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EP-4737439-A1 - IONIZABLE LIPID AND USE THEREOF

EP4737439A1EP 4737439 A1EP4737439 A1EP 4737439A1EP-4737439-A1

Abstract

The present invention provides an ionizable lipid and a drug delivery system comprising the ionizable lipid. Specifically, the present invention provides an ionizable lipid having the structure of formula (1), or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof. Lipid nanoparticles constructed by using the ionizable lipid can realize safe and efficient delivery of nucleic acid drugs, small molecule drugs, peptide drugs and protein drugs.

Inventors

  • ZHANG, YUANYUAN
  • LI, KE
  • GU, Hanqing
  • ZHANG, Huicong
  • SONG, JIN
  • HUANG, Huiya
  • XU, Zengjun

Assignees

  • Axter Therapeutics (Beijing) Co., Ltd.

Dates

Publication Date
20260506
Application Date
20240617

Claims (14)

  1. An ionizable lipid, or a pharmaceutically acceptable salt, a tautomer or a stereoisomer thereof, wherein, the ionizable lipid has the structure of Formula I below: wherein, R 1 and R 2 are each independently selected from -(CH 2 ) n -, wherein n is a positive integer ranging from 1 to 14; X and Y are each independently-CH- or N; Li has the structure of -(L 1a -L 1b )- from right to left, or is absent, wherein, L 1a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 1b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; L 2 has the structure of -(L 2a -L 2b )- from left to right, or is absent; wherein, L 2a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 2b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; R 3 , R 4 , R 5 and R 6 are each independently H, CH 3 , C 2 -C 30 hydrocarbyl group, or -(CH 2 ) s -R a -(CH 2 ) g -R b -(CH 2 ) m -CH 3 , wherein, s, g are each independently selected from a positive integer ranging from 1 to 20, m is selected from a integer ranging from 0 to 20; R a , R b are each independently absent or selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; and, R 3 and R 4 are not both H; and R 5 and R 6 are not both H; R 7 is selected from C 1 -C 5 hydrocarbyl group, or -(CH 2 ) m O(CH 2 ) n -, wherein m, n are each independently selected from 1, 2, 3.
  2. The ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1, wherein, the ionizable lipid has the structure represented by Formula (I-1) below: wherein, R 1 and R 2 are each independently selected from -(CH 2 ) n -, wherein n is a positive integer ranging from 1 to 14; Li has the structure of -(L 1a -L 1b )- from right to left, or is absent, wherein, L 1a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 1b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; L 2 has the structure of -(L 2a -L 2b )- from left to right, or is absent; wherein, L 2a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 2b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; R 3 , R 4 , R 5 and R 6 are each independently C 2 -C 20 hydrocarbyl group; R 7 is selected from C 1 -C 5 hydrocarbyl group, or -(CH 2 ) m O(CH 2 ) n -, wherein m, n are each independently selected from 1, 2, 3.
  3. The ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1, wherein, the ionizable lipid has the structure represented by Formula (I-2) below: wherein, R 1 and R 2 are each independently selected from -(CH 2 ) n -, wherein n is a positive integer ranging from 1 to 14; Li has the structure of -(L 1a -L 1b )- from right to left, or is absent, wherein, L 1a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 1b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; L 2 has the structure of -(L 2a -L 2b )- from left to right, or is absent; wherein, L 2a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 2b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; R 3 has the structure of -R 3a -R 3b -R 3c -R 3d -R 3c , R 4 has the structure of -R 4a -R 4b -R 4c -R 4d -R 4c , R 5 has the structure of -R 5a -R 56 -R 5c -R 5d -R 5c ; wherein, R 3a , R 3c , R 4a , R 4c , R 5a , R 5c are each independently -(CH 2 ) n -, wherein n is selected from a positive integer ranging from 1 to 14; R 3b , R 3d , R 4b , R 4d , R 5b , R 5d are each independently absent or selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-, -(C=C)-(CH 2 )-(C=C)-, -(C=C)-, -CH 2 -, -(C≡C)-; R 3c , R 4c , R 5c are each independently C 2 -C 20 hydrocarbyl group; R 7 is selected from C 1 -C 5 hydrocarbyl group, or -(CH 2 ) m O(CH 2 ) n -, wherein m, n are each independently selected from 1, 2, 3.
  4. The ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1, wherein, the ionizable lipid has the structure represented by Formula (I-3) below: wherein, R 1 and R 2 are each independently selected from -(CH 2 ) n -, wherein n is a positive integer ranging from 1 to 14; Li has the structure of -(L 1a -L 1b )- from right to left, or is absent, wherein, L 1a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 1b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; L 2 has the structure of -(L 2a -L 2b )- from left to right, or is absent; wherein, L 2a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 2b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; R 3 has the structure of -R 3a -R 3b -R 3c -R 3d -R 3c , R 4 has the structure of -R 4a -R 4b -R 4c -R 4d -R 4c ; R 5 has the structure of -R 5a -R 56 -R 5c -R 5d -R 5c , R 6 has the structure of -R 6a -R 6b -R 6c -R 6d -R 6c ; wherein, R 3a , R 3c , R 4a , R 4c , R 5a , R 5c , R 6a and R 6c are each independently -(CH 2 ) n -, wherein n is selected from a positive integer ranging from 1 to 14; R 3b , R 3d , R 4b , R 4d , R 5b , R 5a , R 6b and R 6d are each independently absent or selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-, -(C=C)-(CH 2 )-(C=C)-, -(C=C)-, -CH 2 -, -(C≡C)-; R 3c , R 4c , R 5c , R 6c are each independently C 2 -C 20 hydrocarbyl group; R 7 is selected from C 1 -C 5 hydrocarbyl group, or -(CH 2 ) m O(CH 2 ) n -, wherein m, n are each independently selected from 1, 2, 3.
  5. The ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1, wherein, R 3 , R 4 , R 5 and R 6 are each independently C 5 -C 15 alkyl.
  6. The ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1, wherein, the ionizable lipid has the structure represented by Formula (I-1) below: wherein, R 1 and R 2 are each independently selected from -(CH 2 ) n -, wherein n is a positive integer ranging from 4 to 8; Li is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -CH(OH)-; L 2 is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -CH(OH)-; R 3 has the structure of -R 3a -R 3b -R 3c -R 3d -R 3e , R 4 has the structure of -R 4a -R 4b -R 4c -R 4d -R 4e ; R 5 has the structure of -R 5a -R 5b -R 5c -R 5d -R 5e , R 6 has the structure of -R 6a -R 6b -R 6c -R 6d -R 6e ; wherein, R 3a , R 3c , R 4a , R 4c , R 5a , R 5c , R 6a and R 6c are each independently -(CH 2 ) n -, wherein n is selected from a positive integer ranging from 1 to 14; and R 3 , R 4 , R 5 and R 6 each independently has 4-20 CH 2 structural moieties; R 3b , R 3d , R 4b , R 4d , R 5b , R 5d , R 6b and R 6d are each independently absent or selected from the following functional groups: -(C=O)O-, -O(C=O)-, -(S-S)-, -(C=C)-(CH 2 )-(C=C)-, -CH(OH)-; R 3e , R 4e , R 5e , R 6e are each independently C 2 -C 20 hydrocarbyl group; R 7 is C 1 -C 3 hydrocarbyl group, or -(CH 2 ) 2 -O-(CH 2 ) 2 -.
  7. The ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1, wherein, the ionizable lipid has the structure represented by the Formula below:
  8. A method for preparing the ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1, wherein, the method comprises: method I, method II and method III; wherein, method I comprises the following steps: (S1) under the protection of an inert gas, compounds A1 and A2 are reacted to obtain compound A3; (S2) under the protection of an inert gas, the tert-butoxycarbonyl (Boc) group of A3 is removed to obtain A4; (S3) under the protection of an inert gas, A4 is reacted with A5 or A6 to obtain A7 (i.e., the compound represented by (I-1)); wherein, R 1 and R 2 are each independently selected from -(CH 2 ) n -, wherein n is a positive integer ranging from 1 to 14; G 1 and G 2 are each independently selected from an active functional group; Li has the structure of -(L 1a -L 1b )- from right to left, or is absent, wherein, L 1a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 1b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; L 2 has the structure of -(L 2a -L 2b )- from left to right, or is absent; wherein, L 2a is selected from the following functional groups: O, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 2b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; R 3 , R 4 , R 5 and R 6 are each independently C 2 -C 20 hydrocarbyl group; R 7 is selected from C 1 -C 5 hydrocarbyl group, or -(CH 2 ) m O(CH 2 ) n -, wherein m, n are each independently selected from 1, 2, 3; method II comprises the following steps: (D1) under the protection of an inert gas, compound B1 is reacted with B2 to obtain compound B3; (D2) under the protection of an inert gas, compound B3 is reacted with B4 to obtain compound B5; (D3) under the protection of an inert gas, compound B5 is reacted with B6 to obtain compound B7, i.e., the compound represented by (1-2); wherein, R 1 and R 2 are each independently selected from -(CH 2 ) n -, wherein n is a positive integer ranging from 1 to 14; G 1 and G 2 are each independently selected from an active functional group; L 1 has the structure of -(L 1a -L 1b )- from right to left, or is absent, wherein, L 1a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 1b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; L 2 has the structure of -(L 2a -L 2b )- from left to right, or is absent; wherein, L 2a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 26 is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; R 3 has the structure of -R 3a -R 3b -R 3c -R 3d -R 3c , R 4 has the structure of -R 4a -R 4b -R 4c -R 4d -R 4c ; R 5 has the structure of -R 5a -R 5b -R 5c -R 5d -R 5e ; wherein, R 3a , R 3c , R 4a , R 4c , R 5a , R 5c are each independently -(CH 2 ) n -, wherein n is selected from a positive integer ranging from 1 to 14; R 3b , R 3d , R 4b , R 4d , R 5b , R 5d are each independently absent or selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-, -(C=C)-(CH 2 )-(C=C)-, -(C=C)-, -CH 2 -, -(C≡C)-; R 3c , R 4c , R 5c are each independently C 2 -C 20 hydrocarbyl group; R 6 is H; R 7 is selected from C 1 -C 5 hydrocarbyl group, or -(CH 2 ) m O(CH 2 ) n -, wherein m, n are each independently selected from 1, 2, 3; method III comprises the following steps: (M1) under the protection of an inert gas, compounds C1 and C2 are reacted to obtain C3; (M2) under the protection of an inert gas, compound C3 undergoes de-Boc deprotection to obtain compound C4; (M3) under the protection of an inert gas, compound C4 is reacted with C5 or C6 to obtain compound C7, i.e., the compound represented by Formula (I-3); wherein, R 1 and R 2 are each independently selected from -(CH 2 ) n -, wherein n is a positive integer ranging from 1 to 14; G 1 and G 2 are each independently selected from an active functional group; L 1 has the structure of -(L 1a -L 1b )- from right to left, or is absent, wherein, L 1a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 1b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; L 2 has the structure of -(L 2a -L 2b )- from left to right, or is absent; wherein, L 2a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-; L 2b is -(CH 2 ) n -, wherein n is selected from 0, 1, 2, 3 or 4; R 3 has the structure of -R 3a -R 3b -R 3c -R 3d -R 3c , R 4 has the structure of -R 4a -R 4b -R 4c -R 4d -R 4c ; R 5 has the structure of -R 5a -R 5b -R 5c -R 5d -R 5e , R 6 has the structure of -R 6a -R 6b -R 6c -R 6d -R 6e ; wherein, R 3a , R 3c , R 4a , R 4c , R 5a , R 5c , R 6a and R 6c are each independently -(CH 2 ) n -, wherein n is selected from a positive integer ranging from 1 to 14; R 3b , R 3d , R 4b , R 4d , R 5b , R 5a , R 6b and R 6d are each independently absent or selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-, -(C=C)-(CH 2 )-(C=C)-, -(C=C)-, -CH 2 -, -(C≡C)-; R 3c , R 4c , R 5c , R 6c are each independently C 2 -C 20 hydrocarbyl group; R 7 is selected from C 1 -C 5 hydrocarbyl group, or -(CH 2 ) m O(CH 2 ) n -, wherein m, n are each independently selected from 1, 2, 3.
  9. A lipid nanoparticle (LNP), wherein, the lipid nanoparticle comprises the ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1.
  10. A lipid nanoparticle pharmaceutical formulation, wherein, the lipid nanoparticle pharmaceutical formulation comprises: i) the lipid nanoparticle according to claim 9; ii) a biologically active substance encapsulated in the lipid nanoparticle; and iii) a pharmaceutically acceptable carrier.
  11. A method for preparing the lipid nanoparticle pharmaceutical formulation according to claim 10, wherein, the method comprises: (a) mixing the ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1, and optional auxiliary lipids with an organic solvent to obtain a lipid organic phase; (b) mixing a biologically active substance with an aqueous solvent to obtain an aqueous phase containing the biologically active substance; (c) mixing the lipid organic phase in step (a) with the aqueous phase in step (b) to obtain the lipid nanoparticle pharmaceutical formulation.
  12. Use of the ionizable lipid, or pharmaceutically acceptable salt, tautomer or stereoisomer thereof according to claim 1 for the manufacture of a drug delivery system.
  13. Use of the lipid nanoparticle according to claim 9 in the manufacture of a medicament for treating and/or preventing a tumor, an infectious disease and a rare disease.
  14. Use of the ionizable lipid, or pharmaceutically acceptable salt thereof according to claim 1, wherein, it is used for the manufacture of a lipid nanoparticle pharmaceutical formulation, and the lipid nanoparticle pharmaceutical formulation is used for delivering a biologically active substance to cells in a subject in need thereof.

Description

Technical Field The present disclosure relates to the field of biomedicine, and specifically relates to an ionizable lipid and use thereof in drug delivery. Background In recent years, messenger RNA drugs have become a key therapeutic means for preventing and treating infectious diseases and tumors. The messenger RNA drug technology has been recognized by the industry. Benefiting from its short research and development cycle, low risk of insertional mutagenesis and diversity in encoding proteins. mRNA is highly suitable for the development of vaccines or therapeutic drugs. However, mRNA itself is highly unstable and susceptible to degradation by ubiquitous RNases. Additionally, due to the inherent negative charge and large molecular weight (typically greater than 106 Da) of mRNA, mRNA molecules are restricted from entering cells. Therefore, the development of appropriate delivery carriers to protect fragile mRNA molecules and deliver them into the cytoplasm holds great significance. Currently, a variety of mRNA delivery carriers have been developed, including lipid nanoparticles (LNPs), inorganic nanoparticles, polymeric nanoparticles, viral vectors and exosomes, etc. At present, LNPs are widely used as drug delivery carriers, and their main components include ionizable lipids, phospholipids, cholesterol and polyethylene glycol-containing lipids. The most important component in LNPs is the ionizable lipid. Early permanently positively charged cationic lipids exhibit short in vivo circulation time, high toxicity and severe allergic reactions, which is because their inherent positive charge causes them to adsorb proteins during in vivo circulation, making them liable to be captured and cleared by the reticuloendothelial system. The inherent positive charge interacts with negatively charged cell membranes, causing membrane destabilization and subsequent severe toxicity; permanently positively charged cationic lipids can activate the complement system, leading to allergic reactions. Ionizable lipids are electrically neutral under physiological pH conditions. Therefore, LNPs prepared from ionizable lipids exhibit relatively high safety. The ionizable lipid endows the LNP with lysosomal escape capability, and through the proton sponge effect and membrane fusion mechanism, enables the LNP to escape and release mRNA into the cytoplasm, where the mRNA binds to the protein-encoding ribosomes for translation of the encoded protein. In short, the development of a suitable ionizable lipid is one of the keys for developing LNPs with high safety and high lysosomal escape efficiency. Therefore, it is of great significance to develop an ionizable lipid with low toxicity and high delivery efficiency. Summary The present disclosure provides an ionizable lipid with low toxicity and high delivery efficiency. In a first aspect of the present disclosure, provides an ionizable lipid, or a pharmaceutically acceptable salt, a tautomer or a stereoisomer thereof, wherein, the ionizable lipid has the structure of Formula I below: wherein, R1 and R2 are each independently selected from -(CH2)n-, wherein n is a positive integer ranging from 1 to 14;X and Y are each independently -CH- or N;L1 has the structure of -(L1a-L1b)- from right to left, or is absent, wherein, L1a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-, preferably selected from -O-, -(C=O)O-, -O(C=O)-, -CH(OH)-; L1b is -(CH2)n-, wherein n is selected from 0, 1, 2, 3 or 4;L2 has the structure of -(L2a-L2b)- from left to right, or is absent; wherein, L2a is selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-, preferably selected from -O-, -(C=O)O-, -O(C=O)-, -CH(OH)-; L2b is -(CH2)n-, wherein n is selected from 0, 1, 2, 3 or 4;R3, R4, R5 and R6 are each independently H, CH3, C2-C30 hydrocarbyl group (e.g., C2-C30 alkyl, C2-C30 alkenyl, C2-C30 alkynyl), or -(CH2)s-Ra-(CH2)g-Rb-(CH2)m-CH3, wherein, s, g are each independently selected from a positive integer ranging from 1 to 20, m is selected from a integer ranging from 0 to 20, preferably s+g+m is 2-35;Ra, Rb are each independently absent or selected from the following functional groups: -O-, -(C=O)O-, -O(C=O)-, -(S-S)-, -O(S=O)-, -(C=O)S-, -S(C=O)-, -(C=S)O-, -NH(C=O)-, -(C=S)NH-, -NH(C=S)-, -(C=O)NH-, -CH(OH)-, preferably selected from -O-, -(C=O)O-, -O(C=O)-, -CH(OH)-;and, R3 and R4 are not both H; and R5 and R6 are not both H;R7 is selected from C1-C5 hydrocarbyl group, or -(CH2)mO(CH2)n-, wherein m, n are each independently selected from 1, 2, 3. In another preferred embodiment, the R3, R4, R5 and R6 are each independently C4-C30 hydrocarbyl group (e.g., C4-C30 alkyl, C4-C30 alkenyl, C4-C30 alkynyl), preferably is C4-C20 hydrocarbyl group (e.g., C4-C20 alkyl, C4-C20 alkeny