of the present invention).

[0020] In particular, the present invention provides an ionic lipid in which n is 1.

[0021] In particular, the present invention provides ionic lipids in which m is an integer selected from 1, 2, and 3.

[0022] In particular, the present invention allows R1 to be -H and -C in each case and R2 to be -H and -C in each case independently. 1-8 Selected from alkyl groups, and the above-C 1-8 Each alkyl group is independently -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 The present invention provides an ionic lipid substituted with one to three substituents independently selected from the alkenyl, wherein the total number of carbon atoms in R1 and R2 is at least eight.

[0023] In particular, the present invention provides ionic lipids in which Y1 is independently selected from directly bonded and -CH2- in each case.

[0024] In particular, the present invention provides an ionic lipid in which Y2 is independently selected from -O- in each case.

[0025] In particular, the present invention provides ionic lipids in which B1 is independently = O in each case.

[0026] In particular, the present invention allows Z to be independently -C in each case. 1-3 We provide ionic lipids selected from alkylenes.

[0027] In particular, the present invention provides ionic lipids in which R3 is independently selected from -CH3, -OH, -CH2-OH, and -CH2-NH2 in each case.

[0028] In further embodiments, the present invention provides lipids, particularly ionic lipids, selected from the list defined herein, including the following:

[0029] [Table A-1] [Table A-2] [Table A-3] [Table A-4] [Table A-5] [Table A-6] [Table A-7]

[0030] In a further embodiment, the present invention provides lipid nanoparticles or lipid nanoparticle compositions comprising lipids as defined herein, particularly ionic lipids. The nanoparticle compositions may further contain additional lipids, such as phospholipids, sterols, and / or PEG lipids, which may or may not act as stabilizers.

[0031] In further embodiments, the lipid nanoparticles or lipid nanoparticle compositions as defined herein further comprise an active agent, particularly nucleic acids, preferably mRNA.

[0032] In a further embodiment, the present invention provides the use of lipids as defined herein, particularly ionic lipids, in the production of lipid nanoparticles or lipid nanoparticle compositions.

[0033] In a further embodiment, the present invention relates to formula (I): [ka] (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is optionally and independently substituted with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR4R 4’ Cy1, -C(O)-C 1-6 Alkilen-NR4R 4’ , -C(O)-C 1-6 Alkylene-Cy1,-C(O)OC 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkylene-Cy1,-OC(O)-C 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Substituting with one to three substituents independently selected from alkylene-Cy1, R4 extends to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group may be optionally and independently substituted with one to three substituents independently selected from Het1 and Ar1, or R4 and R 4'In each case, together with the N atom to which they are bonded, they form a 5- to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy1 is independently a 5- to 10-membered aromatic or non-aromatic ring in each case, and optionally and independently contains 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, the above Cy1 contains at least one N atom, Het1 is, independently in each case, a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, and optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, Ar1 is independently a 5-membered or 6-membered aromatic ring in each case, and optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally a -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 The present invention provides ionic lipids represented by (substituted with one to three substituents independently selected from the alkyl-OH group).

[0034] In a final embodiment, the present invention provides a pharmaceutical composition comprising one or more nanoparticles as defined herein and a pharmaceutically acceptable agent such as a carrier or excipient. Such pharmaceutical compositions are particularly suitable for various applications such as prophylactic vaccines, therapeutic vaccines, protein replacement therapy, gene editing, gene silencing, and small molecule delivery. [Brief explanation of the drawing]

[0035] [Figure 1] This figure shows the viability of HEK 293T cells after incubation for 24 hours with 50 ng / well or 200 ng / well of each LNP preparation. [Figure 2] This figure shows the relative mean fluorescence intensity (MFI) of eGFP in HEK 293T cells after incubation for 24 hours with 50 ng / well or 200 ng / well of each LNP formulation. [Figure 3] This figure shows the viability of HEK 293T cells after incubation for 24 hours with 50 ng / well or 200 ng / well of each LNP preparation. [Figure 4] This figure shows the relative mean fluorescence intensity (MFI) of eGFP in HEK 293T cells after incubation for 24 hours with 50 ng / well or 200 ng / well of each LNP formulation. [Figure 5]This figure shows the average radiance measured in vivo (supine position) for different LNP formulations containing fluc mRNA. [Figure 6] This figure shows the average radiance measured ex vivo for different LNP formulations containing fluc mRNA. [Figure 7] This figure shows the mean hEPO levels in the blood measured at different time points 24 hours after injection. Three injections were administered at one-week intervals. [Modes for carrying out the invention]

[0036] Detailed description of the invention The present invention will now be described further. The following sections will further specify various aspects of the present invention. Each aspect specified herein may be combined with any other aspect(s) unless explicitly stated otherwise. In particular, any feature shown to be preferred or advantageous may be combined with any other feature(s) shown to be preferred or advantageous.

[0037] Unless otherwise indicated by the context, the asterisk is used herein to indicate the point in which the indicated monovalent or divalent radical is linked to a structure in which it is involved and which the radical forms part.

[0038] As already described herein, in the first embodiment, the present invention relates to formula (I): [ka] (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6Alkenylene- and -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is optionally and independently substituted with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR4R 4’ Cy1, -C(O)-C 1-6 Alkilen-NR4R 4’ , -C(O)-C 1-6 Alkylene-Cy1,-C(O)OC 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkylene-Cy1,-OC(O)-C 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Substituting with one to three substituents independently selected from alkylene-Cy1, R4 extends to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group may be optionally and independently substituted with one to three substituents independently selected from Het1 and Ar1, or R4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5- to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy1 is independently a 5- to 10-membered aromatic or non-aromatic ring in each case, and optionally and independently contains 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, the above Cy1 contains at least one N atom, Het1 is, independently in each case, a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, and optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, Ar1 is independently a 5-membered or 6-membered aromatic ring in each case, and optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally a -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6The present invention provides lipids, particularly ionic lipids, that are represented by (substituted with one to three substituents independently selected from the alkyl-OH group).

[0039] When describing the compounds / lipids of the present invention, unless otherwise indicated by the context, the terms used should be interpreted according to the following definitions.

[0040] The term "alkyl" can refer to the compound C, either by itself or as part of another substituent. x H 2x+1 This refers to a fully saturated hydrocarbon of the form (wherein x is a number of 1 or more). Generally, the alkyl groups of the present invention contain 1 to 20 carbon atoms. The alkyl groups may be linear or branched and may be substituted as shown herein. Where a subscript is used after a carbon atom in this specification, the subscript indicates the number of carbon atoms that the specified group may contain. For example, C 1-4 Alkyl refers to an alkyl group with 1 to 4 carbon atoms. Examples of alkyl groups include methyl, ethyl, n-propyl, i-propyl, butyl and their isomers (e.g., n-butyl, i-butyl, and t-butyl), pentyl and its isomers, hexyl and its isomers, heptyl and its isomers, octyl and its isomers, nonyl and its isomers, decyl and its isomers, undecyl and its isomers, dodecyl and its isomers, tridecyl and its isomers, tetradecyl and its isomers, pentadecyl and its isomers, hexadecyl and its isomers, heptadecyl and its isomers, octadecyl and its isomers, nonadecyl and its isomers, eicosanyl and its isomers. The term "optionally substituted alkyl" refers to an alkyl group that is optionally substituted with one or more substituents (e.g., one to four substituents, e.g., one, two, three, or four substituents) at any available bond site. Non-limiting examples of such substituents include esters, carboxylic acids, alkyl moieties, alkene moieties, alkyne moieties, etc. An example of an optionally substituted alkyl group is -C 1-6 When referring to alkyl, it also refers to groups containing the alkyl groups mentioned above, for example, -OC 1-6Alkyl, -OC(O)-C 1-6 Alkyl, -C(O)OC 1-6 This refers to alkyl groups, etc.

[0041] In the context of the present invention, the alkyl, alkenyl, and alkynyl moieties as defined herein may further include one or more heteroatoms selected from N, S, or O, in that, for example, carbon atoms in the alkyl, alkene, or alkyne chain are replaced by heteroatoms. When two or more C atoms are replaced by heteroatoms, the heteroatoms may be adjacent or distant, as long as they produce a chemically stable compound, i.e., a compound robust enough to withstand isolation from the reaction mixture in a useful purity and formulation into therapeutic agents. An example of a stable combination of two adjacent heteroatoms is a disulfide (-SS-) group. When carbon atoms in the alkyl, alkenyl, or alkynyl chain are replaced by N atoms, the N atoms may be N or NH, depending on the number of bonds bonded to the C atoms.

[0042] As used herein, the terms “alkenyl” or “alkene” mean a linear, cyclic, or branched hydrocarbon radical containing at least one carbon-carbon double bond, unless otherwise specified. Examples of alkenyl radicals include ethenyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl, and hexadienyl, whether terminal or internal. Generally, the alkenyl or alkene moieties of the present invention contain 2 to 20 carbon atoms. An optionally substituted alkenyl refers to an alkenyl having one or more substituents (e.g., one, two, three, or four) that are optionally selected from those defined above for substituted alkyl groups.

[0043] As used herein, the term "alkynyl" means a linear or branched hydrocarbon radical containing at least one carbon-carbon triple bond, unless otherwise specified. Examples of alkynyl radicals include ethynyl, propynyl, butynyl, pentynyl, hexynyl, and hexadinyl, whether terminal or internal. An optionally substituted alkynyl refers to an alkynyl having one or more (e.g., one, two, three, or four) substituents, selected from those defined above for the substituted alkyl.

[0044] The term "cycloalkyl" refers to a cyclic alkyl group, i.e., a monovalent saturated or unsaturated hydrocarbyl group having one, two, or three cyclic structures, either by itself or as part of another substituent. Cycloalkyls include all saturated or partially saturated (including one or two double bonds) hydrocarbon groups containing one to three rings, including monocyclic, bicyclic, or polycyclic alkyl groups. Cycloalkyls may contain three or more carbon atoms in the ring, and generally, according to the present invention, contain three to fifteen carbon atoms. Examples of cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, adamantanyl, and cyclodecyl, with cyclopropyl being particularly preferred. "Optionally substituted cycloalkyl" refers to a cycloalkyl having one or more substituents (e.g., one to three substituents, e.g., one, two, three, or four substituents) that are optionally selected from the above-defined substituent alkyls.

[0045] If the defined alkyl group is divalent, that is, if it has two single bonds to bond to two other groups, it is called an "alkylene" group. Non-limiting examples of alkylene groups include methylene, ethylene, methylmethylene, trimethylene, propylene, tetramethylene, ethylethylene, 1,2-dimethylethylene, pentamethylene, and hexamethylene. Similarly, if the alkenyl group and alkynyl group defined above are divalent radicals having single bonds to bond to two other groups, they are called "alkenylene" and "alkynylene," respectively.

[0046] As used herein, the term “heterocyclic” refers to a non-aromatic, fully saturated or partially unsaturated cyclic group having, by itself or as part of another group, at least one heteroatom in at least one carbon-carbon-containing ring (e.g., a monocyclic group of 3 to 13 members, a bicyclic group of 7 to 17 members, or a tricyclic group of 10 to 20 members, or containing a total of 3 to 10 ring atoms). Each ring of a heterocyclic group containing heteroatoms may have one, two, three, or four heteroatoms selected from nitrogen, oxygen, and / or sulfur atoms, the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. The heterocyclic group may be bonded to any heteroatom or carbon atom of the ring or ring system, as long as the valence allows. The rings of a polycyclic heterocyclic group may be condensed, bridged, and / or bonded via one or more spiroatoms. An arbitrarily substituted heterocyclic compound refers to a heterocyclic compound having one or more substituents (e.g., one to four substituents, or e.g., one, two, three, or four substituents) arbitrarily selected from those defined above for the substituted alkyl. Non-restrictive examples of heterocyclic compounds include piperidinyl, azepanyl, and morpholinyl.

[0047] As used herein, the term “aryl” (also referred to herein as an aromatic heterocycle) refers to a polyunsaturated aromatic hydrocarbyl group having a single ring (i.e., phenyl) or multiple aromatic rings fused to each other (e.g., naphthalene or anthracene) or covalently bonded, typically containing 6 to 10 atoms, with at least one ring being aromatic. The aromatic ring may optionally contain one to three additional rings fused thereto (either cycloalkyl, heterocyclyl, or heteroaryl). Aryls are also intended to include partially hydrogenated derivatives of the carbocyclic systems listed herein. Non-limiting examples of aryls include phenyl, etc.

[0048] The aryl rings or heterocycles defined herein can be optionally substituted at any available bond site with one or more substituents (e.g., one to five substituents, e.g., one, two, three, or four substituents). Non-limiting examples of such substituents include halogens, hydroxyls, oxos, nitros, aminos, hydrazines, aminocarbonyls, azides, cyanos, alkyls, cycloalkyls, alkenyls, alkynyls, cycloalkylalkyls, alkylaminos, alkoxys, -SO2-NH2, aryls, heteroaryls, aralkyls, haloalkyls, haloalkoxys, alkoxycarbonyls, alkylaminocarbonyls, heteroarylalkyls, alkylsulfonamides, heterocyclyls, alkylcarbonylaminoalkyls, aryloxys, alkylcarbonyls, acyls, arylcarbonyls, aminocarbonyls, alkylsulfoxides, -SO2R a (In the formula, R a (The element is selected from alkyl or cycloalkyl, alkylthio, carboxyl, etc.)

[0049] When a carbon atom in an aryl group is replaced by a heteroatom, the resulting ring is referred to herein as a heteroaryl ring.

[0050] As used herein, the term "heteroaryl" refers, either by itself or as part of another group, to an aromatic ring of 5 to 12 carbon atoms, or a ring system typically comprising 1 to 3 fused or covalently bonded rings containing 5 to 8 atoms, at least one of which is aromatic, and one or more carbon atoms in one or more of these rings may be replaced by oxygen, nitrogen, or sulfur atoms, the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. Such rings may be fused to aryl, cycloalkyl, heteroaryl, or heterocyclyl rings. Non-limiting examples of such heteroaryls include pyridinyl and azepinyl.

[0051] An "arbitrarily substituted heteroaryl" refers to a heteroaryl having one or more substituents (e.g., one to four substituents, e.g., one, two, three, or four substituents) arbitrarily selected from those defined above for the substituted aryl.

[0052] As used herein, the term "oxo" refers to the =O group.

[0053] As used herein, the terms “alkoxy” or “alkyloxy” refer to the formula -OR x (In the formula, R x This refers to a radical having (where is alkyl). Preferably, the alkoxy is C1-C 10These are alkoxy, C1-C6 alkoxy, or C1-C4 alkoxy. Non-limiting examples of suitable alkoxys include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, and hexyloxy. When the oxygen atom in the alkoxy group is substituted with sulfur, the resulting radical is called a thioalkoxy. A "haloalkoxy" is an alkoxy group in which one or more hydrogen atoms in the alkyl group are substituted with halogens. Non-limiting examples of suitable haloalkoxys include fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy, 2,2,2-trichloroethoxy, trichloromethoxy, 2-bromoethoxy, pentafluoroethyl, 3,3,3-trichloropropoxy, and 4,4,4-trichlorobutoxy.

[0054] The terms "carboxy," "carboxyl," or "hydroxycarbonyl" refer to the group -CO2H, either by itself or as part of another substituent. Therefore, a carboxyalkyl is an alkyl group as defined above, having at least one substituent that is -CO2H.

[0055] The term "alkoxycarbonyl" refers to a compound that is attached to an alkyl radical, either by itself or as part of another substituent, i.e., -C(O)OR e (In the formula, R e This refers to the carboxyl group that forms an alkyl group (as defined above).

[0056] The term "alkylcarbonyloxy" can be used by itself or as part of another substituent, such as -OC(O)R e (In the formula, R e This refers to alkyl groups (as defined above).

[0057] As used in the present invention, the term “substituted” is always intended to mean that one or more hydrogen atoms on the atom specified by “substituted” in this expression are replaced by a group selected from the specified group, provided that the substitution does not exceed the normal valence of the atom and that the substitution results in a chemically stable compound, i.e., a compound robust enough to be isolated from the reaction mixture in a useful purity and formulated into a therapeutic agent.

[0058] If the group is optionally substituted, such group may be substituted one or more times, preferably once, twice, or three times. The substituents can be selected from the group including, for example, halogens, hydroxyls, oxos, nitros, amides, carboxyls, aminos, cyanos, haloalkoxys, and haloalkyls.

[0059] As used herein, terms such as “alkyl, aryl, or cycloalkyl each optionally substituted with” or “alkyl, aryl, or cycloalkyl each optionally substituted with” refer to optionally substituted alkyl, optionally substituted aryl, and optionally substituted cycloalkyl.

[0060] In the context of this invention, the term lipid means a chemically defined substance that is insoluble in water but soluble in alcohols, ethers, and chloroform, among other things. Ionic or cationic lipids are typically lipids composed of three sections: an amine head group, a linker moiety, and a hydrophobic tail. In the context of compounds or lipids, the term "ionic" (or alternatively, cationic) refers to an ion (usually H + This means the presence of any uncharged group in the compound or lipid that can be dissociated by obtaining an ion, and thus become positively charged itself. Alternatively, any uncharged group in the compound or lipid may obtain electrons and thus become negatively charged.

[0061] All lipids as defined herein may exist as different isomers / stereomers. In particular, lipids as defined herein may exist in trans or cis configurations, such as when they contain double bonds. In preferred embodiments, lipids as defined herein exist in a cis configuration. In the context of the present invention, the term "cis" means that the functional groups are on the same side of the plane, and the term "trans" means that the functional groups are on opposite sides.

[0062] As used herein, if a compound has one or more stereocenters, each stereocenter may have an R or S configuration unless otherwise specified. Therefore, a compound may be a racemic mixture of enantiomers and / or diastereoisomers, or may have an excess of one or more enantiomers and / or diastereoisomers, such as more than 60%, more than 70%, more than 80%, more than 85%, more than 90%, more than 95%, more than 98%, more than 99%, etc.

[0063] This new class of ionic lipids is conceived to possess improved properties compared to currently available classes of ionic lipids and to be (re)metabolizable into vitamin B derivatives (e.g., pyridoxine, pyridoxamine, pyridoxal) and / or other benign fragments.

[0064] In certain embodiments of the present invention, the present invention provides lipids, particularly ionic lipids, represented by formula (I), as defined herein and to which one or more of the following are applied. n is an integer selected from 1, 2, and 3. In particular, n is an integer selected from 1 and 2. More specifically, n is 1, m is an integer selected from 0, 1, 2, 3, and 4. In particular, m is an integer selected from 1, 2, 3, and 4. More specifically, m is an integer selected from 1, 2, and 3. More specifically, m is 3, The sum of n and m is at least 4. In particular, the sum of n and m is 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In particular, R1 is independently -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. More specifically, R1 is independently -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group is independently -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -C(O)OC 1-20 Alkyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkenyl, More specifically, R1 is independently -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group is independently -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In particular, R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. More specifically, R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group is independently -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -C(O)OC 1-20 Alkyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkenyl, More specifically, R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group is independently -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. In particular, in the cases of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is 10 to 30. More specifically, in the cases of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is between 12 and 28. More specifically, in the cases of R1 and R2, the total number of carbon atoms in R1 and R2, along with the nitrogen atoms to which they are bonded, is 14 to 26. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, In particular, R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or is optionally and independently substituted with one to three -OH substituents. In particular, R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from Alkinil, More specifically, R7 is independent in each case, -C 1-20 Alkyl and -C2-20 selected from alkenyl, more specifically, each R7 is independently, in each case, -C 8-20 alkyl, and -C 8-20 selected from alkenyl, Y is independently, in each case, a direct bond, -C 1-6 alkylene-, -C 2-6 alkenylene- and -C[[ID=!4]] 2-6 selected from alkynylene-, wherein the above -C 1-6 alkylene-, -C 2-6 alkenylene- and -C 2-6 each of alkynylene- optionally and independently contains one or more heteroatoms selected from N, O and S, and / or is optionally and independently substituted with one to three -OH substituents, in particular, Y is independently, in each case, a direct bond, -C 1-6 alkylene-, -C 2-6 alkenylene- and -C 2-6 selected from alkynylene-, more specifically, Y is independently, in each case, selected from a direct bond and -CH2-, FG is independently, in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a selected from -, in particular, FG is independently, in each case, -O-, -NR a -, -OC(O)-, -OC(O)O-, -NR a C(O)-, -NR a C(O)O-, -OC(O)NR a -, -NR aC(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, More specifically, FG is independently -O- and -NR in each case. a -, -OC(O)-, -NR a C(O)-, -NR a C(O)O- and -OC(O)NR a - Selected from, More specifically, FG is independently -OC(O)- and -NR in each case. a Selected from C(O)-, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, In particular, R a In each case, it is independently selected from -H and -CH3. More specifically, R a In each case, it is -H, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, In particular, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C2-12 Alkenylene-, and -C 2-12 Selected from alkynylene- and above-C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, More specifically, Z is independent in each case, direct bond, and -C 1-12 Selected from alkylene-, and above-C 1-12 Each alkylene- comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or optionally and independently from -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, More specifically, Z is independent in each case, -C 1-12 Selected from alkylene, More specifically, Z is independent in each case, -C 1-6 Selected from alkylene, More specifically, Z is independent in each case, -C 1-3 Selected from alkylene, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. In particular, x is an integer independently selected from 1 to 5 in each case, and y is an integer independently selected from 1 to 5 in each case. More specifically, x is an integer independently selected from 1 to 3 in each case, and y is an integer independently selected from 1 to 3 in each case. More specifically, x is an integer independently selected from 1 or 2 in each case, and y is an integer independently selected from 1 or 2 in each case. R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6Alkynyl, -OH, -O-C 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl, wherein the -C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl is optionally and independently -OH, -O-C 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , Cy1, -C(O)-C 1-6 Alkylene-NR4R 4’ , -C(O)-C 1-6 Alkylene-Cy1, -C(O)O-C 1-6 Alkylene-NR4R 4’ , -C(O)O-C 1-6 Alkylene-Cy1, -OC(O)-C 1-6 Alkylene-NR4R 4’ , and -OC(O)-C 1-6 Alkylene-Cy1 and is substituted with one to three substituents independently selected from In particular, R3 is independently in each case -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -OH, -O-C 1-6 Alkyl, -C(O)H, -OC(O)-C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Alkyl-SH, and -C 1-6 Alkyl-NR4R 4' Selected from More specifically, R3 is independently in each case -C 1-6 Alkyl, -OH, -O-C 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -C 1-6 Alkyl-OH, and -C 1-6 Alkyl-NR4R 4' Selected from Even more specifically, R3 is independently in each case -CH3, -OH, -CH2-OH, and -CH2-NR4R 4' Selected from More specifically, R3 is independently -CH3, -OH, -CH2-OH, and -CH2-NH in each case. 2' Selected from, R4 extends to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group may be optionally and independently substituted with one to three substituents independently selected from Het1 and Ar1, or R4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5- to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, In particular, R4 is in each case and R 4' In each case, the following are independently selected: -H, -CH3, -CH2-Ph, -C(O)-CH3, and -C(O)OC(CH3)3, or In particular, R4 is in each case and R 4' In each case, together with the N atoms to which they are bonded, they form a 5- to 7-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, More specifically, R4 extends to each case and R 4' In each case, together with the N atom to which they are bonded, they form a 5- to 7-membered non-aromatic heterocycle, and the heterocycle is selected from pyrrolidine, piperidine, azepine, and piperazine. More specifically, R4 is in each case and R 4'In each case, together with the N atom to which they are bonded, they form a 5- to 7-membered non-aromatic heterocycle, and the above heterocycle is an azepine. Cy1 is independently a 5- to 10-membered aromatic or non-aromatic ring in each case, and optionally and independently contains 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, the above Cy1 contains at least one N atom, In particular, Cy1 is independently a 5- to 7-membered non-aromatic ring containing at least one N atom in each case, optionally and independently containing 1 to 4 additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, More specifically, Cy1 is independently selected from pyrrolidine, piperidine, piperazine, and azepine in each case, and arbitrarily and independently, -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, More specifically, Cy1 is independently selected from pyrrolidine, piperidine, piperazine, and azepine in each case, or In particular, Cy1 is independently a 5- to 10-membered aromatic ring containing at least one N atom in each case, optionally and independently containing 1 to 4 additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, More specifically, Cy1 is independently a 5- or 6-membered aromatic ring containing at least one N atom in each case, optionally and independently containing 1 to 4 additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, More specifically, Cy1 is independently selected in each case from pyrrole, imidazole, pyrazole, oxazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, oxazine, and thiazine, and is arbitrarily and independently selected from -halo and -C. 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, More specifically, Cy1 is independently selected in each case from pyrrole, imidazole, pyrazole, oxazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, oxazine, and thiazine. Het1 is, independently in each case, a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, and optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, In particular, Het1 is independently a 5- to 7-membered non-aromatic heterocycle containing at least one N atom in each case, optionally and independently containing one to three additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, More specifically, Het1 is independently selected from pyrrolidine, piperidine, piperazine, and azepine in each case, and arbitrarily and independently, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, More specifically, Het1 is independently selected from pyrrolidine, piperidine, piperazine, and azepine in each case. Ar1 is independently a 5-membered or 6-membered aromatic ring in each case, and optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally a -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, In particular, Ar1 is independently selected in each case from phenyl, pyrrole, imidazole, pyrazole, oxazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, oxazine, and thiazine, and is optionally and independently -halo, -C 1-6Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with one to three substituents independently selected from, In particular, Ar1 is independently phenyl in each case, and optionally and independently, -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with one to three substituents independently selected from, More specifically, Ar1 is phenyl in each case, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, In particular, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, More specifically, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Selected from alkyl and -Bn.

[0065] In particular, the present invention provides an ionic lipid in which the sum of n and m is at least 4, for example, 4 or 5.

[0066] In a particular embodiment of the present invention, the sum of n and m is 4.

[0067] In certain embodiments of the present invention, n is an integer selected from 1 and 2. In preferred embodiments of the present invention, n is 1.

[0068] In an alternative embodiment, the present invention is defined herein by formula (Ia): [ka] (In the formula, m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is optionally and independently substituted with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, Ra These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR4R 4’ Cy1, -C(O)-C 1-6 Alkilen-NR4R 4’ , -C(O)-C 1-6 Alkylene-Cy1,-C(O)OC 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6Alkylene-Cy1,-OC(O)-C 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Substituting with one to three substituents independently selected from alkylene-Cy1, R4 extends to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group may be optionally and independently substituted with one to three substituents independently selected from Het1 and Ar1, or R4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5- to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy1 is independently a 5- to 10-membered aromatic or non-aromatic ring in each case, and optionally and independently contains 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with 1 to 5 substituents independently selected from, the above Cy1 contains at least one N atom, Het1 is, independently in each case, a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, and optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently containing -C 1-6 Alkyl and -C 1-6Substituted with one to three substituents independently selected from the alkyl-OH group, Ar1 is independently a 5-membered or 6-membered aromatic ring in each case, and optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally a -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 The present invention provides lipids, particularly ionic lipids, that are represented by (substituted with one to three substituents independently selected from the alkyl-OH group).

[0069] In certain embodiments of the present invention, m is an integer selected from 1, 2, 3, and 4. In other specific embodiments of the present invention, m is an integer selected from 2, 3, and 4. In a preferred embodiment of the present invention, m is 3.

[0070] In particular, the present invention allows R1 to be independently -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20An ionic lipid is provided in which each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7.

[0071] In particular, the present invention allows R2 to be independently -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20 An ionic lipid is provided in which each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7.

[0072] In particular, the present invention allows, R1 independently determines -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 An ionic lipid is provided in which each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7.

[0073] In particular, the present invention allows, R7 is independent in each case, -C 1-20 Alkyl and -C 2-20 Selected from alkenyl, and the above-C 1-20 Alkyl and -C 2-20An ionic lipid is provided in which each alkenyl is optionally and independently substituted with one to three -OH substituents.

[0074] In particular, the present invention allows, R1 independently determines -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R7 is independent in each case, -C 1-20 Alkyl and -C 2-20 Selected from alkenyl, and the above-C 1-20 Alkyl and -C 2-20 An ionic lipid is provided in which each alkenyl is optionally and independently substituted with one to three -OH substituents.

[0075] In particular, the present invention allows R7 to be independently -C in each case. 8-20 Alkyl and -C 8-20 Selected from alkenyl, and the above-C 8-20 Alkyl and -C 8-20 An ionic lipid is provided in which each alkenyl is optionally and independently substituted with one to three -OH substituents.

[0076] In particular, the present invention allows, R1 independently determines -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20Each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R7 is independent in each case, -C 8-20 Alkyl and -C 8-20 Selected from alkenyl, and the above-C 8-20 Alkyl and -C 8-20 An ionic lipid is provided in which each alkenyl is optionally and independently substituted with one to three -OH substituents.

[0077] In particular, the present invention allows, R1 independently determines -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -C(O)OC 1-20 Alkyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkenyl, R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20Alkenyl, -C(O)OC 1-20 Alkyl and -C(O)OC 2-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0078] In particular, the present invention allows, R1 independently determines -H and -C in each case. 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0079] In particular, according to the present invention, R1 is independent in each case and R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -C(O)OC 1-20 Alkyl and -C(O)OC2-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0080] In particular, the present invention allows R1 to be independent in each case and R2 to be independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0081] In particular, the present invention allows R1 to be independent in each case and R2 to be independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -C(O)OC 1-20 Alkyl and -C(O)OC 2-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0082] In particular, the present invention allows R1 to be independent in each case and R2 to be independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0083] In particular, the present invention provides, as defined herein, where R1 is independently in each case and R2 is independently in each case, -C 1-12 Selected from alkyl groups, and the above-C 1-12 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -C(O)OC 1-20 Alkyl and -C(O)OC 2-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0084] In particular, the present invention allows R1 to be independent in each case and R2 to be independent in each case, -C 1-12 Selected from alkyl groups, and the above-C 1-12 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0085] In particular, the present invention allows R1 to be independent in each case and R2 to be independent in each case, -C 1-12 Selected from alkyl groups, and the above-C 1-12 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Ionic lipids are provided that are substituted with one to three substituents independently selected from the alkenyl.

[0086] In particular, the present invention allows, R1 is -H in each case, R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 An ionic lipid is provided in which each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents independently selected from -OH, -OC(O)-R7, and -C(O)O-R7.

[0087] In particular, the present invention provides ionic lipids in which Y is independently selected from directly bonded and -CH2- groups in each case.

[0088] In particular, the present invention allows FG to be independently -O- and -NR in each case. a -, -OC(O)-, -NR a C(O)-, -NR a C(O)O- and -OC(O)NR a - An ionic lipid selected from is provided.

[0089] In particular, the present invention allows FG to independently produce -OC(O)- and -NR in each case. a Ionic lipids selected from C(O)- are provided.

[0090] In a more specific embodiment of the present invention, an ionic lipid is provided, in each case independently selected from -OC(O)- and -NHC(O)-, as defined herein.

[0091] In particular, the present invention allows, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-, and -C 2-12 Selected from alkynylene- and above-C1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Ionic lipids are provided that are substituted with one to three substituents independently selected from alkyl groups.

[0092] In particular, the present invention allows Z to be directly bonded and -C independently in each case. 1-12 An ionic lipid selected from alkylenes is provided.

[0093] In particular, the present invention allows Z to be independently -C in each case. 1-12 An ionic lipid selected from alkylenes is provided.

[0094] In particular, according to the present invention, R3 is independently -CH3, -OH, -CH2-OH, -CH2-SH, -CH2-NR4R in each case. 4’ An ionic lipid selected from , and -C(O)H is provided.

[0095] In particular, the present invention allows, R3 independently becomes -CH3, -OH, -CH2-OH, -CH2-SH, -CH2-NR4R in each case. 4’ Selected from , and -C(O)H, R4 in each case and R 4' These are -H and -C, respectively, independently in each case. 1-6 Ionic lipids selected from alkyl groups are provided.

[0096] In particular, the present invention provides ionic lipids in which R3 is independently selected from -CH3, -OH, -CH2-OH, and -CH2-NH2 in each case.

[0097] In certain embodiments, the present invention is defined herein by formula (Ia): [ka] (In the formula, m is an integer selected from 3 and 4. R1 is independently -H, -C in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. R2 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl comprises one or more heteroatoms selected optionally and independently from O, N, and S, and / or is substituted with one to three substituents selected optionally and independently from -OH, -OC(O)-R7, and -C(O)O-R7. In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or is optionally and independently substituted with one to three -OH substituents. Y is independently selected in each case from direct bonds and -CH2- bonds. FG is independent in each case, -O-, -NR a -, -OC(O)-, -NR a C(O)-, -NR a C(O)O- and -OC(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. The present invention provides lipids, particularly ionic lipids, represented by R3 (which is independently selected from -CH3, -OH, -CH2-OH, and -CH2-NH2 in each case).

[0098] In a more specific embodiment, the present invention is defined herein by formula (Ia): [ka] (In the formula, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group optionally and independently contains one or more heteroatoms selected from O, N, and S, and / or optionally and independently contains -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, along with the N atoms to which they are bonded, is at least 8. R7 is independent in each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or is optionally and independently substituted with one to three -OH substituents. Y is independently selected in each case from direct bonds and -CH2- bonds. FG is independent in each case, -O-, -NR a -, -OC(O)-, -NR a C(O)-, -NR a C(O)O- and -OC(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, and -C 1-12 Selected from alkylene, The present invention provides lipids, particularly ionic lipids, represented by R3 (which is independently selected from -CH3, -OH, -CH2-OH, and -CH2-NH2 in each case).

[0099] In certain embodiments, the present invention is n is 1, m is an integer selected from 3 and 4. R1 is independent of each case and R2 is independent of each case, -H, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl optionally contains one or more heteroatoms, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC 1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4'In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0100] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is -H in each case, R2 in each case, -C 1-20 It is alkyl, and the above -C 1-20 Each alkyl group optionally further comprises one or more heteroatoms and / or optionally and independently comprises -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC 1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0101] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is -H in each case, R2 in each case, -C 1-20 It is alkyl, and the above -C 1-20 Each alkyl group optionally further comprises one or more heteroatoms and / or optionally and independently comprises -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -OC(O)-C 8-20 Alkinyl, -C(O)OC 8-20 Alkyl, -C(O)OC 8-20 Alkenyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0102] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is -H in each case, R2 in each case, -C 1-20 It is alkyl, and the above -C 1-20 Each alkyl group optionally further comprises one or more heteroatoms and / or optionally and independently comprises -OC(O)-C 8-20 Alkyl and -OC(O)-C 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0103] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is -H in each case, R2 in each case, -C 1-8 It is alkyl, and the above -C 1-8 Each alkyl group optionally further comprises one or more heteroatoms and / or optionally and independently comprises -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -OC(O)-C 8-20 Alkinyl, -C(O)OC 8-20 Alkyl, -C(O)OC 8-20 Alkenyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0104] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is -H in each case, R2 in each case, -C 1-8 It is alkyl, and the above -C 1-8 Each alkyl group optionally further comprises one or more heteroatoms and / or optionally and independently comprises -OC(O)-C 8-20 Alkyl and -OC(O)-C 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4'In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0105] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is -H in each case, R2 in each case, -C 1-8 It is alkyl, and the above -C 1-8 Each alkyl group optionally further comprises one or more heteroatoms and / or optionally and independently comprises -OC(O)-C 8-20 Alkyl and -OC(O)-C 8-20 Substituted with two substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4'In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0106] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group is independently -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC 1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4'In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0107] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group independently forms -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -OC(O)-C 8-20 Alkinyl, -C(O)OC 8-20 Alkyl, -C(O)OC 8-20 Alkenyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4'In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0108] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group is independently -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC.1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4'In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0109] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-20 Selected from alkyl groups, and the above-C 1-20 Each alkyl group is independent of -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0110] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-8 Selected from alkyl groups, and the above-C 1-8 Each alkyl group independently forms -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -OC(O)-C 8-20 Alkinyl, -C(O)OC 8-20 Alkyl, -C(O)OC 8-20 Alkenyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0111] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-8 Selected from alkyl groups, and the above-C 1-8 Each alkyl group is independently -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0112] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-8 Selected from alkyl groups, and the above-C 1-8 Each alkyl group is independent of -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0113] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent of each case and R2 is independent of each case, -H, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl optionally contains one or more heteroatoms, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC 1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independently selected in each case from direct bonds and -CH2- bonds. FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0114] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent of each case and R2 is independent of each case, -H, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl optionally contains one or more heteroatoms, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC 1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0115] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent of each case and R2 is independent of each case, -H, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl optionally contains one or more heteroatoms, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC 1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, with direct bonding and -C 1-6 Selected from alkylene, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’ , and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0116] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent of each case and R2 is independent of each case, -H, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl optionally contains one or more heteroatoms, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC 1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, -C 1-6 Selected from alkylene, R3 is independent in each case: -halo, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl and -OC(O)-C 1-6 Selected from alkyl groups, and the above-C 1-6 Alkyl, -C 2-6 Alkenyl and -C 2-6 Each of the alkynyl groups can be arbitrarily and independently either -OH or -OC. 1-6 Alkyl, -OC(O)-C 1-6 Alkyl, -NR4R 4’ , -C(O)-C 1-6 Alkilen-NR4R 4’ -C(O)OC 1-6 Alkilen-NR4R 4’, and -OC(O)-C 1-6 Alkilen-NR4R 4' Substituted with one to three substituents independently selected from, R4 in each case and R 4' These are independently -H and -C in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl groups, and the above-C 1-6 Each alkyl group is optionally and independently substituted with an aryl substituent, each of which is a 5- to 8-membered aromatic ring, optionally containing 1 to 3 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, OH, -OC 1-6 Alkyl, -SC 1-6 Substituting with one to three substituents selected from alkyl and -NH2, or R4 and R 4' In each case, together with the N atoms to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further contains one or more additional N atoms, and / or optionally, -C 1-6 Alkyl and -C 1-6 We provide lipids, as defined herein and represented by formula (I), particularly ionic lipids, which are substituted with one to three substituents selected from alkyl-OH groups.

[0117] In another specific embodiment, the present invention, n is 1, m is an integer selected from 3 and 4. R1 is independent of each case and R2 is independent of each case, -H, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20Each alkynyl optionally contains one or more heteroatoms, and / or optionally and independently contains -OC(O)-C 1-20 Alkyl, -OC(O)-C 2-20 Alkenyl, -OC(O)-C 2-20 Alkinyl, -C(O)OC 1-20 Alkyl, -C(O)OC 2-20 Alkenyl and -C(O)OC 2-20 Substituted with one to three substituents independently selected from the alkynyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene, FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene- and above-C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each of the alkynylene groups can be optionally and independently formed as -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, The present invention provides lipids, particularly ionic lipids, as defined herein and represented by formula (I), wherein R3 is independently selected from -CH3, -OH, -CH2-OH, and -CH2-NH2 in each case.

[0118] In a more specific embodiment, the present invention is n is 1, m is an integer selected from 3 and 4. R1 is independent in each case and R2 is independent in each case, -C 1-8Selected from alkyl groups, and the above-C 1-8 Each alkyl group is independently -OC(O)-C 8-20 Alkyl, -OC(O)-C 8-20 Alkenyl, -C(O)OC 8-20 Alkyl and -C(O)OC 8-20 Substituted with one to three substituents independently selected from the alkenyl, In each case of R1 and R2, the total number of C atoms in R1 and R2, including the N atoms to which they are bonded, is at least 8. Y is independently selected in each case from direct bonds and -CH2- bonds. FG is independently selected from -OC(O)- and -NR4C(O)- in each case. Z is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene-, and -C 2-6 Selected from alkynylenes, The present invention provides lipids, particularly ionic lipids, as defined herein and represented by formula (I), wherein R3 is independently selected from -CH3, -OH, -CH2-OH, and -CH2-NH2 in each case.

[0119] The present invention further provides two specific variants of the lipids defined herein, namely those in which the lipid tail is indirectly bound to the -NH- portion via a carboxylic acid-containing linker moiety (represented by formulas IIa and IIb), and those in which the lipid tail tails are directly bound to the -N- portion via a carboxylic acid-containing linker moiety (represented by formulas IIIa and IIIb).

[0120] Therefore, in certain embodiments, the present invention is defined herein by formula (IIa) or formula (IIb): [ka] (In the formula, X1 is directly joined in each case, X2 in each case, and X3 in each case independently, -C1-6 Alkylene-,-C 2-6 Alkenylene-, and -C 2-6 Selected from alkynylene, R5 extends to each case and R 5' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, X1, X2, X3, R5 and R 5' In each of these cases, X1, X2, X3, R5 and R, which are associated with the N atom to which they are bonded. 5' The total number of C atoms is at least 5. Y, FG, Z, R3, R4, R 4' The present invention provides lipids, particularly ionic lipids, represented by (where n and m are as defined in any one embodiment of the present invention).

[0121] In another specific embodiment, the present invention provides lipids, particularly ionic lipids, that are defined herein and represented by formula (IIa) or formula (IIb), to which one or more of the following are applicable. X1 is directly joined in each case, X2 in each case, and X3 in each case independently, -C 1-6 Alkylene-,-C 2-6 Alkenylene-, and -C 2-6 Selected from alkynylene, In particular, X1 independently applies -C in each case, X2 independently applies -C in each case, and X3 independently applies -C in each case. 1-6 It is alkylene-, R5 extends to each case and R 5' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, In particular, R5 is in each case and R 5' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from Alkinil, More specifically, R5 extends to each case and R 5' In each case, -C 1-20 Alkyl and -C 2-20 Selected from Alkenil, More specifically, R5 is in each case and R 5' In each case, -C 8-20 Alkyl and -C 8-20 Selected from Alkenil.

[0122] In particular, the present invention allows R5 to extend to each case and R 5' In each case, independently, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Ionic lipids selected from alkynyls are provided.

[0123] In particular, the present invention allows X1 to be independent in each case, X2 to be independent in each case, and X3 to be independent in each case, -C1-6 An ionic lipid selected from alkylenes is provided.

[0124] In particular, the present invention allows, X1 in each case, X2 in each case, and X3 in each case independently, -C 1-6 Selected from alkylene, R5 in each case and R 5' In each case, independently, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Ionic lipids selected from alkynyls are provided.

[0125] In particular, the present invention allows R5 to extend to each case and R 5' In each case, independently, -C 1-20 Alkyl and -C 2-20 Ionic lipids selected from alkenyls are provided.

[0126] In particular, the present invention allows, X1 in each case, X2 in each case, and X3 in each case independently, -C 1-6 Selected from alkylene, R5 in each case and R 5' In each case, independently, -C 1-20 Alkyl and -C 2-20 Ionic lipids selected from alkenyls are provided.

[0127] In particular, the present invention allows R5 to extend to each case and R 5' In each case, independently, -C 8-20 Alkyl and -C 8-20 Ionic lipids selected from alkenyls are provided.

[0128] In particular, the present invention allows, X1 in each case, X2 in each case, and X3 in each case independently, -C 1-6 Selected from alkylene, R5 in each case and R 5' In each case, independently, -C 8-20 Alkyl and -C 8-20 Ionic lipids selected from alkenyls are provided.

[0129] Therefore, in more specific embodiments, the present invention is defined herein by formula (IIIa) or formula (IIIb): [ka] (In the formula, X4 is independent in each case and X5 is independent in each case, -C 1-20 Alkylene-,-C 2-20 Alkenylene-, and -C 2-20 Selected from alkynylene, R6 extends to each case and R 6' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, and the above -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, X4, X5, R6 and R 6' In each of these cases, X4, X5, R6 and R, which are associated with the N atom to which they are bonded. 6' The total number of C atoms is at least 6. Y, FG, Z, R3, R4, R 4' The present invention provides lipids, particularly ionic lipids, represented by (where n and m are as defined in any one embodiment of the present invention).

[0130] In another specific embodiment, the present invention provides lipids, particularly ionic lipids, that are represented by formula (IIIa) or formula (IIIb), as defined herein and to which one or more of the following are applicable. X4 is independent in each case and X5 is independent in each case, -C 1-20 Alkylene-,-C 2-20 Alkenylene-, and -C 2-20 Selected from alkynylene, In particular, X4 and X5 are independent of each case, -C 1-20 Selected from alkylene, More specifically, X4 is independent in each case and X5 is independent in each case, -C 1-8 Selected from alkylene, R6 extends to each case and R 6' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from Alkinil, In particular, R6 is in each case and R 6' In each case, -C 1-20 Alkyl and -C 2-20 Selected from Alkenil, More specifically, R6 extends to each case and R 6' In each case, -C 8-20 Alkyl and -C 8-20 Selected from Alkenil.

[0131] In particular, the present invention allows, R6 in each case and R 6' In each case, independently, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Ionic lipids selected from alkynyls are provided.

[0132] In particular, the present invention allows X4 to be independently in each case and X5 to be independently in each case, -C 1-20An ionic lipid selected from alkylenes is provided.

[0133] In particular, the present invention allows, X4 and X5 independently in each case, -C 1-20 Selected from alkylene, R6 in each case and R 6' In each case, independently, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Ionic lipids selected from alkynyls are provided.

[0134] In particular, the present invention allows X4 to be independently in each case and X5 to be independently in each case, -C 1-12 An ionic lipid selected from alkylenes is provided.

[0135] In particular, the present invention allows, X4 and X5 independently in each case, -C 1-12 Selected from alkylene, R6 in each case and R 6' In each case, independently, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Ionic lipids selected from alkynyls are provided.

[0136] In particular, the present invention allows R6 to extend to each case and R 6' In each case, independently, -C 1-20 Alkyl and -C 2-20 Ionic lipids selected from alkenyls are provided.

[0137] In particular, the present invention allows, X4 and X5 independently in each case, -C 1-20 Selected from alkylene, R6 in each case and R 6' In each case, independently, -C 1-20Alkyl and -C 2-20 Ionic lipids selected from alkenyls are provided.

[0138] In particular, the present invention allows, X4 and X5 independently in each case, -C 1-12 Selected from alkylene, R6 in each case and R 6' In each case, independently, -C 1-20 Alkyl and -C 2-20 Ionic lipids selected from alkenyls are provided.

[0139] In particular, the present invention allows, X4 and X5 independently in each case, -C 1-20 Selected from alkylene, R6 in each case and R 6' In each case, independently, -C 8-20 Alkyl and -C 8-20 Ionic lipids selected from alkenyls are provided.

[0140] In particular, the present invention allows, X4 and X5 independently in each case, -C 1-12 Selected from alkylene, R6 in each case and R 6' In each case, independently, -C 8-20 Alkyl and -C 8-20 Ionic lipids selected from alkenyls are provided.

[0141] In more specific embodiments, the present invention is defined herein by formula (IVa), formula (IVb), formula (IVc), formula (IVd), or formula (IVe): [ka] (In the formula, Y, FG, Z, R1, R2, R3, R4, R 4'The present invention provides lipids, particularly ionic lipids, represented by (where m is as defined in any one embodiment of the present invention).

[0142] In more specific embodiments, the present invention is defined herein by formula (Va), formula (Va'), formula (Vb), formula (Vb'), formula (Vc), formula (Vd), formula (Vd'), or formula (Ve): [ka] The present invention provides lipids, particularly ionic lipids, represented by the formula (wherein Z, R1, R2, and R7 are as defined in any one embodiment of the present invention).

[0143] In more specific embodiments, the present invention is defined herein by formulas (VaN), (Va'N), (VbN), (Vb'N), (VcN), (VdN), (Vd'N), or (VeN): [ka] The present invention provides lipids, particularly ionic lipids, represented by the formula (wherein Z, R1, and R2 are as defined in any one embodiment of the present invention).

[0144] In more specific embodiments, the present invention is defined herein by formula (VIa), formula (VIa'), formula (VIb), formula (VIb'), formula (VIc), formula (VId), formula (VId'), or formula (VIe): [ka] (In the formula, Z is independent in each case, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, The present invention provides lipids, particularly ionic lipids, represented by R1 and R2 as defined in any one embodiment of the present invention.

[0145] In more specific embodiments, the present invention is defined herein by formulas (VIaN), (VIa'N), (VIbN), (VIb'N), (VIcN), (VIdN), (VId'N), or (VIeN): [ka] (In the formula, Z is independent in each case, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene -OC(O)-, -(CH2-CH2-O-) x , and -(CH2-CH(CH3)-O-) y Selected from the above -C 1-12 Alkylene-,-C 2-12 Alkenylene- and -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, The present invention provides lipids, particularly ionic lipids, represented by R1 and R2 as defined in any one embodiment of the present invention.

[0146] In further embodiments, the present invention provides lipids, particularly ionic lipids, selected from the list defined herein, including the following:

[0147] In a more specific embodiment, the present invention provides compounds selected from any of the tables disclosed herein.

[0148] In a further embodiment, the present invention provides lipid nanoparticles or lipid nanoparticle compositions comprising lipids as defined herein, particularly ionic lipids.

[0149] As used herein, the term “nanoparticles” refers to any particles having a diameter that makes them suitable for systemic administration, particularly intravenous administration, of an active drug, and typically having a diameter of less than 1,000 nanometers (nm), preferably less than 500 nm, and more preferably less than 200 nm, for example, 50 nm to 200 nm, preferably 80 nm to 160 nm.

[0150] In very specific embodiments, the nanoparticles of the present invention may be in the form of lipid nanoparticles or lipid nanoparticle compositions comprising lipids as defined herein, particularly ionic lipids.

[0151] In the context of this invention, the term lipid nanoparticles (LNPs) are also referred to as solid lipid nanoparticles (SLNPs) and mean nanoparticles containing lipids. They are often used as drug delivery systems or pharmaceutical formulations. LNPs as drug delivery vehicles were first approved in 2018 and are currently used in several candidate RNA-based vaccines. Lipid nanoparticles are typically spherical with an average diameter of 10 to 1000 nanometers and have a lipid core matrix that can solubilize lipophilic molecules. The term lipid is used herein in a broader sense and includes triglycerides, diglycerides, monoglycerides, fatty acids, steroids (e.g., cholesterol), and waxes. Biological membrane lipids such as phospholipids, sphingomyelin, bile acids, and sterols are typically used as stabilizers for LNPs.

[0152] Therefore, in the context of the present invention, the nanoparticles disclosed herein further comprise one or more additional lipids that act as stabilizers or do not act as stabilizers, such as helper lipids (e.g., phospholipids), sterols and / or stabilizing lipids (e.g., PEGylated lipids).

[0153] Alternatively, the nanoparticles of the present invention may be in any other suitable form, such as liposomes, lipid nanoemulsions (LNEs), nanostructured lipid carriers (NLCs), hybrid lipid-polymer nanoparticles, or hybrid lipid-metal nanoparticles.

[0154] In the context of this invention, liposomes are nanoparticles in the form of a lipid bilayer structure. Such liposomes are typically composed of phospholipids and cholesterol, and in this invention, are combined with one or more ionic lipids as defined herein. LNEs consist of submicron-sized lipid droplets stabilized by a surfactant in aqueous solution. Medical LNEs mostly consist of plant-based lipid droplets stabilized by phospholipids and / or other lipids such as ionic lipids. NLCs are considered alternative SLNPs in which the solid lipid component is replaced by a liquid lipid, thereby providing a larger loading capacity for the active drug. Hybrid LNPs typically consist of a therapeutic agent-containing polymer core encased in an inner lipid layer and an outer lipid layer, the outer lipid layer often containing PEGylated lipids. Due to the properties of both lipids and polymers, these hybrid LNPs exhibit excellent stability, sustained release, and high biocompatibility. Hybrid lipid-metal nanoparticles can be obtained by coating metal nanoparticles with lipids, thereby improving biocompatibility, nanoparticle stability, and endocytosis efficiency. Suitable hybrid lipid-metal nanoparticles include, for example, hybrid lipid-coated silver nanoparticles (lipid-AgNPs), lipid-aluminum nanoparticles, and liposome gold nanoparticles (LiposAuNPs).

[0155] In the context of the present invention, the term "PEG lipid" or, alternatively, "PEGylated lipid" means any suitable lipid modified with a PEG (polyethylene glycol) group.

[0156] In the context of the present invention, the term "phospholipid" means a lipid molecule consisting of two hydrophobic fatty acid "tails" and a hydrophilic "head" consisting of a phosphate group. These two components are most often linked by a glycerol molecule, and therefore, the phospholipids of the present invention are preferably glycerol-phospholipids. Furthermore, the phosphate group is often modified with a simple organic molecule, such as choline (i.e., phosphocholine) or ethanolamine (i.e., phosphoethanolamine).

[0157] In the context of the present invention, the term "sterol" is also known as steroid alcohol and refers to a subgroup of steroids found naturally in plants, animals, and fungi, or produced by certain bacteria. In the context of the present invention, any suitable sterol, preferably cholesterol, may be used, such as those selected from the list including cholesterol, ergosterol, campesterol, oxysterol, antrosterol, desmosterol, nicasterol, sitosterol, and stigmasterol.

[0158] In further embodiments of the present invention, the nanoparticles and nanoparticle compositions as defined herein further comprise cargo molecules such as pharmaceutically active agents (e.g., small molecules), or biomolecules such as peptides, proteins, or nucleic acids. Therefore, the nanoparticles and nanoparticle compositions of the present invention are particularly suitable for intracellular delivery of these cargo molecules. Accordingly, the present invention provides for the use of the nanoparticles and nanoparticle compositions as defined herein for intracellular delivery of cargo molecules.

[0159] In certain embodiments, the nanoparticles or nanoparticle compositions defined herein further comprise active agents, such as small molecules, therapeutic peptides, therapeutic proteins, nucleic acids, or any combination thereof.

[0160] In certain embodiments, the active agent of the present invention is a therapeutic nucleic acid.

[0161] In the context of the present invention, "nucleic acid" may include deoxyribonucleic acid, ribonucleic acid, recombinant molecules, and chemically synthesized molecules. In particular, nucleic acids may include DNA, genomic DNA, cDNA, RNA, tRNA, mRNA, small interfering RNA (siRNA), microRNA (miRNA), antisense oligonucleotides, ribozymes, plasmids, immunostimulatory nucleic acids, antisense nucleic acids, antagonist (anti-miR), miR, super miR, U1 receptor, and aptamers.

[0162] According to the present invention, nucleic acids may be single-stranded or double-stranded and may be in the form of linear or covalently closed circular molecules. Nucleic acids can be used for cell introduction, i.e., cell transfection, in the form of RNA, which can be prepared, for example, by in vitro transcription from a DNA template. RNA can be further modified before application by sequence stabilization, capping, and / or polyadenylation.

[0163] In the context of this invention, the term "RNA" refers to a molecule comprising, and preferably entirely or substantially composed of, ribonucleotide residues. "Ribonucleotide" refers to a nucleotide having a hydroxyl group at the 2' position of a β-D-ribofuranosyl group. This term includes double-stranded RNA, single-stranded RNA, isolated RNA, e.g., partially purified RNA, essentially pure RNA, synthetic RNA, RNA produced by recombination, and modified RNA that differs from naturally occurring RNA by the addition, deletion, substitution and / or alteration of one or more nucleotides. Such alterations include, for example, the addition of non-nucleotide substances at one or more nucleotides of RNA, either at the terminal(s) or internally. Nucleotides in an RNA molecule may also include non-standard nucleotides, e.g., nucleotides not naturally occurring, or chemically synthesized nucleotides or deoxynucleotides. These modified RNAs may be referred to as analogs. Nucleic acids may be contained in a vector. As used herein, the term "vector" includes any vector known to those skilled in the art, including plasmid vectors, cosmid vectors, phage vectors such as lambda phages, viral vectors such as adenovirus vectors or baculovirus vectors, or artificial chromosome vectors such as bacterial artificial chromosomes (BACs) or yeast artificial chromosomes, or analogs of naturally occurring RNA.

[0164] According to the present invention, the term "RNA" includes, and more preferably relates to, "mRNA," where "mRNA" means "messenger RNA" and relates to a "transcript" that can be prepared using DNA as a template and encodes a peptide or protein. mRNA typically includes a 5' untranslated region (5'-UTR), a protein or peptide coding region, and a 3' untranslated region (3'-UTR). mRNA has a limited half-life both intracellularly and in vitro. Preferably, mRNA is prepared by in vitro transcription using a DNA template. In one embodiment of the present invention, RNA is obtained by in vitro transcription or chemical synthesis. Methodologies for in vitro transcription are known to those skilled in the art. For example, there are various commercially available in vitro transcription kits.

[0165] In a further embodiment, the present invention provides a pharmaceutical composition comprising one or more nanoparticles as defined herein and a pharmaceutically acceptable agent such as a carrier or excipient.

[0166] The present invention also provides nanoparticles and pharmaceutical compositions according to the present invention for use in human medicine or veterinary medicine. The use of nanoparticles and pharmaceutical compositions according to the present invention for human medicine or veterinary medicine is also intended. Furthermore, the present invention provides methods for preventing and treating disorders in humans and animals by administering nanoparticles or pharmaceutical compositions according to the present invention to subjects that require them.

[0167] Such pharmaceutical compositions are particularly suitable for various applications such as preventive vaccines, therapeutic vaccines, protein replacement therapy, gene editing, gene silencing, and small molecule delivery.

[0168] In certain embodiments, the nanoparticles and pharmaceutical compositions defined herein can be used to induce an immune response in a subject by providing a pharmaceutical composition in which the active agent is an immunostimulatory oligonucleotide. For example, the present invention provides a vaccine comprising one or more nanoparticles according to the present invention. For that purpose, the vaccine intended herein comprises at least one active agent, for example, a nucleic acid molecule, for example, an mRNA molecule encoding an antigen in which an adaptive immune response is initiated. This antigen may exist in the form of a weakened or dead microorganism, protein or peptide, or nucleic acid encoding an antigen, for example, a disease-related antigen, for example, a tumor antigen. The vaccine may be a prophylactic vaccine (e.g., to prevent or mitigate the effects of a future infection by any natural or "wild" pathogen) or a therapeutic vaccine (e.g., to actively treat or alleviate the symptoms of an ongoing disease).

[0169] In another embodiment, the nanoparticles and pharmaceutical compositions defined herein can be used to treat diseases or disorders characterized by the overexpression of polypeptides in a subject by providing the pharmaceutical compositions of the present invention to a subject, wherein the active agent is a nucleic acid selected from siRNA, microRNA, and antisense oligonucleotides, and the siRNA, microRNA, or antisense oligonucleotide comprises a polynucleotide or its complement that specifically binds to a polynucleotide encoding a polypeptide. In a preferred embodiment, the nucleic acid is siRNA or miRNA.

[0170] In another embodiment, the nanoparticles and pharmaceutical compositions defined herein can be used to treat diseases or disorders characterized by polypeptide underexpression in a subject by providing the pharmaceutical compositions of the present invention to a subject, wherein the active agent is a plasmid encoding a polypeptide or a functional variant or fragment thereof, as in the context of protein replacement therapy.

[0171] In further embodiments, the nanoparticles and compositions defined herein can be used as transfection agents comprising the compositions or nanoparticles described herein, wherein the compositions or nanoparticles comprise nucleic acids. When the transfection agent comes into contact with cells, it can efficiently deliver nucleic acids to the cells. Another embodiment is a method of delivering nucleic acids into cells by obtaining or forming the compositions or nanoparticles described herein and bringing the compositions or lipid particles into contact with cells.

[0172] In a very specific embodiment, the present invention provides nanoparticles and pharmaceutical compositions used for the treatment of cancer or infectious diseases.

[0173] The ionic lipids of the present invention can be prepared according to the reaction schemes provided in the following examples, but those skilled in the art will understand that these are merely illustrative examples of the present invention, and that the compounds of the present invention can be prepared by any of several standard synthesis processes commonly used by those skilled in organic chemistry. [Examples]

[0174] Example 1: Preparation of lipids 1.General information Unless otherwise specified, all glassware was oven-dried before use, and all reactions were carried out under an argon atmosphere using standard Schlenk technique. Dry solvents were purchased from Acros Organics or Sigma-Aldrich and used without further purification. All reagents were purchased from commercial sources and used without further purification unless otherwise specified. Amines were purchased from commercial sources or prepared according to the method described in International Publication No. 2022 / 136641. The progress of the reactions was monitored by thin-layer chromatography (TLC) performed on aluminum plates coated with 0.2 mm thick Kieselgel F254. Visualization was achieved by ultraviolet light (254 nm) or staining with potassium permanganate. Flash column chromatography was performed using silica gel 60 (230-400 mesh, Merck ans co.). Mass spectra were obtained using Finnigan MAT 8200 (70 eV) and Agilent 5973 (70 eV) by electrospray ionization (ESI) or electron impulse ionization (EI). All 1H NMR and 13C NMR spectra were recorded using a Bruker AV-400 in chloroform-d1 or DMSO-d6. Chemical shifts are expressed in parts per million (ppm) relative to tetramethylsilane, with the solvent peak used as an internal standard (CDCl3: 1 H = 7.26 ppm, 13 C = 77.16 ppm; CD3SOCD3: 1 H = 2.50 ppm, 13 C = 39.52 ppm). The coupling constant is shown in Hz. 1 1H NMR resolution patterns are shown as singlets (s), broads (brd), doublets (d), triplets (t), quartets (q), pentets (p), sextets (se), septets (sep), octets (o), or combinations thereof. Uninterpretable resolution patterns are shown as multiplets (m).

[0175] 2. Lipid synthesis 2.1 The general synthesis route A for hydrophobic tail fragment 1, where R1=R2, is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 1

[0176] 2.2 The general synthesis route B for hydrophobic tail fragment 2, where R1≠R2, is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 2

[0177] 2.3 The general synthesis route C for hydrophobic tail fragment 3, where R1=R2, is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 1 Hydrophobic tail fragment 3

[0178] 2.4 The general synthesis route D for hydrophobic tail fragment 4, where R1≠R2, is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 2 Hydrophobic tail fragment 4

[0179] 2.5 The general synthesis route E for hydrophobic tail fragment 5, where R1=R2, is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 1 Hydrophobic tail fragment 5

[0180] 2.6 The general synthesis route F for the hydrophobic tail fragment 6, where R1≠R2, is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 1 Hydrophobic tail fragment 6

[0181] 2.7 The general synthesis route G for the hydrophobic tail fragment 7 with R1=R2 is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 1 Hydrophobic tail fragment 7

[0182] 2.8 The general synthesis route H for hydrophobic tail fragment 8 where R1≠R2 is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 1 Hydrophobic tail fragment 8

[0183] 2.9 The general synthesis route I for hydrophobic tail fragments 9 and 11, where R1=R2, is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 1 Hydrophobic tail fragment 9 Death Martin Hydrophobic tail fragment 11

[0184] 2.10 The general synthesis route J for hydrophobic tail fragments 10 and 12, where R1≠R2, is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 2 Hydrophobic tail fragment 10 Death Martin Hydrophobic tail fragment 12

[0185] 2.11 The general synthesis route K for the hydrophobic tail fragment 13 with R1=R2 is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 13

[0186] 2.12 The general synthesis pathway L for lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Pyridoxine, acetone, or acetone dimethyl ketal

[0187] 2.13 The general synthesis route M of lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 3 or 4

[0188] 2.14 The general synthesis pathway N for lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Pyridine: Pyridine

[0189] 2.15 The general synthesis pathway O for lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Dess-Martin: Dess-Martin

[0190] 2.16 The general synthesis pathway P for lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 5 or 6 Pyridoxal

[0191] 2.17 The general synthesis route Q of lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 5 or 6 Pyridoxal

[0192] The general synthesis pathway R for lipids according to formula (I) 2.18 is shown below (where Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 5 or 6

[0193] 2.19 The general synthesis pathway S for lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 7 or 8 Pyridoxal: Pyridoxal

[0194] 2.20 The general synthesis pathway T of lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 3 or 4 Pyridoxamine

[0195] 2.21 The general synthesis route U of lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Carbodiimide: Carbodiimide Deprotection: Deprotection

[0196] 2.22 The general synthesis pathway V for lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka]

[0197] 2.23 The general synthesis pathway W for lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Deprotection: Deprotection Dess-Martin: Dess-Martin

[0198] 2.24 The general synthesis route X of lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 11 or 12 Pyridoxamine

[0199] 2.25 The general synthesis route Y of lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl). [ka] Hydrophobic tail fragment 5 or 6

[0200] Example 2: In vitro experiment Materials and methods mRNA synthesis mRNA encoding eGFP was prepared in vitro by T7-mediated transcription from a linear DNA template (peTheRNAvs3 vector) incorporating the 5' and 3' UTRs and a poly(A) tail. The final mRNA was prepared using Cap1, with 100% uridine replaced with N1-methyl-pseudo-uridine.

[0201] LNP synthesis Lipid-based nanoparticles were generated by microfluidic mixing of mRNA solution and lipid solution in sodium acetate buffer (100 mM, pH 4) at a volume ratio of 3:1 using a NanoAssemblr Benchtop (Precision Nanosystems) at rates of 9 mL / min, 12 mL / min, or 16 mL / min. The lipid solution contained a mixture of the ionic lipid of interest, DSPC (Avanti), cholesterol (Sigma), and DMG-PEG2000 (Avanti). LNPs were dialyzed against TBS (TBS volume 10,000 times the LNP volume) using a slide-a-lyzer dialysis cassette (20K MWCO, 3 mL, ThermoFisher). Size, polydispersity, and zeta potential were measured using a Zetasizer Nano (Malvern). mRNA encapsulation was measured by a standard Ribogreen RNA assay (Invitrogen).

[0202] MC3 is an ionic lipid that is considered to be known at the current level of technology, and was used as a control.

[0203] The apparent pKa of the prescribed LNPs was determined via a TNS binding assay, as described by Sabnis et al. (Molecular Therapy, Vol. 26, No. 6, 2018).

[0204] cell line The following summarizes the optimal culture conditions for each cell type, including recommendations for growth medium, subculturing ratio, and medium refresh. To harvest adherent cells, the used growth medium was discarded, the cells were rinsed twice with phosphate-buffered saline (PBS) (Sigma), and then the cells were loosened with trypsin-EDTA (0.05%) (Gibco, Thermo Fisher Scientific). The medium should be refreshed every 2-3 days, whenever the cells reach approximately 70% confluence. Cell viability was determined using the Vi-Cell XR Cell Viability Analyzer (Beckman Coulter).

[0205] [Table B] Cell type: Cell type Description: Source:Supplier Growth medium: Growth medium Subcultivation ration: Subcultivation ratio Adherent human embryonic kidney cells: Adherent human embryonic kidney cells DDEM-high glucose:MEM-high glucose (10% FBS, 4 mM glutamine, 2 mM P / S) 1:2~1:10 Abbreviations: DMEM: Dulbecco's modified Eagle medium, P / S: Penicillin / Streptomycin, FBS: Fetal bovine serum

[0206] Transfection Cells were seeded in 96-well plates at a density of 3.0–4.0 × 10⁴ cells / 100 μl of complete growth medium (specific to each cell type). Transfection was performed when the cells reached 70–90% confluence. Positive control lipofectamine (MessengerMAX, Invitrogen) was diluted with OptiMEM (sera-reduced, Gibco) and incubated for 10 minutes. During this time, eGFP mRNA and LNPs encapsulating eGFP mRNA were diluted with OptiMEM to mRNA concentrations of 200 ng / well and 50 ng / well, respectively. mRNA:lipid complexes were incubated in a 1:1 ratio for 5 minutes and added in four strands to each condition. Cells were incubated at 37°C and 5% CO₂ for 24 hours. Subsequently, cells were harvested using 1×TrypLE select enzyme (Gibco) and stained with the viability / death marker SYTOX blue (Life Technologies) in FACS buffer (PBS supplemented with 1% bovine serum albumin (BSA) and 0.09% azide (all from Sigma)). After the addition of the viability marker, cells were immediately acquired using an Attune Nxt flow cytometer (ThermoFisher Scientific).

[0207] eGFP expression Cells were stained with SYTOX blue to evaluate eGFP expression. eGFP expression levels were determined within a gate of SYTOX blue-negative cells. Relative mean fluorescence intensity (rel MFI) was calculated by dividing the MFI value of the expression marker by the MFI value of untransfected cells.

[0208] Data was acquired using an Attune Nxt cytometer and analyzed with FlowJo software. Flow cytometry data was analyzed using FlowJo version 10 software.

[0209] Example 2a LNPs were generated with a standard molar ratio of ionic lipid / DSPC / cholesterol / DMG-PEG2000 of approximately 50 / 10 / 38.5 / 1.5. eGFP mRNA was encapsulated in all LNPs as a reporter mRNA with an mRNA / ionic lipid molar ratio of 1 / 6.

[0210] Table 1 below lists the relevant physicochemical properties for different LNP compositions based on IL12, IL13, IL14, and MC3.

[0211] Figure 1 shows that the LNP containing ionic lipids according to the present invention may not have a significant effect on the viability of transfected HEK-293T cells.

[0212] Figure 2 shows the relative mean fluorescence intensity of eGFP expression in HEK-293T cells when incubated with the indicated LNPs at mRNA concentrations of 50 ng / well and 200 ng / well (measured as the increase in eGFP MFI compared to untreated cells). As is clear from Figure 2, the ionic lipid-containing LNPs according to the present invention may be able to efficiently transfect HEK 293T cells to the same or better degree as control MC3 cells.

[0213] Table 1. Physicochemical properties of LNPs [Table 1] Ionizable lipids Composition: composition Ratio: Ratio Size:

[0214] Example 2b LNPs were generated with a standard molar ratio of ionic lipid / DSPC / cholesterol / DMG-PEG2000 of approximately 50 / 10 / 38.5 / 1.5. eGFP mRNA was encapsulated in all LNPs as a reporter mRNA with an mRNA / ionic lipid molar ratio of 1 / 6.

[0215] Table 2 below lists the relevant physicochemical properties for different LNP compositions based on IL14, IL19, IL20, IL21, IL25, IL27, and IL28, as well as MC3.

[0216] Table 2. Physicochemical properties of LNPs [Table 2] Ionizable lipids Composition: composition Ratio: Ratio Size:

[0217] Figure 3 shows that the LNP containing ionic lipids according to the present invention may not have a significant effect on the viability of transfected HEK-293T cells.

[0218] Figure 4 shows the relative mean fluorescence intensity (measured as the increase in eGFP MFI compared to untreated cells) of eGFP expression in HeK-293T cells when incubated with the indicated LNPs at mRNA concentrations of 50 ng / well and 200 ng / well. As is clear from Figure 4, the ionic lipid-containing LNPs according to the present invention may reach or exceed levels of eGFP expression equivalent to or exceeding those of the MC3 control.

[0219] Example 3: In vivo experiment Bioluminescence imaging after intravenous administration of LNPs containing fluc mRNA. Materials and methods animal Mice were housed in IVCs under specific pathogen-free conditions. All animal experiments were conducted with the approval of the ethics committee, and animal management followed established guidelines. Six-week-old (20 g-23 g) female Balb / C mice were obtained from Charles River International Laboratories, Inc. (France) and housed with free access to water and standard laboratory animal feed (maximum 5 mice per cage).

[0220] Intravenous injection For intravenous injection, mice were placed in a warming chamber for venous dilation for 10 minutes or less, or their cages were placed under a red lamp for 10–20 minutes. Once adequately warmed, the mice were individually restrained. The tails were wiped with gauze moistened with 70% ethanol. The needle of a BD Microfine syringe (20 G–25 G) containing LNP solution was carefully inserted into one of the lateral caudal veins, and the plunger was slowly pressurized to inject the maximum volume of 100 μL (for 20 g–25 g mice). The needle was withdrawn from the vein, and the puncture site was gently compressed with dry gauze to stop local bleeding. The animals were then observed in their cages for at least 10 minutes. Each injection corresponded to 10 μg of Fluc mRNA.

[0221] Luminescence imaging Imaging was performed 24 hours after intravenous injection of the LNP preparation. Each mouse was intraperitoneally injected with 100 μl of D-luciferin (30 mg / mL). The mice were then placed in an anesthetic induction chamber with oxygen supply (0.4 L / min to 0.8 L / min) and isoflurane (5%) until they became comatose. Next, the isoflurane flow rate was reduced (3%) to maintain comatoseness until the mice were ready for imaging. The mice were placed in stages in an IVIS Lumina II (PerkinElmer) using the same anesthetic flow rate (3% to 4% isoflurane), with a maximum of 3 mice per group. Imaging was performed using field D with parameters set to luminescence, automatic exposure with background overlay, and media binning (4). Animal imaging was performed within 15 minutes after luciferin injection (signal peak). Once in vivo images were acquired, the mice were sacrificed by cervical dislocation, dissected, and the liver, spleen, and inguinal lymph nodes were imaged under similar imaging conditions.

[0222] mRNA synthesis Firefly luciferase (Fluc) mRNA was prepared from a linear peTheRNA vector using eTheRNA-optimized in vitro transcription (IVT) reaction conditions and purified via cellulose. Uridine was completely substituted with N1-methylpseudridine (N1Ψ) to generate N1Ψ-modified mRNA.

[0223] LNP generation Lipid-based nanoparticles were generated by microfluidic mixing of mRNA solution and lipid solution in sodium acetate buffer (100 mM, pH 4) at a volume ratio of 3:1 using a NanoAssemblr Benchtop (Precision Nanosystems) at a rate of 12 mL / min or 16 mL / min. The lipid solution contained a mixture of the ionic lipid of interest, DSPC or DOPE (Avanti), cholesterol (Sigma), and DMG-PEG2000 (Avanti).

[0224] LNPs were generated with standard molar ratios of ionic lipid / DSPC or DOPE / cholesterol / DMG-PEG2000 of approximately 50 / 10 / 38.5 / 1.5. eGFP mRNA was encapsulated in all LNPs as a reporter mRNA with an mRNA / ionic lipid molar ratio of 1 / 6.

[0225] Table 3 below lists the relevant physicochemical properties for different LNP compositions based on IL14, IL19, IL20, IL21, IL25, IL27, and IL28, as well as MC3.

[0226] Table 3. Physicochemical properties of LNPs [Table 3] Ionizable lipids Composition: composition Ratio: Ratio Size:

[0227] Figure 5 shows the in vivo mean radiance (photons / second / cm²) captured by IVIS. 2 The graph shows the normalized values ​​(normalized by a function of steradians). The mouse is positioned so that the images are taken in a supine position. As shown in the graph, LNPs containing ionic lipids according to the present invention may be similar to MC3-based LNPs in terms of mean radiance.

[0228] Figure 6 shows the ex vivo mean radiance of the resected organs, more specifically, the liver, spleen, and inguinal lymph nodes. Therefore, the LNP containing ionic lipids according to the present invention may have similar performance to MC3.

[0229] Example 4: In vivo experiment hEPO expression induced by repeated intravenous administration of LNPs containing hEPO mRNA Materials and methods: animal Mice were housed in IVCs under specific pathogen-free conditions. All animal experiments were conducted with the approval of the Animal Experiment Ethics Committee, and animal management followed established guidelines. Six-week-old (20 g-23 g) female Balb / C mice were obtained from Charles River International Laboratories, Inc. (France) and housed with free access to water and standard laboratory animal feed (maximum 5 mice per cage).

[0230] Intravenous injection For intravenous injection, mice were placed in a warming chamber for venous dilation for 10 minutes or less, or their cages were placed under a red lamp for 10–20 minutes. Once adequately warmed, the mice were individually restrained. The tails were wiped with gauze moistened with 70% ethanol. The needle of a BD Microfine Syringe (20 G–25 G) containing the LNP solution was carefully inserted into one of the lateral caudal veins, and the plunger was slowly pressurized to inject the maximum volume of 100 μL (for 20 g–25 g mice). The needle was withdrawn from the vein, and the puncture site was gently compressed with dry gauze to stop local bleeding. The animals were then observed in their cages for at least 10 minutes. Each injection corresponded to 5 μg of Fluc mRNA, and each mouse was injected three times at one-week intervals using batches of the LNP preparation. The LNP preparation was kept at 4°C, and its physicochemical properties were monitored before use (Tables 6–4). Blood samples were collected 24 hours after injection, and the hEPO protein content was determined using a commercially available hEPO-ELISA kit according to the manufacturer's protocol.

[0231] mRNA synthesis Human erythropoietin (hEPO) mRNA was prepared from a linear peTheRNA vector using eTheRNA-optimized in vitro transcription (IVT) reaction conditions and purified via cellulose. Uridine was completely substituted with N1-methylpseudridine (N1Ψ) to generate N1Ψ-modified mRNA.

[0232] LNP generation Lipid-based nanoparticles were generated by microfluidic mixing of an mRNA solution and a lipid solution in sodium acetate buffer (100 mM, pH 4) at a volume ratio of 3:1 and a rate of 12 mL / min using a NanoAssemblr Benchtop (Precision Nanosystems). The lipid solution contained a mixture of the target ionic lipid, DSPC (Avanti), cholesterol (Sigma), and DMG-PEG2000 (Avanti).

[0233] LNPs were dialyzed against TBS (TBS volume 10,000 times the LNP volume) using a slide-a-lyzer dialysis cassette (20K MWCO, 3 mL, ThermoFisher). Size, polydispersity, and zeta potential were measured using a Zetasizer Nano (Malvern). mRNA encapsulation was measured using a standard Ribogreen RNA assay (Invitrogen).

[0234] LNPs were generated with a standard molar ratio of ionic lipid / DSPC / cholesterol / DMG-PEG2000 of approximately 50 / 10 / 38.5 / 1.5. Fluc mRNA was encapsulated in all LNPs as a reporter mRNA with an mRNA / ionic lipid molar ratio of 1 / 6.

[0235] Table 4 below lists the relevant physicochemical properties for LNP compositions based on IL14 at different time points.

[0236] Table 4. Physicochemical properties of LNPs [Table 4] Timepoints: Composition: composition Ratio: Ratio Size:

[0237] Figure 7 shows the mean hEPO concentration in the blood 24 hours after intravenous injection, expressed as mIU / mL. As shown, hEPO expression may not be affected by repeated administration of LNPs containing ionic lipids according to the present invention. [Explanation of symbols]

[0238] Drawing translation Figure 1 HEK293T viability HEK293T viability Viability (%) Survival rate (%) 50 ng / well 50 ng / well 200 ng / well Figure 2 HEK293T Relative MFI relative MFI eGFP (au) Relative MFI eGFP (arbitrary unit) 50 ng / well 50 ng / well 200 ng / well Figure 3 HEK293T viability HEK293T viability Viability (%) Survival rate (%) 50 ng / well 50 ng / well 200 ng / well Figure 4 HEK293T Relative MFI Relative MFI eGFP 50 ng / well 50 ng / well 200 ng / well Figure 5 Average radiance in supine view Avg Radiance [p / s / cm2 [sr] Average radiance [p / s / cm] 2 / sr] Figure 6 Ratios in organs Avg Radiance [p / s / cm 2 [sr] Average radiance [p / s / cm] 2 / sr] Liver Spleen LN lymph nodes Figure 7 prior to injection injection 1 injection 1 injection 2 injection 2 injection 3 injection 3

Claims

1. Equation (I): 【Chemistry 1】 (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R 1 is, independently in each case, -H, -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl, wherein said -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl each optionally and independently contains one or more heteroatoms selected from O, N and S, and / or is optionally and independently substituted with one to three substituents selected from -OH, -OC(O)-R 7 , and -C(O)O-R 7 and is substituted with one to three substituents selected independently therefrom, R 2 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 1 and R 2 In each of these cases, the R atom that is bonded to them is 1 and R 2 The total number of C atoms is at least 8. R 7 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene-, and the -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is substituted optionally and independently with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene-OC(O)-,-(CH 2 -CH 2 -O-) x , and -(CH 2 -CH(CH 3 )-O-) y Selected from, -C 1-12 Alkylene-, the aforementioned -C 2-12 Alkenylene- and the aforementioned -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R 3 is, independently in each case, -halo, -C 1-6 alkyl, -C 2-6 alkenyl, -C 2-6 alkynyl, -OH, -O-C 1-6 alkyl, -C(O)H, and -OC(O)-C 1-6 alkyl, selected from 1-6 the -C 2-6 alkyl, the -C 2-6 alkenyl and the -C 1-6 alkynyl each is, optionally and independently, -OH, -O-C 1-6 alkyl, -SH, -OC(O)-C 4 R 4’ , Cy​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ R 4 in each case and R 4' in each case independently is -H, -C 1-6 alkyl, -C(O)-C 1-6 alkyl, and -C(O)O-C 1-6 alkyl, wherein each of said -C 1-6 alkyl is optionally and independently substituted with one to three substituents selected from Het 1 , and Ar 1 or R 4 and R 4' in each case together with the N atom to which they are attached form a 5- to 10-membered aromatic or non-aromatic heterocyclic ring, said heterocyclic ring optionally further comprising one or more additional heteroatoms selected from O, N and S, and / or optionally substituted with one to three substituents selected from -C 1-6 alkyl, and -C 1-6 alkyl-OH, Cy 1 Each of these is independently a 5- to 10-membered aromatic or non-aromatic ring, optionally and independently containing 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with one to five substituents independently selected from the Cy 1 It contains at least one N atom, Het 1 In each case, independently, is a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, Ar 1 Each of these is independently a 5-membered or 6-membered aromatic ring, optionally and independently comprising one or more heteroatoms selected from O, N, and S, and / or optionally -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms and / or optionally -C 1-6 Alkyl and -C 1-6 Ionic lipids represented by (substituting with one to three substituents independently selected from the alkyl-OH group).

2. Equation (I): 【Chemistry 2】 (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R 1 These are -H and -C, independently in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 2 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 1 and R 2 In each of these cases, the R atom that is bonded to them is 1 and R 2 The total number of C atoms is at least 8. R 7 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, with direct bonding and -CH 2 - Selected from, FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene-OC(O)-,-(CH 2 -CH 2 -O-) x , and -(CH 2 -CH(CH 3 )-O-) y Selected from, -C 1-12 Alkylene-, the aforementioned -C 2-12 Alkenylene- and the aforementioned -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R 3 These are -halo and -C, respectively, independently in each case. 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl, the -C 1-6 Alkyl, the aforementioned -C 2-6 Alkenyl and the aforementioned -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR 4 R 4’ Cy 1 , -C(O)-C 1-6 Alkilen-NR 4 R 4’ , -C(O)-C 1-6 Alkylene-Cy 1 -C(O)OC 1-6 Alkilen-NR 4 R 4’ -C(O)OC 1-6 Alkylene-Cy 1 -OC(O)-C 1-6 Alkilen-NR 4 R 4’ , and -OC(O)-C 1-6 Alkylene-Cy 1 Substituted with one to three substituents independently selected from, R 4 This applies to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl, the -C 1-6 Each alkyl group can be optionally and independently selected as Het 1 , and Ar 1 Substituting with one to three substituents independently selected from or R 4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy 1 Each of these is independently a 5- to 10-membered aromatic or non-aromatic ring, optionally and independently containing 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with one to five substituents independently selected from the Cy 1 It contains at least one N atom, Het 1 In each case, independently, is a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, Ar 1 Each of these is independently a 5-membered or 6-membered aromatic ring, optionally and independently comprising one or more heteroatoms selected from O, N, and S, and / or optionally -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms and / or optionally -C 1-6 Alkyl and -C 1-6 The ionic lipid according to claim 1, represented by (substituted with one to three substituents independently selected from the alkyl-OH group).

3. Equation (I): 【Transformation 3】 (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R 1 These are -H and -C, independently in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 2 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 1 and R 2 In each of these cases, the R atom that is bonded to them is 1 and R 2 The total number of C atoms is at least 8. R 7 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene-, and the -C 1-6 Alkylene-, the aforementioned -C 2-6 Alkenylene- and the aforementioned -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is substituted optionally and independently with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -OC(O)-, -NR a C(O)-, -NR a C(O)O- and -OC(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene-OC(O)-,-(CH 2 -CH 2 -O-) x , and -(CH 2 -CH(CH 3 )-O-) y Selected from, -C 1-12 Alkylene-, the aforementioned -C 2-12 Alkenylene- and the aforementioned -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R 3 These are -halo and -C, respectively, independently in each case. 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl, the -C 1-6 Alkyl, the aforementioned -C 2-6 Alkenyl and the aforementioned -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR 4 R 4’ Cy 1 , -C(O)-C 1-6 Alkilen-NR 4 R 4’ , -C(O)-C 1-6 Alkylene-Cy 1 -C(O)OC 1-6 Alkilen-NR 4 R 4’ -C(O)OC 1-6 Alkylene-Cy 1 -OC(O)-C 1-6 Alkilen-NR 4 R 4’ , and -OC(O)-C 1-6 Alkylene-Cy 1 Substituted with one to three substituents independently selected from, R 4 This applies to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl, the -C 1-6 Each alkyl group can be optionally and independently selected as Het 1 , and Ar 1 Substituting with one to three substituents independently selected from or R 4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy 1 Each of these is independently a 5- to 10-membered aromatic or non-aromatic ring, optionally and independently containing 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with one to five substituents independently selected from the Cy 1 It contains at least one N atom, Het 1 In each case, independently, is a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, Ar 1 Each of these is independently a 5-membered or 6-membered aromatic ring, optionally and independently comprising one or more heteroatoms selected from O, N, and S, and / or optionally -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms and / or optionally -C 1-6 Alkyl and -C 1-6 The ionic lipid according to claim 1 or 2, represented by (substituted with one to three substituents independently selected from the alkyl-OH group).

4. Equation (I): 【Chemistry 4】 (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R 1 These are -H and -C, independently in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 2 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 1 and R 2 In each of these cases, the R atom that is bonded to them is 1 and R 2 The total number of C atoms is at least 8. R 7 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene-, and the -C 1-6 Alkylene-, the aforementioned -C 2-6 Alkenylene- and the aforementioned -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is substituted optionally and independently with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene-OC(O)-,-(CH 2 -CH 2 -O-) x , and -(CH 2 -CH(CH 3 )-O-) y Selected from, -C 1-12 Alkylene-, the aforementioned -C 2-12 Alkenylene- and the aforementioned -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R 3 In each case, independently, -CH 3 -OH, -CH 2 -OH, -CH 2 -SH, -CH 2 -NR 4 R 4’ Selected from , and -C(O)H, R 4 This applies to each case and R 4' These are -H and -C, respectively, independently in each case. 1-6 An ionic lipid according to any one of claims 1 to 3, represented by (selected from alkyl). (Multi-multi)

5. Equation (I): 【Transformation 5】 (In the formula, n is an integer selected from 1, 2, and 3. m is an integer selected from 0, 1, 2, 3, and 4. The sum of n and m is at least 4. R 1 These are -H and -C, independently in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 2 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 1 and R 2 In each of these cases, the R atom that is bonded to them is 1 and R 2 The total number of C atoms is at least 8. R 7 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, direct bond, -C 1-6 Alkylene-,-C 2-6 Alkenylene- and -C 2-6 Selected from alkynylene-, and the -C 1-6 Alkylene-, the aforementioned -C 2-6 Alkenylene- and the aforementioned -C 2-6 Each alkynylene- contains one or more heteroatoms selected optionally and independently from N, O, and S, and / or is substituted optionally and independently with one to three -OH substituents. FG is independent in each case, -O-, -NR a -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O-, -NR a C(O)-, -C(O)NR a -, -NR a C(O)O-, -OC(O)NR a -, -NR a C(S)O-, -NR a C(O)S-, -OC(S)NR a -, -SC(O)NR a -, and -NR a C(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, and -C 1-12 Selected from alkylene, R 3 These are -halo and -C, respectively, independently in each case. 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkinyl, -OH, -OC 1-6 Alkyl, -C(O)H, and -OC(O)-C 1-6 Selected from alkyl, the -C 1-6 Alkyl, the aforementioned -C 2-6 Alkenyl and the aforementioned -C 2-6 Each of the alkynyl groups can be optionally and independently -OH, -OC. 1-6 Alkyl, -SH, -OC(O)-C 1-6 Alkyl, -NR 4 R 4’ Cy 1 , -C(O)-C 1-6 Alkilen-NR 4 R 4’ , -C(O)-C 1-6 Alkylene-Cy 1 -C(O)OC 1-6 Alkilen-NR 4 R 4’ -C(O)OC 1-6 Alkylene-Cy 1 -OC(O)-C 1-6 Alkilen-NR 4 R 4’ , and -OC(O)-C 1-6 Alkylene-Cy 1 Substituted with one to three substituents independently selected from, R 4 This applies to each case and R 4' These are -H and -C, independently in each case. 1-6 Alkyl, -C(O)-C 1-6 Alkyl and -C(O)OC 1-6 Selected from alkyl, the -C 1-6 Each alkyl group can be optionally and independently selected as Het 1 , and Ar 1 Substituting with one to three substituents independently selected from or R 4 and R 4' In each case, together with the N atom to which they are bonded, they form a 5-membered to 10-membered aromatic heterocycle or non-aromatic heterocycle, wherein the heterocycle optionally further comprises one or more additional heteroatoms selected from O, N, and S, and / or optionally, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents selected from alkyl-OH, Cy 1 Each of these is independently a 5- to 10-membered aromatic or non-aromatic ring, optionally and independently containing 1 to 5 heteroatoms selected from O, N, and S, and / or optionally and independently containing -halo, -C 1-6 Alkyl, -C 1-6 alkyl-OH, -OH, -NR b R b’ , and -C 1-6 Alkyl-NR b R b' Substituted with one to five substituents independently selected from the Cy 1 It contains at least one N atom, Het 1 In each case, independently, is a 5- to 10-membered non-aromatic heterocycle containing at least one N atom, optionally and independently containing one or more additional heteroatoms selected from O, N, and S, and / or optionally and independently, -C 1-6 Alkyl and -C 1-6 Substituted with one to three substituents independently selected from the alkyl-OH group, Ar 1 Each of these is independently a 5-membered or 6-membered aromatic ring, optionally and independently comprising one or more heteroatoms selected from O, N, and S, and / or optionally -halo, -C 1-6 Alkyl, -C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, -SC 1-6 Alkyl and -NR b R b' Substituted with one to three substituents independently selected from, R b This applies to each case and R b' These are -H and -C, independently in each case. 1-6 Alkyl and C 1-6 Selected from alkyl-Ph, or R b and R b' In each case, together with the N atoms to which they are bonded, they form a 5- to 10-membered non-aromatic heterocycle, the heterocycle optionally further comprising one or more additional N atoms and / or optionally -C 1-6 Alkyl and -C 1-6 An ionic lipid according to any one of claims 1 to 4, represented by (substituted with one to three substituents independently selected from the alkyl-OH group). (Multi-multi)

6. Equation (Ia): 【Transformation 6】 (In the formula, m is an integer selected from 3 and 4. R 1 These are -H and -C, independently in each case. 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 2 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC(O)-R 7 , and -C(O)OR 7 Substituted with one to three substituents independently selected from, R 1 and R 2 In each of these cases, the R atom that is bonded to them is 1 and R 2 The total number of C atoms is at least 8. R 7 In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, Y is independent in each case, directly bonded, and -CH 2 - Selected from, FG is independent in each case, -O-, -NR a -, -OC(O)-, -NR a C(O)-, -NR a C(O)O- and -OC(O)NR a - Selected from, R a These are -H and -C, respectively, independently in each case. 1-6 Selected from alkyl groups, Z is independent in each case, direct bond, -C 1-12 Alkylene-,-C 2-12 Alkenylene-,-C 2-12 Alkinylene-,-C 1-12 Alkylene-C(O)-, -C 1-12 Alkylene-OC(O)-,-(CH 2 -CH 2 -O-) x , and -(CH 2 -CH(CH 3 )-O-) y Selected from, -C 1-12 Alkylene-, the aforementioned -C 2-12 Alkenylene- and the aforementioned -C 2-12 Each alkynylene- contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -halo, -OH, and -OC. 1-6 Substituted with one to three substituents independently selected from the alkyl group, x is an integer independently selected from 1 to 10 in each case, and y is an integer independently selected from 1 to 10 in each case. R 3 In each case, independently, -CH 3 -OH, -CH 2 -OH, -CH 2 -SH, -CH 2 -NR 4 R 4’ Selected from , and -C(O)H, R 4 This applies to each case and R 4' These are -H and -C, respectively, independently in each case. 1-6 An ionic lipid according to any one of claims 1 to 5, represented by (selected from alkyl). (Multi-multi)

7. Formula (IIa), or formula (IIb): 【Transformation 7】 (In the formula, X 1 In each case, X 2 In each case, and X 3 These are independent in each case, direct coupling, -C 1-6 Alkylene-,-C 2-6 Alkenylene-, and -C 2-6 Selected from alkynylene, R 5 This applies to each case and R 5' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, X 1 , X 2 , X 3 , R 5 and R 5' In each of these cases, the X with the N atom to which they are bonded. 1 , X 2 , X 3 , R 5 and R 5' The total number of C atoms is at least 5. Y, FG, Z, R 3 , R 4 , R 4' Cy 1 , Het 1 Ar 1 , R a , R b , R b' An ionic lipid according to any one of claims 1 to 6, represented as follows: n and m are as described in any one of claims 1 to 6. (Multi-multi)

8. Formula (IIIa), or formula (IIIb): 【Transformation 8】 (In the formula, X 4 This applies to each case and X 5 In each case, -C 1-12 Selected from alkylene, R 6 This applies to each case and R 6' In each case, -C 1-20 Alkyl, -C 2-20 Alkenyl and -C 2-20 Selected from alkynyl, the -C 1-20 Alkyl, the aforementioned -C 2-20 Alkenyl and the aforementioned -C 2-20 Each alkynyl contains, optionally and independently, one or more heteroatoms selected from O, N, and S, and / or optionally and independently, -OH, -OC 1-20 Alkyl, -OC 2-20 Alkenyl, -OC(O)-C 1-20 Alkyl and -OC(O)-C 2-20 Substituted with one to three substituents selected from alkenyls, X 4 , X 5 , R 6 and R 6' In each of these cases, the X with the N atom to which they are bonded. 4 , X 5 , R 6 and R 6' The total number of C atoms is at least 6. Y, FG, Z, R 3 , R 4 , R 4' Cy 1 , Het 1 Ar 1 , R a , R b , R b' An ionic lipid according to any one of claims 1 to 6, represented as follows: n and m are as described in any one of claims 1 to 6. (Multi-multi)

9. Formula (IIIb): 【Chemistry 9】 (In the formula, n is 1, m is 3, X 4 This applies to each case and X 5 In each case, -C 1-12 Selected from alkylene, R 6 This applies to each case and R 6' In each case, -C 8-20 Alkyl, -C 8-20 Alkenyl and -C 8-20 Selected from Alkinil, Y, FG, Z, R 3 , R 4 , R 4' Cy 1 , Het 1 Ar 1 , R a , R b , and R b' An ionic lipid according to any one of claims 1 to 6, which is represented as described in any one of claims 1 to 6. (Multi-multi)

10. The ionic lipid according to claim 1, selected from the list including the following: Table 1-1 Table 1-2 Table 1-3 Table 1-4 Table 1-5 Table 1-6 Table 1-7 table

11. Lipid nanoparticles or lipid nanoparticle compositions comprising the ionic lipid described in any one of claims 1 to 10. (Multi-Multi)

12. Lipid nanoparticles or lipid nanoparticle composition according to claim 11, further comprising phospholipids, sterols and / or PEG lipids.

13. Lipid nanoparticles or lipid nanoparticle compositions according to claim 11 or 12, further comprising an active agent, particularly nucleic acid, preferably mRNA. (Multi-multi)

14. Use of an ionic lipid according to any one of claims 1 to 10 in the production of lipid nanoparticles or lipid nanoparticle compositions. (Multi-multi)

15. A pharmaceutical composition comprising lipid nanoparticles or a lipid nanoparticle composition according to any one of claims 11 to 13, and a pharmaceutically acceptable agent. (Multi-multi)

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