Lipid compounds, lipid nanoparticles, and pharmaceutical compositions

Abstract

Provided herein are lipid compounds, e.g., a compound of Formula (I) comprising an amine (heterocyclic) "head group" and a "hydrocarbon tail" moiety, and pharmaceutical compositions thereof. Also provided are lipid nanoparticles, each comprising a lipid compound of Formula (I), as a promising delivery vehicle for a variety of therapeutic agents, including small molecule drugs, proteins, and nucleic acids.

Description

Attorney Docket No.277A002WO01 LIPID COMPOUNDS, LIPID NANOPARTICLES, AND PHARMACEUTICAL COMPOSITIONS CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of the priority of U.S. Provisional Application Nos.63 / 587,643, filed October 3, 2023; 63 / 605,438, filed December 1, 2023; and 63 / 646,273, filed May 13, 2024; the disclosure of each of which is incorporated herein by reference in its entirety. FIELD

[0002] Provided herein are lipid compounds. Also provided are lipid nanoparticles and pharmaceutical compositions, each comprising a lipid compound. BACKGROUND

[0003] Lipid nanoparticles (LNPs) are a promising delivery vehicle for a variety of therapeutic agents, including small molecule drugs, proteins, and nucleic acids. Akinc et al., Nat. Nanotechnol.2019, 14, 1084-87; Hou et al., Nat. Rev. Mater.2021, 6, 1078-94. The two FDA-approved COVID-19 mRNA vaccines, mRNA-1273 and BNT162b, employ lipid nanoparticles for antigen mRNA delivery. Polack et al., N. Engl. J. Med.2020, 383, 2603-15; Baden et al., N. Engl. J. Med.2021, 384, 403-16. However, it remains challenging to deliver a therapeutic agent efficiently, especially a highly charged nucleic acid, such as an mRNA. Weng et al., Biotechnol. Adv.2020, 40, 107534; Hou et al., Nat. Rev. Mater.2021, 6, 1078-94. To achieve therapeutic effects, for example, a highly charged mRNA molecule has to reach specific target cells and produce sufficient proteins of interest. Hou et al., Nat. Rev. Mater.2021, 6, 1078-94. Therefore, there is a need for a lipid compound for delivering a therapeutic agent efficiently. SUMMARY OF THE DISCLOSURE

[0004] Provided herein is a compound of Formula (I):Attorney Docket No.277A002WO01 or an enantiomer, a mixture of two or morediastereomers, a tautomer, a an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein: R1is heterocyclyl; R4is , hydrogen, C1-6alkyl, or hydroxyl; R2a,each independently hydrogen, C1-20alkyl, C1-20heteroalkyl, C2-20 alkenyl, C2-20 alkynyl, C1-20 alkoxy, C1-20 heteroalkoxy, C2-20 alkenoxy, or C2-20 alkynoxy; R2b, R3b, and R4bare each independently C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, C2-20alkynyl, C1-20alkoxy, C1-20heteroalkoxy, C2-20alkenoxy, or C2-20alkynoxy; A1is –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; A2, A3, and A4are each independently a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; L1, L2, L3, and L4are each independently a bond, C1-20alkylene, C1-20heteroalkylene, C2-20alkenylene, or C2-20alkynylene; X, Y, and Z are each independently C(H) or N; each R1a, R1b, and R1dis independently hydrogen, deuterium, C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl; and m and n are each independently an integer of 0, 1, 2, 3, or 4; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, alkoxy, heteroalkoxy, alkenoxy, and alkynoxy is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-Attorney Docket No.277A002WO01 10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) –C(O)Ra, –C(O)ORa, –C(O)NRbRc, –C(O)SRa, –C(NRa)NRbRc, –C(S)Ra, –C(S)ORa, –C(S)NRbRc, –ORa, –OC(O)Ra, –OC(O)ORa, –OC(O)NRbRc, –OC(O)SRa, –OC(NRa)NRbRc, –OC(S)Ra, –OC(S)ORa, –OC(S)NRbRc, –OP(O)(ORb)ORc, –OS(O)Ra, –OS(O)2Ra, –OS(O)NRbRc, –OS(O)2NRbRc, –NRbRc, –NRaC(O)Rd, –NRaC(O)ORd, –NRaC(O)NRbRc, –NRaC(O)SRd, –NRaC(NRd)NRbRc, –NRaC(S)Rd, –NRaC(S)ORd, –NRaC(S)NRbRc, –NRaS(O)Rd, –NRaS(O)2Rd, –NRaS(O)NRbRc, –NRaS(O)2NRbRc, –SRa, –S(O)Ra, –S(O)2Ra, –S(O)NRbRc, and –S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, and heterocyclyl; and (c) –C(O)Re, –C(O)ORe, –C(O)NRfRg, –C(O)SRe, –C(NRe)NRfRg, –C(S)Re, –C(S)ORe, –C(S)NRfRg, –ORe, –OC(O)Re, –OC(O)ORe, –OC(O)NRfRg, –OC(O)SRe, –OC(NRe)NRfRg, –OC(S)Re, –OC(S)ORe, –OC(S)NRfRg, –OP(O)(ORf)ORg, –OS(O)Re, –OS(O)2Re, –OS(O)NRfRg, –OS(O)2NRfRg, –NRfRg, –NReC(O)Rh, –NReC(O)ORf, –NReC(O)NRfRg, –NReC(O)SRf, –NReC(NRh)NRfRg, –NReC(S)Rh, –NReC(S)ORf, –NReC(S)NRfRg, –NReS(O)Rh, –NReS(O)2Rh, –NReS(O)NRfRg, –NReS(O)2NRfRg, –SRe, –S(O)Re, –S(O)2Re, –S(O)NRfRg, and –S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

[0005] Provided herein is a compound of Formula (I):Attorney Docket No.277A002WO01 or an enantiomer, a mixture of two or morediastereomers, a tautomer, a an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein: R1is heterocyclyl; , hydrogen, or C1-6alkyl; each independently hydrogen, C1-20alkyl, C1-20heteroalkyl,C2-20 alkenyl, 20 20 C1-20 heteroalkoxy, C2-20 alkenoxy, or C2-20 alkynoxy; R2b, R3b, and R4bare each independently C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, C2-20alkynyl, C1-20alkoxy, C1-20heteroalkoxy, C2-20alkenoxy, or C2-20alkynoxy; A1is –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; A2, A3, and A4are each independently a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; L1, L2, L3, and L4are each independently a bond, C1-20alkylene, C1-20heteroalkylene, C2-20alkenylene, or C2-20alkynylene; X, Y, and Z are each independently C(H) or N; each R1a, R1b, and R1dis independently hydrogen, deuterium, C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl; and m and n are each independently an integer of 0, 1, 2, 3, or 4; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, alkoxy, heteroalkoxy, alkenoxy, and alkynoxy is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-Attorney Docket No.277A002WO01 10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) –C(O)Ra, –C(O)ORa, –C(O)NRbRc, –C(O)SRa, –C(NRa)NRbRc, –C(S)Ra, –C(S)ORa, –C(S)NRbRc, –ORa, –OC(O)Ra, –OC(O)ORa, –OC(O)NRbRc, –OC(O)SRa, –OC(NRa)NRbRc, –OC(S)Ra, –OC(S)ORa, –OC(S)NRbRc, –OP(O)(ORb)ORc, –OS(O)Ra, –OS(O)2Ra, –OS(O)NRbRc, –OS(O)2NRbRc, –NRbRc, –NRaC(O)Rd, –NRaC(O)ORd, –NRaC(O)NRbRc, –NRaC(O)SRd, –NRaC(NRd)NRbRc, –NRaC(S)Rd, –NRaC(S)ORd, –NRaC(S)NRbRc, –NRaS(O)Rd, –NRaS(O)2Rd, –NRaS(O)NRbRc, –NRaS(O)2NRbRc, –SRa, –S(O)Ra, –S(O)2Ra, –S(O)NRbRc, and –S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, and heterocyclyl; and (c) –C(O)Re, –C(O)ORe, –C(O)NRfRg, –C(O)SRe, –C(NRe)NRfRg, –C(S)Re, –C(S)ORe, –C(S)NRfRg, –ORe, –OC(O)Re, –OC(O)ORe, –OC(O)NRfRg, –OC(O)SRe, –OC(NRe)NRfRg, –OC(S)Re, –OC(S)ORe, –OC(S)NRfRg, –OP(O)(ORf)ORg, –OS(O)Re, –OS(O)2Re, –OS(O)NRfRg, –OS(O)2NRfRg, –NRfRg, –NReC(O)Rh, –NReC(O)ORf, –NReC(O)NRfRg, –NReC(O)SRf, –NReC(NRh)NRfRg, –NReC(S)Rh, –NReC(S)ORf, –NReC(S)NRfRg, –NReS(O)Rh, –NReS(O)2Rh, –NReS(O)NRfRg, –NReS(O)2NRfRg, –SRe, –S(O)Re, –S(O)2Re, –S(O)NRfRg, and –S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

[0006] Provided herein is a compound of Formula (I):Attorney Docket No.277A002WO01 or an enantiomer, a mixture of two or morediastereomers, a tautomer, a an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein: R1is heterocyclyl; or hydrogen; independently hydrogen, C1-20alkyl, C1-20heteroalkyl,C2-20 alkenyl, C2-20 alkynyl, C1-20 alkoxy, C1-20 heteroalkoxy, C2-20 alkenoxy, or C2-20 alkynoxy; R2b, R3b, and R4bare each independently C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, C2-20alkynyl, C1-20alkoxy, C1-20heteroalkoxy, C2-20alkenoxy, or C2-20alkynoxy; A1is –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; A2, A3, and A4are each independently a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; L1, L2, L3, and L4are each independently a bond, C1-20alkylene, C1-20heteroalkylene, C2-20alkenylene, or C2-20alkynylene; X, Y, and Z are each independently C(H) or N; each R1a, R1b, and R1dis independently hydrogen, deuterium, C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl; and m and n are each independently an integer of 0, 1, 2, 3, or 4; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, alkoxy, heteroalkoxy, alkenoxy, and alkynoxy is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-Attorney Docket No.277A002WO01 10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) –C(O)Ra, –C(O)ORa, –C(O)NRbRc, –C(O)SRa, –C(NRa)NRbRc, –C(S)Ra, –C(S)ORa, –C(S)NRbRc, –ORa, –OC(O)Ra, –OC(O)ORa, –OC(O)NRbRc, –OC(O)SRa, –OC(NRa)NRbRc, –OC(S)Ra, –OC(S)ORa, –OC(S)NRbRc, –OP(O)(ORb)ORc, –OS(O)Ra, –OS(O)2Ra, –OS(O)NRbRc, –OS(O)2NRbRc, –NRbRc, –NRaC(O)Rd, –NRaC(O)ORd, –NRaC(O)NRbRc, –NRaC(O)SRd, –NRaC(NRd)NRbRc, –NRaC(S)Rd, –NRaC(S)ORd, –NRaC(S)NRbRc, –NRaS(O)Rd, –NRaS(O)2Rd, –NRaS(O)NRbRc, –NRaS(O)2NRbRc, –SRa, –S(O)Ra, –S(O)2Ra, –S(O)NRbRc, and –S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, and heterocyclyl; and (c) –C(O)Re, –C(O)ORe, –C(O)NRfRg, –C(O)SRe, –C(NRe)NRfRg, –C(S)Re, –C(S)ORe, –C(S)NRfRg, –ORe, –OC(O)Re, –OC(O)ORe, –OC(O)NRfRg, –OC(O)SRe, –OC(NRe)NRfRg, –OC(S)Re, –OC(S)ORe, –OC(S)NRfRg, –OP(O)(ORf)ORg, –OS(O)Re, –OS(O)2Re, –OS(O)NRfRg, –OS(O)2NRfRg, –NRfRg, –NReC(O)Rh, –NReC(O)ORf, –NReC(O)NRfRg, –NReC(O)SRf, –NReC(NRh)NRfRg, –NReC(S)Rh, –NReC(S)ORf, –NReC(S)NRfRg, –NReS(O)Rh, –NReS(O)2Rh, –NReS(O)NRfRg, –NReS(O)2NRfRg, –SRe, –S(O)Re, –S(O)2Re, –S(O)NRfRg, and –S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

[0007] Also provided herein is a lipid nanoparticle comprising a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.Attorney Docket No.277A002WO01

[0008] Additionally, provided herein is a lipid nanoparticle comprising (i) a nucleic acid and (ii) a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0009] Furthermore, provided herein is a pharmaceutical composition comprising a lipid nanoparticle that comprises (i) a nucleic acid and (ii) a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof. DETAILED DESCRIPTION

[0010] To facilitate understanding of the disclosure set forth herein, a number of terms are defined below.

[0011] Generally, the nomenclature used herein and the laboratory procedures in organic chemistry, medicinal chemistry, and biochemistry described herein are those well-known and commonly employed in the art. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0012] The term “alkyl” refers to a linear or branched saturated monovalent hydrocarbon radical, wherein the alkyl is optionally substituted with one or more substituents Q as described herein. For example, C1-6alkyl refers to a linear saturated monovalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkyl is a linear saturated monovalent hydrocarbon radical that has 1 to 20 (C1-20), 1 to 15 (C1-15), 1 to 10 (C1-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated monovalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 alkyl groups are also referred as “lower alkyl.” Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (including all isomeric forms, e.g., n-propyl and isopropyl), butyl (including all isomeric forms, e.g., n-butyl, isobutyl, sec-butyl, and t-butyl), pentyl (including all isomericAttorney Docket No.277A002WO01 forms, e.g., n-pentyl, isopentyl, sec-pentyl, neopentyl, and tert-pentyl), and hexyl (including all isomeric forms, e.g., n-hexyl, isohexyl, and sec-hexyl).

[0013] The terms “alkylene” and “alkanediyl” are used interchangeably herein in reference to a linear or branched saturated divalent hydrocarbon radical, wherein the alkanediyl is optionally substituted with one or more substituents Q as described herein. For example, C1-6 alkanediyl refers to a linear saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkanediyl is a linear saturated divalent hydrocarbon radical that has 1 to 30 (C1-30), 1 to 20 (C1-20), 1 to 15 (C1-15), 1 to 10 (C1-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated divalent hydrocarbon radical of 3 to 30 (C3-30), 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 alkanediyl groups are also referred as “lower alkanediyl.” Examples of alkanediyl groups include, but are not limited to, methanediyl, ethanediyl (including all isomeric forms, e.g., ethane-1,1-diyl and ethane-1,2- diyl), propanediyl (including all isomeric forms, e.g., propane-1,1-diyl, propane-1,2-diyl, and propane-1,3-diyl), butanediyl (including all isomeric forms, e.g., butane-1,1-diyl, butane-1,2- diyl, butane-1,3-diyl, and butane-1,4-diyl), pentanediyl (including all isomeric forms, e.g., pentane-1,1-diyl, pentane-1,2-diyl, pentane-1,3-diyl, and pentane-1,5-diyl), and hexanediyl (including all isomeric forms, e.g., hexane-1,1-diyl, hexane-1,2-diyl, hexane-1,3-diyl, and hexane-1,6-diyl). Examples of substituted alkanediyl groups include, but are not limited to, –C(O)CH2–, –C(O)(CH2)2–, –C(O)(CH2)3–, –C(O)(CH2)4–, –C(O)(CH2)5–, –C(O)(CH2)6–, –C(O)(CH2)7–, –C(O)(CH2)8–, –C(O)(CH2)9–, –C(O)(CH2)10–, –C(O)CH2C(O)–, –C(O)(CH2)2C(O)–, –C(O)(CH2)3C(O)–, –C(O)(CH2)4C(O)–, or –C(O)(CH2)5C(O)–.

[0014] The term “heteroalkyl” refers to a linear or branched saturated monovalent hydrocarbon radical that contains one or more heteroatoms on its main chain, each independently selected from O, S, and N. The heteroalkyl is optionally substituted with one or more substituents Q as described herein. For example, C1-6heteroalkyl refers to a linear saturated monovalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the heteroalkyl is a linear saturated monovalent hydrocarbon radical that has 1 to 20 (C1-20), 1 to 15 (C1-15), 1 to 10 (C1-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated monovalent hydrocarbon radical of 3 to 20Attorney Docket No.277A002WO01 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 heteroalkyl groups are also referred as “lower heteroalkyl.” Examples of heteroalkyl groups include, but are not limited to, –OCH3, –OCH2CH3, –CH2OCH3, –NHCH3, –ONHCH3, –NHOCH3, –SCH3, –CH2NHCH2CH3, and –NHCH2CH2CH3. Examples of substituted heteroalkyl groups include, but are not limited to, –CH2NHC(O)CH3 and –NHC(O)CH2CH3.

[0015] The terms “heteroalkylene” and “heteroalkanediyl” are used interchangeably herein in reference to a linear or branched saturated divalent hydrocarbon radical that contains one or more heteroatoms in its main chain, each independently selected from O, S, and N. The heteroalkylene is optionally substituted with one or more substituents Q as described herein. For example, C1-6 heteroalkylene refers to a linear saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the heteroalkylene is a linear saturated divalent hydrocarbon radical that has 1 to 20 (C1-20), 1 to 15 (C1-15), 1 to 10 (C1-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated divalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6and branched C3-6heteroalkylene groups are also referred as “lower heteroalkylene.” Examples of heteroalkylene groups include, but are not limited to, –CH2O–, –(CH2)2O–, –(CH2)3O–, –(CH2)4O–, –(CH2)5O–, –(CH2)6O–, –(CH2)7O–, –(CH2)8O–, –(CH2)9O–, –(CH2)10O–, –CH2OCH2–, –CH2CH2O–, –(CH2CH2O)2–, –(CH2CH2O)3–, –(CH2CH2O)4–, –(CH2CH2O)5–, –CH2NH–, –CH2NHCH2–, –CH2CH2NH–, –CH2S–, –CH2SCH2–, and –CH2CH2S–. Examples of substituted heteroalkylene groups include, but are not limited to, –C(O)CH2O–, –C(O)(CH2)2O–, –C(O)(CH2)3O–, –C(O)(CH2)4O–, –C(O)(CH2)5O–, –C(O)(CH2)6O–, –C(O)(CH2)7O–, –C(O)(CH2)8O–, –C(O)(CH2)9O–, –C(O)(CH2)10O–, –C(O)CH2OCH2CH2O–, –C(O)CH2O(CH2CH2O)2–, –C(O)CH2O(CH2CH2O)3–, –C(O)CH2O(CH2CH2O)4, –C(O)CH2O(CH2CH2O)5–, –CH2NHC(O)CH2–, or –CH2CH2C(O)NH–.

[0016] The term “alkenyl” refers to a linear or branched monovalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon double bond(s). The alkenyl is optionally substituted with one or more substituents Q as described herein. The term “alkenyl” embraces radicals having a “cis”Attorney Docket No.277A002WO01 or “trans” configuration or a mixture thereof, or alternatively, a “Z” or “E” configuration or a mixture thereof, as appreciated by those of ordinary skill in the art. For example, C2-6 alkenyl refers to a linear unsaturated monovalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkenyl is a linear monovalent hydrocarbon radical of 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-6) carbon atoms, or a branched monovalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, propenyl (including all isomeric forms, e.g., propen-1-yl, propen-2-yl, and allyl), and butenyl (including all isomeric forms, e.g., buten- 1-yl, buten-2-yl, buten-3-yl, and 2-buten-1-yl).

[0017] The terms “alkenylene” and “alkenediyl” are used interchangeably herein in reference to a linear or branched divalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon double bond(s). The alkenediyl is optionally substituted with one or more substituents Q as described herein. The term “alkenediyl” embraces radicals having a “cis” or “trans” configuration or a mixture thereof, or alternatively, a “Z” or “E” configuration or a mixture thereof, as appreciated by those of ordinary skill in the art. For example, C2-6alkenediyl refers to a linear unsaturated divalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated divalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkenediyl is a linear divalent hydrocarbon radical of 2 to 30 (C2-30), 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-6) carbon atoms, or a branched divalent hydrocarbon radical of 3 to 30 (C3-30), 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. Examples of alkenediyl groups include, but are not limited to, ethenediyl (including all isomeric forms, e.g., ethene-1,1- diyl and ethene-1,2-diyl), propenediyl (including all isomeric forms, e.g., 1-propene-1,1-diyl, 1- propene-1,2-diyl, and 1-propene-1,3-diyl), butenediyl (including all isomeric forms, e.g., 1- butene-1,1-diyl, 1-butene-1,2-diyl, and 1-butene-1,4-diyl), pentenediyl (including all isomeric forms, e.g., 1-pentene-1,1-diyl, 1-pentene-1,2-diyl, and 1-pentene-1,5-diyl), and hexenediyl (including all isomeric forms, e.g., 1-hexene-1,1-diyl, 1-hexene-1,2-diyl, 1-hexene-1,3-diyl, 1- hexene-1,4-diyl, 1-hexene-1,5-diyl, and 1-hexene-1,6-diyl).

[0018] The term “alkynyl” refers to a linear or branched monovalent hydrocarbonAttorney Docket No.277A002WO01 radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon triple bond(s). An alkynyl group does not contain a carbon- carbon double bond. The alkynyl is optionally substituted with one or more substituents Q as described herein. For example, C2-6 alkynyl refers to a linear unsaturated monovalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated monovalent hydrocarbon radical of 4 to 6 carbon atoms. In certain embodiments, the alkynyl is a linear monovalent hydrocarbon radical of 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-6) carbon atoms, or a branched monovalent hydrocarbon radical of 4 to 20 (C4-20), 4 to 15 (C4-15), 4 to 10 (C4-10), or 4 to 6 (C4-6) carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl (–C≡CH), propynyl (including all isomeric forms, e.g., 1-propynyl (–C≡CCH3) and propargyl (–CH2C≡CH)), butynyl (including all isomeric forms, e.g., 1-butyn-1-yl and 2-butyn- 1-yl), pentynyl (including all isomeric forms, e.g., 1-pentyn-1-yl and 1-methyl-2-butyn-1-yl), and hexynyl (including all isomeric forms, e.g., 1-hexyn-1-yl and 2-hexyn-1-yl).

[0019] The terms “alkynylene” and “alkynediyl” are used interchangeably herein in reference to a linear or branched divalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon triple bond(s). An alkynylene group does not contain a carbon-carbon double bond. The alkynediyl is optionally substituted with one or more substituents Q as described herein. For example, C2-6 alkynediyl refers to a linear unsaturated divalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated divalent hydrocarbon radical of 4 to 6 carbon atoms. In certain embodiments, the alkynediyl is a linear divalent hydrocarbon radical of 2 to 30 (C2-30), 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-6) carbon atoms, or a branched divalent hydrocarbon radical of 4 to 30 (C4-30), 4 to 20 (C4-20), 4 to 15 (C4-15), 4 to 10 (C4-10), or 4 to 6 (C4-6) carbon atoms. Examples of alkynediyl groups include, but are not limited to, ethynediyl, propynediyl (including all isomeric forms, e.g., 1-propyne-1,3-diyl and 1-propyne-3,3-diyl), butynediyl (including all isomeric forms, e.g., 1-butyne-1,3-diyl, 1-butyne-1,4-diyl, and 2- butyne-1,1-diyl), pentynediyl (including all isomeric forms, e.g., 1-pentyne-1,3-diyl, 1-pentyne- 1,4-diyl, and 2-pentyne-1,1-diyl), and hexynediyl (including all isomeric forms, e.g., 1-hexyne- 1,3-diyl, 1-hexyne-1,4-diyl, and 2-hexyne-1,1-diyl).

[0020] The term “cycloalkyl” refers to a cyclic monovalent hydrocarbon radical, which isAttorney Docket No.277A002WO01 optionally substituted with one or more substituents Q as described herein. In one embodiment, the cycloalkyl is a saturated or unsaturated but non-aromatic, and / or bridged or non-bridged, and / or fused bicyclic group. In certain embodiments, the cycloalkyl has from 3 to 20 (C3-20), from 3 to 15 (C3-15), from 3 to 10 (C3-10), or from 3 to 7 (C3-7) carbon atoms. In one embodiment, the cycloalkyl is monocyclic. In another embodiment, the cycloalkyl is bicyclic. In yet another embodiment, the cycloalkyl is tricyclic. In still another embodiment, the cycloalkyl is polycyclic. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl, bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, decalinyl, and adamantyl.

[0021] The term “aryl” refers to a monovalent monocyclic aromatic hydrocarbon radical and / or monovalent polycyclic aromatic hydrocarbon radical that contain at least one aromatic carbon ring. In certain embodiments, the aryl has from 6 to 20 (C6-20), from 6 to 15 (C6-15), or from 6 to 10 (C6-10) ring carbon atoms. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, fluorenyl, azulenyl, anthryl, phenanthryl, pyrenyl, biphenyl, and terphenyl. The aryl also refers to bicyclic or tricyclic carbon rings, where one of the rings is aromatic and the others of which may be saturated, partially unsaturated, or aromatic, for example, dihydronaphthyl, indenyl, indanyl, or tetrahydronaphthyl (tetralinyl). In one embodiment, the aryl is monocyclic. In another embodiment, the aryl is bicyclic. In yet another embodiment, the aryl is tricyclic. In still another embodiment, the aryl is polycyclic. In certain embodiments, the aryl is optionally substituted with one or more substituents Q as described herein.

[0022] The term “aralkyl” or “arylalkyl” refers to a monovalent alkyl group substituted with one or more aryl groups. In certain embodiments, the aralkyl has from 7 to 30 (C7-30), from 7 to 20 (C7-20), or from 7 to 16 (C7-16) carbon atoms. Examples of aralkyl groups include, but are not limited to, benzyl, phenylethyl (including all isomeric forms, e.g., 1-phenylethyl and 2- phenylethyl), and phenylpropyl (including all isomeric forms, e.g., 1-phenylpropyl, 2- phenylpropyl, and 3-phenylpropyl). In certain embodiments, the aralkyl is optionally substituted with one or more substituents Q as described herein.

[0023] The term “heteroaryl” refers to a monovalent monocyclic aromatic group orAttorney Docket No.277A002WO01 monovalent polycyclic aromatic group that contain at least one aromatic ring, wherein at least one aromatic ring contains one or more heteroatoms, each independently selected from O, S, and N, in the ring. For a heteroaryl group containing a heteroaromatic ring and a nonaromatic heterocyclic ring, the heteroaryl group is not bonded to the rest of a molecule through its nonaromatic heterocyclic ring. Each ring of a heteroaryl group can contain one or two O atoms, one or two S atoms, and / or one to four N atoms; provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom. In certain embodiments, the heteroaryl has from 5 to 20, from 5 to 15, or from 5 to 10 ring atoms. In one embodiment, the heteroaryl is monocyclic. Examples of monocyclic heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl, and triazolyl. In another embodiment, the heteroaryl is bicyclic. Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzoisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl, benzoxazolyl, furopyrindyl (including all isomeric forms, e.g., furo[2,3-b]pyridinyl, furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl, furo[3,2-c]pyridinyl, furo[3,4-b]pyridinyl, and furo[3,4-c]pyridinyl), imidazopyridinyl (including all isomeric forms, e.g., imidazo[1,2-a]pyridinyl, imidazo[4,5- b]pyridinyl, and imidazo[4,5-c]pyridinyl), imidazothiazolyl (including all isomeric forms, e.g., imidazo[2,1-b]thiazolyl and imidazo[4,5-d]thiazolyl), indazolyl, indolizinyl, indolyl, isobenzofuranyl, isobenzothienyl (i.e., benzo[c]thienyl), isoindolyl, isoquinolinyl, naphthyridinyl (including all isomeric forms, e.g., 1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, and 1,8-naphthyridinyl), oxazolopyridinyl (including all isomeric forms, e.g., oxazolo[4,5- b]pyridinyl, oxazolo[4,5-c]pyridinyl, oxazolo[5,4-b]pyridinyl, and oxazolo[5,4-c]pyridinyl), phthalazinyl, pteridinyl, purinyl, pyrrolopyridyl (including all isomeric forms, e.g., pyrrolo[2,3- b]pyridinyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-b]pyridinyl, and pyrrolo[3,2-c]pyridinyl), quinolinyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidyl (including all isomeric forms, e.g., [1,2,5]thiadiazolo[3,4-d]pyrimidinyl and [1,2,3]thiadiazolo[4,5-d]pyrimidinyl), and thienopyridyl (including all isomeric forms, e.g., thieno[2,3-b]pyridinyl, thieno[2,3-c]pyridinyl, thieno[3,2-b]pyridinyl, and thieno[3,2-c]pyridinyl). In yet another embodiment, the heteroaryl is tricyclic. Examples of tricyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, perimidinyl, phenanthrolinyl, phenanthridinylAttorney Docket No.277A002WO01 (including all isomeric forms, e.g., 1,5-phenanthrolinyl, 1,6-phenanthrolinyl, 1,7- phenanthrolinyl, 1,9-phenanthrolinyl, and 2,10-phenanthrolinyl), phenarsazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and xanthenyl. In certain embodiments, the heteroaryl is optionally substituted with one or more substituents Q as described herein.

[0024] The term “heterocyclyl” or “heterocyclic” refers to a monovalent monocyclic non-aromatic ring system or monovalent polycyclic ring system that contains at least one non- aromatic ring, wherein one or more of the non-aromatic ring atoms are heteroatoms, each independently selected from O, S, and N; and the remaining ring atoms are carbon atoms. For a heterocyclyl group containing a heteroaromatic ring and a nonaromatic heterocyclic ring, the heterocyclyl group is not bonded to the rest of a molecule through the heteroaromatic ring. In certain embodiments, the heterocyclyl or heterocyclic group has from 3 to 20, from 3 to 15, from 3 to 10, from 3 to 8, from 4 to 7, or from 5 to 6 ring atoms. In certain embodiments, the heterocyclyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may be fused or bridged, and in which nitrogen or sulfur atoms may be optionally oxidized, nitrogen atoms may be optionally quaternized, and some rings may be partially or fully saturated, or aromatic. The heterocyclyl may be attached to the main structure at any heteroatom or carbon atom which results in the creation of a stable compound. Examples of heterocyclyls and heterocyclic groups include, but are not limited to, azepinyl, benzodioxanyl, benzodioxolyl, benzofuranonyl, chromanyl, decahydroisoquinolinyl, dihydrobenzofuranyl, dihydrobenzisothiazolyl, dihydrobenzisoxazinyl (including all isomeric forms, e.g., 1,4-dihydrobenzo[d][1,3]oxazinyl, 3,4-dihydrobenzo[c][1,2]-oxazinyl, and 3,4-dihydrobenzo[d][1,2]oxazinyl), dihydrobenzothienyl, dihydroisobenzofuranyl, dihydrobenzo[c]thienyl, dihydrofuryl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl, oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4-piperidonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothienyl, thiamorpholinyl, thiazolidinyl, thiochromanyl, tetrahydroquinolinyl, and 1,3,5-trithianyl. In certain embodiments, the heterocyclyl is optionally substituted with one or more substituents Q as described herein.Attorney Docket No.277A002WO01

[0025] The term “halogen,” “halide,” or “halo” refers to fluoro, chloro, bromo, and / or iodo.

[0026] The term “alkoxy” or “alkyloxy” refers to –O–alkyl, where the alkyl group is as defined herein.

[0027] The term “heteroalkoxy” or “heteroalkyloxy” refers to –O–heteroalkyl, where the heteroalkyl group is as defined herein.

[0028] The term “alkenoxy” or “alkenyloxy” refers to –O–alkenyl, where the alkenyl group is as defined herein.

[0029] The term “alkynoxy” or “alkynyloxy” refers to –O–alkynyl, where the alkynyl group is as defined herein.

[0030] The term “optionally substituted” is intended to mean that a group or substituent, such as an alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, alkoxy, heteroalkoxy, alkenoxy, or alkynoxy, may be substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, each of which is independently selected from, e.g., (a) deuterium (–D), cyano (–CN), halo, imino (=NH), nitro (–NO2), and oxo (=O); (b) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) –C(O)Ra, –C(O)ORa, –C(O)NRbRc, –C(O)SRa, –C(NRa)NRbRc, –C(S)Ra, –C(S)ORa, –C(S)NRbRc, –ORa, –OC(O)Ra, –OC(O)ORa, –OC(O)NRbRc, –OC(O)SRa, –OC(NRa)NRbRc, –OC(S)Ra, –OC(S)ORa, –OC(S)NRbRc, –OS(O)Ra, –OS(O)2Ra, –OS(O)NRbRc, –OS(O)2NRbRc, –NRbRc, –NRaC(O)Rd, –NRaC(O)ORd, –NRaC(O)NRbRc, –NRaC(O)SRd, –NRaC(NRd)NRbRc, –NRaC(S)Rd, –NRaC(S)ORd, –NRaC(S)NRbRc, –NRaS(O)Rd, –NRaS(O)2Rd, –NRaS(O)NRbRc, –NRaS(O)2NRbRc, –SRa, –S(O)Ra, –S(O)2Ra, –S(O)NRbRc, and –S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached formAttorney Docket No.277A002WO01 heterocyclyl optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa. As used herein, all groups that can be substituted are “optionally substituted.”

[0031] In one embodiment, each Qais independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, and heterocyclyl; and (c) –C(O)Re, –C(O)ORe, –C(O)NRfRg, –C(O)SRe, –C(NRe)NRfRg, –C(S)Re, –C(S)ORe, –C(S)NRfRg, –ORe, –OC(O)Re, –OC(O)ORe, –OC(O)NRfRg, –OC(O)SRe, –OC(NRe)NRfRg, –OC(S)Re, –OC(S)ORe, –OC(S)NRfRg, –OS(O)Re, –OS(O)2Re, –OS(O)NRfRg, –OS(O)2NRfRg, –NRfRg, –NReC(O)Rh, –NReC(O)ORf, –NReC(O)NRfRg, –NReC(O)SRf, –NReC(NRh)NRfRg, –NReC(S)Rh, –NReC(S)ORf, –NReC(S)NRfRg, –NReS(O)Rh, –NReS(O)2Rh, –NReS(O)NRfRg, –NReS(O)2NRfRg, –SRe, –S(O)Re, –S(O)2Re, –S(O)NRfRg, and –S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

[0032] In certain embodiments, “optically active” and ”enantiomerically active” refer to a collection of molecules, which has an enantiomeric excess of no less than about 80%, no less than about 90%, no less than about 91%, no less than about 92%, no less than about 93%, no less than about 94%, no less than about 95%, no less than about 96%, no less than about 97%, no less than about 98%, no less than about 99%, no less than about 99.5%, or no less than about 99.8%. In certain embodiments, an optically active compound comprises about 95% or more of one enantiomer and about 5% or less of the other enantiomer based on the total weight of the enantiomeric mixture in question. In certain embodiments, an optically active compound comprises about 98% or more of one enantiomer and about 2% or less of the other enantiomer based on the total weight of the enantiomeric mixture in question. In certain embodiments, an optically active compound comprises about 99% or more of one enantiomer and about 1% or less of the other enantiomer based on the total weight of the enantiomeric mixture in question.

[0033] In describing an optically active compound, the prefixes R and S are used to denote the absolute configuration of the compound about its chiral center(s). The (+) and (-) areAttorney Docket No.277A002WO01 used to denote the optical rotation of the compound, that is, the direction in which a plane of polarized light is rotated by the optically active compound. The (-) prefix indicates that the compound is levorotatory, that is, the compound rotates the plane of polarized light to the left or counterclockwise. The (+) prefix indicates that the compound is dextrorotatory, that is, the compound rotates the plane of polarized light to the right or clockwise. However, the sign of optical rotation, (+) and (-), is not related to the absolute configuration of the compound, R and S.

[0034] The term “isotopically enriched” refers to a compound that contains an unnatural proportion of an isotope at one or more of the atoms that constitute such a compound. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes, including, but not limited to, hydrogen (1H), deuterium (2H), tritium (3H), carbon-11 (11C), carbon-12 (12C), carbon-13 (13C), carbon-14 (14C), nitrogen-13 (13N), nitrogen-14 (14N), nitrogen-15 (15N), oxygen-14 (14O), oxygen-15 (15O), oxygen-16 (16O), oxygen-17 (17O), oxygen-18 (18O), fluorine-17 (17F), fluorine-18 (18F), phosphorus-31 (31P), phosphorus-32 (32P), phosphorus-33 (33P), sulfur-32 (32S), sulfur-33 (33S), sulfur-34 (34S), sulfur-35 (35S), sulfur-36 (36S), chlorine-35 (35Cl), chlorine-36 (36Cl), chlorine-37 (37Cl), bromine-79 (79Br), bromine-81 (81Br), iodine-123 (123I), iodine-125 (125I), iodine-127 (127I), iodine-129 (129I), and iodine-131 (131I). In certain embodiments, an isotopically enriched compound is in a stable form, that is, non-radioactive. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes, including, but not limited to, hydrogen (1H), deuterium (2H), carbon-12 (12C), carbon-13 (13C), nitrogen-14 (14N), nitrogen-15 (15N), oxygen-16 (16O), oxygen-17 (17O), oxygen-18 (18O), fluorine-17 (17F), phosphorus-31 (31P), sulfur-32 (32S), sulfur- 33 (33S), sulfur-34 (34S), sulfur-36 (36S), chlorine-35 (35Cl), chlorine-37 (37Cl), bromine-79 (79Br), bromine-81 (81Br), and iodine-127 (127I). In certain embodiments, an isotopically enriched compound is in an unstable form, that is, radioactive. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes, including, but not limited to, tritium (3H), carbon-11 (11C), carbon-14 (14C), nitrogen-13 (13N), oxygen-14 (14O), oxygen-15 (15O), fluorine-18 (18F), phosphorus-32 (32P), phosphorus-33 (33P), sulfur-35 (35S), chlorine-36 (36Cl), iodine-123 (123I), iodine-125 (125I), iodine-129 (129I), and iodine-131 (131I). It will be understood that, in a compound as provided herein, any hydrogen can be2H, as example, or any carbon can be13C, as example, or any nitrogen can be15N, as example, or any oxygen can be18O, as example, where feasible according to the judgment of oneAttorney Docket No.277A002WO01 of ordinary skill in the art.

[0035] The term “isotopic enrichment” refers to the percentage of incorporation of a less prevalent isotope (e.g., D for deuterium or hydrogen-2) of an element at a given position in a molecule in the place of a more prevalent isotope (e.g.,1H for protium or hydrogen-1) of the element. As used herein, when an atom at a particular position in a molecule is designated as a particular less prevalent isotope, it is understood that the abundance of that isotope at that position is substantially greater than its natural abundance.

[0036] The term “isotopic enrichment factor” refers to the ratio between the isotopic abundance in an isotopically enriched compound and the natural abundance of a specific isotope.

[0037] The term “hydrogen” or the symbol “H” refers to the composition of naturally occurring hydrogen isotopes, which include protium (1H), deuterium (2H or D), and tritium (3H), in their natural abundances. Protium is the most common hydrogen isotope having a natural abundance of more than 99.98%. Deuterium is a less prevalent hydrogen isotope having a natural abundance of about 0.0156%.

[0038] The term “deuterium enrichment” refers to the percentage of incorporation of deuterium at a given position in a molecule in the place of hydrogen. For example, deuterium enrichment of 1% at a given position means that 1% of molecules in a given sample contain deuterium at the specified position. Because the naturally occurring distribution of deuterium is about 0.0156% on average, deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is about 0.0156% on average. As used herein, when a particular position in an isotopically enriched compound is designated as having deuterium, it is understood that the abundance of deuterium at that position in the compound is substantially greater than its natural abundance (0.0156%).

[0039] The term “carbon” or the symbol “C” refers to the composition of naturally occurring carbon isotopes, which include carbon-12 (12C) and carbon-13 (13C) in their natural abundances. Carbon-12 is the most common carbon isotope having a natural abundance of more than 98.89%. Carbon-13 is a less prevalent carbon isotope having a natural abundance of about 1.11%.Attorney Docket No.277A002WO01

[0040] The term “carbon-13 enrichment” or “13C enrichment” refers to the percentage of incorporation of carbon-13 at a given position in a molecule in the place of carbon. For example, carbon-13 enrichment of 10% at a given position means that 10% of molecules in a given sample contain carbon-13 at the specified position. Because the naturally occurring distribution of carbon-13 is about 1.11% on average, carbon-13 enrichment at any position in a compound synthesized using non-enriched starting materials is about 1.11% on average. As used herein, when a particular position in an isotopically enriched compound is designated as having carbon- 13, it is understood that the abundance of carbon-13 at that position in the compound is substantially greater than its natural abundance (1.11%).

[0041] The terms “substantially pure” and “substantially homogeneous” mean, when referred to a substance, sufficiently homogeneous to appear free of readily detectable impurities as determined by a standard analytical method used by one of ordinary skill in the art, including, but not limited to, thin layer chromatography (TLC), gel electrophoresis, high performance liquid chromatography (HPLC), gas chromatography (GC), nuclear magnetic resonance (NMR), and mass spectrometry (MS); or sufficiently pure such that further purification would not detectably alter the physical, chemical, biological, and / or pharmacological properties, such as enzymatic and biological activities, of the substance. In certain embodiments, “substantially pure” or “substantially homogeneous” refers to a collection of molecules, wherein at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 99.5% by weight of the molecules are a single compound, including a single enantiomer, a racemic mixture, or a mixture of enantiomers, as determined by standard analytical methods. As used herein, when an atom at a particular position in an isotopically enriched molecule is designated as a particular less prevalent isotope, a molecule that contains other than the designated isotope at the specified position is an impurity with respect to the isotopically enriched compound. Thus, for a deuterated compound that has an atom at a particular position designated as deuterium, a compound that contains a protium at the same position is an impurity.

[0042] The term “solvate” refers to a complex or aggregate formed by one or more molecules of a solute, e.g., a compound provided herein, and one or more molecules of a solvent, which are present in a stoichiometric or non-stoichiometric amount. Suitable solvents include, but are not limited to, water, methanol, ethanol, n-propanol, isopropanol, and acetic acid. InAttorney Docket No.277A002WO01 certain embodiments, the solvent is pharmaceutically acceptable. In one embodiment, the complex or aggregate is in a crystalline form. In another embodiment, the complex or aggregate is in a noncrystalline form. Where the solvent is water, the solvate is a hydrate. Examples of hydrates include, but are not limited to, a hemihydrate, monohydrate, dihydrate, trihydrate, tetrahydrate, and pentahydrate.

[0043] For a divalent group described herein, no orientation is implied by the direction in which the divalent group is presented. For example, unless a particular orientation is specified, the formula –C(O)O– represents both –C(O)O– and –OC(O)–.

[0044] The phrase “an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof” has the same meaning as the phrase “(i) an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant of the compound referenced therein; (ii) a pharmaceutically acceptable salt, solvate, or hydrate of the compound referenced therein; or (iii) a pharmaceutically acceptable salt, solvate, or hydrate of an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant of the compound referenced therein.” Compounds

[0045] In one embodiment, provided herein is a compound of Formula (I): or an enantiomer, a mixtureof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein: R1is heterocyclyl;Attorney Docket No.277A002WO01 R4is , hydrogen, C1-6 alkyl, or hydroxyl; R2a, each independently hydrogen, C1-20alkyl, C1-20heteroalkyl,C2-20alkenyl, C2-20 20C1-20heteroalkoxy, C2-20alkenoxy, or C2-20alkynoxy; R2b, R3b, and R4bare each independently C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C2-20alkynyl, C1-20alkoxy, C1-20heteroalkoxy, C2-20alkenoxy, or C2-20alkynoxy; A1is –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; A2, A3, and A4are each independently a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; L1, L2, L3, and L4are each independently a bond, C1-20 alkylene, C1-20 heteroalkylene, C2-20alkenylene, or C2-20alkynylene; X, Y, and Z are each independently C(H) or N; each R1a, R1b, and R1dis independently hydrogen, deuterium, C1-6 alkyl, C1-6 heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl; and m and n are each independently an integer of 0, 1, 2, 3, or 4; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, alkoxy, heteroalkoxy, alkenoxy, and alkynoxy is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) –C(O)Ra, –C(O)ORa, –C(O)NRbRc, –C(O)SRa, –C(NRa)NRbRc, –C(S)Ra, –C(S)ORa, –C(S)NRbRc, –ORa, –OC(O)Ra, –OC(O)ORa, –OC(O)NRbRc, –OC(O)SRa, –OC(NRa)NRbRc, –OC(S)Ra, –OC(S)ORa, –OC(S)NRbRc, –OP(O)(ORb)ORc, –OS(O)Ra, –OS(O)2Ra, –OS(O)NRbRc, –OS(O)2NRbRc, –NRbRc, –NRaC(O)Rd, –NRaC(O)ORd, –NRaC(O)NRbRc, –NRaC(O)SRd, –NRaC(NRd)NRbRc, –NRaC(S)Rd, –NRaC(S)ORd, –NRaC(S)NRbRc, –NRaS(O)Rd, –NRaS(O)2Rd, –NRaS(O)NRbRc, –NRaS(O)2NRbRc, –SRa, –S(O)Ra, –S(O)2Ra,Attorney Docket No.277A002WO01 –S(O)NRbRc, and –S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) –C(O)Re, –C(O)ORe, –C(O)NRfRg, –C(O)SRe, –C(NRe)NRfRg, –C(S)Re, –C(S)ORe, –C(S)NRfRg, –ORe, –OC(O)Re, –OC(O)ORe, –OC(O)NRfRg, –OC(O)SRe, –OC(NRe)NRfRg, –OC(S)Re, –OC(S)ORe, –OC(S)NRfRg, –OP(O)(ORf)ORg, –OS(O)Re, –OS(O)2Re, –OS(O)NRfRg, –OS(O)2NRfRg, –NRfRg, –NReC(O)Rh, –NReC(O)ORf, –NReC(O)NRfRg, –NReC(O)SRf, –NReC(NRh)NRfRg, –NReC(S)Rh, –NReC(S)ORf, –NReC(S)NRfRg, –NReS(O)Rh, –NReS(O)2Rh, –NReS(O)NRfRg, –NReS(O)2NRfRg, –SRe, –S(O)Re, –S(O)2Re, –S(O)NRfRg, and –S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

[0046] In another embodiment, provided herein is a compound of Formula (I): or an enantiomer, a mixtureof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein: R1is heterocyclyl; , hydrogen, or C1-6 alkyl;each independently hydrogen, C1-20alkyl, C1-20heteroalkyl,Attorney Docket No.277A002WO01 C2-20 alkenyl, C2-20 alkynyl, C1-20 alkoxy, C1-20 heteroalkoxy, C2-20 alkenoxy, or C2-20 alkynoxy; R2b, R3b, and R4bare each independently C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C2-20alkynyl, C1-20alkoxy, C1-20heteroalkoxy, C2-20alkenoxy, or C2-20alkynoxy; A1is –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; A2, A3, and A4are each independently a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; L1, L2, L3, and L4are each independently a bond, C1-20alkylene, C1-20heteroalkylene, C2-20alkenylene, or C2-20alkynylene; X, Y, and Z are each independently C(H) or N; each R1a, R1b, and R1dis independently hydrogen, deuterium, C1-6 alkyl, C1-6 heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl; and m and n are each independently an integer of 0, 1, 2, 3, or 4; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, alkoxy, heteroalkoxy, alkenoxy, and alkynoxy is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) –C(O)Ra, –C(O)ORa, –C(O)NRbRc, –C(O)SRa, –C(NRa)NRbRc, –C(S)Ra, –C(S)ORa, –C(S)NRbRc, –ORa, –OC(O)Ra, –OC(O)ORa, –OC(O)NRbRc, –OC(O)SRa, –OC(NRa)NRbRc, –OC(S)Ra, –OC(S)ORa, –OC(S)NRbRc, –OP(O)(ORb)ORc, –OS(O)Ra, –OS(O)2Ra, –OS(O)NRbRc, –OS(O)2NRbRc, –NRbRc, –NRaC(O)Rd, –NRaC(O)ORd, –NRaC(O)NRbRc, –NRaC(O)SRd, –NRaC(NRd)NRbRc, –NRaC(S)Rd, –NRaC(S)ORd, –NRaC(S)NRbRc, –NRaS(O)Rd, –NRaS(O)2Rd, –NRaS(O)NRbRc, –NRaS(O)2NRbRc, –SRa, –S(O)Ra, –S(O)2Ra, –S(O)NRbRc, and –S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one orAttorney Docket No.277A002WO01 more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) –C(O)Re, –C(O)ORe, –C(O)NRfRg, –C(O)SRe, –C(NRe)NRfRg, –C(S)Re, –C(S)ORe, –C(S)NRfRg, –ORe, –OC(O)Re, –OC(O)ORe, –OC(O)NRfRg, –OC(O)SRe, –OC(NRe)NRfRg, –OC(S)Re, –OC(S)ORe, –OC(S)NRfRg, –OP(O)(ORf)ORg, –OS(O)Re, –OS(O)2Re, –OS(O)NRfRg, –OS(O)2NRfRg, –NRfRg, –NReC(O)Rh, –NReC(O)ORf, –NReC(O)NRfRg, –NReC(O)SRf, –NReC(NRh)NRfRg, –NReC(S)Rh, –NReC(S)ORf, –NReC(S)NRfRg, –NReS(O)Rh, –NReS(O)2Rh, –NReS(O)NRfRg, –NReS(O)2NRfRg, –SRe, –S(O)Re, –S(O)2Re, –S(O)NRfRg, and –S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

[0047] In yet another embodiment, provided herein is a compound of Formula (I): or an enantiomer, a mixtureof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein: R1is heterocyclyl; or hydrogen;independently hydrogen, C1-20alkyl, C1-20heteroalkyl, C2-20 alkenyl, C2-20 alkynyl, C1-20 alkoxy, C1-20 heteroalkoxy, C2-20 alkenoxy, or C2-20 alkynoxy; R2b, R3b, and R4bare each independently C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C2-20alkynyl, C1-20alkoxy, C1-20heteroalkoxy, C2-20alkenoxy, or C2-20alkynoxy;Attorney Docket No.277A002WO01 A1is –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; A2, A3, and A4are each independently a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; L1, L2, L3, and L4are each independently a bond, C1-20alkylene, C1-20heteroalkylene, C2-20alkenylene, or C2-20alkynylene; X, Y, and Z are each independently C(H) or N; each R1a, R1b, and R1dis independently hydrogen, deuterium, C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl; and m and n are each independently an integer of 0, 1, 2, 3, or 4; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, alkoxy, heteroalkoxy, alkenoxy, and alkynoxy is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) –C(O)Ra, –C(O)ORa, –C(O)NRbRc, –C(O)SRa, –C(NRa)NRbRc, –C(S)Ra, –C(S)ORa, –C(S)NRbRc, –ORa, –OC(O)Ra, –OC(O)ORa, –OC(O)NRbRc, –OC(O)SRa, –OC(NRa)NRbRc, –OC(S)Ra, –OC(S)ORa, –OC(S)NRbRc, –OP(O)(ORb)ORc, –OS(O)Ra, –OS(O)2Ra, –OS(O)NRbRc, –OS(O)2NRbRc, –NRbRc, –NRaC(O)Rd, –NRaC(O)ORd, –NRaC(O)NRbRc, –NRaC(O)SRd, –NRaC(NRd)NRbRc, –NRaC(S)Rd, –NRaC(S)ORd, –NRaC(S)NRbRc, –NRaS(O)Rd, –NRaS(O)2Rd, –NRaS(O)NRbRc, –NRaS(O)2NRbRc, –SRa, –S(O)Ra, –S(O)2Ra, –S(O)NRbRc, and –S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;Attorney Docket No.277A002WO01 wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) –C(O)Re, –C(O)ORe, –C(O)NRfRg, –C(O)SRe, –C(NRe)NRfRg, –C(S)Re, –C(S)ORe, –C(S)NRfRg, –ORe, –OC(O)Re, –OC(O)ORe, –OC(O)NRfRg, –OC(O)SRe, –OC(NRe)NRfRg, –OC(S)Re, –OC(S)ORe, –OC(S)NRfRg, –OP(O)(ORf)ORg, –OS(O)Re, –OS(O)2Re, –OS(O)NRfRg, –OS(O)2NRfRg, –NRfRg, –NReC(O)Rh, –NReC(O)ORf, –NReC(O)NRfRg, –NReC(O)SRf, –NReC(NRh)NRfRg, –NReC(S)Rh, –NReC(S)ORf, –NReC(S)NRfRg, –NReS(O)Rh, –NReS(O)2Rh, –NReS(O)NRfRg, –NReS(O)2NRfRg, –SRe, –S(O)Re, –S(O)2Re, –S(O)NRfRg, and –S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

[0048] In certain embodiments, in Formula (I), A2is a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; wherein each R1a, R1b, and R1dis as defined herein. In certain embodiments, in Formula (I), A2is a bond, –C(O)O–, –OC(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (I), A2is a bond, –C(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (I), A2is a bond. In certain embodiments, in Formula (I), A2is –C(O)O–. In certain embodiments, in Formula (I), A2is –O–. In certain embodiments, in Formula (I), A2is –OC(O)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (I), A2is –OC(O)N(H)–. In certain embodiments, in Formula (I), A2is –OC(S)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (I), A2is –OC(S)N(H)–.

[0049] In certain embodiments, in Formula (I), A3is a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; wherein each R1a, R1b, and R1dis as defined herein. In certain embodiments, in Formula (I), A3is a bond, –C(O)O–, –OC(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (I), A3is a bond, –C(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–;Attorney Docket No.277A002WO01 wherein each R1bis as defined herein. In certain embodiments, in Formula (I), A3is a bond. In certain embodiments, in Formula (I), A3is –C(O)O–. In certain embodiments, in Formula (I), A3is –O–. In certain embodiments, in Formula (I), A3is –OC(O)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (I), A3is –OC(O)N(H)–. In certain embodiments, in Formula (I), A3is –OC(S)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (I), A3is –OC(S)N(H)–.

[0050] In one embodiment, provided herein is a compound of Formula (II): or an enantiomer, a of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R4, R2a, R2b, R3a, R3b, A1, L1, L2, L3, X, Y, m, and n are each as defined herein.

[0051] In another embodiment, provided herein is a compound of Formula (III): or an enantiomer, aof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R4, R2a, R2b, R3a, R3b, A1, L1, L2, L3, X, Y, m, and n are each as defined herein.

[0052] In yet another embodiment, provided herein is a compound of Formula (IV):Attorney Docket No.277A002WO01 or an enantiomer, a of two or morediastereomers, a a or more or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R4, R2a, R2b, R3a, R3b, A1, L1, L2, L3, X, Y, m, and n are each as defined herein.

[0053] In yet another embodiment, provided herein is a compound of Formula (V): or an enantiomer, a mixtureof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R4, R2a, R2b, R3a, R3b, A1, L1, L2, L3, X, Y, m, and n are each as defined herein.

[0054] In still another embodiment, provided herein is a compound of Formula (VI): or an enantiomer, a mixtureof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R4, R2a, R2b, R3a, R3b, A1, L1, L2, L3, X, Y, m, and n are each as defined herein.

[0055] In certain embodiments, in any one of Formulae (I) to (VI), R4is ,Attorney Docket No.277A002WO01 wherein R4a, R4b, A4, and L4are each as defined herein. In certain embodiments, in any one of Formulae (I) to (VI), R4is hydrogen. In certain embodiments, in any one of Formulae (I) to (VI), R4is C1-6alkyl, optionally substituted with one or more substituents. In certain embodiments, in any one of Formulae (I) to (VI), R4is hydroxymethyl. In certain embodiments, in any one of Formulae (I) to (VI), R4is hydroxyl.

[0056] In one embodiment, provided herein is a compound of Formula (VII): or an enantiomer, aof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, A1, A2, A3, A4, L1, L2, L3, L4, X, Y, Z, m, and n are each as defined herein.

[0057] In certain embodiments, in Formula (VII), A2is a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; wherein each R1a, R1b, and R1dis as defined herein. In certain embodiments, in Formula (VII), A2is a bond, –C(O)O–, –OC(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A2is a bond, –C(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A2is a bond. In certain embodiments, in Formula (VII), A2is –C(O)O–. In certain embodiments, in Formula (VII), A2is –O–. In certain embodiments, in Formula (VII), A2is –OC(O)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A2is –OC(O)N(H)–. In certain embodiments, in Formula (VII), A2is –OC(S)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A2is –OC(S)N(H)–.Attorney Docket No.277A002WO01

[0058] In certain embodiments, in Formula (VII), A3is a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; wherein each R1a, R1b, and R1dis as defined herein. In certain embodiments, in Formula (VII), A3is a bond, –C(O)O–, –OC(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A3is a bond, –C(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A3is a bond. In certain embodiments, in Formula (VII), A3is –C(O)O–. In certain embodiments, in Formula (VII), A3is –O–. In certain embodiments, in Formula (VII), A3is –OC(O)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A3is –OC(O)N(H)–. In certain embodiments, in Formula (VII), A3is –OC(S)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A3is –OC(S)N(H)–.

[0059] In certain embodiments, in Formula (VII), A4is a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; wherein each R1a, R1b, and R1dis as defined herein. In certain embodiments, in Formula (VII), A4is a bond, –C(O)O–, –OC(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A4is a bond, –C(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–; wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A4is a bond. In certain embodiments, in Formula (VII), A4is –C(O)O–. In certain embodiments, in Formula (VII), A4is –O–. In certain embodiments, in Formula (VII), A4is –OC(O)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A4is –OC(O)N(H)–. In certain embodiments, in Formula (VII), A4is –OC(S)N(R1b)–, wherein each R1bis as defined herein. In certain embodiments, in Formula (VII), A4is –OC(S)N(H)–.

[0060] In one embodiment, provided herein is a compound of Formula (VIII):Attorney Docket No.277A002WO01 or an enantiomer, a of two or morediastereomers, a a or more or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, A1, L1, L2, L3, L4, X, Y, Z, m, and n are each as defined herein.

[0061] In another embodiment, provided herein is a compound of Formula (IX): or an enantiomer, aof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, A1, L1, L2, L3, L4, X, Y, Z, m, and n are each as defined herein.

[0062] In yet another embodiment, provided herein is a compound of Formula (X):Attorney Docket No.277A002WO01 or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, A1, L1, L2, L3, L4, X, Y, Z, m, and n are each as defined herein.

[0063] In yet another embodiment, provided herein is a compound of Formula (XI): or an enantiomer, a of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, A1, L1, L2, L3, L4, X, Y, Z, m, and n are each as defined herein.

[0064] In still another embodiment, provided herein is a compound of Formula (XII): or an enantiomer, aof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, A1, L1, L2, L3, L4, X, Y, Z, m, and n are each as defined herein.

[0065] In certain embodiments, in any one of Formulae (VII) to (XII), R4ais (i) hydrogen; or (ii) C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, C1-20alkoxy, C1-20heteroalkoxy, or C2-20 alkenoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais (i) hydrogen; or (ii) C1-20alkyl, C1-20Attorney Docket No.277A002WO01 heteroalkyl, C2-20 alkenyl, or C1-20 alkoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais hydrogen. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais C1-20alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais C1-20 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais C2-20alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais C1-20 alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais C2-20alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais hydrogen, butyl, hexyl, octyl, nonyl, pentadecyl, heptadecyl, octadecyl, tridecyl, (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-pentadec-8-enyl, (Z)-heptadec-8- enyl, octadec-9-enyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or octoxy. In certain embodiments, in any one of Formulae (VII) to (XII), R4ais hydrogen, but-1-yl, hex-1-yl, oct-1-yl, non-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, tridec-1-yl, (Z)-non-2-en-1-yl, (Z)-dec-4-en-1-yl, (Z)-tridec-8-en-1- yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9-en-1-yl, (8Z,11Z)-hexadec-8,11- dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or n- octoxy.

[0066] In certain embodiments, in any one of Formulae (VII) to (XII), R4bis C1-20alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C1-20 alkoxy, C1-20 heteroalkoxy, or C2-20 alkenoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4bis C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, or C1-20alkoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4bis C1-20 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4bis C1-20heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4bis C2-20 alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4bis C1-20alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), R4bis C2-20 alkenoxy, optionally substituted with one or more substituents Q. InAttorney Docket No.277A002WO01 certain embodiments, in any one of Formulae (VII) to (XII), R4bis butyl, hexyl, octyl, nonyl, tridecyl, pentadecyl, heptadecyl, octadecyl, (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-pentadec-8-enyl, (Z)-heptadec-8-enyl, octadec-9-enyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or octoxy. In certain embodiments, in any one of Formulae (VII) to (XII), R4bis but-1-yl, hex-1-yl, oct-1-yl, non-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, tridec-1-yl, (Z)-non-2-en-1-yl, (Z)-dec-4-en-1-yl, (Z)- tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9-en-1-yl, (8Z,11Z)- hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien- 1-yl, or n-octoxy.

[0067] In certain embodiments, in any one of Formulae (VII) to (XII), L4is (i) a bond; or (ii) C1-20 alkylene, C1-20 heteroalkylene, or C2-20 alkenylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), L4is (i) a bond; or (ii) C1-20alkylene or C1-20heteroalkylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), L4is a bond. In certain embodiments, in any one of Formulae (VII) to (XII), L4is C1-20 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), L4is C1-20heteroalkylene, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (VII) to (XII), L4is a bond, ethane-1,2-yl, –CH2C(O)O–, –(CH2)2C(O)O–, –(CH2)3C(O)O–, –(CH2)4C(O)O–, –(CH2)5C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, –(CH2)8C(O)O–, or –(CH2)2O(CH2)2OC(O)–. In certain embodiments, in any one of Formulae (VII) to (XII), L4is a bond, ethane-1,2-yl, –(CH2)4C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, or –(CH2)2O(CH2)2OC(O)–.

[0068] In certain embodiments, in any one of Formulae (VII) to (XII), Z is C(H). In certain embodiments, in any one of Formulae (VII) to (XII), Z is N.

[0069] In certain embodiments, in any one of Formulae (I) to (XII), R1is ionizable heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is N-containing heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is monocyclic heterocyclyl, optionally substituted with one or more substituents Q. In certainAttorney Docket No.277A002WO01 embodiments, in any one of Formulae (I) to (XII), R1is 3-, 4-, 5-, 6-, or 7-membered heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is 3-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is 4-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is 5-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is 6-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is 7-membered heterocyclyl, optionally substituted with one or more substituents Q.

[0070] In certain embodiments, in any one of Formulae (I) to (XII), R1is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl, each optionally substituted with one or more substituents, wherein each substituent is independently (i) C1-6 alkyl, C1-6heteroalkyl, C3-10cycloalkyl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (ii) –OR1aor –C(O)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, in any one of Formulae (I) to (XII), R1is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl, each optionally substituted with one or more substituents, wherein each substituent is independently methyl, ethyl, isopropyl, fluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3,3- trifluoropropyl, 3-fluoro-2-(fluoromethyl)propyl, 2-hydroxyethyl, hydroxymethyl, (dimethyl- amino)methyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan-3-yl, tetrahydropyran-4-yl, hydroxy, methoxy, or (2-hydroxyethyl)carbamoyl.

[0071] In certain embodiments, in any one of Formulae (I) to (XII), R1is aziridin-1-yl, azetidin-1-yl, azetidin-3-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholino, or piperazin-1-yl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R1is aziridin-1-yl, azetidin-1-yl, azetidin-3-yl, pyrrolidin-1-yl, piperidin- 1-yl, morpholino, or piperazin-1-yl, each optionally substituted with one or more substituents, wherein each substituent is independently (i) C1-6alkyl, C1-6heteroalkyl, C3-10cycloalkyl, orAttorney Docket No.277A002WO01 heterocyclyl, each optionally substituted with one or more substituents Q; or (ii) –OR1aor –C(O)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, in any one of Formulae (I) to (XII), R1is aziridin-1-yl, azetidin-1-yl, azetidin-3-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholino, or piperazin-1-yl, each optionally substituted with one or more substituents, wherein each substituent is independently methyl, ethyl, isopropyl, fluoromethyl, 2- fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoro-propyl, 3,3,3-trifluoropropyl, 3- fluoro-2-(fluoromethyl)propyl, 2-hydroxyethyl, hydroxymethyl, (dimethylamino)methyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan-3-yl, tetrahydropyran-4-yl, hydroxy, methoxy, or (2- hydroxyethyl)carbamoyl.

[0072] In certain embodiments, in any one of Formulae (I) to (XII), R1is aziridin-1-yl, 2- methylaziridin-1-yl, 2-ethylaziridin-1-yl, azetidin-1-yl, 1-methylazetidin-3-yl, 1-ethylazetidin-3- yl, 1-isopropyl-azetidin-3-yl, 3-methylazetidin-1-yl, 3-ethylazetidin-1-yl, 1-isopropylazetidin-3- yl, 3-(fluoro-methyl)azetidin-1-yl, 1-(2-fluoroethyl)azetidin-3-yl, 1-(2,2-difluoroethyl)azetidin-3- yl, 1-(2,2,2-trifluoroethyl)azetidin-3-yl, 1-(3-fluoropropyl)azetidin-3-yl, 1-(3,3,3-trifluoro- propyl)azetidin-3-yl, 1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl, 1,3-dimethylazetidin-3- yl, 1-(2-hydroxyethyl)azetidin-3-yl, 1-cyclobutylazetidin-3-yl, 1-cyclopentylazetidin-3-yl, 1- cyclohexylazetidin-3-yl, 1-(oxetan-3-yl)azetidin-3-yl, 1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl, 3-hydroxyazetidin-1-yl, 3-methoxyazetidin-1-yl, 3-(hydroxymethyl)azetidin-1-yl, 3-((dimethyl- amino)methyl)-azetidin-1-yl, 3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl, pyrrolidin-1-yl, 2- methylpyrrolidin-1-yl, 3-methylpyrrolidin-1-yl, 3,4-dimethylpyrrolidin-1-yl, piperidin-1-yl, morpholino, 4-methyl-piperazin-1-yl, or 4-(2-hydroxyethyl)piperazin-1-yl.

[0073] In certain embodiments, in any one of Formulae (I) to (XII), R1; wherein:each R5is independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) –C(O)R1a, –C(O)OR1a, –C(O)NR1bR1c, –C(O)SR1a, –C(NR1a)NR1bR1c, –C(S)R1a, –C(S)OR1a,Attorney Docket No.277A002WO01 –C(S)NR1bR1c, –OR1a, –OC(O)R1a, –OC(O)OR1a, –OC(O)NR1bR1c, –OC(O)SR1a, –OC(NR1a)NR1bR1c, –OC(S)R1a, –OC(S)OR1a, –OC(S)NR1bR1c, –OS(O)R1a, –OS(O)2R1a, –OS(O)NR1bR1c, –OS(O)2NR1bR1c, –NR1bR1c, –NR1aC(O)R1d, –NR1aC(O)OR1d, –NR1aC(O)NR1bR1c, –NR1aC(O)SR1d, –NR1aC(NR1d)NR1bR1c, –NR1aC(S)R1d, –NR1aC(S)OR1d, –NR1aC(S)NR1bR1c, –NR1aS(O)R1d, –NR1aS(O)2R1d, –NR1aS(O)NR1bR1c, or –NR1aS(O)2NR1bR1c; or two R5together with the carbon atom to which they are attached form oxo; R6is (i) hydrogen, deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) –C(O)R1a, –C(O)OR1a, –C(O)NR1bR1c, –C(O)SR1a, –C(NR1a)NR1bR1c, –C(S)R1a, –C(S)OR1a, –C(S)NR1bR1c, –OR1a, –OC(O)R1a, –OC(O)OR1a, –OC(O)NR1bR1c, –OC(O)SR1a, –OC(NR1a)NR1bR1c, –OC(S)R1a, –OC(S)OR1a, –OC(S)NR1bR1c, –OS(O)R1a, –OS(O)2R1a, –OS(O)NR1bR1c, –OS(O)2NR1bR1c, –NR1bR1c, –NR1aC(O)R1d, –NR1aC(O)OR1d, –NR1aC(O)NR1bR1c, –NR1aC(O)SR1d, –NR1aC(NR1d)NR1bR1c, –NR1aC(S)R1d, –NR1aC(S)OR1d, –NR1aC(S)NR1bR1c, –NR1aS(O)R1d, –NR1aS(O)2R1d, –NR1aS(O)NR1bR1c, or –NR1aS(O)2NR1bR1c; R7is (i) hydrogen; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) –C(O)R1a, –C(O)OR1a, –C(O)NR1bR1c, –C(O)SR1a, –C(NR1a)NR1bR1c, –C(S)R1a, –C(S)OR1a, –C(S)NR1bR1c, –S(O)R1a, –S(O)2R1a, –S(O)NR1bR1c, or –S(O)2NR1bR1c; each R1a, R1b, R1c, and R1dis independently hydrogen, deuterium, C1-6alkyl, C1-6heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; p and q are each independently an integer of 0, 1, or 2; and each r is independently an integer of 0, 1, 2, 3, 4, 5, or 6.

[0074] In certain embodiments, in any one of Formulae (I) to (XII), R1, wherein R5, R6, p, and r are each as defined herein. In certain embodiments,Attorney Docket No.277A002WO01 Formulae (I) to (XII), R1is , wherein R5, R7, q, and r are each as defined herein.

[0075] In certain embodiments, each R5is independently (i) C1-6alkyl or C1-6heteroalkyl, each optionally substituted with one or more substituents Q; (ii) –OR1a, wherein R1ais as defined herein; or (iii) two R5together with the carbon atom to which they are attached form oxo. In certain embodiments, each R5is independently (i) C1-6alkyl or C1-6heteroalkyl, each optionally substituted with one or more substituents Q; or (ii) –OR1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently C1-6 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently methyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, or dimethylaminomethyl. In certain embodiments, each R5is independently methyl or fluoromethyl. In certain embodiments, each R5is independently –OR1a, wherein R1ais as defined herein. In certain embodiments, R5is hydroxyl. In certain embodiments, each R5is independently –OR1a, wherein R1ais C1-6 alkyl or C1-6 heteroalkyl, each optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently C1-6alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently hydroxyl, methoxy, ethoxy, or trifluoromethoxy. In certain embodiments, each R5is independently methyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, dimethylaminomethyl, hydroxyl, methoxy, ethoxy, or trifluoromethoxy. In certain embodiments, each R5is independently methyl, fluoromethyl, or methoxy.

[0076] In certain embodiments, R6is (i) hydrogen; (ii) C1-6 alkyl or C1-6 heteroalkyl, each optionally substituted with one or more substituents Q; or (iii) –C(O)NR1bR1cor –OR1a, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, R6is hydrogen. In certain embodiments, R6is C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is C1-6alkyl, optionally substituted with –NRbRc, wherein Rband Rcare each as defined herein. In certain embodiments, R6is C1-6alkyl, optionally substituted with –NRbRc, wherein Rband Rcare each independently hydrogen or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is C1-6heteroalkyl, optionally substitutedAttorney Docket No.277A002WO01 with one or more substituents Q. In certain embodiments, R6is –C(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is –OR1a, wherein R1ais as defined herein. In certain embodiments, R6is methyl, ethyl, fluoromethyl, hydroxymethyl, dimethyl- aminomethyl, 2-hydroxyethylcarbamoyl, hydroxyl, or methoxy.

[0077] In certain embodiments, R7is C1-6 alkyl, C1-6 heteroalkyl, C3-10 cycloalkyl, or heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, R7C1-6alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is C1-6 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is methyl, ethyl, isopropyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2- trifluoroethyl, 3-fluoropropyl, 3,3,3-trifluoropropyl, 2-fluoromethyl-3-fluoropropyl, or 2- hydroxyethyl.

[0078] In certain embodiments, R7is C3-10 cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is monocyclic C3-10cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is cyclopropyl, cyclobutyl, cyclopropyl, or cyclohexyl, each optionally substituted with one or more substituents Q. In certain embodiments, R7is cyclobutyl, cyclopropyl, or cyclohexyl, each optionally substituted with one or more substituents Q.

[0079] In certain embodiments, R7is heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is monocyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 3-, 4-, 5-, 6-, or 7- membered heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, R7is 3-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 4-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 5-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 6- membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 7-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is oxetanyl or tetrahydropyranyl, each optionally substituted with one or more substituents Q. In certain embodiments, R7is oxetan-3-yl orAttorney Docket No.277A002WO01 tetrahydropyran-4-yl, each optionally substituted with one or more substituents Q.

[0080] In certain embodiments, R7is methyl, ethyl, isopropyl, 2-fluoroethyl, 2,2- difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3,3-trifluoropropyl, 3-fluoro-2- (fluoromethyl)propyl, 2-hydroxyethyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan-3-yl, or tetrahydropyran-4-yl.

[0081] In certain embodiments, p is an integer of 0. In certain embodiments, p is an integer of 1. In certain embodiments, p is an integer of 2.

[0082] In certain embodiments, q is an integer of 0. In certain embodiments, q is an integer of 1. In certain embodiments, q is an integer of 2.

[0083] In certain embodiments, r is an integer of 0, 1, or 2. In certain embodiments, r is an integer of 0. In certain embodiments, r is an integer of 1. In certain embodiments, r is an integer of 2.

[0084] In certain embodiments, in any one of Formulae (I) to (XII), A1is –C(O)O–, –OC(O)O–, –C(O)N(R1b)–, –O–, –OC(O)N(R1b)–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–, wherein each R1a, R1b, and R1dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XII), A1is –C(O)O–, –C(O)N(R1b)–, –O–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–, wherein each R1a, R1b, and R1dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XII), A1is –C(O)O–. In certain embodiments, in any one of Formulae (I) to (XII), A1is –C(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, in any one of Formulae (I) to (XII), A1is –C(O)N(H)–. In certain embodiments, in any one of Formulae (I) to (XII), A1is –O–. In certain embodiments, in any one of Formulae (I) to (XII), A1is –N(R1b)–, wherein R1bis as defined herein. In certain embodiments, in any one of Formulae (I) to (XII), A1is –N(R1b)–, wherein R1bis (i) hydrogen; or (ii) C1-6 alkyl or C1-6 heteroalkyl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), A1is –N(H)– or –N(CH3)–. In certain embodiments, in any one of Formulae (I) to (XII), A1is –N(R1a)C(O)N(R1d)–, wherein each R1aand R1dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XII), A1is –N(H)C(O)N(H)–. In certain embodiments, in any one of Formulae (I) to (XII), A1Attorney Docket No.277A002WO01 is –N(R1a)C(S)N(R1d)–, wherein each R1aand R1dis as defined herein. In certain embodiments, in any one of Formulae (I) to (XII), A1is –N(H)C(S)N(H)–.

[0085] In certain embodiments, in any one of Formulae (I) to (XII), L1is (i) a bond; or (ii) C1-20 alkylene, C1-20 heteroalkylene, or C2-20 alkenylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L1is (i) a bond; or (ii) C1-20alkylene or C1-20heteroalkylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L1is a bond. In certain embodiments, in any one of Formulae (I) to (XII), L1is C1-20 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L1is C1-20heteroalkylene, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L1is a bond, ethane-1,2-yl, propane- 1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, or –(CH2)2O(CH2)2O(CH2)2–.

[0086] In certain embodiments, in any one of Formulae (I) to (XII), R2ais (i) hydrogen; or (ii) C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C1-20 alkoxy, C1-20 heteroalkoxy, or C2-20 alkenoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2ais (i) hydrogen; or (ii) C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, or C1-20alkoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2ais hydrogen. In certain embodiments, in any one of Formulae (I) to (XII), R2ais C1-20alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2ais C1-20heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2ais C2-20alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2ais C1-20alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2ais C2-20 alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2ais hydrogen, butyl, hexyl, octyl, nonyl, tridecyl, pentadecyl, heptadecyl, octadecyl, (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)- tridec-8-enyl, (Z)-pentadec-8-enyl, (Z)-heptadec-8-enyl, octadec-9-enyl, (8Z,11Z)-hexadec-8,11- dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or octoxy. In certain embodiments, in any one of Formulae (I) to (XII), R2ais hydrogen, but-1-yl, hex-1-yl,Attorney Docket No.277A002WO01 oct-1-yl, non-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, tridec-1-yl, (Z)-non-2-en-1-yl, (Z)- dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9- en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)- heptadec-8,11,14-trien-1-yl, or n-octoxy.

[0087] In certain embodiments, in any one of Formulae (I) to (XII), R2bis C1-20 alkyl, C1-20heteroalkyl, C2-20alkenyl, C1-20alkoxy, C1-20heteroalkoxy, or C2-20alkenoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2bis C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, or C1-20 alkoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2bis C1-20alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2bis C1-20 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2bis C2-20alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2bis C1-20 alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2bis C2-20alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R2bis butyl, hexyl, octyl, nonyl, tridecyl, pentadecyl, heptadecyl, octadecyl, (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-pentadec-8-enyl, (Z)-heptadec-8-enyl, octadec-9-enyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11- dienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or octoxy. In certain embodiments, in any one of Formulae (I) to (XII), R2bis but-1-yl, hex-1-yl, oct-1-yl, non-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, tridec-1-yl, (Z)-non-2-en-1-yl, (Z)-dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)- pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9-en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or n-octoxy.

[0088] In certain embodiments, in any one of Formulae (I) to (XII), L2is (i) a bond; or (ii) C1-20alkylene, C1-20heteroalkylene, or C2-20alkenylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L2is (i) a bond; or (ii) C1-20 alkylene or C1-20 heteroalkylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L2is a bond. In certain embodiments, in any one of Formulae (I) to (XII), L2is C1-20alkylene, optionallyAttorney Docket No.277A002WO01 substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L2is C1-20 heteroalkylene, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L2is a bond, ethane-1,2-yl, –CH2C(O)O–, –(CH2)2C(O)O–, –(CH2)3C(O)O–, –(CH2)4C(O)O–, –(CH2)5C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, –(CH2)8C(O)O–, or –(CH2)2O(CH2)2OC(O)–. In certain embodiments, in any one of Formulae (I) to (XII), L2is a bond, ethane-1,2-yl, –(CH2)4C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, or –(CH2)2O(CH2)2OC(O)–.

[0089] In certain embodiments, in any one of Formulae (I) to (XII), X is C(H). In certain embodiments, in any one of Formulae (I) to (XII), X is N.

[0090] In certain embodiments, in any one of Formulae (I) to (XII), R3ais (i) hydrogen; or (ii) C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C1-20 alkoxy, C1-20 heteroalkoxy, or C2-20 alkenoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3ais (i) hydrogen; or (ii) C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, or C1-20 alkoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3ais hydrogen. In certain embodiments, in any one of Formulae (I) to (XII), R3ais C1-20alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3ais C1-20heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3ais C2-20alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3ais C1-20alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3ais C2-20alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3ais hydrogen, butyl, hexyl, octyl, nonyl, tridecyl, pentadecyl, heptadecyl, octadecyl, (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)- tridec-8-enyl, (Z)-pentadec-8-enyl, (Z)-heptadec-8-enyl, octadec-9-enyl, (8Z,11Z)-hexadec-8,11- dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or octoxy. In certain embodiments, in any one of Formulae (I) to (XII), R3ais hydrogen, but-1-yl, hex-1-yl, oct-1-yl, non-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, tridec-1-yl, (Z)-non-2-en-1-yl, (Z)- dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9- en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)-Attorney Docket No.277A002WO01 heptadec-8,11,14-trien-1-yl, or n-octoxy.

[0091] In certain embodiments, in any one of Formulae (I) to (XII), R3bis C1-20 alkyl, C1-20heteroalkyl, C2-20alkenyl, C1-20alkoxy, C1-20heteroalkoxy, or C2-20alkenoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3bis C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, or C1-20 alkoxy, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3bis C1-20alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3bis C1-20 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3bis C2-20alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3bis C1-20 alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3bis C2-20alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), R3bis butyl, hexyl, octyl, nonyl, tridecyl, pentadecyl, heptadecyl, octadecyl, (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-pentadec-8-enyl, (Z)-heptadec-8-enyl, octadec-9-enyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11- dienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or octoxy. In certain embodiments, in any one of Formulae (I) to (XII), R3bis but-1-yl, hex-1-yl, oct-1-yl, non-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, tridec-1-yl, (Z)-non-2-en-1-yl, (Z)-dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)- pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9-en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or n-octoxy.

[0092] In certain embodiments, in any one of Formulae (I) to (XII), L3is (i) a bond; or (ii) C1-20alkylene, C1-20heteroalkylene, or C2-20alkenylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L3is (i) a bond; or (ii) C1-20 alkylene or C1-20 heteroalkylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L3is a bond. In certain embodiments, in any one of Formulae (I) to (XII), L3is C1-20 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L3is C1-20heteroalkylene, optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formulae (I) to (XII), L3is a bond, ethane-1,2-yl,Attorney Docket No.277A002WO01 –CH2C(O)O–, –(CH2)2C(O)O–, –(CH2)3C(O)O–, –(CH2)4C(O)O–, –(CH2)5C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, –(CH2)8C(O)O–, or –(CH2)2O(CH2)2OC(O)–. In certain embodiments, in any one of Formulae (I) to (XII), L3is a bond, ethane-1,2-yl, –(CH2)4C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, or –(CH2)2O(CH2)2OC(O)–.

[0093] In certain embodiments, in any one of Formulae (I) to (XII), Y is C(H). In certain embodiments, in any one of Formulae (I) to (XII), Y is N.

[0094] In certain embodiments, in any one of Formulae (I) to (XII), X and Y are each C(H). In certain embodiments, in any one of Formulae (I) to (XII), X and Y are each N.

[0095] In certain embodiments, in any one of Formulae (VII) to (XII), X, Y, and Z are each C(H). In certain embodiments, in any one of Formulae (VII) to (XII), X, Y, and Z are each N.

[0096] In certain embodiments, in any one of Formulae (I) to (XII), m is an integer of 0. In certain embodiments, in any one of Formulae (I) to (XII), m is an integer of 1. In certain embodiments, in any one of Formulae (I) to (XII), m is an integer of 2. In certain embodiments, in any one of Formulae (I) to (XII), m is an integer of 3. In certain embodiments, in any one of Formulae (I) to (XII), m is an integer of 4.

[0097] In certain embodiments, in any one of Formulae (I) to (XII), n is an integer of 0. In certain embodiments, in any one of Formulae (I) to (XII), n is an integer of 1. In certain embodiments, in any one of Formulae (I) to (XII), n is an integer of 2. In certain embodiments, in any one of Formulae (I) to (XII), n is an integer of 3. In certain embodiments, in any one of Formulae (I) to (XII), n is an integer of 4.

[0098] The groups, R1, R4, R5, R6, R7, R2a, R2b, R3a, R3b, R4a, R4b, A1, A2, A3, A4, L1, L2, L3, L4, X, Y, Z, m, n, p, q, and r, in formulae described herein, including Formulae (I) to (XII), are defined in the embodiments described herein. All combinations of the embodiments provided herein for such groups are within the scope of this disclosure.

[0099] In certain embodiments, R1is ionizable heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is N-containing heterocyclyl, optionallyAttorney Docket No.277A002WO01 substituted with one or more substituents Q. In certain embodiments, R1is monocyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is 3-, 4-, 5-, 6-, or 7-membered heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, R1is 3-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is 4-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is 5- membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is 6-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is 7-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl, each optionally substituted with one or more substituents Q.

[0100] In certain embodiments, R1is bicyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is bridged, fused, or spiro heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, R1is bridged heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is fused heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R1is spiro heterocyclyl, optionally substituted with one or more substituents Q.

[0101] In certain embodiments, R1, wherein R5, R6, p, and r are each asdefined herein. In certain embodiments, R1is , wherein R5, R6, and r are each as defined herein. In certain embodiments, R1is , wherein R5, R6, and r are each as defined herein. In certain , wherein R5, R6, and r are each as defined herein.Attorney Docket No.277A002WO01

[0102] In certain embodiments, R1is , wherein R5, R7, q, and r are each as defined herein. In certain embodiments, R1is , wherein R5, R7, and r are each asdefined herein. In certain embodiments, R1is , wherein R5, R7, and r are each as defined herein. In certain , wherein R5, R7, and r are each as defined herein.

[0103] In certain embodiments, R4, wherein R4a, R4b, A4, L4, and Z are each as defined herein. In certain In cer4tain embodiments, R is C1-6 alkyl, optionally substituted with one or more substituents. In certain embodiments, R4is hydroxymethyl.

[0104] In certain embodiments, R5is deuterium. In certain embodiments, R5is cyano. In certain embodiments, R5is halo. In certain embodiments, each R5is independently fluoro, chloro, or bromo. In certain embodiments, R5is nitro. In certain embodiments, each R5is independently C1-6alkyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently methyl, each optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently methyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, or dimethylaminomethyl. In certain embodiments, each R5is independently methyl or fluoromethyl. In certain embodiments, each R5is independently C1-6 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently C2-6alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently C2-6alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently C3-10cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments,Attorney Docket No.277A002WO01 each R5is independently monocyclic C3-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently bicyclic C4-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently bridged, fused, or spiro C4-10cycloalkyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently bridged C4-10cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently fused C4-10cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently spiro C5-10cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently C6-14 aryl, optionally substituted with one or more substituents Q. In certain embodiments, R5is phenyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently bicyclic C8-14 aryl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently C7-15 aralkyl, optionally substituted with one or more substituents Q.

[0105] In certain embodiments, each R5is independently heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently 5- or 6-membered heteroaryl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently 5- membered heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently 6-membered heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently bicyclic heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently 5,5-, 5,6-, or 6,6-fused heteroaryl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently 5,5-fused heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently 5,6-fused heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, each R5is independently 6,6-fused heteroaryl, optionally substituted with one, two, or three substituents Q.Attorney Docket No.277A002WO01

[0106] In certain embodiments, each R5is independently heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently monocyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently 3-, 4-, 5-, 6-, or 7-membered heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently 3-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently 4-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently 5-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently 6-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently 7-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently bicyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently bridged, fused, or spiro heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently bridged heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently fused heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently spiro heterocyclyl, optionally substituted with one or more substituents Q.

[0107] In certain embodiments, each R5is independently –C(O)R1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –C(O)OR1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –C(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, each R5is independently –C(O)SR1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –C(NR1a)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, each R5is independently –C(S)R1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –C(S)OR1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –C(S)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, each R5is independently –OR1a, wherein R1ais as defined herein. In certain embodiments, R5is hydroxyl. In certain embodiments, each R5is independently –OR1a, wherein R1ais C1-5 alkyl or C1-5 heteroalkyl, each optionally substituted with one or moreAttorney Docket No.277A002WO01 substituents Q. In certain embodiments, each R5is independently C1-5 alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, each R5is independently hydroxyl, methoxy, ethoxy, or trifluoromethoxy. In certain embodiments, each R5is independently –OC(O)R1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –OC(O)OR1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –OC(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, each R5is independently –OC(O)SR1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –OC(NR1a)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, each R5is independently –OC(S)R1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –OC(S)OR1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –OC(S)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, each R5is independently –OS(O)R1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –OS(O)2R1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –OS(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, each R5is independently –OS(O)2NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, each R5is independently –NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, each R5is independently –NR1aC(O)R1d, wherein R1aand R1dare each as defined herein. In certain embodiments, each R5is independently –NR1aC(O)OR1d, wherein R1aand R1dare each as defined herein. In certain embodiments, each R5is independently –NR1aC(O)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, each R5is independently –NR1aC(O)SR1d, wherein R1aand R1dare each as defined herein. In certain embodiments, each R5is independently –NR1aC(NR1d)NR1bR1c, wherein R1a, R1b, R1c, and R1dare each as defined herein. In certain embodiments, each R5is independently –NR1aC(S)R1d, wherein R1aand R1dare each as defined herein. In certain embodiments, each R5is independently –NR1aC(S)OR1d, wherein R1aand R1dare each as defined herein. In certain embodiments, each R5is independently –NR1aC(S)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, each R5is independently –NR1aS(O)R1d, wherein R1aand R1dare each as defined herein. In certain embodiments, each R5is independently –NR1aS(O)2R1d, wherein R1aand R1dare each as defined herein. In certain embodiments, each R5is independently –NR1aS(O)NR1bR1c, wherein R1a, R1b, and R1care eachAttorney Docket No.277A002WO01 as defined herein. In certain embodiments, each R5is independently –NR1aS(O)2NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, each R5is independently –SR1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –S(O)R1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –S(O)2R1a, wherein R1ais as defined herein. In certain embodiments, each R5is independently –S(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, each R5is independently –S(O)2NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, two R5together with the carbon atom to which they are attached form oxo.

[0108] In certain embodiments, R6is hydrogen. In certain embodiments, R6is deuterium. In certain embodiments, R6is cyano. In certain embodiments, R6is halo. In certain embodiments, R6is fluoro, chloro, or bromo. In certain embodiments, R6is nitro. In certain embodiments, R6is C1-6alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is C1-6 alkyl, optionally substituted with –NRbRc, wherein Rband Rcare each as defined herein. In certain embodiments, R6is C1-6 alkyl, optionally substituted with –NRbRc, wherein Rband Rcare each independently hydrogen or C1-6alkyl optionally substituted with one or more substituents Q. In certain embodiments, R6is methyl or ethyl, each optionally substituted with one or more substituents Q. In certain embodiments, R6is methyl, ethyl, fluoromethyl, hydroxymethyl, or dimethylaminomethyl. In certain embodiments, R6is C1-6heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is C2-6 alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is C2-6alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is C3-10cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is monocyclic C3-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is bicyclic C4-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is bridged, fused, or spiro C4-10 cycloalkyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is bridged C4-10cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is fused C4-10 cycloalkyl, optionally substituted with one, two, or threeAttorney Docket No.277A002WO01 substituents Q. In certain embodiments, R6is spiro C5-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is C6-14 aryl, optionally substituted with one or more substituents Q. In certain embodiments, R6is phenyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is bicyclic C8-14 aryl, optionally substituted with one or more substituents Q. In certain embodiments, R6is C7-15 aralkyl, optionally substituted with one or more substituents Q.

[0109] In certain embodiments, R6is heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, R6is monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is 5- or 6-membered heteroaryl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is 5-membered heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is 6-membered heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is bicyclic heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is 5,5-, 5,6-, or 6,6-fused heteroaryl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is 5,5-fused heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is 5,6-fused heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is 6,6-fused heteroaryl, optionally substituted with one, two, or three substituents Q.

[0110] In certain embodiments, R6is heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is monocyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is 3-, 4-, 5-, 6-, or 7- membered heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, R6is 3-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is 4-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is 5-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is 6- membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is 7-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is bicyclic heterocyclyl, optionally substituted withAttorney Docket No.277A002WO01 one or more substituents Q. In certain embodiments, R6is bridged, fused, or spiro heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, R6is bridged heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is fused heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R6is spiro heterocyclyl, optionally substituted with one or more substituents Q.

[0111] In certain embodiments, R6is –C(O)R1a, wherein R1ais as defined herein. In certain embodiments, R6is –C(O)OR1a, wherein R1ais as defined herein. In certain embodiments, R6is –C(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is 2-hydroxyethylcarbamoyl. In certain embodiments, R6is –C(O)SR1a, wherein R1ais as defined herein. In certain embodiments, R6is –C(NR1a)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, R6is –C(S)R1a, wherein R1ais as defined herein. In certain embodiments, R6is –C(S)OR1a, wherein R1ais as defined herein. In certain embodiments, R6is –C(S)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is –OR1a, wherein R1ais as defined herein. In certain embodiments, R6is –OR1a, wherein R1ais C1-8alkyl or C1-8heteroalkyl, each optionally substituted with one or more substituents Q. In certain embodiments, R6is C1-8alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R6is hydroxyl, methoxy, ethoxy, or trifluoromethoxy. In certain embodiments, R6is –OC(O)R1a, wherein R1ais as defined herein. In certain embodiments, R6is –OC(O)OR1a, wherein R1ais as defined herein. In certain embodiments, R6is –OC(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is –OC(O)SR1a, wherein R1ais as defined herein. In certain embodiments, R6is –OC(NR1a)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, R6is –OC(S)R1a, wherein R1ais as defined herein. In certain embodiments, R6is –OC(S)OR1a, wherein R1ais as defined herein. In certain embodiments, R6is –OC(S)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is –OS(O)R1a, wherein R1ais as defined herein. In certain embodiments, R6is –OS(O)2R1a, wherein R1ais as defined herein. In certain embodiments, R6is –OS(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is –OS(O)2NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is –NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is –NR1aC(O)R1d, wherein R1aand R1dare each as definedAttorney Docket No.277A002WO01 herein. In certain embodiments, R6is –NR1aC(O)OR1d, wherein R1aand R1dare each as defined herein. In certain embodiments, R6is –NR1aC(O)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, R6is –NR1aC(O)SR1d, wherein R1aand R1dare each as defined herein. In certain embodiments, R6is –NR1aC(NR1d)NR1bR1c, wherein R1a, R1b, R1c, and R1dare each as defined herein. In certain embodiments, R6is –NR1aC(S)R1d, wherein R1aand R1dare each as defined herein. In certain embodiments, R6is –NR1aC(S)OR1d, wherein R1aand R1dare each as defined herein. In certain embodiments, R6is –NR1aC(S)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, R6is –NR1aS(O)R1d, wherein R1aand R1dare each as defined herein. In certain embodiments, R6is –NR1aS(O)2R1d, wherein R1aand R1dare each as defined herein. In certain embodiments, R6is –NR1aS(O)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, R6is –NR1aS(O)2NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, R6is –SR1a, wherein R1ais as defined herein. In certain embodiments, R6is –S(O)R1a, wherein R1ais as defined herein. In certain embodiments, R6is –S(O)2R1a, wherein R1ais as defined herein. In certain embodiments, R6is –S(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R6is –S(O)2NR1bR1c, wherein R1band R1care each as defined herein.

[0112] In certain embodiments, R7is hydrogen. In certain embodiments, R7is C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is methyl, ethyl, propyl, or butyl, each optionally substituted with one or more substituents Q. In certain embodiments, R7is methyl, ethyl, isopropyl, fluoroethyl, difluoroethyl, trifluoroethyl, fluoropropyl, difluoropropyl, trifluoropropyl, or hydroxyethyl. In certain embodiments, R7is methyl, ethyl, isopropyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3,3-trifluoropropyl, 2-fluoromethyl-3-fluoropropyl, or 2-hydroxyethyl. In certain embodiments, R7is C1-6 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is C2-6alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is C2-6 alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is C3-10 cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is monocyclic C3-10cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each optionally substituted with one, two, or threeAttorney Docket No.277A002WO01 substituents Q. In certain embodiments, R7is bicyclic C4-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is bridged, fused, or spiro C4-10cycloalkyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is bridged C4-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is fused C4-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is spiro C5-10cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is C6-14aryl, optionally substituted with one or more substituents Q. In certain embodiments, R7is phenyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is bicyclic C7-14aryl, optionally substituted with one or more substituents Q. In certain embodiments, R7is C7-15 aralkyl, optionally substituted with one or more substituents Q.

[0113] In certain embodiments, R7is heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, R7is monocyclic heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is 5- or 6-membered heteroaryl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is 5-membered heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is 6-membered heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is bicyclic heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R6is 5,5-, 5,6-, or 6,6-fused heteroaryl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is 5,5-fused heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is 5,6-fused heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, R7is 6,6-fused heteroaryl, optionally substituted with one, two, or three substituents Q.

[0114] In certain embodiments, R7is heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is monocyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 3-, 4-, 5-, 6-, or 7- membered heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, R7is 3-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 4-membered heterocyclyl, optionally substitutedAttorney Docket No.277A002WO01 with one or more substituents Q. In certain embodiments, R7is 5-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 6- membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is 7-membered heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is oxetanyl or tetrahydropyranyl, each optionally substituted with one or more substituents Q. In certain embodiments, R7is oxetan-3-yl or tetrahydropyran-4-yl, each optionally substituted with one or more substituents Q. In certain embodiments, R7is bicyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is bridged, fused, or spiro heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, R7is bridged heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is fused heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R7is spiro heterocyclyl, optionally substituted with one or more substituents Q.

[0115] In certain embodiments, R7is –C(O)R1a, wherein R1ais as defined herein. In certain embodiments, R7is –C(O)OR1a, wherein R1ais as defined herein. In certain embodiments, R7is –C(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R7is –C(O)SR1a, wherein R1ais as defined herein. In certain embodiments, R7is –C(NR1a)NR1bR1c, wherein R1a, R1b, and R1care each as defined herein. In certain embodiments, R7is –C(S)R1a, wherein R1ais as defined herein. In certain embodiments, R7is –C(S)OR1a, wherein R1ais as defined herein. In certain embodiments, R7is –C(S)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R7is –S(O)R1a, wherein R1ais as defined herein. In certain embodiments, R7is –S(O)2R1a, wherein R1ais as defined herein. In certain embodiments, R7is –S(O)NR1bR1c, wherein R1band R1care each as defined herein. In certain embodiments, R7is –S(O)2NR1bR1c, wherein R1band R1care each as defined herein.

[0116] In certain embodiments, R2ais hydrogen. In certain embodiments, R2ais C1-20 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R2ais unsubstituted C1-20 alkyl. In certain embodiments, R2ais C1-20 alkyl, substituted with one or more substituents Q. In certain embodiments, R2ais C1-20 alkyl, substituted with one or more halo. In certain embodiments, R2ais C1-20alkyl, substituted with one or more fluoro. In certain embodiments, R2ais C1-20alkyl, substituted with one, two, or three fluoro.Attorney Docket No.277A002WO01

[0117] In certain embodiments, R2ais methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R2ais butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R2ais methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R2ais n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q.

[0118] In certain embodiments, R2ais C1-20heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R2ais trifluoromethyl, trifluoroethyl, trifluoro- propyl, trifluorobutyl, trifluoropentyl, trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluoro- nonyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluorotetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluorooctadecyl, trifluoro- nonadecyl, or trifluoroeicosyl. In certain embodiments, R2ais trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluorononyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluoro-tetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluoro- octadecyl, trifluorononadecyl, or trifluoroeicosyl. In certain embodiments, R2ais trifluoro- methyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoroprop-1-yl, 4,4,4-trifluorobut-1-yl, 5,5,5-trifluoropent- 1-yl, 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon- 1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13-trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16-trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19-trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl. In certain embodiments, R2ais 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon-1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13- trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16- trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19-Attorney Docket No.277A002WO01 trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl.

[0119] In certain embodiments, R2ais C2-20 alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R2ais nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, nonadecenyl, nonadecenyl, tetradecdienyl, pentadecdienyl, hexadecdienyl, heptadecdienyl, octadecdienyl, nonadecdienyl, heptadectrienyl, or nonadectrienyl, each optionally substituted with one or more substituents Q. In certain embodiments, R2ais (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-tetradec-8-enyl, (Z)-penta-dec-8-enyl, (Z)-hexadec-8-enyl, (Z)-heptadec-8- enyl, (Z)-octadec-8-enyl, (Z)-nonadec-8-enyl, (Z)-nonadec-10-enyl, (Z)-nonadec-12-enyl, (8Z,11Z)-tetradec-8,11-dienyl, (8Z,11Z)-pentadec-8,11-dienyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z)-octadec-8,11-dienyl, (8Z,11Z)-nonadec-8,11-dienyl, (5Z,8Z,11Z)-heptadec-5,8,11-trienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or (7Z,10Z,13Z)- nonadec-7,10,13-trienyl. In certain embodiments, R2ais (Z)-tridec-8-en-1-yl, (Z)-tetradec-8-en- 1-yl, (Z)-pentadec-8-en-1-yl, (Z)-hexadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, (Z)-octadec-8-en-1- yl, (Z)-nonadec-8-en-1-yl, (Z)-nonadec-10-en-1-yl, (Z)-nonadec-12-en-1-yl, (8Z,11Z)-tetradec- 8,11-dien-1-yl, (8Z,11Z)-pentadec-8,11-dien-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)- heptadec-8,11-dien-1-yl, (8Z,11Z)-octadec-8,11-dien-1-yl, (8Z,11Z)-nonadec-8,11-dien-1-yl, (5Z,8Z,11Z)-heptadec-5,8,11-trien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or (7Z,10Z,13Z)-nonadec-7,10,13-trien-1-yl. In certain embodiments, R2ais C2-20alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R2ais C1-20alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R2ais n- octoxy. In certain embodiments, R2ais C1-20heteroalkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R2ais C2-20alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, R2ais C2-20 alkynoxy, optionally substituted with one or more substituents Q.

[0120] In certain embodiments, R2bis C1-20alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R2bis unsubstituted C1-20 alkyl. In certain embodiments, R2bis C1-20 alkyl, substituted with one or more substituents Q. In certain embodiments, R2bis C1-20alkyl, substituted with one or more halo. In certain embodiments, R2bis C1-20alkyl, substituted with one or more fluoro. In certain embodiments, R2bis C1-20alkyl,Attorney Docket No.277A002WO01 substituted with one, two, or three fluoro.

[0121] In certain embodiments, R2bis methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R2bis butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R2bis methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R2bis n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q.

[0122] In certain embodiments, R2bis C1-20 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R2bis trifluoromethyl, trifluoroethyl, trifluoro- propyl, trifluorobutyl, trifluoropentyl, trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluoro- nonyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluorotetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluorooctadecyl, trifluoro- nonadecyl, or trifluoroeicosyl. In certain embodiments, R2bis trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluorononyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluoro-tetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluoro- octadecyl, trifluorononadecyl, or trifluoroeicosyl. In certain embodiments, R2bis trifluoro- methyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoroprop-1-yl, 4,4,4-trifluorobut-1-yl, 5,5,5-trifluoropent- 1-yl, 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon- 1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13-trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16-trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19-trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl. In certain embodiments, R2bis 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon-1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13-Attorney Docket No.277A002WO01 trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16- trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19- trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl.

[0123] In certain embodiments, R2bis C2-20 alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R2bis nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, nonadecenyl, nonadecenyl, tetradecdienyl, pentadecdienyl, hexadecdienyl, heptadecdienyl, octadecdienyl, nonadecdienyl, heptadectrienyl, or nonadectrienyl, each optionally substituted with one or more substituents Q. In certain embodiments, R2bis (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-tetradec-8-enyl, (Z)-penta-dec-8-enyl, (Z)-hexadec-8-enyl, (Z)-heptadec-8- enyl, (Z)-octadec-8-enyl, (Z)-nonadec-8-enyl, (Z)-nonadec-10-enyl, (Z)-nonadec-12-enyl, (8Z,11Z)-tetradec-8,11-dienyl, (8Z,11Z)-pentadec-8,11-dienyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z)-octadec-8,11-dienyl, (8Z,11Z)-nonadec-8,11-dienyl, (5Z,8Z,11Z)-heptadec-5,8,11-trienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or (7Z,10Z,13Z)- nonadec-7,10,13-trienyl. In certain embodiments, R2bis (Z)-tridec-8-en-1-yl, (Z)-tetradec-8-en- 1-yl, (Z)-pentadec-8-en-1-yl, (Z)-hexadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, (Z)-octadec-8-en-1- yl, (Z)-nonadec-8-en-1-yl, (Z)-nonadec-10-en-1-yl, (Z)-nonadec-12-en-1-yl, (8Z,11Z)-tetradec- 8,11-dien-1-yl, (8Z,11Z)-pentadec-8,11-dien-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)- heptadec-8,11-dien-1-yl, (8Z,11Z)-octadec-8,11-dien-1-yl, (8Z,11Z)-nonadec-8,11-dien-1-yl, (5Z,8Z,11Z)-heptadec-5,8,11-trien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or (7Z,10Z,13Z)-nonadec-7,10,13-trien-1-yl. In certain embodiments, R2bis C2-20 alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R2bis C1-20alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R2bis n- octoxy. In certain embodiments, R2bis C1-20 heteroalkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R2bis C2-20 alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, R2bis C2-20alkynoxy, optionally substituted with one or more substituents Q.

[0124] In certain embodiments, R3ais hydrogen. In certain embodiments, R3ais C1-20 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R3ais unsubstituted C1-20alkyl. In certain embodiments, R3ais C1-20alkyl, substituted with one or moreAttorney Docket No.277A002WO01 substituents Q. In certain embodiments, R3ais C1-20 alkyl, substituted with one or more halo. In certain embodiments, R3ais C1-20 alkyl, substituted with one or more fluoro. In certain embodiments, R3ais C1-20alkyl, substituted with one, two, or three fluoro.

[0125] In certain embodiments, R3ais methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R3ais butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R3ais methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R3ais n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q.

[0126] In certain embodiments, R3ais C1-20heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R3ais trifluoromethyl, trifluoroethyl, trifluoro- propyl, trifluorobutyl, trifluoropentyl, trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluoro- nonyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluorotetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluorooctadecyl, trifluoro- nonadecyl, or trifluoroeicosyl. In certain embodiments, R3ais trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluorononyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluoro-tetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluoro- octadecyl, trifluorononadecyl, or trifluoroeicosyl. In certain embodiments, R3ais trifluoro- methyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoroprop-1-yl, 4,4,4-trifluorobut-1-yl, 5,5,5-trifluoropent- 1-yl, 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon- 1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13-trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16-trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19-trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl. In certain embodiments, R3aisAttorney Docket No.277A002WO01 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon-1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13- trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16- trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19- trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl.

[0127] In certain embodiments, R3ais C2-20alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R3ais nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, nonadecenyl, nonadecenyl, tetradecdienyl, pentadecdienyl, hexadecdienyl, heptadecdienyl, octadecdienyl, nonadecdienyl, heptadectrienyl, or nonadectrienyl, each optionally substituted with one or more substituents Q. In certain embodiments, R3ais (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-tetradec-8-enyl, (Z)-penta-dec-8-enyl, (Z)-hexadec-8-enyl, (Z)-heptadec-8- enyl, (Z)-octadec-8-enyl, (Z)-nonadec-8-enyl, (Z)-nonadec-10-enyl, (Z)-nonadec-12-enyl, (8Z,11Z)-tetradec-8,11-dienyl, (8Z,11Z)-pentadec-8,11-dienyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z)-octadec-8,11-dienyl, (8Z,11Z)-nonadec-8,11-dienyl, (5Z,8Z,11Z)-heptadec-5,8,11-trienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or (7Z,10Z,13Z)- nonadec-7,10,13-trienyl. In certain embodiments, R3ais (Z)-tridec-8-en-1-yl, (Z)-tetradec-8-en- 1-yl, (Z)-pentadec-8-en-1-yl, (Z)-hexadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, (Z)-octadec-8-en-1- yl, (Z)-nonadec-8-en-1-yl, (Z)-nonadec-10-en-1-yl, (Z)-nonadec-12-en-1-yl, (8Z,11Z)-tetradec- 8,11-dien-1-yl, (8Z,11Z)-pentadec-8,11-dien-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)- heptadec-8,11-dien-1-yl, (8Z,11Z)-octadec-8,11-dien-1-yl, (8Z,11Z)-nonadec-8,11-dien-1-yl, (5Z,8Z,11Z)-heptadec-5,8,11-trien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or (7Z,10Z,13Z)-nonadec-7,10,13-trien-1-yl. In certain embodiments, R3ais C2-20alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R3ais C1-20 alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R3ais n- octoxy. In certain embodiments, R3ais C1-20heteroalkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R3ais C2-20 alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, R3ais C2-20 alkynoxy, optionally substituted with one or more substituents Q.

[0128] In certain embodiments, R3bis C1-20alkyl, optionally substituted with one or moreAttorney Docket No.277A002WO01 substituents Q. In certain embodiments, R3bis unsubstituted C1-20 alkyl. In certain embodiments, R3bis C1-20 alkyl, substituted with one or more substituents Q. In certain embodiments, R3bis C1-20alkyl, substituted with one or more halo. In certain embodiments, R3bis C1-20 alkyl, substituted with one or more fluoro. In certain embodiments, R3bis C1-20 alkyl, substituted with one, two, or three fluoro.

[0129] In certain embodiments, R3bis methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R3bis butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R3bis methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R3bis n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q.

[0130] In certain embodiments, R3bis C1-20 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R3bis trifluoromethyl, trifluoroethyl, trifluoro- propyl, trifluorobutyl, trifluoropentyl, trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluoro- nonyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluorotetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluorooctadecyl, trifluoro- nonadecyl, or trifluoroeicosyl. In certain embodiments, R3bis trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluorononyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluoro-tetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluoro- octadecyl, trifluorononadecyl, or trifluoroeicosyl. In certain embodiments, R3bis trifluoro- methyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoroprop-1-yl, 4,4,4-trifluorobut-1-yl, 5,5,5-trifluoropent- 1-yl, 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon- 1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13-trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl,Attorney Docket No.277A002WO01 16,16,16-trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19-trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl. In certain embodiments, R3bis 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon-1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13- trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16- trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19- trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl.

[0131] In certain embodiments, R3bis C2-20 alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R3bis nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, nonadecenyl, nonadecenyl, tetradecdienyl, pentadecdienyl, hexadecdienyl, heptadecdienyl, octadecdienyl, nonadecdienyl, heptadectrienyl, or nonadectrienyl, each optionally substituted with one or more substituents Q. In certain embodiments, R3bis (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-tetradec-8-enyl, (Z)-penta-dec-8-enyl, (Z)-hexadec-8-enyl, (Z)-heptadec-8- enyl, (Z)-octadec-8-enyl, (Z)-nonadec-8-enyl, (Z)-nonadec-10-enyl, (Z)-nonadec-12-enyl, (8Z,11Z)-tetradec-8,11-dienyl, (8Z,11Z)-pentadec-8,11-dienyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z)-octadec-8,11-dienyl, (8Z,11Z)-nonadec-8,11-dienyl, (5Z,8Z,11Z)-heptadec-5,8,11-trienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or (7Z,10Z,13Z)- nonadec-7,10,13-trienyl. In certain embodiments, R3bis (Z)-tridec-8-en-1-yl, (Z)-tetradec-8-en- 1-yl, (Z)-pentadec-8-en-1-yl, (Z)-hexadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, (Z)-octadec-8-en-1- yl, (Z)-nonadec-8-en-1-yl, (Z)-nonadec-10-en-1-yl, (Z)-nonadec-12-en-1-yl, (8Z,11Z)-tetradec- 8,11-dien-1-yl, (8Z,11Z)-pentadec-8,11-dien-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)- heptadec-8,11-dien-1-yl, (8Z,11Z)-octadec-8,11-dien-1-yl, (8Z,11Z)-nonadec-8,11-dien-1-yl, (5Z,8Z,11Z)-heptadec-5,8,11-trien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or (7Z,10Z,13Z)-nonadec-7,10,13-trien-1-yl. In certain embodiments, R3bis C2-20 alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R3bis C1-20alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R3bis n- octoxy. In certain embodiments, R3bis C1-20 heteroalkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R3bis C2-20alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, R3bis C2-20alkynoxy, optionally substituted with one or more substituents Q.Attorney Docket No.277A002WO01

[0132] In certain embodiments, R4ais hydrogen. In certain embodiments, R4ais C1-20 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R4ais unsubstituted C1-20alkyl. In certain embodiments, R4ais C1-20alkyl, substituted with one or more substituents Q. In certain embodiments, R4ais C1-20 alkyl, substituted with one or more halo. In certain embodiments, R4ais C1-20 alkyl, substituted with one or more fluoro. In certain embodiments, R4ais C1-20alkyl, substituted with one, two, or three fluoro.

[0133] In certain embodiments, R4ais methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R4ais butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R4ais methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R4ais n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q.

[0134] In certain embodiments, R4ais C1-20heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R4ais trifluoromethyl, trifluoroethyl, trifluoro- propyl, trifluorobutyl, trifluoropentyl, trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluoro- nonyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluorotetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluorooctadecyl, trifluoro- nonadecyl, or trifluoroeicosyl. In certain embodiments, R4ais trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluorononyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluoro-tetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluoro- octadecyl, trifluorononadecyl, or trifluoroeicosyl. In certain embodiments, R4ais trifluoro- methyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoroprop-1-yl, 4,4,4-trifluorobut-1-yl, 5,5,5-trifluoropent- 1-yl, 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon- 1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl,Attorney Docket No.277A002WO01 13,13,13-trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16-trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19-trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl. In certain embodiments, R4ais 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon-1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13- trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16- trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19- trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl.

[0135] In certain embodiments, R4ais C2-20alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R4ais nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, nonadecenyl, nonadecenyl, tetradecdienyl, pentadecdienyl, hexadecdienyl, heptadecdienyl, octadecdienyl, nonadecdienyl, heptadectrienyl, or nonadectrienyl, each optionally substituted with one or more substituents Q. In certain embodiments, R4ais (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-tetradec-8-enyl, (Z)-penta-dec-8-enyl, (Z)-hexadec-8-enyl, (Z)-heptadec-8- enyl, (Z)-octadec-8-enyl, (Z)-nonadec-8-enyl, (Z)-nonadec-10-enyl, (Z)-nonadec-12-enyl, (8Z,11Z)-tetradec-8,11-dienyl, (8Z,11Z)-pentadec-8,11-dienyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z)-octadec-8,11-dienyl, (8Z,11Z)-nonadec-8,11-dienyl, (5Z,8Z,11Z)-heptadec-5,8,11-trienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or (7Z,10Z,13Z)- nonadec-7,10,13-trienyl. In certain embodiments, R4ais (Z)-tridec-8-en-1-yl, (Z)-tetradec-8-en- 1-yl, (Z)-pentadec-8-en-1-yl, (Z)-hexadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, (Z)-octadec-8-en-1- yl, (Z)-nonadec-8-en-1-yl, (Z)-nonadec-10-en-1-yl, (Z)-nonadec-12-en-1-yl, (8Z,11Z)-tetradec- 8,11-dien-1-yl, (8Z,11Z)-pentadec-8,11-dien-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)- heptadec-8,11-dien-1-yl, (8Z,11Z)-octadec-8,11-dien-1-yl, (8Z,11Z)-nonadec-8,11-dien-1-yl, (5Z,8Z,11Z)-heptadec-5,8,11-trien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or (7Z,10Z,13Z)-nonadec-7,10,13-trien-1-yl. In certain embodiments, R4ais C2-20alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R4ais C1-20 alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R4ais n- octoxy. In certain embodiments, R4ais C1-20heteroalkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R4ais C2-20alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, R4ais C2-20 alkynoxy, optionally substitutedAttorney Docket No.277A002WO01 with one or more substituents Q.

[0136] In certain embodiments, R4bis C1-20 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R4bis unsubstituted C1-20alkyl. In certain embodiments, R4bis C1-20 alkyl, substituted with one or more substituents Q. In certain embodiments, R4bis C1-20 alkyl, substituted with one or more halo. In certain embodiments, R4bis C1-20alkyl, substituted with one or more fluoro. In certain embodiments, R4bis C1-20alkyl, substituted with one, two, or three fluoro.

[0137] In certain embodiments, R4bis methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R4bis butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, or eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R4bis methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q. In certain embodiments, R4bis n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n- dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n- nonadecyl, or n-eicosyl, each optionally substituted with one or more substituents Q.

[0138] In certain embodiments, R4bis C1-20heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R4bis trifluoromethyl, trifluoroethyl, trifluoro- propyl, trifluorobutyl, trifluoropentyl, trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluoro- nonyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluorotetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluorooctadecyl, trifluoro- nonadecyl, or trifluoroeicosyl. In certain embodiments, R4bis trifluorohexyl, trifluoroheptyl, trifluorooctyl, trifluorononyl, trifluorodecyl, trifluoroundecyl, trifluorododecyl, trifluorotridecyl, trifluoro-tetradecyl, trifluoropentadecyl, trifluorohexadecyl, trifluoroheptadecyl, trifluoro- octadecyl, trifluorononadecyl, or trifluoroeicosyl. In certain embodiments, R4bis trifluoro- methyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoroprop-1-yl, 4,4,4-trifluorobut-1-yl, 5,5,5-trifluoropent-Attorney Docket No.277A002WO01 1-yl, 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon- 1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13-trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16-trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19-trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl. In certain embodiments, R4bis 6,6,6-trifluorohex-1-yl, 7,7,7-trifluorohept-1-yl, 8,8,8-trifluorooct-1-yl, 9,9,9-trifluoronon-1-yl, 10,10,10-trifluorodec-1-yl, 11,11,11-trifluoroundec-1-yl, 12,12,12-trifluorododec-1-yl, 13,13,13- trifluorotridec-1-yl, 14,14,14-trifluorotetradec-1-yl, 15,15,15-trifluoropentadec-1-yl, 16,16,16- trifluorohexadec-1-yl, 17,17,17-trifluoroheptadec-1-yl, 18,18,18-trifluorooctadec-1-yl, 19,19,19- trifluorononadec-1-yl, or 20,20,20-trifluoroeicosyl.

[0139] In certain embodiments, R4bis C2-20 alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R4bis nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, nonadecenyl, nonadecenyl, tetradecdienyl, pentadecdienyl, hexadecdienyl, heptadecdienyl, octadecdienyl, nonadecdienyl, heptadectrienyl, or nonadectrienyl, each optionally substituted with one or more substituents Q. In certain embodiments, R4bis (Z)-non-2-enyl, (Z)-dec-4-enyl, (Z)-tridec-8-enyl, (Z)-tetradec-8-enyl, (Z)-penta-dec-8-enyl, (Z)-hexadec-8-enyl, (Z)-heptadec-8- enyl, (Z)-octadec-8-enyl, (Z)-nonadec-8-enyl, (Z)-nonadec-10-enyl, (Z)-nonadec-12-enyl, (8Z,11Z)-tetradec-8,11-dienyl, (8Z,11Z)-pentadec-8,11-dienyl, (8Z,11Z)-hexadec-8,11-dienyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z,11Z)-octadec-8,11-dienyl, (8Z,11Z)-nonadec-8,11-dienyl, (5Z,8Z,11Z)-heptadec-5,8,11-trienyl, (8Z,11Z,14Z)-heptadec-8,11,14-trienyl, or (7Z,10Z,13Z)- nonadec-7,10,13-trienyl. In certain embodiments, R4bis (Z)-tridec-8-en-1-yl, (Z)-tetradec-8-en- 1-yl, (Z)-pentadec-8-en-1-yl, (Z)-hexadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, (Z)-octadec-8-en-1- yl, (Z)-nonadec-8-en-1-yl, (Z)-nonadec-10-en-1-yl, (Z)-nonadec-12-en-1-yl, (8Z,11Z)-tetradec- 8,11-dien-1-yl, (8Z,11Z)-pentadec-8,11-dien-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)- heptadec-8,11-dien-1-yl, (8Z,11Z)-octadec-8,11-dien-1-yl, (8Z,11Z)-nonadec-8,11-dien-1-yl, (5Z,8Z,11Z)-heptadec-5,8,11-trien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or (7Z,10Z,13Z)-nonadec-7,10,13-trien-1-yl. In certain embodiments, R4bis C2-20 alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R4bis C1-20alkoxy, optionally substituted with one or more substituents Q. In certain embodiments, R4bis n- octoxy. In certain embodiments, R4bis C1-20 heteroalkoxy, optionally substituted with one orAttorney Docket No.277A002WO01 more substituents Q. In certain embodiments, R4bis C2-20 alkenoxy, optionally substituted with one or more substituents Q. In certain embodiments, R4bis C2-20 alkynoxy, optionally substituted with one or more substituents Q.

[0140] In certain embodiments, A1is –C(O)O–. In certain embodiments, A1is –C(O)S–. In certain embodiments, A1is –OC(O)O–. In certain embodiments, A1is –OC(O)S–. In certain embodiments, A1is –C(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A1is –C(O)N(H)–. In certain embodiments, A1is –C(S)N(R1b)–, wherein R1bis as defined herein. n certain embodiments, A1is –C(S)N(H)–. In certain embodiments, A1is –O–. In certain embodiments, A1is –OC(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A1is –OC(O)N(H)–. In certain embodiments, A1is –OC(S)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A1is –OC(S)N(H)–. In certain embodiments, A1is –N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A1is –N(R1b)–, wherein R1bis hydrogen or C1-20alkyl, optionally substituted with one or more substituents Q. In certain embodiments, A1is –N(H)– or –N(CH3)–. In certain embodiments, A1is –N(R1a)C(O)N(R1d)–, wherein R1aand R1dare each as defined herein. In certain embodiments, A1is –N(H)C(O)N(H)–. In certain embodiments, A1is –N(R1a)C(S)N(R1d)–, wherein R1aand R1dare each as defined herein. In certain embodiments, A1is –N(H)C(S)N(H)–.

[0141] In certain embodiments, A2is a bond. In certain embodiments, A2is –C(O)O–. In certain embodiments, A2is –C(O)S–. In certain embodiments, A2is –OC(O)O–. In certain embodiments, A2is –OC(O)S–. In certain embodiments, A2is –C(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A2is –C(O)N(H)–. In certain embodiments, A2is –C(S)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A2is –C(S)N(H)–. In certain embodiments, A2is –O–. In certain embodiments, A2is –OC(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A2is –OC(O)N(H)–. In certain embodiments, A2is –OC(S)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A2is –OC(S)N(H)–. In certain embodiments, A2is –N(R1a)C(O)N(R1d)–, wherein R1aand R1dare each as defined herein. In certain embodiments, A2is –N(H)C(O)N(H)–. In certain embodiments, A2is –N(R1a)C(S)N(R1d)–, wherein R1aand R1dare each as defined herein. In certain embodiments, A2is –N(H)C(S)N(H)–.Attorney Docket No.277A002WO01

[0142] In certain embodiments, A3is a bond. In certain embodiments, A3is –C(O)O–. In certain embodiments, A3is –C(O)S–. In certain embodiments, A3is –OC(O)O–. In certain embodiments, A3is –OC(O)S–. In certain embodiments, A3is –C(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A3is –C(O)N(H)–. In certain embodiments, A3is –C(S)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A3is –C(S)N(H)–. In certain embodiments, A3is –O–. In certain embodiments, A3is –OC(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A3is –OC(O)N(H)–. In certain embodiments, A3is –OC(S)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A3is –OC(S)N(H)–. In certain embodiments, A3is –N(R1a)C(O)N(R1d)–, wherein R1aand R1dare each as defined herein. In certain embodiments, A3is –N(H)C(O)N(H)–. In certain embodiments, A3is –N(R1a)C(S)N(R1d)–, wherein R1aand R1dare each as defined herein. In certain embodiments, A3is –N(H)C(S)N(H)–.

[0143] In certain embodiments, A4is a bond. In certain embodiments, A4is –C(O)O–. In certain embodiments, A4is –C(O)S–. In certain embodiments, A4is –OC(O)O–. In certain embodiments, A4is –OC(O)S–. In certain embodiments, A4is –C(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A4is –C(O)N(H)–. In certain embodiments, A4is –C(S)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A4is –C(S)N(H)–. In certain embodiments, A4is –O–. In certain embodiments, A4is –OC(O)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A4is –OC(O)N(H)–. In certain embodiments, A4is –OC(S)N(R1b)–, wherein R1bis as defined herein. In certain embodiments, A4is –OC(S)N(H)–. In certain embodiments, A4is –N(R1a)C(O)N(R1d)–, wherein R1aand R1dare each as defined herein. In certain embodiments, A4is –N(H)C(O)N(H)–. In certain embodiments, A4is –N(R1a)C(S)N(R1d)–, wherein R1aand R1dare each as defined herein. In certain embodiments, A4is –N(H)C(S)N(H)–.

[0144] In certain embodiments, L1is a bond. In certain embodiments, L1is C1-20 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, L1is unsubstituted C1-20 alkylene. In certain embodiments, L1is C1-20 alkylene, substituted with one or more substituents Q. In certain embodiments, L1is C1-20 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, L1is unsubstituted C1-10alkylene. In certain embodiments, L1is C1-10alkylene, substituted with one or more substituents Q.Attorney Docket No.277A002WO01

[0145] In certain embodiments, L1is methanediyl, ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, decanediyl, undecanediyl, dodecanediyl, tridecanediyl, tetradecanediyl, pentadecanediyl, hexadecanediyl, heptadecanediyl, octadecanediyl, nonadecanediyl, or eicosanediyl, each optionally substituted with one or more substituents Q. In certain embodiments, L1is ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, or decanediyl, each optionally substituted with one or more substituents Q. In certain embodiments, L1is butanediyl, pentanediyl, hexanediyl, heptanediyl, or octanediyl, each optionally substituted with one or more substituents Q.

[0146] In certain embodiments, L1is methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9- diyl, decane-1,10-diyl, undecane-1,11-diyl, dodecane-1,12-diyl, tridecane-1,13-diyl, tetradecane- 1,14-diyl, pentadecane-1,15-diyl, hexadecane-1,16-diyl, heptadecane-1,17-diyl, octadecane-1,18- diyl, nonadecane-1,19-diyl, or eicosane-1,20-diyl, each optionally substituted with one or more substituents Q. In certain embodiments, L1is ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, or decane- 1,10-diyl, each optionally substituted with one or more substituents Q. In certain embodiments, L1is butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, or octane-1,8-diyl, each optionally substituted with one or more substituents Q.

[0147] In certain embodiments, L1is methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9- diyl, decane-1,10-diyl, undecane-1,11-diyl, dodecane-1,12-diyl, tridecane-1,13-diyl, tetradecane- 1,14-diyl, pentadecane-1,15-diyl, hexadecane-1,16-diyl, heptadecane-1,17-diyl, octadecane-1,18- diyl, nonadecane-1,19-diyl, or eicosane-1,20-diyl, each of which is unsubstituted. In certain embodiments, L1is ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane- 1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, or decane-1,10-diyl, each of which is unsubstituted. In certain embodiments, L1is butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6- diyl, heptane-1,7-diyl, or octane-1,8-diyl, each of which is unsubstituted.

[0148] In certain embodiments, L1is C1-20 heteroalkylene, optionally substituted with one or more substituents Q. In certain embodiments, L1is –(CH2)2O(CH2)2–, –(CH2)2O(CH2)3–,Attorney Docket No.277A002WO01 –(CH2)3O(CH2)3–, or –(CH2)2O(CH2)2O(CH2)2–. In certain embodiments, L1is –(CH2)2O(CH2)2–, –(CH2)2O(CH2)3–, or –(CH2)3O(CH2)3–. In certain embodiments, L1is –(CH2)2O(CH2)2–. In certain embodiments, L1is –(CH2)2O(CH2)3–. In certain embodiments, L1is –(CH2)3O(CH2)3–. In certain embodiments, L1is –(CH2)2O(CH2)2O(CH2)2–. In certain embodiments, L1is C2-20 alkenylene, optionally substituted with one or more substituents Q. In certain embodiments, L1is C2-20alkynylene, optionally substituted with one or more substituents Q.

[0149] In certain embodiments, L2is a bond. In certain embodiments, L2is C1-20 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, L2is unsubstituted C1-20alkylene. In certain embodiments, L2is C1-20alkylene, substituted with one or more substituents Q. In certain embodiments, L2is C1-20 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, L2is unsubstituted C1-10 alkylene. In certain embodiments, L2is C1-10alkylene, substituted with one or more substituents Q.

[0150] In certain embodiments, L2is methanediyl, ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, decanediyl, undecanediyl, dodecanediyl, tridecanediyl, tetradecanediyl, pentadecanediyl, hexadecanediyl, heptadecanediyl, octadecanediyl, nonadecanediyl, or eicosanediyl, each optionally substituted with one or more substituents Q. In certain embodiments, L2is ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, or decanediyl, each optionally substituted with one or more substituents Q. In certain embodiments, L2is butanediyl, pentanediyl, hexanediyl, heptanediyl, or octanediyl, each optionally substituted with one or more substituents Q.

[0151] In certain embodiments, L2is methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9- diyl, decane-1,10-diyl, undecane-1,11-diyl, dodecane-1,12-diyl, tridecane-1,13-diyl, tetradecane- 1,14-diyl, pentadecane-1,15-diyl, hexadecane-1,16-diyl, heptadecane-1,17-diyl, octadecane-1,18- diyl, nonadecane-1,19-diyl, or eicosane-1,20-diyl, each optionally substituted with one or more substituents Q. In certain embodiments, L2is ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, or decane- 1,10-diyl, each optionally substituted with one or more substituents Q. In certain embodiments,Attorney Docket No.277A002WO01 L2is butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, or octane-1,8-diyl, each optionally substituted with one or more substituents Q.

[0152] In certain embodiments, L2is methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9- diyl, decane-1,10-diyl, undecane-1,11-diyl, dodecane-1,12-diyl, tridecane-1,13-diyl, tetradecane- 1,14-diyl, pentadecane-1,15-diyl, hexadecane-1,16-diyl, heptadecane-1,17-diyl, octadecane-1,18- diyl, nonadecane-1,19-diyl, or eicosane-1,20-diyl, each of which is unsubstituted. In certain embodiments, L2is ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane- 1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, or decane-1,10-diyl, each of which is unsubstituted. In certain embodiments, L1is butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6- diyl, heptane-1,7-diyl, or octane-1,8-diyl, each of which is unsubstituted.

[0153] In certain embodiments, L2is C1-20 heteroalkylene, optionally substituted with one or more substituents Q. In certain embodiments, L2is –(CH2)2O(CH2)2–, –(CH2)2O(CH2)3–, –(CH2)3O(CH2)3–, or –(CH2)2O(CH2)2O(CH2)2–. In certain embodiments, L2is –(CH2)2O(CH2)2–, –(CH2)2O(CH2)3–, or –(CH2)3O(CH2)3–. In certain embodiments, L2is –(CH2)2O(CH2)2–. In certain embodiments, L2is –(CH2)2O(CH2)3–. In certain embodiments, L2is –(CH2)3O(CH2)3–. In certain embodiments, L2is –(CH2)2O(CH2)2O(CH2)2–. In certain embodiments, L2is –CH2C(O)O–, –(CH2)2C(O)O–, –(CH2)3C(O)O–, –(CH2)4C(O)O–, –(CH2)5C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, –(CH2)8C(O)O–, –(CH2)9C(O)O–, or –(CH2)10C(O)O–. In certain embodiments, L2is C2-20alkenylene, optionally substituted with one or more substituents Q. In certain embodiments, L2is C2-20 alkynylene, optionally substituted with one or more substituents Q.

[0154] In certain embodiments, L3is a bond. In certain embodiments, L3is C1-20alkylene, optionally substituted with one or more substituents Q. In certain embodiments, L3is unsubstituted C1-20 alkylene. In certain embodiments, L3is C1-20 alkylene, substituted with one or more substituents Q. In certain embodiments, L3is C1-20alkylene, optionally substituted with one or more substituents Q. In certain embodiments, L3is unsubstituted C1-10 alkylene. In certain embodiments, L3is C1-10 alkylene, substituted with one or more substituents Q.

[0155] In certain embodiments, L3is methanediyl, ethanediyl, propanediyl, butanediyl,Attorney Docket No.277A002WO01 pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, decanediyl, undecanediyl, dodecanediyl, tridecanediyl, tetradecanediyl, pentadecanediyl, hexadecanediyl, heptadecanediyl, octadecanediyl, nonadecanediyl, or eicosanediyl, each optionally substituted with one or more substituents Q. In certain embodiments, L3is ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, or decanediyl, each optionally substituted with one or more substituents Q. In certain embodiments, L3is butanediyl, pentanediyl, hexanediyl, heptanediyl, or octanediyl, each optionally substituted with one or more substituents Q.

[0156] In certain embodiments, L3is methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9- diyl, decane-1,10-diyl, undecane-1,11-diyl, dodecane-1,12-diyl, tridecane-1,13-diyl, tetradecane- 1,14-diyl, pentadecane-1,15-diyl, hexadecane-1,16-diyl, heptadecane-1,17-diyl, octadecane-1,18- diyl, nonadecane-1,19-diyl, or eicosane-1,20-diyl, each optionally substituted with one or more substituents Q. In certain embodiments, L3is ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, or decane- 1,10-diyl, each optionally substituted with one or more substituents Q. In certain embodiments, L3is butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, or octane-1,8-diyl, each optionally substituted with one or more substituents Q.

[0157] In certain embodiments, L3is methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9- diyl, decane-1,10-diyl, undecane-1,11-diyl, dodecane-1,12-diyl, tridecane-1,13-diyl, tetradecane- 1,14-diyl, pentadecane-1,15-diyl, hexadecane-1,16-diyl, heptadecane-1,17-diyl, octadecane-1,18- diyl, nonadecane-1,19-diyl, or eicosane-1,20-diyl, each of which is unsubstituted. In certain embodiments, L3is ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane- 1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, or decane-1,10-diyl, each of which is unsubstituted. In certain embodiments, L1is butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6- diyl, heptane-1,7-diyl, or octane-1,8-diyl, each of which is unsubstituted.

[0158] In certain embodiments, L3is C1-20 heteroalkylene, optionally substituted with one or more substituents Q. In certain embodiments, L3is –(CH2)2O(CH2)2–, –(CH2)2O(CH2)3–, –(CH2)3O(CH2)3–, or –(CH2)2O(CH2)2O(CH2)2–. In certain embodiments, L3isAttorney Docket No.277A002WO01 –(CH2)2O(CH2)2–, –(CH2)2O(CH2)3–, or –(CH2)3O(CH2)3–. In certain embodiments, L3is –(CH2)2O(CH2)2–. In certain embodiments, L3is –(CH2)2O(CH2)3–. In certain embodiments, L3is –(CH2)3O(CH2)3–. In certain embodiments, L3is –(CH2)2O(CH2)2O(CH2)2–. In certain embodiments, L3is –CH2C(O)O–, –(CH2)2C(O)O–, –(CH2)3C(O)O–, –(CH2)4C(O)O–, –(CH2)5C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, –(CH2)8C(O)O–, –(CH2)9C(O)O–, or –(CH2)10C(O)O–. In certain embodiments, L3is C2-20alkenylene, optionally substituted with one or more substituents Q. In certain embodiments, L3is C2-20alkynylene, optionally substituted with one or more substituents Q.

[0159] In certain embodiments, L4is a bond. In certain embodiments, L4is C1-20alkylene, optionally substituted with one or more substituents Q. In certain embodiments, L4is unsubstituted C1-20 alkylene. In certain embodiments, L4is C1-20 alkylene, substituted with one or more substituents Q. In certain embodiments, L4is C1-20 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, L4is unsubstituted C1-10alkylene. In certain embodiments, L4is C1-10 alkylene, substituted with one or more substituents Q.

[0160] In certain embodiments, L4is methanediyl, ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, decanediyl, undecanediyl, dodecanediyl, tridecanediyl, tetradecanediyl, pentadecanediyl, hexadecanediyl, heptadecanediyl, octadecanediyl, nonadecanediyl, or eicosanediyl, each optionally substituted with one or more substituents Q. In certain embodiments, L4is ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, or decanediyl, each optionally substituted with one or more substituents Q. In certain embodiments, L4is butanediyl, pentanediyl, hexanediyl, heptanediyl, or octanediyl, each optionally substituted with one or more substituents Q.

[0161] In certain embodiments, L4is methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9- diyl, decane-1,10-diyl, undecane-1,11-diyl, dodecane-1,12-diyl, tridecane-1,13-diyl, tetradecane- 1,14-diyl, pentadecane-1,15-diyl, hexadecane-1,16-diyl, heptadecane-1,17-diyl, octadecane-1,18- diyl, nonadecane-1,19-diyl, or eicosane-1,20-diyl, each optionally substituted with one or more substituents Q. In certain embodiments, L4is ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, or decane-Attorney Docket No.277A002WO01 1,10-diyl, each optionally substituted with one or more substituents Q. In certain embodiments, L4is butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, or octane-1,8-diyl, each optionally substituted with one or more substituents Q.

[0162] In certain embodiments, L4is methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9- diyl, decane-1,10-diyl, undecane-1,11-diyl, dodecane-1,12-diyl, tridecane-1,13-diyl, tetradecane- 1,14-diyl, pentadecane-1,15-diyl, hexadecane-1,16-diyl, heptadecane-1,17-diyl, octadecane-1,18- diyl, nonadecane-1,19-diyl, or eicosane-1,20-diyl, each of which is unsubstituted. In certain embodiments, L4is ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane- 1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, or decane-1,10-diyl, each of which is unsubstituted. In certain embodiments, L1is butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6- diyl, heptane-1,7-diyl, or octane-1,8-diyl, each of which is unsubstituted.

[0163] In certain embodiments, L4is C1-20heteroalkylene, optionally substituted with one or more substituents Q. In certain embodiments, L4is –(CH2)2O(CH2)2–, –(CH2)2O(CH2)3–, –(CH2)3O(CH2)3–, or –(CH2)2O(CH2)2O(CH2)2–. In certain embodiments, L4is –(CH2)2O(CH2)2–, –(CH2)2O(CH2)3–, or –(CH2)3O(CH2)3–. In certain embodiments, L4is –(CH2)2O(CH2)2–. In certain embodiments, L4is –(CH2)2O(CH2)3–. In certain embodiments, L4is –(CH2)3O(CH2)3–. In certain embodiments, L4is –(CH2)2O(CH2)2O(CH2)2–. In certain embodiments, L4is –CH2C(O)O–, –(CH2)2C(O)O–, –(CH2)3C(O)O–, –(CH2)4C(O)O–, –(CH2)5C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, –(CH2)8C(O)O–, –(CH2)9C(O)O–, or –(CH2)10C(O)O–. In certain embodiments, L4is C2-20 alkenylene, optionally substituted with one or more substituents Q. In certain embodiments, L4is C2-20alkynylene, optionally substituted with one or more substituents Q.

[0164] In certain embodiments, X is C(H). In certain embodiments, X is N.

[0165] In certain embodiments, Y is C(H). In certain embodiments, Y is N.

[0166] In certain embodiments, Z is C(H). In certain embodiments, Z is N.

[0167] In certain embodiments, m is an integer of 0. In certain embodiments, m is an integer of 1. In certain embodiments, m is an integer of 2. In certain embodiments, m is anAttorney Docket No.277A002WO01 integer of 3. In certain embodiments, m is an integer of 4.

[0168] In certain embodiments, n is an integer of 0. In certain embodiments, n is an integer of 1. In certain embodiments, n is an integer of 2. In certain embodiments, n is an integer of 3. In certain embodiments, n is an integer of 4.

[0169] In certain embodiments, p is an integer of 1. In certain embodiments, p is an integer of 2.

[0170] In certain embodiments, q is an integer of 0. In certain embodiments, q is an integer of 1. In certain embodiments, q is an integer of 2.

[0171] In certain embodiments, r is an integer of 0. In certain embodiments, r is an integer of 1. In certain embodiments, r is an integer of 2. In certain embodiments, r is an integer of 3. In certain embodiments, r is an integer of 4. In certain embodiments, r is an integer of 5. In certain embodiments, r is an integer of 6.

[0172] In one embodiment, provided herein is a compound of: 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane-1,3- diyl dioleate A001; 2-((oleoyloxy)methyl)-2-(((4-(pyrrolidin-1-yl)butanoyl)oxy)methyl)propane-1,3- diyl dioleate A002; 2-(((5-(dimethylamino)pentanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane- 1,3-diyl dioleate A003; 2-((oleoyloxy)methyl)-2-(((5-(piperidin-1-yl)pentanoyl)oxy)methyl)propane-1,3- diyl dioleate A004; 2-(((5-morpholinopentanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane-1,3-diyl dioleate A005; 2-(((5-(4-methylpiperazin-1-yl)pentanoyl)oxy)methyl)-2-((oleoyloxy)methyl)- propane-1,3-diyl dioleate A006; or 2-(((3-(dimethylamino)propyl)amino)methyl)-2-((oleoyloxy)methyl)propane-1,3- diyl dioleate A007; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or moreAttorney Docket No.277A002WO01 diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0173] In another embodiment, provided herein is a compound of: 2-((oleoyloxy)methyl)-2-(((3-(pyrrolidin-1-yl)propanoyl)oxy)methyl)propane- 1,3-diyl dioleate A008; 2-(((3-(dimethylamino)propanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane- 1,3-diyl dioleate A009; 2-(((3-morpholinopropanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane-1,3-diyl dioleate A010; 2-(((3-(4-methylpiperazin-1-yl)propanoyl)oxy)methyl)-2-((oleoyloxy)methyl)- propane-1,3-diyl dioleate A011; 2-(((5-(dimethylamino)pentanoyl)oxy)methyl)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A012; 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A013; or 2-(((3-(dimethylamino)propanoyl)oxy)methyl)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A014; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0174] In yet another embodiment, provided herein is a compound of 2-(((4-(dimethyl- amino)butanoyl)oxy)methyl)-2-((((4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoyl)- oxy)methyl)propane-1,3-diyl (4Z,4'Z,7Z,7'Z,10Z,10'Z,13Z,13'Z,16Z,16'Z,19Z,19'Z)-bis(docosa- 4,7,10,13,16,19-hexaenoate) A015, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0175] In yet another embodiment, provided herein is a compound of: 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-(hydroxymethyl)propane-1,3-diyl dioleate A051; orAttorney Docket No.277A002WO01 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-(hydroxymethyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A052; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0176] In yet another embodiment, provided herein is a compound of: 7-hydroxy-7-(4-((1-methylpiperidine-4-carbonyl)oxy)butyl)tridecane-1,13-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A061; 7-hydroxy-7-(4-((1-methylpiperidine-4-carbonyl)oxy)butyl)tridecane-1,13-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A062; (Z)-11-(hexadec-9-enoyloxy)-5-(6-((2-hexyldecanoyl)oxy)hexyl)-5-hydroxy- undecyl 1-methylpiperidine-4-carboxylate A063; 7-(4-(dimethylamino)butyl)-7-hydroxytridecane-1,13-diyl (9Z,9'Z)-bis(hexadec-9- enoate) A064; or 7-(4-(dimethylamino)butyl)-7-hydroxytridecane-1,13-diyl (9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate) A065; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0177] In yet another embodiment, provided herein is a compound of: 2-(3-(dimethylamino)propanamido)-2-((((Z)-hexadec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A101; 2-(3-(dimethylamino)propanamido)-2-(((octadecylcarbamoyl)oxy)methyl)- propane-1,3-diyl bis(octadecylcarbamate) A102; O,O’-(2-(3-(dimethylamino)propanamido)-2-(((octadecylcarbamothioyl)oxy)- methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A103; N-(1,3-bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(dimethylamino)propanamide A104; 2-(3-(3-(dimethylamino)propyl)ureido)-2-((((Z)-hexadec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A105;Attorney Docket No.277A002WO01 2-(3-(3-(dimethylamino)propyl)ureido)-2-(((octadecylcarbamoyl)oxy)methyl)- propane-1,3-diyl bis(octadecylcarbamate) A106; O,O’-(2-(3-(3-(dimethylamino)propyl)ureido)-2-(((octadecylcarbamothioyl)oxy)- methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A107; 1-(1,3-bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(3-(dimethylamino)propyl)urea A108; 2-(3-(3-(dimethylamino)propyl)thioureido)-2-((((Z)-hexadec-9-enoyl)oxy)- methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A109; 2-(3-(3-(dimethylamino)propyl)thioureido)-2-(((octadecylcarbamoyl)oxy)- methyl)propane-1,3-diyl bis(octadecylcarbamate) A110; O,O’-(2-(3-(3-(dimethylamino)propyl)thioureido)-2-(((octadecylcarbamothioyl)- oxy)methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A111; or 1-(1,3-bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(3-(dimethylamino)propyl)thiourea A112; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0178] In yet another embodiment, provided herein is 3-(dimethylamino)propyl (3- (octadecyloxy)-2,2-bis((octadecyloxy)methyl)-propyl) carbonate A151; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0179] In yet another embodiment, provided herein is a compound of: 2-(azetidin-1-ylmethyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A201; 2-(aziridin-1-ylmethyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A202; 2-((2-methylaziridin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane- 1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A203; 2-((2-ethylaziridin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-Attorney Docket No.277A002WO01 1,3-diyl (9Z,9’Z)-bis(tetradic-9-enoate) A204; 2-(aziridin-1-ylmethyl)-2-((decanoyloxy)methyl)propane-1,3-diyl bis(decanoate) A205; 2-(aziridin-1-ylmethyl)-2-((palmitoyloxy)methyl)propane-1,3-diyl dipalmitate A206; 2-(((2-(aziridin-1-yl)ethyl)amino)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A207; 2-((3-methylazetidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane- 1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A208; 2-((3-methoxyazetidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A209; 2-((3-(fluoromethyl)azetidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A210; 2-(azetidin-1-ylmethyl)-2-((decanoyloxy)methyl)propane-1,3-diyl bis(decanoate) A211; 2-(azetidin-1-ylmethyl)-2-((palmitoyloxy)methyl)propane-1,3-diyl dipalmitate A212; 2-(((2-(azetidin-1-yl)ethyl)(methyl)amino)methyl)-2-((((Z)-tetradec-9-enoyl)- oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A213; 2-(((2-(azetidin-1-yl)ethyl)(methyl)amino)methyl)-2-((decanoyloxy)methyl)- propane-1,3-diyl bis(decanoate) A214; 2-(((2-(azetidin-1-yl)ethyl)(methyl)amino)methyl)-2-((palmitoyloxy)methyl)- propane-1,3-diyl dipalmitate A215; 2-(pyrrolidin-1-ylmethyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A216; 2-((2-methylpyrrolidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A217; 2-((3-methylpyrrolidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A218; 2-((3,4-dimethylpyrrolidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A219;Attorney Docket No.277A002WO01 2-((decanoyloxy)methyl)-2-(pyrrolidin-1-ylmethyl)propane-1,3-diyl bis(decanoate) A220; 2-((palmitoyloxy)methyl)-2-(pyrrolidin-1-ylmethyl)propane-1,3-diyl dipalmitate A221; 2-((methyl(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-2-((((Z)-tetradec-9-enoyl)- oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A222; 2-((decanoyloxy)methyl)-2-((methyl(2-(pyrrolidin-1-yl)ethyl)amino)methyl)- propane-1,3-diyl bis(decanoate) A223; or 2-((methyl(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-2-((palmitoyloxy)methyl)- propane-1,3-diyl dipalmitate A224; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0180] In yet another embodiment, provided herein is a compound of: 2-(((3-(dimethylamino)propyl)(methyl)amino)methyl)-2-((oleoyloxy)methyl)- propane-1,3-diyl dioleate A225; or 2-((4-methylpiperazin-1-yl)methyl)-2-((oleoyloxy)methyl)propane-1,3-diyl dioleate A226; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0181] In still another embodiment, provided herein is 2-((2-(aziridin-1-yl)ethoxy)- methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)-propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A301; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0182] In one embodiment, provided herein is a compound of: 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B001;Attorney Docket No.277A002WO01 1-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2- yl oleate B002; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B003; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B004; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B005; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B006; 1-(((1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B007; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B008; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B009; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B010; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-2-(oleoyloxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B011; 1-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)- propan-2-yl oleate B012; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl distearate B013; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B014; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B015; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)-octadeca- 9,12-dienoate B016; 1-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B017; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B018; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B019;Attorney Docket No.277A002WO01 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B020; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B021; 1-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B022; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B023; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B024; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B025; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B026; 1-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B027; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl distearate B028; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B029; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B030; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B031; 1-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B032; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B033; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B034; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B035; 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B036; 1-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B037;Attorney Docket No.277A002WO01 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B038; 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B039; 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B040; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B041; 1-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2- yl oleate B042; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl distearate B043; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B044; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B045; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B046; 1-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B047; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B048; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B049; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B050; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B051; 1-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan- 2-yl oleate B052; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearateAttorney Docket No.277A002WO01 B053; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B054; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B055; 2-(oleoyloxy)-3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B056; 1-(palmitoyloxy)-3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)- propan-2-yl oleate B057; 3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B058; 3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B059; 3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B060; 3-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyl- oxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B061; 1-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-3- (palmitoyloxy)propan-2-yl oleate B062; 3-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,2-diyl distearate B063; 3-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,2-diyl dipalmitate B064; 3-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,2-diyl bis(decanoate) B065; 3-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-2-(oleoyloxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B066; 1-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyl- oxy)propan-2-yl oleate B067; 3-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl distearate B068;Attorney Docket No.277A002WO01 3-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B069; 3-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B070; 3-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B071; 1-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyl- oxy)propan-2-yl oleate B072; 3-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B073; 3-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B074; or 3-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B075; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0183] In another embodiment, provided herein is a compound of: 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B101; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B102; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B103; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B104; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B105; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B106; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-Attorney Docket No.277A002WO01 octadeca-9,12-dienoate B107; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B108; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B109; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B110; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B111; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B112; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B113; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B114; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B115; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B116; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B117; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B118; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B119; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B120; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B121; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B122; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B123; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B124; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B125; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B126; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B127;Attorney Docket No.277A002WO01 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B128; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B129; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B130; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B131; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B132; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B133; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,3-diyl distearate B134; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B135; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(((9Z,12Z)- octadeca-9,12-dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B136; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B137; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)- propyl oleate B138; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,3-diyl distearate B139; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B140; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B141; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B142; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleateAttorney Docket No.277A002WO01 B143; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B144; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B145; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B146; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B147; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B148; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B149; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B150; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-(((1-(2,2,2-trifluoroethyl)azetidin-3- yl)carbamoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B151; 3-(palmitoyloxy)-2-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B152; 3-(palmitoyloxy)-2-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propyl oleate B153; 2-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B154; 2-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B155; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B156; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B157; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B158;Attorney Docket No.277A002WO01 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B159; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B160; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-(((1-(3,3,3-trifluoropropyl)azetidin-3- yl)carbamoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B161; 3-(palmitoyloxy)-2-(((1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B162; 3-(palmitoyloxy)-2-(((1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)- propyl oleate B163; 2-(((1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B164; 2-(((1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B165; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-3- (((9Z,12Z)-octadeca-9,12-dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B166; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-3- (palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B167; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-3- (palmitoyloxy)propyl oleate B168; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,3-diyl distearate B169; or 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,3-diyl dipalmitate B170; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0184] In yet another embodiment, provided herein is a compound of: 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B201; 3-(((1-ethyl-2-oxoazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-Attorney Docket No.277A002WO01 dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B202; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B203; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B204; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B205; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-((((1-(2,2,2-trifluoroethyl)azetidin-3- yl)carbamoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B206; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B207; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B208; 3-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B209; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-((((1-(3,3,3-trifluoropropyl)azetidin- 3-yl)carbamoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B210; 3-(((1-(1,3-difluoropropan-2-yl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)- octadeca-9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B211; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B212; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-((((1-(oxetan-3-yl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B213; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-((((1-(tetrahydro-2H-pyran-4-yl)- azetidin-3-yl)carbamoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B214; 3-(((1-cyclohexylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B215; 3-(((1-cyclopentylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B216; 3-(((1-cyclobutylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B217;Attorney Docket No.277A002WO01 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B218; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-2-((((9Z,12Z)- octadeca-9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B219; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B220; 3-((methyl(1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl)carbamoyl)oxy)-2- ((((9Z,12Z)-octadeca-9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B221; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B222; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2-hydroxyethyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B223; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-ethyl-2-oxoazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B224; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-methylazetidin-3-yl)carbamoyl)oxy)- methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B225; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-ethylazetidin-3-yl)carbamoyl)oxy)- methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B226; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-isopropylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B227; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2,2,2-trifluoroethyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B228; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2,2-difluoroethyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B229; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2-fluoroethyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B230; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(3-fluoropropyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B231; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(3,3,3-trifluoropropyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B232;Attorney Docket No.277A002WO01 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(1,3-difluoropropan-2-yl)azetidin-3- yl)carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B233; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1,3-dimethylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B234; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(oxetan-3-yl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B235; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(tetrahydro-2H-pyran-4-yl)azetidin-3- yl)carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B236; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-cyclohexylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B237; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-cyclopentylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B238; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-cyclobutylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B239; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-(((methyl(1-methylazetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B240; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2-hydroxyethyl)azetidin-3-yl)- (methyl)carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B241; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-isopropylazetidin-3-yl)(methyl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B242; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-(((methyl(1-(tetrahydro-2H-pyran-4-yl)- azetidin-3-yl)carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B243; or 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-ethylazetidin-3-yl)(methyl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B244; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0185] In yet another embodiment, provided herein is a compound of: 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-(oleoyloxy)propyl 3-((dimethyl- amino)methyl)azetidine-1-carboxylate B301; 2-(oleoyloxy)-3-(palmitoyloxy)propyl 3-((dimethylamino)methyl)azetidine-1-Attorney Docket No.277A002WO01 carboxylate B302; 3-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,2-diyl distearate B303; 3-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,2-diyl dipalmitate B304; 3-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,2-diyl bis(decanoate) B305; 1-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propan-2-yl 3-((dimethylamino)methyl)azetidine-1-carboxylate B306; 1-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(palmitoyloxy)propan-2-yl 3- ((dimethylamino)methyl)azetidine-1-carboxylate B307; 1-(oleoyloxy)-3-(palmitoyloxy)propan-2-yl 3-((dimethylamino)methyl)azetidine- 1-carboxylate B308; 2-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,3-diyl distearate B309; 2-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,3-diyl dipalmitate B310; 3-(((9Z,12Z)-heptadeca-9,12-dienoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)methyl)propyl 3-((dimethylamino)methyl)azetidine-1-carboxylate B311; or 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-dienoyl)oxy)- methyl)propyl 3-((dimethylamino)methyl)azetidine-1-carboxylate B312; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0186] In yet another embodiment, provided herein is a compound of: 2-(((3-(dimethylamino)propyl)amino)methyl)-2-((oleoyloxy)methyl)propane-1,3- diyl dioleate B401; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) B402; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) B403;Attorney Docket No.277A002WO01 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2- hexyldecanoate) B404; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyldecanoate) B405; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B406; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B407; 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B408; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B409; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) B410; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec- 9-enoate) B411; 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)- bis(hexadec-9-enoate) B412; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) B413; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B414; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B415; di(heptadecan-9-yl) O,O'-(2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)- oxy)methyl)propane-1,3-diyl) diadipate B416; di(heptadecan-9-yl) O,O'-(2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)- oxy)methyl)propane-1,3-diyl) diadipate B417; O,O'-(2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl) di(heptadecan-9-yl) diadipate B418; di(heptadecan-9-yl) O,O'-(2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)-Attorney Docket No.277A002WO01 propane-1,3-diyl) diadipate B419; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyldecanoate) B420; 2-(((6-(3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl)hexanoyl)oxy)methyl)- propane-1,3-diyl bis(2-hexyldecanoate) B421; O,O'-(2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3- diyl) di(pentadecan-7-yl) diadipate B422; O,O'-(2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane- 1,3-diyl) di(pentadecan-7-yl) diadipate B423; O,O'-(2-(((6-(3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl)hexanoyl)oxy)- methyl)propane-1,3-diyl) di(pentadecan-7-yl) diadipate B424; 2-(((3-(2-(2-(3-(hydroxymethyl)azetidin-1-yl)ethoxy)ethoxy)propanoyl)oxy)- methyl)propane-1,3-diyl bis(2-hexyldecanoate) B425; 2-(((3-(2-(2-(4-(2-hydroxyethyl)piperazin-1-yl)ethoxy)ethoxy)propanoyl)oxy)- methyl)propane-1,3-diyl bis(2-hexyldecanoate) B426; 2-(((3-(2-(2-(3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl)ethoxy)ethoxy)- propanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyldecanoate) B427; di((Z)-non-2-en-1-yl) 9-((4-(3-(hydroxymethyl)azetidin-1-yl)butanoyl)oxy)- heptadecanedioate B428; di((Z)-non-2-en-1-yl) 9-((4-(4-(2-hydroxyethyl)piperazin-1-yl)butanoyl)oxy)- heptadecanedioate B429; di((Z)-non-2-en-1-yl) 9-((4-(3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl)- butanoyl)oxy)heptadecanedioate B430; 8-(4-(3-(hydroxymethyl)azetidin-1-yl)butanamido)-3,6,10,13-tetraoxapenta- decane-1,15-diyl bis(2-hexyldecanoate) B431; or 2-((2-(2-(2-(3-(hydroxymethyl)azetidin-1-yl)ethoxy)ethoxy)ethoxy)methyl)- propane-1,3-diyl bis(2-hexyldecanoate) B432; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0187] In yet another embodiment, provided herein is a compound of:Attorney Docket No.277A002WO01 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate) B433; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyl- decanoate) B434; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B435; 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B436; O,O'-(2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane- 1,3-diyl) di(undecan-3-yl) diadipate B437; O,O'-(2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl) di(undecan-3- yl) diadipate B438; O,O'-(2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl) di(undecan-3-yl) diadipate B439; O,O'-(2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3- diyl) di(undecan-3-yl) diadipate B440; 2-(((4-(4-(2-hydroxyethyl)piperazin-1-yl)butanoyl)oxy)methyl)propane-1,3-diyl dioleate B441; 2-(((4-(3-hydroxyazetidin-1-yl)butanoyl)oxy)methyl)propane-1,3-diyl dioleate B442; 2-(((4-(3-(hydroxymethyl)azetidin-1-yl)butanoyl)oxy)methyl)propane-1,3-diyl dioleate B443; 2-((3-(azetidin-1-yl)propanoyl)oxy)propane-1,3-diyl dioleate B444; 3-((2-hexyldecanoyl)oxy)-2-(((4-(4-(2-hydroxyethyl)piperazin-1-yl)butanoyl)- oxy)methyl)propyl oleate B445; 3-((4-(azetidin-1-yl)butanoyl)oxy)-2-(((2-hexyldecanoyl)oxy)methyl)propyl oleate B446; 3-((2-hexyldecanoyl)oxy)-2-(((4-(3-hydroxyazetidin-1-yl)butanoyl)oxy)methyl)- propyl oleate B447; 3-((2-hexyldecanoyl)oxy)-2-(((4-(3-(hydroxymethyl)azetidin-1-yl)butanoyl)oxy)- methyl)propyl oleate B448; 3-((2-hexyldecanoyl)oxy)-2-(((4-(4-(2-hydroxyethyl)piperazin-1-yl)butanoyl)-Attorney Docket No.277A002WO01 oxy)methyl)propyl nonyl adipate B449; 3-((4-(azetidin-1-yl)butanoyl)oxy)-2-(((2-hexyldecanoyl)oxy)methyl)propyl nonyl adipate B450; 3-((2-hexyldecanoyl)oxy)-2-(((4-(3-hydroxyazetidin-1-yl)butanoyl)oxy)methyl)- propyl nonyl adipate B451; 3-((2-hexyldecanoyl)oxy)-2-(((4-(3-(hydroxymethyl)azetidin-1-yl)butanoyl)oxy)- methyl)propyl nonyl adipate B452; 3-((2-hexyldecanoyl)oxy)-2-(((3-(4-(2-hydroxyethyl)piperazin-1-yl)propanoyl)- oxy)methyl)propyl nonyl adipate B453; 3-((3-(azetidin-1-yl)propanoyl)oxy)-2-(((2-hexyldecanoyl)oxy)methyl)propyl nonyl adipate B454; 3-((2-hexyldecanoyl)oxy)-2-(((3-(3-hydroxyazetidin-1-yl)propanoyl)oxy)- methyl)propyl nonyl adipate B455; or 3-((2-hexyldecanoyl)oxy)-2-(((3-(3-(hydroxymethyl)azetidin-1-yl)propanoyl)- oxy)methyl)propyl 6-oxohexadecanoate B456; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0188] In yet another embodiment, provided herein is a compound of: (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(4-(2-hydroxyethyl)- piperazin-1-yl)pentanoate B501; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(3-hydroxyazetidin-1- yl)pentanoate B502; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(azetidin-1-yl)- pentanoate B503; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 3-(azetidin-1-yl)- propanoate B504; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 3-(pyrrolidin-1-yl)- propanoate B505; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 3-(piperidin-1-yl)- propanoate B506;Attorney Docket No.277A002WO01 (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 4-(azetidin-1-yl)- butanoate B507; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 4-(pyrrolidin-1-yl)- butanoate B508; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 4-(piperidin-1-yl)- butanoate B509; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(azetidin-1-yl)- pentanoate B510; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(3-(hydroxymethyl)- azetidin-1-yl)pentanoate B511; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(3-((2-hydroxyethyl)- carbamoyl)azetidin-1-yl)pentanoate B512; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(pyrrolidin-1-yl)- pentanoate B513; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(piperidin-1-yl)- pentanoate B514; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-morpholinopentanoate B515; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(4-(2-hydroxyethyl)- piperazin-1-yl)pentanoate B516; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-((1-methylazetidin-3- yl)amino)pentanoate B517; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(pyrrolidin-1-yl)- propyl)carbamate B521; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(piperidin-1-yl)- propyl)carbamate B522; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-morpholinopropyl)- carbamate B523; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(4-methylpiperazin-1- yl)propyl)carbamate B524; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(pyrrolidin-1-Attorney Docket No.277A002WO01 yl)butyl)carbamate B525; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(azetidin-1-yl)propyl)- carbamothioate B531; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(pyrrolidin-1-yl)- propyl)carbamothioate B532; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(piperidin-1-yl)- propyl)carbamothioate B533; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(pyrrolidin-1-yl)- butyl)carbamothioate B534; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(piperidin-1-yl)butyl)- carbamothioate B535; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(1-methylazetidin-3- yl)propyl)carbamothioate B536; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(dimethylamino)- butyl)carbamothioate B537; or (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(dimethylamino)butyl) carbonate B541; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0189] In yet another embodiment, provided herein is a compound of: bis(2-butyloctyl) 10-(N-(3-(azetidin-1-yl)propyl)nonanamido)nonadecanedioate B601; (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-((1-methylazetidin-3- yl)amino)butanoate B602; N-(2,3-bis(((9Z,12Z)-octadeca-9,12-dien-1-yl)oxy)propyl)-1-methylazetidin-3- amine B603; or bis(2-butyloctyl) 10-(N-(3-((1-methylazetidin-3-yl)amino)propyl)nonanamido)- nonadecanedioate B604; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; orAttorney Docket No.277A002WO01 a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0190] In yet another embodiment, provided herein is a compound of: 2-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)propane-1,3-diyl dioleate B701; 2-(azetidin-1-ylmethyl)propane-1,3-diyl dioleate B702; 2-((3-hydroxyazetidin-1-yl)methyl)propane-1,3-diyl dioleate B703; or 2-((dimethylamino)methyl)propane-1,3-diyl dioleate B704; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0191] In still another embodiment, provided herein is a compound of: 3-(((3-(diethylamino)propoxy)carbonyl)oxy)-2-(((15-methylhexadecanoyl)oxy)- methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B711; 3-(((3-(diethylamino)propoxy)carbonyl)oxy)-2-(((8-(2-hexylcyclopropyl)- octanoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B712; 3-(((3-(diethylamino)propoxy)carbonyl)oxy)-2-(((8-(2-((2-pentylcyclopropyl)- methyl)cyclopropyl)octanoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B713; 2-((((9Z,12Z)-octadeca-9,12-dienoyl)oxy)methyl)propane-1,3-diyl bis(15-methyl- hexadecanoate) B714; or 2-((((9Z,12Z)-octadeca-9,12-dienoyl)oxy)methyl)propane-1,3-diyl bis(8-(2- hexylcyclopropyl)octanoate) B715; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0192] In certain embodiments, a compound provided herein is deuterium-enriched. In certain embodiments, a compound provided herein is carbon-13 enriched. In certain embodiments, a compound provided herein is carbon-14 enriched. In certain embodiments, a compound provided herein contains one or more less prevalent isotopes for other elements, including, but not limited to,15N for nitrogen;17O or18O for oxygen, and34S,35S, or36S for sulfur.Attorney Docket No.277A002WO01

[0193] In certain embodiments, a compound provided herein has an isotopic enrichment factor of no less than about 5, no less than about 10, no less than about 20, no less than about 50, no less than about 100, no less than about 200, no less than about 500, no less than about 1,000, no less than about 2,000, no less than about 5,000, or no less than about 10,000. In any events, however, an isotopic enrichment factor for a specified isotope is no greater than the maximum isotopic enrichment factor for the specified isotope, which is the isotopic enrichment factor when a compound at a given position is 100% enriched with the specified isotope. Thus, the maximum isotopic enrichment factor is different for different isotopes. The maximum isotopic enrichment factor is 6,410 for deuterium and 90 for carbon-13.

[0194] In certain embodiments, a compound provided herein has a deuterium enrichment factor of no less than about 64 (about 1% deuterium enrichment), no less than about 130 (about 2% deuterium enrichment), no less than about 320 (about 5% deuterium enrichment), no less than about 640 (about 10% deuterium enrichment), no less than about 1,300 (about 20% deuterium enrichment), no less than about 3,200 (about 50% deuterium enrichment), no less than about 4,800 (about 75% deuterium enrichment), no less than about 5,130 (about 80% deuterium enrichment), no less than about 5,450 (about 85% deuterium enrichment), no less than about 5,770 (about 90% deuterium enrichment), no less than about 6,090 (about 95% deuterium enrichment), no less than about 6,220 (about 97% deuterium enrichment), no less than about 6,280 (about 98% deuterium enrichment), no less than about 6,350 (about 99% deuterium enrichment), or no less than about 6,380 (about 99.5% deuterium enrichment). The deuterium enrichment can be determined using conventional analytical methods known to one of ordinary skill in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy. In certain embodiments, at least one of the atoms of a compound provided herein, as specified as deuterium-enriched, has deuterium enrichment of no less than about 50%, no less than about 70%, no less than about 80%, no less than about 90%, or no less than about 98%.

[0195] In certain embodiments, a compound provided herein is isolated or purified. In certain embodiments, a compound provided herein has a purity of at least about 90%, at least about 95%, at least about 98%, at least about 99%, or at least about 99.5% by weight.

[0196] The compounds provided herein are intended to encompass all possibleAttorney Docket No.277A002WO01 stereoisomers unless a particular stereochemistry is specified. Where a compound provided herein contains an alkenyl group, the compound may exist as one or mixture of geometric cis / trans (or Z / E) isomers. Where structural isomers are interconvertible, the compound may exist as a single tautomer or a mixture of tautomers. This can take the form of proton tautomerism in the compound that contains, for example, an imino, keto, or oxime group; or so- called valence tautomerism in the compound that contains an aromatic moiety. It follows that a single compound may exhibit more than one type of isomerism.

[0197] A compound provided herein can be enantiomerically pure, such as a single enantiomer or a single diastereomer, or be stereoisomeric mixtures, such as a mixture of enantiomers, e.g., a racemic mixture of two enantiomers; or a mixture of two or more diastereomers. As such, one of ordinary skill in the art will recognize that administration of a compound in its (R) form is equivalent, for the compound that undergoes epimerization in vivo, to administration of the compound in its (S) form. Conventional techniques for the preparation / isolation of individual enantiomers include synthesis from a suitable optically pure precursor, asymmetric synthesis from achiral starting materials, or resolution of an enantiomeric mixture, for example, chiral chromatography, recrystallization, resolution, diastereomeric salt formation, or derivatization into diastereomeric adducts followed by separation.

[0198] When a compound provided herein contains an acidic or basic moiety, it can also be provided as a pharmaceutically acceptable salt. See, Berge et al., J. Pharm. Sci.1977, 66, 1- 19; Handbook of Pharmaceutical Salts: Properties, Selection, and Use, 2nded.; Stahl and Wermuth Eds.; John Wiley & Sons, 2011. In certain embodiments, a pharmaceutically acceptable salt of a compound provided herein is a solvate. In certain embodiments, a pharmaceutically acceptable salt of a compound provided herein is a hydrate.

[0199] Suitable acids for use in the preparation of pharmaceutically acceptable salts of a compound provided herein include, but are not limited to, acetic acid, 2,2-dichloroacetic acid, acylated amino acids, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, boric acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclamic acid, cyclohexanesulfamic acid, dodecylsulfuric acid, ethane-1,2-disulfonicAttorney Docket No.277A002WO01 acid, ethanesulfonic acid, 2-hydroxy-ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, D-gluconic acid, D-glucuronic acid, L-glutamic acid, α- oxoglutaric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, (+)-L-lactic acid, (±)-DL-lactic acid, lactobionic acid, lauric acid, maleic acid, (-)-L-malic acid, malonic acid, (±)-DL-mandelic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, perchloric acid, phosphoric acid, L- pyroglutamic acid, saccharic acid, salicylic acid, 4-amino-salicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, tannic acid, (+)-L-tartaric acid, thiocyanic acid, p- toluenesulfonic acid, undecylenic acid, and valeric acid.

[0200] Suitable bases for use in the preparation of pharmaceutically acceptable salts of a compound provided herein include, but are not limited to, inorganic bases, such as magnesium hydroxide, calcium hydroxide, potassium hydroxide, zinc hydroxide, and sodium hydroxide; and organic bases, such as primary, secondary, tertiary, and quaternary, aliphatic and aromatic amines, including, but not limited to, L-arginine, benethamine, benzathine, choline, deanol, diethanolamine, diethylamine, dimethylamine, dipropylamine, diisopropylamine, 2-(diethyl- amino)ethanol, ethanolamine, ethylamine, ethylenediamine, isopropylamine, N-methyl- glucamine, hydrabamine, 1H-imidazole, L-lysine, morpholine, 4-(2-hydroxyethyl)-morpholine, methylamine, piperidine, piperazine, propylamine, pyrrolidine, 1-(2-hydroxyethyl)-pyrrolidine, pyridine, quinuclidine, quinoline, isoquinoline, triethanolamine, trimethylamine, triethylamine, N-methyl-D-glucamine, 2-amino-2-(hydroxymethyl)-1,3-propanediol, and tromethamine. Lipid Nanoparticles

[0201] In one embodiment, provided herein is a lipid nanoparticle comprising a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0202] In another embodiment, provided herein is a lipid nanoparticle comprising (i) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture ofAttorney Docket No.277A002WO01 enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (ii) a phospholipid; and (iii) cholesterol.

[0203] In yet another embodiment, provided herein is a lipid nanoparticle comprising (i) a nucleic acid and (ii) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0204] In still another embodiment, provided herein is a lipid nanoparticle comprising (i) a nucleic acid; (ii) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (iii) a phospholipid; and (iv) cholesterol.

[0205] In certain embodiments, the lipid nanoparticle provided herein further comprises a conjugated lipid. In certain embodiments, the conjugated lipid comprises a polyethylene glycol (PEG)-conjugated lipid. In certain embodiments, the conjugated lipid is a PEG-conjugated lipid.

[0206] Thus, in one embodiment, provided herein is a lipid nanoparticle comprising (i) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (ii) a phospholipid; (iii) cholesterol; and (iv) a PEG-conjugated lipid.

[0207] In another embodiment, provided herein is a lipid nanoparticle comprising (i) a nucleic acid; (ii) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (iii) a phospholipid; (iv) cholesterol; and (v) a PEG-conjugated lipid.Attorney Docket No.277A002WO01

[0208] In certain embodiments, the nucleic acid is a DNA. In certain embodiments, the nucleic acid is an RNA. In certain embodiments, the nucleic acid is an mRNA. In certain embodiments, the nucleic acid is an siRNA. In certain embodiments, the nucleic acid is an antisense oligonucleotide.

[0209] In certain embodiments, the phospholipid is dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), 1,2-dielaidoylphosphatidylethanolamine, dimyristoylphosphatidylethanolamine (DMPE), dioleoylphosphatidylethanolamine (DOPE), dipalmitoylphosphatidylethanolamine (DPPE), distearoylphosphatidylethanolamine (DSPE), palmitoyloleoylphosphatidylethanolamine (POPE), 1-stearoyl-2-oleoylphosphatidyethanolamine (SOPE), 1,2-dipalmitoylphosphatidyl-N-methylethanolamine, 1,2-dipalmitoylphosphatidyl-N,N- dimethylethanolamine, dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), palmitoyloleoylphosphatidylcholine (POPC), or a combination thereof.

[0210] In certain embodiments, the PEG-conjugated lipid is a PEG-diacylglycerol (DAG), a PEG-dialkyloxypropyl (DAA), a PEG-phospholipid, a PEG-ceramide, or a combination thereof. In certain embodiments, the PEG-conjugated lipid is 2-(polyethylene glycol)-N,N-ditetradecylacetamide (ALC-0159), 1,2-dimyristoyl-sn-glycero-3-methoxy- polyethylene glycol (PEG-DMG), PEG-c-DMG, PEG-DSG, PEG-DSPE, or a combination thereof. Pharmaceutical Compositions

[0211] In one embodiment, provided herein is a pharmaceutical composition comprising a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; and a pharmaceutically acceptable excipient.

[0212] In another embodiment, provided herein is a pharmaceutical composition comprising a lipid nanoparticle that comprises a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two orAttorney Docket No.277A002WO01 more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; and a pharmaceutically acceptable excipient.

[0213] In yet another embodiment, provided herein is a pharmaceutical composition comprising a lipid nanoparticle and a pharmaceutically acceptable excipient; wherein the lipid nanoparticle comprises (i) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (ii) a phospholipid; and (iii) cholesterol.

[0214] In yet another embodiment, provided herein is a pharmaceutical composition comprising a lipid nanoparticle and a pharmaceutically acceptable excipient; wherein the lipid nanoparticle comprises (i) a therapeutic agent and (ii) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0215] In yet another embodiment, provided herein is a pharmaceutical composition comprising a lipid nanoparticle and a pharmaceutically acceptable excipient; wherein the lipid nanoparticle comprises (i) a therapeutic agent; (ii) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (iii) a phospholipid; and (iv) cholesterol.

[0216] In yet another embodiment, provided herein is a pharmaceutical composition comprising a lipid nanoparticle and a pharmaceutically acceptable excipient; wherein the lipid nanoparticle comprises (i) a nucleic acid and (ii) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.Attorney Docket No.277A002WO01

[0217] In still another embodiment, provided herein is a pharmaceutical composition comprising a lipid nanoparticle and a pharmaceutically acceptable excipient; wherein the lipid nanoparticle comprises (i) a nucleic acid; (ii) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (iii) a phospholipid; and (iv) cholesterol.

[0218] In certain embodiments, the pharmaceutical composition provided herein further comprises a conjugated lipid. In certain embodiments, the conjugated lipid comprises a PEG- conjugated lipid.

[0219] Thus, in one embodiment, provided herein is a pharmaceutical composition comprising a lipid nanoparticle and a pharmaceutically acceptable excipient; wherein the lipid nanoparticle comprises (i) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (ii) a phospholipid; (iii) cholesterol; and (iv) PEG-conjugated lipid.

[0220] In another embodiment, provided herein is a pharmaceutical composition comprising a lipid nanoparticle and a pharmaceutically acceptable excipient; wherein the lipid nanoparticle comprises (i) a nucleic acid; (ii) a compound provided herein, e.g., a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (iii) a phospholipid; (iv) cholesterol; and (v) PEG-conjugated lipid.

[0221] In certain embodiments, the therapeutic agent is a nucleic acid. In certain embodiments, the nucleic acid is a DNA. In certain embodiments, the nucleic acid is an RNA. In certain embodiments, the nucleic acid is an mRNA. In certain embodiments, the nucleic acid is an siRNA. In certain embodiments, the nucleic acid is an antisense oligonucleotide.Attorney Docket No.277A002WO01

[0222] In certain embodiments, the phospholipid is DPPG, DMPE, DOPE, DPPE, DSPE, POPE, SOPE, 1,2-dipalmitoylphosphatidyl-N-methylethanolamine, 1,2-dipalmitoylphosphatidyl- N,N-dimethylethanolamine, DOPC, DPPC, DSPC, POPC, or a combination thereof.

[0223] In certain embodiments, the PEG-conjugated lipid is a DAG, DAA, PEG- phospholipid, PEG-ceramide, or a combination thereof. In certain embodiments, the PEG- conjugated lipid is ALC-0159, PEG-DMG, PEG-c-DMG, PEG-DSG, PEG-DSPE, or a combination thereof.

[0224] The disclosure will be further understood by the following non-limiting examples. EXAMPLES

[0225] As used herein, the symbols and conventions used in these processes, schemes and examples, regardless of whether a particular abbreviation is specifically defined, are consistent with those used in the contemporary scientific literature, for example, the Journal of the American Chemical Society, the Journal of Medicinal Chemistry, or the Journal of Biological Chemistry. Specifically, but without limitation, the following abbreviations may be used in the examples and throughout the specification: g (grams); mg (milligrams); mL (milliliters); ^L (microliters); mM (millimolar); ^M (micromolar); mmol (millimoles); min (minute or minutes); h (hour or hours); ACN (acetonitrile); DCC (N,N’-dicyclohexylcarbodiimide); DCM (dichloro- methane); DMAP (4-dimethylaminopyridine); DMF (dimethylformamide); EDCI (1-ethyl-3-(3- dimethylaminopropyl)carbodiimide); MeOH (methanol); Ms (methanesulfonyl); TEA or Et3N (triethylamine); MS (mass spectrometry); NMR (nuclear magnetic resonance); and prep-HPLC (preparative high performance liquid chromatography).

[0226] For all of the following examples, standard work-up and purification methods known to those skilled in the art can be utilized. Unless otherwise indicated, all temperatures are expressed in ºC (degrees Centigrade). All reactions are conducted at room temperature unless otherwise specified. Synthetic methodologies illustrated herein are intended to exemplify the applicable chemistry through the use of specific examples and are not indicative of the scope of the disclosure. Example 1Attorney Docket No.277A002WO01 Preparation of 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane-1,3- diyl dioleate A001

[0227] Scheme 1 O

[0228] Preparation of 2-(bromomethyl)-2-((oleoyloxy)methyl)propane-1,3-diyl dioleate 1.2. To a solution of oleic acid (18.4 g, 65.1 mmol) in DCM (300 mL) was added EDCI ^HCl (12.5 g, 65.2 mmol). After the mixture was stirred under Ar for 10 min, a solution of 2- (bromomethyl)-2-(hydroxymethyl)propane-1,3-diol (3.9 g, 19.6 mmol) in DCM (16 mL) and ACN (4 mL) was added, followed by addition of DMAP (1.96 mmol). After stirring under Ar for 18-32 h, the reaction mixture was concentrated under vacuum, dispersed in DCM (200 mL), washed with saturated brine (150 mL x 2), dried over anhydrous Na2SO4, and concentrated toAttorney Docket No.277A002WO01 yield a crude product (22 g), which was purified by silica-gel flash chromatography to afford compound 1.2 (13.2 g) in 61% yield.1H NMR (400 MHz, CDCl3) δ 5.33 (m, 6H), 4.12 (s, 6H), 3.45 (s, 2H), 2.30 (t, J = 7.3 Hz, 6H), 2.00 (q, 12H), 1.59 (m, 6H), 1.29-1.25 (b, 62H), 0.88 (t, J = 6.9 Hz, 9H).

[0229] Preparation of 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-((oleoyloxy)- methyl)propane-1,3-diyl dioleate A001. A mixture of potassium 4-(dimethylamino)butanoate (0.62 g, 3.66 mmol) in dry DMF (10 mL) was stirred at 70 °C under Ar for 15 min, followed by addition of compound 1.2 (1.2 g, 1.21 mmol) and 18-crown-6 (0.121 mmol) in dry DMF (2 mL). After stirring at 70 °C under Ar for 18-32 h, the reaction mixture was concentrated, dispersed in DCM (20 mL), washed with saturated brine (100 mL x 2), dried over anhydrous Na2SO4, and concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with DCM / MeOH / TEA (80:20:1) to afford compound A001 (0.61 g) in 48% yield.1H NMR (400 MHz, CDCl3) δ 5.33 (m, 6H), 4.09 (s, 8H), 2.61 (b, 2H), 2.46 (s, 6H), 2.41 (t, J = 7.2 Hz, 2H), 2.30 (t, J = 7.4 Hz, 6H), 2.00 (q, 12H), 1.59 (m, 6H), 1.29-1.25 (b, 62H), 0.88 (t, J = 6.9 Hz, 9H); MS (ESI) m / z: 1043.5 [M+H]+. Example 2 Preparation of 2-(((3-(dimethylamino)propyl)amino)methyl)-2-((oleoyloxy)methyl)propane-1,3- diyl dioleate A007

[0230] Compound A007 was prepared as shown in Scheme 2.

[0231] A mixture of compound 1.2 (1.2 g, 1.21 mmol), K2CO3 (0.460 g, 3.3 mmol), KI (0.018 g, 0.1 mmol), and N,N-dimethyl-1,3-propanediamine (0.34 g, 3.3 mmol) in DMF (7 mL) was stirred at 70 °C under Ar for 18-32 h. The reaction mixture was then concentrated and theAttorney Docket No.277A002WO01 residue was dispersed in DCM (20 mL), washed with saturated brine (100 mL x 2), dried over anhydrous Na2SO4, and concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with MeOH in DCM to afford compound A007 (17 mg) in 10% yield. MS (ESI) m / z: 1014.9 [M+H]+.Preparation of 2-(3-(dimethylamino)propanamido)-2-((((Z)-hexadec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A101

[0232] Compound A101 is prepared as shown in Scheme 3.Attorney Docket No.277A002WO01Preparation of 2-(3-(dimethylamino)propanamido)-2-(((octadecylcarbamoyl)oxy)methyl)- propane-1,3-diyl bis(octadecylcarbamate) A102

[0233] Compound A102 is prepared as shown in Scheme 4.Attorney Docket No.277A002WO01 Example 5 Preparation of O,O’-(2-(3-(dimethylamino)propanamido)-2-(((octadecylcarbamothioyl)oxy)- methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A103

[0234] Example 6 Preparation of N-(1,3-bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(dimethylamino)propanamide A104

[0235] Compound A104 is prepared as shown in Scheme 6.Attorney Docket No.277A002WO01Preparation of 2-(3-(3-(dimethylamino)propyl)ureido)-2-((((Z)-hexadec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A105

[0236] asExample 8Attorney Docket No.277A002WO01 Preparation of 2-(3-(3-(dimethylamino)propyl)ureido)-2-(((octadecylcarbamoyl)oxy)methyl)- propane-1,3-diyl bis(octadecylcarbamate) A106Preparation of O,O’-(2-(3-(3-(dimethylamino)propyl)ureido)-2-(((octadecylcarbamothioyl)oxy)- methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A107

[0238] Compound A107 is prepared as shown in Scheme 9.Attorney Docket No.277A002WO01Preparation of 1-(1,3-bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(3-(dimethylamino)propyl)urea A108

[0239] Compound A108 is prepared as shown in Scheme 10.Example 11 Preparation of 2-(3-(3-(dimethylamino)propyl)thioureido)-2-((((Z)-hexadec-9-enoyl)oxy)-Attorney Docket No.277A002WO01 methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A109

[0240] Preparation of 2-(3-(3-(dimethylamino)propyl)thioureido)-2-(((octadecylcarbamoyl)oxy)- methyl)propane-1,3-diyl bis(octadecylcarbamate) A110Attorney Docket No.277A002WO01

[0241] Compound A110 is prepared as shown in Scheme 12.Preparation of O,O’-(2-(3-(3-(dimethylamino)propyl)thioureido)-2-(((octadecylcarbamothioyl)- oxy)methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A111asExample 14 Preparation of 3-(dimethylamino)propyl (3-(octadecyloxy)-2,2-bis((octadecyloxy)methyl)propyl)Attorney Docket No.277A002WO01 carbonate A151

[0243]

[0244] Preparation of 3-(octadecyloxy)-2,2-bis((octadecyloxy)methyl)propan-1-ol 14.2. A mixture of pentaerythritol (1.36 g, 10 mmol), 1-bromooctadecane 14.1 (20 g, 60 mmol), and NaOH (4 g, 100 mmol) in DMSO (200 mL) was stirred for 5 days. The reaction mixture was then extracted with EtOAc. The combined organic layers were concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound 14.2 (3.4 g) in 38% yield.1H NMR (300 MHz, CDCl3) δ 3.70 (s, 1H), 3.43 (s, 1H),3.40-3.33 (m, 8H), 1.56-1.51 (m, 7H),(m, 94H), 0.89-0.86 (m, 9H); MS (ESI)Attorney Docket No.277A002WO01 m / z: 893.6 [M+H]+.

[0245] Preparation of 3-(dimethylamino)propyl (3-(octadecyloxy)-2,2-bis((octadecyl- oxy)methyl)propyl) carbonate A151. A mixture of compound 14.2 (1.2 g, 1.4 mmol), pyridine (220 µL, 2.8 mmol), DMAP (34 mg, 0.3 mmol), and bis(4-nitrophenyl) carbonate (630 mg, 2 mmol) in ACN was stirred for 16 h. 3-Diethylamino-1-propanol (600 µL, 4.2 mmol) was then added. After stirring for 16 h, the reaction mixture was concentrated, diluted with hexanes, washed with water, and concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound A151 (410 mg) in 28% yield. Example 15A Preparation of 2-(azetidin-1-ylmethyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A201

[0246] asAttorney Docket No.277A002WO01 Example 15B Preparation of 2-(((3-(dimethylamino)propyl)(methyl)amino)methyl)-2-((oleoyloxy)methyl)- propane-1,3-diyl dioleate A225 O O

[0247]

[0248] A mixture of 2-(N,N-dimethylamino-3-methylaminopropane)-2-methylhydroxy- 1,3-propanol 15.1b (1.06 g), EDCI (3.45 g), and DMAP (0.54 g) in DMF (40 mL) was stirred at 22 °C under Ar for 15 min, followed by addition of oleic acid (4.34 g). After stirring for 24 h, the reaction mixture was concentrated, diluted with DCM, washed with saturated brine (2 × 150 mL), dried over anhydrous Na2SO4, concentrated, and purified by silica gel column chromatography eluting with isopropanol / acetonitrile buffer to afford compound A225 (1.1 g) in 24% yield.1H NMR (400 MHz, CDCl3) δ 5.19 (m, 6H), 3.89 (s, 6H), 2.95 (m, 2H), 2.70 (s, 6H), 2.36 (m, 4H), 2.18 (t, 6H), 2.11 (s, 3H), 1.86 (m, 14H), 1.47 (q, 6H), 1.42-1.16 (b, 62H), 0.74 (t, 9H); MS (ESI) m / z: 1028.6 [M+H]+.Attorney Docket No.277A002WO01 Example 16 Preparation of 1-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2- yl oleate B002

[0249] Preparation of 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B101Attorney Docket No.277A002WO01

[0250] Compound B101 is prepared as shown in Scheme 17.Preparation of 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B201

[0251] Compound B201 is prepared as shown in Scheme 18.Attorney Docket No.277A002WO01Preparation of 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) B401

[0252] Compound B401 was prepared as shown in Scheme 19.

[0253] (2,2-Dimethyl-1,3-dioxan-5-yl)methyl 6-bromohexanoate 19.3. A mixture of 6- bromohexanoic acid 19.1 (19.5 g, 100 mmol), (2,2-dimethyl-1,3-dioxan-5-yl)methanol 19.2 (14.6 g, 100 mmol), DCC (22.7 g, 110 mmol), and DMAP (1.22 g, 10 mmol) in DCM (200 mL) was stirred overnight. The reaction mixture was then concentrated and the residue was suspended in hexanes (200 mL) and filtered through celite. The organic phase was concentratedAttorney Docket No.277A002WO01 to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound 19.3 (29.7 g) in 92% yield.1H NMR (300 MHz, CDCl3) δ 4.17 (d, J = 7.1 Hz, 2H), 3.99 (dd, J = 12.0, 4.1 Hz, 2H), 3.73 (dd, J = 12.0, 5.8 Hz, 2H), 3.40 (t, J = 6.7 Hz, 2H), 2.34 (t, J = 7.4 Hz, 2H), 2.04-1.75 (m, 1H), 1.92-1.82 (m, 2H), 1.71-1.60 (m, 2H), 1.52-1.47 (m, 2H), 1.44 (s, 3H), 1.40 (s, 3H).

[0254] Preparation of 3-hydroxy-2-(hydroxymethyl)propyl 6-bromohexanoate 19.4. A mixture of compound 19.3 (4.77 g, 14.8 mmol) and DOWEX 50WX8-H (4.77 g, 100 mass %) in MeOH (50 mL) was stirred overnight. The reaction mixture was then filtered through celite. The organic solution was concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound 19.4 (1.92 g) in 46% yield.1H NMR (300 MHz, CDCl3) δ 4.27 (d, J = 6.3 Hz, 2H), 3.82-3.71 (m, 4H), 3.41 (t, J = 6.7 Hz, 2H), 2.39-2.31 (m, 4H), 2.04 (hept, J = 5.1 Hz, 1H), 1.93-1.83 (m, 2H), 1.72-1.61 (m, 2H), 1.53- 1.43 (m, 2H).Attorney Docket No.277A002WO01

[0255] Preparation of 2-(((6-bromohexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) 19.5. A mixture of compound 19.4 (2.63 g, 9.3 mmol), linoleic acid (5.22 g, 18.6 mmol), DCC (4.02 g, 19.5 mmol), DMAP (114 mg, 0.93 mmol) in DCM (90 mL) was stirred overnight. The reaction mixture was then concentrated and the residue was suspended in hexanes (100 mL) and filtered through celite. The organic phase was concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound 19.5 (4.59 g) in 61% yield.1H NMR (300 MHz, CDCl3) δ 5.43-5.28 (m, 8H), 4.13 (d, J = 6.0 Hz, 6H), 3.41 (t, J = 6.7 Hz, 2H), 2.77 (t, J = 5.9 Hz, 4H), 2.43-2.28 (m, 7H), 2.05 (q, J = 6.8 Hz, 8H), 1.92-1.83 (m, 2H), 1.70-1.56 (m, 8H), 1.52-1.44 (m, 2H), 1.38-1.26 (m, 29H), 0.91-0.86 (m, 9H).

[0256] Preparation of 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3- diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) B401. A mixture of compound 19.5 (1 g, 1.24 mmol) and KI (41 mg, 0.25 mmol) in DMF was stirred for about 5 min until the KI was fully dissolved. 3-Hydroxyazetidine hydrochloride (679 mg, 6.2 mmol) and KOH (348 mg, 6.2 mmol) were then added. After stirring for 16 h, the reaction mixture was diluted with EtOAc, washed with water, and concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound B401 (440 mg) in 45% yield.1H NMR (400 MHz, CDCl3) δ 5.41-5.30 (m, 8H), 4.49-4.42 (m, 1H), 4.12 (d, J = 6.0 Hz, 6H), 3.71 (q, J = 7.9 Hz, 2H), 3.02-2.96 (m, 2H), 2.77 (t, J = 6.8 Hz, 4H), 2.51 (q, J = 7.8 Hz, 2H), 2.39 (p, J = 6.2 Hz, 1H), 2.31 (td, J = 7.6, 2.0 Hz, 6H), 2.05 (q, J = 6.9 Hz, 6H), 1.93- 1.83 (m, 2H), 1.66-1.56 (m, 6H), 1.41-1.26 (m, 33H), 0.90-0.87 (m, 6H); MS (ESI) m / z: 800.7 [M+H]+. Example 20 Preparation of 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2- hexyldecanoate) B404Attorney Docket No.277A002WO01

[0257]

[0258] propane- (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) 20.1. A mixture of 2-hexyldecanoic acid (7.93 g, 30.9 mmol), 3-hydroxy-2-(hydroxymethyl)propyl 6-bromohexanoate 19.4 (4.38 g, 15.5 mmol), DCC (6.81 g, 33 mmol), and DMAP (1.83 g, 1.5 mmol) in DCM (150 mL) was stirred overnight. The reaction mixture was then concentrated and the residue was suspended in hexanes (100 mL) and filtered through celite. The organic phase was concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound 20.1 (3.27 g) in 28% yield.1H NMR (300 MHz, CDCl3) δ 4.13 (d, J = 6.1 Hz, 6H),Attorney Docket No.277A002WO01 3.40 (t, J = 6.7 Hz, 2H), 2.40 (dt, J = 11.3, 5.7 Hz, 1H), 2.34 (dd, J = 8.0, 6.8 Hz, 4H), 1.91-1.79 (m, 4H), 1.69-1.55 (m, 4H), 1.50-1.40 (m, 6H), 1.31-1.19 (m, 40H), 0.89-0.85 (m, 12H).

[0259] Preparation of 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3- diyl bis(2-hexyldecanoate) B404. A mixture of compound 20.1 (500 mg, 0.66 mmol) and KI (109.2 mg, 0.66 mmol) in DMC was stirred for about 5 min until KI was fully dissolved. 3- Hydroxyazetidine hydrochloride (360 mg, 3.3 mmol) and KOH (185 mg, 3.3 mmol) were then added. After stirring for 16 h, the reaction mixture was diluted with EtOAc, washed with water, and concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound B404 (140 g) in 28% yield.1H NMR (400 MHz, CDCl3) δ 4.44 (p, J = 5.8 Hz, 1H), 4.12 (d, J = 6.4 Hz, 6H), 3.67 (t, J = 6.7 Hz, 2H), 2.94 (t, J = 7.2 Hz, 2H), 2.46 (t, J = 7.0 Hz, 2H), 2.4-2.25 (m, 5H), 1.57-1.50 (m, 6H), 1.50-1.15 (m, 49H), 0.87 (t, J = 6.8 Hz, 12H); MS (ESI) m / z: 752.4 [M+H]+. Example 21 Preparation of di(heptadecan-9-yl) O,O'-(2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)- oxy)methyl)propane-1,3-diyl) diadipate B416

[0260] was as

[0261] Preparation of 6-(heptadecan-9-yloxy)-6-oxohexanoic acid 21.4. A mixture of heptadecan-9-ol 21.1 (10.26 g, 40 mmol), 6-(heptadecan-9-yloxy)-6-oxohexanoic acid 21.2 (9.45 g, 40 mmol), DCC (9.28 g, 45 mmol), and DMAP (1.01 g, 8 mmol) in DCM (400 mL) was stirred overnight. The reaction mixture was then concentrated and the residue was suspended in hexanes (200 mL). The resulting precipitates were collected by filtration and redissolved in EtOH (200 mL). Pd / C (10%, 0.2 mass%) was then added under Ar. After stirring under hydrogen overnight, the reaction mixture was filtered through celite. The organic phase wasAttorney Docket No.277A002WO01 concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound 21.4 (16.78 g). MS (ESI) m / z: 385.7 [M+H]+.propane- di(heptadecan-9-yl) diadipate 21.5. A mixture of 3-hydroxy-2-(hydroxymethyl)propyl 6- bromohexanoate 19.4 (3.4 g, 12 mmol), compound 21.4 (9.23 g, 24 mmol), DCC (5.78 g, 28 mmol), and DMAP (631 mg, 5 mmol) in DCM (120 mL) was stirred overnight. The reaction mixture was then concentrated and the residue was suspended in hexanes (100 mL) and filtered through celite. The organic phase was concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound 21.5 (6.7 g) in 55% yield. MS (ESI) m / z: 1035.1 [M+H]+.Attorney Docket No.277A002WO01

[0263] Preparation of di(heptadecan-9-yl) O,O'-(2-(((6-(3-(hydroxymethyl)azetidin-1- yl)hexanoyl)-oxy)methyl)propane-1,3-diyl) diadipate B416. A mixture of compound 21.5 (1.52 g, 1.5 mmol) and KI (250 mg, 1.5 mmol) in DMF was stirred for about 5 min until KI was fully dissolved. Azetidine-3-ylmethanol hydrochloride (927 mg, 7.5 mmol) and KOH (421 mg, 7.5 mmol) were then added. After stirring for 16 h, the reaction mixture was diluted with EtOAc, washed with water, and concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with MeOH in DCM to afford compound B416 (850 mg) in 56% yield.1H NMR (400 MHz, CDCl3) δ 4.85 (p, J = 6.3 Hz, 2H), 4.12 (d, J = 6.6 Hz, 6H), 3.74 (d, J = 6.2 Hz, 2H), 3.33 (t, J = 6.8 Hz, 2H), 3.11-3.08 (m, 2H), 2.67-2.59 (m, 1H), 2.44-2.28 (m, 14H), 1.67-1.63 (m, 10H), 1.49 (q, J = 6.4 Hz, 8H), 1.35-1.25 (m, 52H), 0.87 (t, J = 6.8 Hz, 12H); MS (ESI) m / z: 1022.5 [M+H]+. Example 22 Preparation of 2-((3-(azetidin-1-yl)propanoyl)oxy)propane-1,3-diyl dioleate B444

[0264] was asAttorney Docket No.277A002WO01

[0265] Preparation of 2-hydroxypropane-1,3-diyl dioleate 22.2. To a solution of glycerol 22.1 (921 mg, 10 mmol), oleic acid (7.06 g, 25 mmol), and 4-dimethylaminopyridine (252 mg, 2 mmol) in (100 mL) was added EDCI ^HCl (5.75 g, 30 mmol). After stirring at room temperature overnight, the reaction mixture was diluted with water (100 mL) and extracted with hexanes (200 mL x 3). The combined organic layers were concentrated and then purified by silica gel column chromatography eluting with acetone / hexanes to afford compound 22.2 (1.75 g) in 28% yield.1H NMR (400 MHz, CDCl3): δ 5.38 (m, 4H), 4.25-4.00 (m, 5H), 2.46 (m, 1H), 2.35 (m, 4H), 2.01 (m, 8H), 1.63 (m, 6H), 1.39-1.19 (m, 42H), 0.88 (m, 6H).

[0266] Preparation of 2-(acryloyloxy)propane-1,3-diyl dioleate 22.3. To a solution of compound 22.2 (1.75 g, 2.8 mmol) in EtOAc (100 mL) was added acryloyl chloride (344 μL, 4.2 mmol), followed by addition of TEA (1.2 mL, 8.5 mmol). After stirring for 5 h, the reaction mixture was diluted with EtOAc (200 mL) and washed with water (100 mL x 3). The organic layer was concentrated and then purified by silica gel column chromatography eluting with acetone / hexanes to afford compound 22.3 (670 mg) in 35% yield.

[0267] Preparation of 2-((3-(azetidin-1-yl)propanoyl)oxy)propane-1,3-diyl dioleate B444. To a solution of compound 22.3 (670 g, 1 mmol) in isopropyl alcohol (50 mL) were added azetidine hydrochloride (468 mg, 5 mmol) and KOH (281 mg, 5 mmol). After stirring for 16 h, the reaction mixture was diluted with EtOAc (200 mL), washed with water (100 mL x 3), and concentrated to afford compound B444. MS (ESI) m / z: 733.2 [M+H]+. Example 23 Preparation of (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(4-(2-hydroxyethyl)- piperazin-1-yl)pentanoate B501

[0268] Compound B501 was prepared as shown in Scheme 23.

[0269] Preparation of (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-bromo-Attorney Docket No.277A002WO01 pentanoate 23.2. A mixture of 5-bromopentanoic acid (2.17 g, 12 mmol), (6Z,16Z)-12-((Z)-dec- 4-en-1-yl)docosa-6,16-dien-11-ol 23.1 (4.61 g, 10 mmol), DCC (2.68 g, 13 mmol), and DMAP (244 mg, 2 mmol) in DCM (100 mL) was stirred overnight. The reaction mixture was then concentrated and the residue was suspended in hexanes (100 mL) and filtered through celite. The organic phase was concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound 23.2 (4.85 g) in 78% yield.1H NMR (300 MHz, CDCl3) δ 5.42-5.29 (m, 6H), 4.94 (dt, J = 8.4, 4.4 Hz, 1H), 3.41 (t, J = 6.5 Hz, 2H), 2.32 (t, J = 7.2 Hz, 2H), 2.06-1.95 (m, 12H), 1.93-1.86 (m, 2H), 1.82-1.75 (m, 2H), 1.51-1.47 (m, 2H), 1.38-1.23 (m, 29H), 0.88 (t, J = 7.0 Hz, 9H); MS (ESI) m / z: 642.4 [M+H]+.

[0270] - - en- yl 5-(4-(2- hydroxyethyl)-piperazin-1-yl)pentanoate B501. A mixture of compound 23.2 (1 g, 1.6 mmol) and KI (27 mg, 0.16 mmol) was stirred for about 5 min until KI was fully dissolved. 2- (Piperazin-1-yl)ethanol (1.04 g, 8.0 mmol) was then added. After stirring for 16 h, the reaction mixture was diluted with EtOAc, washed with water, and concentrated to yield a crude product, which was purified by silica-gel flash chromatography eluting with acetone in hexanes to afford compound B501 (700 mg) in 65% yield.1H NMR (300 MHz, CDCl3) δ 5.37-5.32 (m, 6H), 4.94Attorney Docket No.277A002WO01 (dt, J = 8.4, 4.5 Hz, 1H), 3.63 (t, J = 5.4 Hz, 2H), 2.60-2.52 (m, 8H), 2.38 (t, J = 7.0 Hz, 2H), 2.31 (t, J = 7.4 Hz, 2H), 2.03-1.98 (m, 12H), 1.69-1.42 (m, 7H), 1.34-1.29 (m, 30H), 0.91-0.86 (m, 9H); MS (ESI) m / z: 673.4 [M+H]+. Example 24 Preparation of 2-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)propane-1,3-diyl dioleate B701

[0271]

[0272] Preparation of 2-(((methylsulfonyl)oxy)methyl)propane-1,3-diyl dioleate 24.2. To a solution of 2-(hydroxymethyl)propane-1,3-diyl dioleate 24.1 (1.5 g, 2.4 mmol) in DCM (100 mL) were added MsCl (183 μL, 2.4 mmol) and TEA (700 μL, 5 mmol). After stirring for 5 h, the reaction mixture was diluted with EtOAc (200 mL) and washed with water (100 mL x 3). The organic layer was concentrated and then purified by silica gel column chromatography eluting with acetone / hexanes to afford compound 24.2 (1.68 g) in a quantitative yield.1H NMR (400 MHz, CDCl3) δ 5.38 (m, 4H), 4.28 (d, J = 6.0 Hz, 2H), 4.17 (m, 4H), 3.03 (s, 3H), 2.49 (m,Attorney Docket No.277A002WO01 1H), 2.32 (m, 4H), 2.01 (m, 8H), 1.66 (m, 6H), 1.35-1.20 (m, 42H), 0.88 (t, J = 7.2 Hz, 6H).

[0273] Preparation of 2-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)propane-1,3-diyl dioleate B701. To a solution of compound 24.2 (713 mg, 1 mmol) and KI (166 mg, 1 mmol) in DMF (50 mL) was added 2-(piperazin-1-yl)ethanol (651 mg, 5 mmol. After stirring for 16 h at 65 °C, the reaction mixture was diluted with EtOAc (300 mL) and washed with water (200 mL x 3). The organic layer was concentrated and then purified by silica gel column chromatography eluting with MeOH / DCM to afford compound B701 (520 mg) in 70% yield.1H NMR (400 MHz, CDCl3) δ 5.36 (m, 4H), 4.16 (m, 2H), 4.04 (m, 2H), 3.68 (m, 1H), 2.85-2.42 (m, 10H), 2.37 (m, 2H), 2.29 (m, 4H), 2.25 (m, 1H), 2.01 (m, 8H), 1.62 (m, 4H), 1.39-1.19 (m, 42H), 0.88 (t, J = 7.2 Hz, 6H). MS (ESI) m / z: 747.5 [M+H]+. Example 25 Preparation of 7-hydroxy-7-(4-((1-methylpiperidine-4-carbonyl)oxy)butyl)tridecane-1,13-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A061 Owas as

[0275] Preparation of 7-hydroxy-7-(4-((1-methylpiperidine-4-carbonyl)oxy)butyl)- tridecane-1,13-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A061. A mixture of 7-(4-((-1-methyl- piperidine-4-carbonyl)oxy-butyl)tridecane-1,13-diol 25.1 (1.07 g, 2.28 mmol), DCC (1.03 g, 5.01 mmol), and DMAP (0.56 g, 4.56 mmol) in ACN (20 mL) was stirred at 22 °C under Ar for 15 min, followed by addition of palmitoleic acid (1.27 g, 5.01 mmol). After stirring for 24 h, the reaction mixture was concentrated, diluted with DCM, washed with saturated brine (2 × 150 mL), dried over anhydrous Na2SO4, concentrated, and purified by silica-gel column chromatography eluting with DCM / MeOH to afford compound A061 (0.81 g) in 39% yield.1H NMR (400 MHz, CDCl3) δ 5.33 (m, 4H), 4.09 (t, J = 7.2 Hz, 2H), 4.04 (t, J = 7.1 Hz, 4H), 2.96Attorney Docket No.277A002WO01 (br s, 2H), 2.44 (m, 4H), 2.27 (t, J = 7.4 Hz, 4H), 1.99 (m, 10H), 1.61 (m, 10H), 1.50-1.23 (m, 56H), 0.87 (t, J = 6.9 Hz, 6H); MS (ESI) m / z: 902.7 [M+H]+.procedures or methodologies exemplified herein.

[0277] 2-((Oleoyloxy)methyl)-2-(((4-(pyrrolidin-1-yl)butanoyl)oxy)methyl)propane-1,3- diyl dioleate A002.1H NMR (300 MHz, CDCl3) δ 5.33 (m, 6H), 4.09 (s, 8H), 2.48 (m, 6H), 2.35 (t, 2H), 2.27 (t, J = 7.4 Hz, 6H), 2.00 (m, 12H), 1.82 (m, 2H), 1.74 (m, 4H), 1.59 (m, 6H), 1.29- 1.25 (b, 62H), 0.88 (t, J = 6.9 Hz, 9H); MS (ESI) m / z: 1069.6 [M+H]+.

[0278] 2-(((5-(Dimethylamino)pentanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane- 1,3-diyl dioleate A003.1H NMR (400 MHz, CDCl3): δ 5.33 (m, 6H), 4.09 (s, 8H), 2.61 (b, 2H), 2.46 (s, 6H), 2.41 (t, J = 7.2 Hz, 2H), 2.30 (t, J = 7.4 Hz, 6H), 2.00 (q, 12H), 1.66 (b, 2H), 1.59 (m, 6H), 1.29-1.25 (b, 62H), 0.88 (t, J = 6.9 Hz, 9H); MS (ESI) m / z: 1057.2 [M+H]+.Attorney Docket No.277A002WO01

[0279] propane-1,3- diyl dioleate A004. MS (ESI) m / z: 1097.6 [M+H]+.

[0280] - 1,3-diyl dioleate A005. MS (ESI) m / z: 1099.4 [M+H]+.

[0281] 2-(((5-(4-Methylpiperazin-1-yl)pentanoyl)oxy)methyl)-2- ((oleoyloxy)methyl)propane-1,3-diyl dioleate A006. MS (ESI) m / z: 1112.0 [M+H]+.Attorney Docket No.277A002WO01

[0282] 2-((Oleoyloxy)methyl)-2-(((3-(pyrrolidin-1-yl)propanoyl)oxy)methyl)propane- 1,3-diyl dioleate A008.1H NMR (300 MHz, CDCl3): δ 5.33 (m, 6H), 4.12 (s, 2H), 4.09 (s, 6H), 3.34 (t, 2H), 3.08 (t, 2H), 2.27 (t, J = 7.4 Hz, 6H), 2.15 (b, 3H), 1.99 (m, 12H), 1.58 (m, 6H), 1.29-1.25 (b, 66H), 0.88 (t, J = 6.9 Hz, 9H); MS (ESI) m / z: 1055.5 [M+H]+.

[0283] propane- 1,3-diyl dioleate A009.1H NMR (400 MHz, CDCl3): δ 5.33 (m, 6H), 4.13 (s, 2H), 4.09 (s, 6H), 3.31 (t, 2H), 3.02 (t, 2H), 2.79 (s, 6H), 2.30 (t, J = 7.4 Hz, 6H), 2.00 (m, 12H), 1.59 (m, 6H), 1.29-1.25 (b, 62H), 0.88 (t, J = 6.9 Hz, 9H); MS (ESI) m / z: 1029.6 [M+H]+. O

[0284] 2-(((3-Morpholinopropanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane-1,3-diyl dioleate A010. MS (ESI) m / z: 1071.5 [M+H]+.

[0285] 2-(((3-(4-Methylpiperazin-1-yl)propanoyl)oxy)methyl)-2-((oleoyloxy)methyl)- propane-1,3-diyl dioleate A011. MS (ESI) m / z: 1084.2 [M+H]+.Attorney Docket No.277A002WO01

[0286] 9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) A012. MS (ESI) m / z: 1050.9 [M+H]+.

[0287] - - 9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) A013. MS (ESI) m / z: 1037.5 [M+H]+.

[0288] 2-(((3-(Dimethylamino)propanoyl)oxy)methyl)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A014. MS (ESI) m / z: 1023 [M+H]+.Attorney Docket No.277A002WO01

[0289] - docosa-4,7,10,13,16,19-hexaenoyl)oxy)methyl)propane-1,3-diyl (4Z,4'Z,7Z,7'Z,10Z,10'Z,13Z,13'Z,16Z,16'Z,19Z,19'Z)-bis(docosa-4,7,10,13,16,19-hexaenoate) A015.

[0290] 2-(((4-(Dimethylamino)butanoyl)oxy)methyl)-2-(hydroxymethyl)propane-1,3- diyl dioleate A051. MS (ESI) m / z: 778.7 [M+H]+.

[0291] 2-(((4-(Dimethylamino)butanoyl)oxy)methyl)-2-(hydroxymethyl)propane-1,3- diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A052. MS (ESI) m / z: 774.5 [M+H]+.Attorney Docket No.277A002WO01

[0292] 7-Hydroxy-7-(4-((1-methylpiperidine-4-carbonyl)oxy)butyl)tridecane-1,13-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A062.1H NMR (400 MHz, CDCl3) δ 5.37 (m, 8H), 4.12 (t, J = 7.2 Hz, 2H), 4.07 (t, J = 7.2 Hz, 4H), 3.03 (m, 2H), 2.79 (t, J = 6.8 Hz, 4H), 2.46 (m, 5H), 2.31 (t, J = 7.2 Hz, 4H), 2.03 (m, 13H), 1.64 (m, 10H), 1.50-1.23 (m, 46H), 0.91 (t, J = 6.9 Hz, 6H); MS (ESI) m / z: 955.3 [M+H]+.undecyl 1-methylpiperidine-4-carboxylate A063.1H NMR (400 MHz, CDCl3) δ 5.33 (m, 2H), 4.07 (t, J = 6.9 Hz, 2H), 4.04 (t, J = 7.1 Hz, 4H), 2.90 (m, 2H), 2.31 (m, 4H), 2.27 (t, J = 7.2 Hz, 4H), 1.99 (m, 5H), 1.79 (m, 2H), 1.61 (m, 10H), 1.51-1.12 (m, 56H), 0.86 (t, J = 6.8 Hz, 9H); MS (ESI) m / z: 905.6 [M+H]+.

[0294] 7-(4-(Dimethylamino)butyl)-7-hydroxytridecane-1,13-diyl (9Z,9'Z)-bis(hexadec- 9-enoate) A064.1H NMR (400 MHz, CDCl3) δ 5.33 (m, 4H), 4.04 (t, J = 6.9 Hz, 4H), 2.43 (t, J = 6.8 Hz, 2H), 2.33 (s, 6H), 2.27 (t, J = 7.2 Hz, 4H), 1.99 (m, 9H), 1.62 (m, 10H), 1.49-1.15 (m, 58H), 0.87 (t, J = 6.8 Hz, 9H); MS (ESI) m / z: 804.2 [M+H]+. O

[0295] 7-(4-(Dimethylamino)butyl)-7-hydroxytridecane-1,13-diyl (9Z,9'Z,12Z,12'Z)-Attorney Docket No.277A002WO01 bis(octadeca-9,12-dienoate) A065.1H NMR (400 MHz, CDCl3) δ 5.34 (m, 8H), 4.04 (t, J = 6.8 Hz, 4H), 2.75 (t, J = 6.8 Hz, 4H), 2.38 (t, J = 6.8 Hz, 2H), 2.27 (m, 12H), 2.02 (m, 9H), 1.62 (m, 8H), 1.48 (m, 2H), 1.49-1.18 (m, 52H), 0.87 (t, J = 6.8 Hz, 9H); MS (ESI) m / z: 856.9 [M+H]+.

[0296] 1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) B402.1H NMR (300 MHz, CDCl3) δ 5.39-5.28 (m, 8H), 4.12 (d, J = 6.0 Hz, 6H), 3.71 (t, J = 4.9 Hz, 2H), 2.84-2.66 (m, 12H), 2.50-2.28 (m, 9H), 2.08-2.01 (m, 8H), 1.67-1.56 (m, 9H), 1.36-1.28 (m, 33H), 0.91-0.86 (m, 6H); MS (ESI) m / z: 858.0 [M+H]+.propane- diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) B403.1H NMR (400 MHz, CDCl3) δ 5.40-5.30 (m, 8H), 4.12 (d, J = 6.3 Hz, 6H), 3.76 (dd, J = 5.1, 1.5 Hz, 2H), 3.51-3.39 (m, 2H), 3.30-3.20 (m, 2H), 2.76 (t, J = 6.1 Hz, 4H), 2.59-2.51 (m, 2H), 2.38 (p, J = 6.2 Hz, 1H), 2.31 (dd, J = 8.2, 7.0 Hz, 6H), 2.05 (q, J = 6.9 Hz, 8H), 1.65-1.59 (m, 7H), 1.42-1.25 (m, 33H), 0.90-0.87 (m, 6H); MS (ESI) m / z: 815.2 [M+H]+.

[0298] 2-(((6-(4-(2-Hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diylAttorney Docket No.277A002WO01 bis(2-hexyldecanoate) B405.1H NMR (400 MHz, CDCl3) δ 4.22 (d, J = 6.1 Hz, 6H), 3.67 (t, J = 6.8 Hz, 2H), 2.70-2.25 (m, 18H), 1.69-1.38 (m, 12H), 1.38-1.17 (m, 43H), 0.90-0.80 (m, 12H); MS (ESI) m / z: 810.1 [M+H]+.

[0299] propane-1,3-diyl ditetradecanoate B406.1H NMR (400 MHz, CDCl3) δ 4.12 (d, J = 6.8 Hz, 6H), 3.62 (t, J = 6.3 Hz, 2H), 2.70-2.43 (m, 9H), 2.43-2.25 (m, 9H), 1.68-1.45 (m, 8H), 1.38-1.20 (m, 44H), 0.93- 0.84 (m, 6H); MS (ESI) m / z: 753.6 [M+H]+.

[0300] propane- B407.1H NMR (400 MHz, CDCl3) δ 4.11 (d, J = 6.8 Hz, 6H), 3.14 (t, J = 7.0 Hz, 4H), 2.37- 2.33 (m, 3H), 2.29 (t, J = 7.2 Hz, 6H), 2.04 (p, J = 7.0 Hz, 2H), 1.64-1.56 (m, 6H), 1.32-1.24 (m, 40H), 0.87 (t, J = 6.8 Hz, 6H); MS (ESI) m / z: 681.0 [M+H]+.

[0301] 2-(((6-(3-Hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B408.1H NMR (400 MHz, CDCl3) δ 4.44 (p, J = 5.86 Hz, 1H), 4.12 (d, J = 6.0 Hz, 6H), 3.68 (dd, J = 8.4, 6.7 Hz, 2H), 2.94 (dd, J = 8.9, 5.5 Hz, 2H), 2.48 (t, J = 7.2 Hz, 2H), 2.38 (p, J = 6.1 Hz, 1H), 2.33-2.28 (m, 6H), 1.95 (brs, 1H), 1.65-1.57 (m, 6H), 1.40-1.25 (m,Attorney Docket No.277A002WO01 44H), 0.88 (t, J = 6.8 Hz, 6H); MS (ESI) m / z: 696.5 [M+H]+.

[0302] 1,3-diyl ditetradecanoate B409.1H NMR (400 MHz, CDCl3) δ 4.12 (d, J = 6.4 Hz, 6H), 3.75 (d, J = 6.6 Hz, 2H), 3.34-3.30 (m, 2H), 3.10-3.07 (m, 2H), 2.63-2.60 (m, 1H), 2.44-2.37 (m, 3H), 2.30 (t, J = 7.1 Hz, 6H), 1.64-1.57 (m, 6H), 1.34-1.25 (m, 45H), 0.87 (t, J = 6.8 Hz, 6H); MS (ESI) m / z: 710.6 [M+H]+.

[0303] propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) B410.1H NMR (400 MHz, CDCl3) δ 5.35-5.32 (m, 4H), 4.12 (d, J = 6.4 Hz, 6H), 3.61 (t, J = 6.5 Hz, 2H), 2.66-2.42 (m, 9H), 2.40-2.28 (m, 10H), 2.03-1.98 (m, 8H), 1.67-1.57 (m, 6H), 1.55-1.48 (m, 2H), 1.34-1.25 (m, 35H), 0.88 (t, J = 6.8 Hz, 6H); MS (ESI) m / z: 805.7 [M+H]+.

[0304] 2-(((6-(Azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)- bis(hexadec-9-enoate) B411.1H NMR (400 MHz, CDCl3) δ 5.35-5.32 (m, 4H), 4.12 (d, J = 6.2 Hz, 6H), 3.20 (t, J = 7.1 Hz, 3H), 2.41-2.36 (m, 2H), 2.30 (t, J = 6.8 Hz, 6H), 2.11-1.98 (m,Attorney Docket No.277A002WO01 12H), 1.64-1.57 (m, 6H), 1.34-1.25 (m, 36H), 0.88 (t, J = 6.8 Hz, 6H); MS (ESI) m / z: 732.6 [M+H]+.

[0305] diyl (9Z,9'Z)- bis(hexadec-9-enoate) B412.1H NMR (400 MHz, CDCl3) δ 5.38-5.30 (m, 4H), 4.45-4.43 (m, 1H), 4.12 (d, J = 6.4 Hz, 6H), 3.70-3.66 (m, 2H), 3.01-2.97 (m, 2H), 2.51-2.47 (m, 2H), 2.38 (p, J = 6.1 Hz, 1H), 2.30 (t, J = 6.8 Hz, 6H), 2.03-1.75 (m, 10H), 1.65-1.59 (m, 6H), 1.34-1.25 (m, 35H), 0.88 (t, J = 6.8 Hz, 6H); MS (ESI) m / z: 748.3 [M+H]+. O

[0306] 2-(((6-(3-(Hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) B413.1H NMR (400 MHz, CDCl3) δ 5.38-5.29 (m, 4H), 4.11 (d, J = 6.4 Hz, 6H), 3.75 (d, J = 6.1 Hz, 2H), 3.28 (t, J = 6.8 Hz, 2H), 3.05 (t, J = 7.2 Hz, 2H), 2.63- 2.58 (m, 1H), 2.41-2.36 (m, 2H), 2.30 (t, J = 6.8 Hz, 6H), 2.03-1.98 (m, 8H), 1.64-1.57 (m, 6H), 1.34-1.27 (m, 38H), 0.87 (t, J = 6.8 Hz, 6H); MS (ESI) m / z: 762.8 [M+H]+.

[0307] 2-(((6-(4-(2-Hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B414.1H NMR (400 MHz, CDCl3) δ 5.38-5.30 (m, 4H), 4.12 (d, J = 6.4 Hz, 6H), 3.66-Attorney Docket No.277A002WO01 3.62 (m, 2H), 2.64-2.58 (m, 10H), 2.41-2.28 (m, 10H), 2.00 (q, J = 6.3 Hz, 8H), 1.67-1.54 (m, 8H), 1.33-1.26 (m, 42H), 0.87 (t, J = 7.1 Hz, 6H); MS (ESI) m / z: 861.9 [M+H]+.diyl dioleate B415.1H NMR (400 MHz, CDCl3) δ 5.37-5.28 (m, 4H), 4.11 (d, J = 6.3 Hz, 6H), 3.74 (d, J = 6.4 Hz, 2H), 3.49-3.36 (m, 2H), 3.28-3.17 (m, 2H), 2.66 (brs, 1H), 2.53-2.46 (m, 2H), 2.37 (p, J = 6.0 Hz, 1H), 2.31-2.27 (m, 6H), 1.99 (q, J = 6.4 Hz, 10H), 1.62-1.58 (m, 6H), 1.38- 1.25 (m, 43H), 0.87 (t, J = 6.8 Hz, 6H); MS (ESI) m / z: 819.1 [M+H]+.- oxy)methyl)propane-1,3-diyl) diadipate B417.1H NMR (400 MHz, CDCl3) δ 4.85 (p, J = 6.2 Hz, 2H), 4.11 (d, J = 6.4 Hz, 6H), 3.76 (brs, 2H), 2.98-2.80 (m, 6H), 2.41-2.29 (m, 11H), 1.67- 1.63 (m, 13H), 1.52-1.47 (m, 9H), 1.29-1.25 (m, 55H), 0.89-0.86 (m, 12H); MS (ESI) m / z: 1066.9 [M+H]+.

[0310] O,O'-(2-(((6-(Azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl) di(heptadecan-9-yl) diadipate B418.1H NMR (400 MHz, CDCl3) δ 4.86 (p, J = 6.4 Hz, 2H),Attorney Docket No.277A002WO01 4.12 (d, J = 6.6 Hz, 6H), 3.22 (brs, 2H), 2.42-2.28 (m, 12H), 2.17-2.07 (m, 2H), 1.68-1.63 (m, 13H), 1.53-1.47 (m, 9H), 1.30-1.25 (m, 50H), 0.87 (t, J = 7.1 Hz, 12H); MS (ESI) m / z: 992.4 [M+H]+.

[0311] oxy)methyl)- propane-1,3-diyl) diadipate B419.1H NMR (400 MHz, CDCl3) δ 4.85 (p, J = 6.3 Hz, 2H), 4.45 (p, J = 5.9 Hz, 1H), 4.12 (d, J = 6.4 Hz, 6H), 3.73-3.70 (m, 2H), 3.00-2.97 (m, 2H), 2.51 (t, J = 6.8 Hz, 2H), 2.41-2.28 (m, 11H), 1.67-1.58 (m, 11H), 1.50 (q, J = 6.3 Hz, 9H), 1.42-1.25 (m, 52H), 0.87 (t, J = 6.8 Hz, 12H); MS (ESI) m / z: 1009.3 [M+H]+.

[0312] 1,3-diyl bis(2-hexyldecanoate) B420. MS (ESI) m / z: 766.8 [M+H]+.

[0313] 2-(((6-(Azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate) B433.1H NMR (400 MHz, CDCl3) δ 5.43-5.27 (m, 8H), 4.13 (d, J = 6.0 Hz, 6H), 3.53 (t, J = 7.2 Hz, 2H), 2.77 (t, J = 6.9 Hz, 4H), 2.50-2.26 (m, 8H), 2.06 (m, 6H), 1.81 (m, 2H), 1.75-1.56 (m, 8H), 1.47 (m, 2H), 1.40-1.25 (m, 34H), 0.89 (t, J = 7.2 Hz, 6H).Attorney Docket No.277A002WO01

[0314] 2-(((6-(Azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyl- decanoate) B434.

[0315] 2-((dioleate B435. MS (ESI) m / z: 788.7 [M+H]+.

[0316] 2-(((6-(3-Hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B436. MS (ESI) m / z: 804.8 [M+H]+.

[0317] O,O'-(2-(((6-(4-(2-Hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane- 1,3-diyl) di(undecan-3-yl) diadipate B437.1H NMR (400 MHz, CDCl3) δ 4.80 (m, 2H), 4.12 (d, J = 6.2 Hz, 6H), 3.80 (m, 1H), 3.30-2.60 (m, 7H), 2.35 (m, 11H), 1.80-1.49 (m, 24H), 1.47-1.22 (m, 28H), 0.87 (m, 12H); MS (ESI) m / z: 898.1 [M+H]+.Attorney Docket No.277A002WO013-yl) diadipate B438. MS (ESI) m / z: 824.9 [M+H]+.

[0319] 1,3-diyl) di(undecan-3-yl) diadipate B439.1H NMR (400 MHz, CDCl3) δ 4.81 (m, 2H), 4.44 (m, 1H), 4.12 (d, J = 6.2 Hz, 6H), 3.66 (t, J = 6.0 Hz, 2H), 2.94 (t, J = 6.3 Hz, 2H), 2.48 (t, J = 6.0 Hz, 2H), 2.46-2.32 (m, 12H), 1.72-1.40 (m, 18H), 1.39-1.19 (m, 28H), 0.86 (m, 12H); MS (ESI) m / z: 841.2 [M+H]+.

[0320] propane- 1,3-diyl) di(undecan-3-yl) diadipate B440.1H NMR (400 MHz, CDCl3) δ 4.83 (m, 2H), 4.12 (d, J = 6.2 Hz, 6H), 3.74 (d, J = 6.0 Hz, 2H), 3.47 (m, 2H), 3.24 (m, 2H), 2.71 (m, 1H), 2.52 (t, J = 6.4 Hz, 2H), 2.47-2.25 (m, 10H), 1.67 (m, 9H), 1.64-1.49 (m, 10H), 1.40 (m, 2H), 1.38-1.19 (m, 28H), 0.86 (m, 12H); MS (ESI) m / z: 854.6 [M+H]+.Attorney Docket No.277A002WO01

[0321] 1,3-diyl dioleate B441.1H NMR (400 MHz, CDCl3) δ 5.35 (m, 4H), 4.12 (d, J = 6.2 Hz, 6H), 3.63 (t, J = 6.0 Hz, 2H), 2.75-2.45 (m, 10H), 2.38 (m, 6H), 2.28 (m, 4H), 2.02 (m, 8H), 1.80 (m, 2H), 1.62 (m, 4H), 1.39-1.19 (m, 40H), 0.88 (t, J = 7.2 Hz, 6H); MS (ESI) m / z: 833.6 [M+H]+.B442.1H NMR (400 MHz, CDCl3) δ 5.31 (m, 4H), 4.49 (m, 1H), 4.12 (d, J = 6.2 Hz, 6H), 3.76 (m, 1H), 3.09 (m, 1H), 2.60 (t, J = 6.9 Hz, 2H), 2.35 (m, 3H), 2.09 (m, 5H), 1.99 (m, 8H), 1.74 (m, 2H), 1.57 (m, 4H), 1.33-1.29 (m, 42H), 0.86 (t, J = 7.2 Hz, 6H); MS (ESI) m / z: 776.4 [M+H]+.

[0323] 2-(((4-(3-(Hydroxymethyl)azetidin-1-yl)butanoyl)oxy)methyl)propane-1,3-diyl dioleate B443.1H NMR (400 MHz, CDCl3) δ 5.37 (m, 4H), 4.12 (d, J = 6.2 Hz, 6H), 4.75 (d, J = 6.2 Hz, 2H), 3.40 (m, 2H), 3.20 (m, 2H), 2.66 (m, 1H), 2.52 (t, J = 6.4 Hz, 2H), 2.47-2.24 (m, 7H), 2.02 (m, 8H), 1.71 (m, 2H), 1.62 (m, 4H), 1.34-1.22 (m, 42H), 0.87 (t, J = 7.2 Hz, 6H); MS (ESI) m / z: 790.6 [M+H]+.Attorney Docket No.277A002WO01

[0324] - oxy)methyl)propyl oleate B445.1H NMR (400 MHz, CDCl3) δ 5.35 (m, 2H), 4.12 (d, J = 6.0 Hz, 6H), 3.66 (t, J = 6.2 Hz, 2H), 2.90-2.50 (m, 11H), 2.50-2.25 (m, 10H), 2.03 (m, 4H), 1.82 (m, 2H), 1.65 (m, 4H), 1.47 (m, 2H), 1.39-1.19 (m, 44H), 0.87 (t, J = 7.2 Hz, 9H); MS (ESI) m / z: 807.4 [M+H]+.- oleate B446.1H NMR (400 MHz, CDCl3) δ 5.35 (m, 2H), 4.12 (d, J = 6.0 Hz, 6H), 3.25 (t, J = 6.2 Hz, 2H), 2.50-2.25 (m, 9H), 2.11 (m, 2H), 2.03 (m, 4H), 1.75-1.50 (m, 6H), 1.44 (m, 2H), 1.39-1.19 (m, 44H), 0.87 (t, J = 7.2 Hz, 9H); MS (ESI) m / z: 734.3 [M+H]+.

[0326] 3-((2-Hexyldecanoyl)oxy)-2-(((4-(3-hydroxyazetidin-1-yl)butanoyl)oxy)methyl)- propyl oleate B447.1H NMR (400 MHz, CDCl3) δ 5.34 (m, 2H), 4.48 (m, 1H), 4.12 (d, J = 6.0 Hz, 6H), 3.80 (m, 2H), 3.12 (m, 2H), 2.62 (t, J = 6.2 Hz, 2H), 2.50-2.25 (m, 6H), 2.02 (m, 4H), 1.76 (m, 2H), 1.59 (m, 4H), 1.45 (m, 2H), 1.39-1.19 (m, 40H), 0.87 (t, J = 7.2 Hz, 9H); MS (ESI) m / z: 750.5 [M+H]+.Attorney Docket No.277A002WO01

[0327] oxy)- methyl)propyl oleate B448.1H NMR (400 MHz, CDCl3) δ 5.44-5.28 (m, 2H), 4.15 (d, J = 6.1 Hz, 5H), 3.78 (d, J = 5.3 Hz, 1H), 3.42 (t, J = 7.1 Hz, 1H), 3.21 (t, J = 6.3 Hz, 1H), 2.68 (s, 1H), 2.54 (t, J = 7.2 Hz, 1H), 2.47-2.24 (m, 8H), 2.03 (d, J = 6.3 Hz, 4H), 1.82 (p, J = 7.7 Hz, 1H), 1.72 (t, J = 7.6 Hz, 1H), 1.68-1.53 (m, 4H), 1.46 (t, J = 8.1 Hz, 3H), 1.29 (d, J = 14.9 Hz, 39H), 0.89 (t, J = 6.6 Hz, 9H); MS (ESI) m / z: 764.9 [M+H]+.

[0328] - - oxy)methyl)propyl nonyl adipate B449.1H NMR (400 MHz, CDCl3) δ 4.12 (d, J = 6.0 Hz, 6H), 4.04 (t, J = 6.4 Hz, 2H), 3.66 (t, J = 6.0 Hz, 2H), 3.77-2.48 (m, 10H), 2.47-2.25 (m, 10H), 1.78 (m, 2H), 1.70-1.49 (m, 18H), 1.45 (m, 2H), 1.40-1.19 (m, 32H), 0.87 (m, 9H); MS (ESI) m / z: 798.2 [M+H]+.

[0329] 3-((4-(Azetidin-1-yl)butanoyl)oxy)-2-(((2-hexyldecanoyl)oxy)methyl)propyl nonyl adipate B450.1H NMR (400 MHz, CDCl3) δ 4.12 (d, J = 6.0 Hz, 6H), 4.04 (t, J = 6.4 Hz, 2H), 3.25 (t, J = 5.9 Hz, 2H), 2.46 (t, J = 6.1 Hz, 2H), 3.42-2.25 (m, 8H), 2.12 (m, 2H), 1.70-1.49 (m, 10H), 1.45 (m, 2H), 1.40-1.19 (m, 33H), 0.87 (m, 9H); MS (ESI) m / z: 724.5 [M+H]+.Attorney Docket No.277A002WO01

[0330] oxy)methyl)- propyl nonyl adipate B451. MS (ESI) m / z: 740.9 [M+H]+.

[0331] butanoyl)oxy)- methyl)propyl nonyl adipate B452.1H NMR (400 MHz, CDCl3) δ 4.13 (d, J = 6.2 Hz, 6H), 4.05 (t, J = 6.4 Hz, 2H), 3.75 (d, J = 6.0 Hz, 2H), 3.60 (m, 2H), 3.44 (m, 2H), 2.79-2.60 (m, 2H), 2.43-2.29 (m, 8H), 1.75 (m, 2H), 1.69-1.52 (m, 8H), 1.45 (m, 2H), 1.40-1.19 (m, 34H), 0.87 (m, 9H); MS (ESI) m / z: 754.4 [M+H]+.

[0332] - propanoyl)- oxy)methyl)propyl nonyl adipate B453.1H NMR (400 MHz, CDCl3) δ 4.13 (d, J = 6.2 Hz, 2H), 4.11 (d, J = 6.0 Hz, 4H), 4.05 (t, J = 6.4 Hz, 2H), 3.69 (t, J = 5.9 Hz, 2H), 2.79-2.59 (m, 11H), 2.51 (t, J = 6.2 Hz, 2H), 2.45-2.25 (m, 6H), 1.69-1.49 (m, 8H), 1.45 (m, 2H), 1.39-1.19 (m, 34H), 0.87 (m, 9H); MS (ESI) m / z: 784.3 [M+H]+.Attorney Docket No.277A002WO01

[0333] propyl nonyl adipate B454.1H NMR (400 MHz, CDCl3) δ 4.13 (m, 6H), 4.05 (t, J = 6.4 Hz, 2H), 3.20 (t, J = 6.3 Hz, 4H), 2.68 (t, J = 6.4 Hz, 2H), 2.48-2.25 (m, 8H), 2.06 (m, 2H), 1.69-1.49 (m, 8H), 1.45 (m, 2H), 1.40-1.18 (m, 34H), 0.87 (m, 9H); MS (ESI) m / z: 710.5 [M+H]+.

[0334] oxy)- methyl)propyl nonyl adipate B455.1H NMR (400 MHz, CDCl3) δ 4.42 (m, 1H), 4.13 (m, 6H), 4.04 (t, J = 6.4 Hz, 2H), 3.68 (t, J = 6.0 Hz, 2H), 3.04 (t, J = 5.9 Hz, 2H), 2.81 (t, J = 6.4 Hz, 2H), 2.46-2.25 (m, 8H), 2.06 (m, 2H), 1.75-1.50 (m, 8H), 1.41 (m, 2H), 1.40-1.17 (m, 34H), 0.86 (m, 9H); MS (ESI) m / z: 726.5 [M+H]+.

[0335] - propanoyl)- oxy)methyl)propyl 6-oxohexadecanoate B456.1H NMR (400 MHz, CDCl3) δ 4.13 (m, 6H), 4.05 (t, J = 6.4 Hz, 2H), 3.75 (d, J = 6.0 Hz, 2H), 3.40 (m, 2H), 3.18 (m, 2H), 2.78 (m, 2H), 2.65 (m, 1H), 2.41 (m, 3H), 2.33 (m, 6H), 1.79-1.50 (m, 9H), 1.44 (m, 2H), 1.38-1.17 (m, 36H), 0.86 (m, 9H); MS (ESI) m / z: 740.8 [M+H]+.Attorney Docket No.277A002WO01

[0336] 1- yl)pentanoate B502.1H NMR (400 MHz, CDCl3) δ 5.35-5.29 (m, 6H), 4.95-4.90 (m, 1H), 4.45- 4.38 (m, 1H), 3.63 (td, J = 6.2, 2.1 Hz, 2H), 2.83 (td, J = 5.8, 2.1 Hz, 2H), 2.44 (t, J = 7.4 Hz, 2H), 2.28 (t, J = 7.5 Hz, 2H), 2.05-1.96 (m, 10H), 1.67-1.57 (m, 5H), 1.55-1.47 (m, 3H), 1.42- 1.22 (m, 30H), 0.91-0.86 (m, 9H); MS (ESI) m / z: 616.8 [M+H]+.

[0337] - - 1-yl)- pentanoate B503.1H NMR (400 MHz, CDCl3) δ 5.41-5.29 (m, 6H), 4.96-4.90 (m, 1H), 3.24- 3.12 (m, 2H), 2.44-2.37 (m, 1H), 2.33-2.25 (m, 2H), 2.06-1.96 (m, 13H), 1.67-1.46 (m, 9H), 1.39-1.23 (m, 30H), 0.91-0.86 (m, 9H); MS (ESI) m / z: 601.1 [M+H]+.

[0338] 2-(Azetidin-1-ylmethyl)propane-1,3-diyl dioleate B702. MS (ESI) m / z: 674.9 [M+H]+.

[0339] 2-((3-Hydroxyazetidin-1-yl)methyl)propane-1,3-diyl dioleate B703. MS (ESI)Attorney Docket No.277A002WO01 m / z: 691.1 [M+H]+.

[0340] NMR (400 MHz, CDCl3) δ 5.35 (m, 4H), 4.20 (m, 2H), 4.07 (m, 2H), 3.68 (m, 1H), 2.46-2.18 (m, 13H), 2.01 (m, 8H), 1.62 (m, 4H), 1.39-1.19 (m, 44H), 0.88 (t, J = 7.2 Hz, 6H); MS (ESI) m / z: 663.4 [M+H]+.

[0341] 3-(( - oxy)- methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B711.1H NMR (400 MHz, CDCl3) δ 5.41-5.26 (m, 4H), 4.15 (dd, J = 20.5, 6.3 Hz, 8H), 2.75 (t, J = 6.1 Hz, 2H), 2.52 (q, J = 7.0 Hz, 6H), 2.41 (p, J = 6.0 Hz, 1H), 2.29 (t, J = 7.6 Hz, 4H), 2.03 (q, J = 6.9 Hz, 4H), 1.87-1.74 (m, 3H), 1.59 (t, J = 7.6 Hz, 4H), 1.54-1.46 (m, 1H), 1.26 (d, J = 19.0 Hz, 36H), 1.11 (d, J = 6.6 Hz, 2H), 1.01 (t, J = 7.1 Hz, 6H), 0.91-0.80 (m, 9H); MS (ESI) m / z: 778.4 [M+H]+.

[0342] 3-(((3-(Diethylamino)propoxy)carbonyl)oxy)-2-(((8-(2-hexylcyclopropyl)- octanoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B712.1H NMR (400 MHz, CDCl3) δ 5.42-5.25 (m, 3H), 4.21-4.10 (m, 6H), 3.65 (s, 2H), 2.76 (t, J = 6.7 Hz, 2H), 2.51 (q, J = 7.0 Hz, 4H), 2.41 (p, J = 6.0 Hz, 1H), 2.29 (t, J = 8.2 Hz, 4H), 2.07-1.99 (m, 3H), 1.80 (p, J = 6.6 Hz, 1H), 1.59 (s, 12H), 1.40-1.21 (m, 37H), 1.12 (d, J = 6.2 Hz, 3H), 1.00 (t, J = 7.1 Hz, 4H),Attorney Docket No.277A002WO01 0.90-0.84 (m, 6H), 0.64 (s, 2H), 0.58-0.51 (m, 1H), -0.32--0.39 (m, 1H); MS (ESI) m / z: 776.4 [M+H]+.

[0343] - methyl)cyclopropyl)octanoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B713.1H NMR (400 MHz, CDCl3) δ 5.42-5.26 (m, 3H), 4.16 (dd, J = 21.0, 5.7 Hz, 7H), 2.75 (t, J = 6.2 Hz, 2H), 2.53 (d, J = 14.4 Hz, 5H), 2.41 (p, J = 6.0 Hz, 1H), 2.29 (t, J = 7.5 Hz, 4H), 2.03 (q, J = 6.9 Hz, 4H), 1.83 (t, J = 7.3 Hz, 2H), 1.60 (t, J = 7.2 Hz, 6H), 1.33 (d, J = 33.8 Hz, 32H), 1.19- 1.08 (m, 2H), 1.02 (t, J = 7.1 Hz, 6H), 0.92-0.82 (m, 6H), 0.82-0.72 (m, 2H), 0.72-0.65 (m, 2H), 0.59 (td, J = 8.3, 4.1 Hz, 2H), -0.25--0.34 (m, 2H); MS (ESI) m / z: 816.8 [M+H]+.

[0344] - propane- methyl- hexadecanoate) B714.1H NMR (400 MHz, CDCl3) δ 5.42-5.26 (m, 4H), 4.11 (d, J = 6.1 Hz, 6H), 2.76 (t, J = 6.7 Hz, 2H), 2.37 (p, J = 6.1 Hz, 1H), 2.29 (t, J = 7.5 Hz, 6H), 2.03 (q, J = 7.0 Hz, 4H), 1.58 (d, J = 13.4 Hz, 13H), 1.24 (s, 57H), 1.13 (q, J = 6.5 Hz, 4H), 0.92-0.77 (m, 15H); MS (ESI) m / z: 891.1 [M+H]+.

[0345] 2-((((9Z,12Z)-Octadeca-9,12-dienoyl)oxy)methyl)propane-1,3-diyl bis(8-(2-Attorney Docket No.277A002WO01 hexylcyclopropyl)octanoate) B715.1H NMR (400 MHz, CDCl3) δ 5.42-5.26 (m, 4H), 4.11 (d, J = 6.1 Hz, 6H), 2.76 (t, J = 6.7 Hz, 2H), 2.38 (p, J = 6.1 Hz, 1H), 2.29 (t, J = 7.6 Hz, 6H), 2.03 (q, J = 6.9 Hz, 4H), 1.59 (q, J = 7.3 Hz, 11H), 1.32 (d, J = 26.6 Hz, 56H), 1.18-1.05 (m, 4H), 0.92- 0.82 (m, 9H), 0.63 (t, J = 5.7 Hz, 4H), 0.58-0.51 (m, 2H), -0.32--0.38 (m, 2H); MS (ESI) m / z: 886.6 [M+H]+.

[0346] The following compounds are prepared similarly according to the synthetic procedures or methodologies exemplified herein.

[0347] 1-(1,3-Bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(3-(dimethylamino)propyl)thiourea A112.

[0348] 2-(Aziridin-1-ylmethyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A202.[0...

Claims

Attorney Docket No.277A002WO01 What is claimed is:

1. A compound of Formula (I): or an enantiomer, a mixture of two or morediastereomers, a tautomer, a or more or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; wherein: R1is heterocyclyl; R4is , hydrogen, C1-6 alkyl, or hydroxyl; R2a, R3a, and R4aare each independently hydrogen, C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, C2-20alkynyl, C1-20alkoxy, C1-20heteroalkoxy, C2-20alkenoxy, or C2-20alkynoxy; R2b, R3b, and R4bare each independently C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C2-20 alkynyl, C1-20 alkoxy, C1-20 heteroalkoxy, C2-20 alkenoxy, or C2-20 alkynoxy; A1is –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; A2, A3, and A4are each independently a bond, –C(O)O–, –C(O)S–, –OC(O)O–, –OC(O)S–, –C(O)N(R1b)–, –C(S)N(R1b)–, –O–, –OC(O)N(R1b)–, –OC(S)N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–; L1, L2, L3, and L4are each independently a bond, C1-20 alkylene, C1-20 heteroalkylene, C2-20alkenylene, or C2-20alkynylene; X, Y, and Z are each independently C(H) or N; each R1a, R1b, and R1dis independently hydrogen, deuterium, C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; and m and n are each independently an integer of 0, 1, 2, 3, or 4; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, alkoxy, heteroalkoxy,Attorney Docket No.277A002WO01 alkenoxy, and alkynoxy is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) –C(O)Ra, –C(O)ORa, –C(O)NRbRc, –C(O)SRa, –C(NRa)NRbRc, –C(S)Ra, –C(S)ORa, –C(S)NRbRc, –ORa, –OC(O)Ra, –OC(O)ORa, –OC(O)NRbRc, –OC(O)SRa, –OC(NRa)NRbRc, –OC(S)Ra, –OC(S)ORa, –OC(S)NRbRc, –OP(O)(ORb)ORc, –OS(O)Ra, –OS(O)2Ra, –OS(O)NRbRc, –OS(O)2NRbRc, –NRbRc, –NRaC(O)Rd, –NRaC(O)ORd, –NRaC(O)NRbRc, –NRaC(O)SRd, –NRaC(NRd)NRbRc, –NRaC(S)Rd, –NRaC(S)ORd, –NRaC(S)NRbRc, –NRaS(O)Rd, –NRaS(O)2Rd, –NRaS(O)NRbRc, –NRaS(O)2NRbRc, –SRa, –S(O)Ra, –S(O)2Ra, –S(O)NRbRc, and –S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6alkyl, C1-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, and heterocyclyl; and (c) –C(O)Re, –C(O)ORe, –C(O)NRfRg, –C(O)SRe, –C(NRe)NRfRg, –C(S)Re, –C(S)ORe, –C(S)NRfRg, –ORe, –OC(O)Re, –OC(O)ORe, –OC(O)NRfRg, –OC(O)SRe, –OC(NRe)NRfRg, –OC(S)Re, –OC(S)ORe, –OC(S)NRfRg, –OP(O)(ORf)ORg, –OS(O)Re, –OS(O)2Re, –OS(O)NRfRg, –OS(O)2NRfRg, –NRfRg, –NReC(O)Rh, –NReC(O)ORf, –NReC(O)NRfRg, –NReC(O)SRf, –NReC(NRh)NRfRg, –NReC(S)Rh, –NReC(S)ORf, –NReC(S)NRfRg, –NReS(O)Rh, –NReS(O)2Rh, –NReS(O)NRfRg, –NReS(O)2NRfRg, –SRe, –S(O)Re, –S(O)2Re, –S(O)NRfRg, and –S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

2. The compound of claim 1, wherein A2is a bond, –C(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–.Attorney Docket No.277A002WO01 3. The compound of claim 1 or 2, wherein A2is a bond.

4. The compound of claim 1 or 2, wherein A2is –C(O)O–.

5. The compound of claim 1 or 2, wherein A2is –O–.

6. The compound of claim 1 or 2, wherein A2is –OC(O)N(R1b)–.

7. The compound of claim 1, 2, or 6, wherein A2is –OC(O)N(H)–.

8. The compound of claim 1 or 2, wherein A2is –OC(S)N(R1b)–.

9. The compound of claim 1, 2, or 8, wherein A2is –OC(S)N(H)–.

10. The compound of any one of claims 1 to 9, wherein A3is a bond, –C(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–.

11. The compound of any one of claims 1 to 10, wherein A3is a bond.

12. The compound of any one of claims 1 to 10, wherein A3is –C(O)O–.

13. The compound of any one of claims 1 to 10, wherein A3is –O–.

14. The compound of any one of claims 1 to 10, wherein A3is –OC(O)N(R1b)–.

15. The compound of any one of claims 1 to 10 and 14, wherein A3is –OC(O)N(H)–.

16. The compound of any one of claims 1 to 10, wherein A3is –OC(S)N(R1b)–.

17. The compound of any one of claims 1 to 10 and 16, wherein A3is –OC(S)N(H)–.

18. The compound of claim 1, 2, or 10, having the structure of Formula (II): or an enantiomer, aof two or moreAttorney Docket No.277A002WO01 diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

19. The compound of claim 1, 2, or 10, having the structure of Formula (III): or an enantiomer, a of two or morediastereomers, a tautomer, a two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

20. The compound of claim 1, 2, or 10, having the structure of Formula (IV): or an enantiomer, aof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

21. The compound of claim 1, 2, or 10, having the structure of Formula (V): or an enantiomer, a mixtureof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

22. The compound of claim 1, 2, or 10, having the structure of Formula (VI):Attorney Docket No.277A002WO01 or an enantiomer, a mixture of two or morediastereomers, a tautomer, a an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

23. The compound of any one of claims 1 to 22, wherein R4is C1-6 alkyl, optionally substituted with one or more substituents Q.

24. The compound of any one of claims 1 to 23, wherein R4is hydroxymethyl.

25. The compound of any one of claims 1 to 23, wherein R4is hydroxyl.

26. The compound of any one of claims 1 to 22, wherein R4is .

27. The compound of any one of claims 1 to 22 and 26, wherein A4is a bond, –C(O)O–, –O–, –OC(O)N(R1b)–, or –OC(S)N(R1b)–.

28. The compound of any one of claims 1 to 22, 26, and 27, wherein A4is a bond.

29. The compound of any one of claims 1 to 22, 26, and 27, wherein A4is –C(O)O–.

30. The compound of any one of claims 1 to 22, 26, and 27, wherein A4is –O–.

31. The compound of any one of claims 1 to 22, 26, and 27, wherein A4is –OC(O)N(R1b)–.

32. The compound of any one of claims 1 to 22, 26, 27, and 31, wherein A4is –OC(O)N(H)–.

33. The compound of any one of claims 1 to 22, 26, and 27, wherein A4is –OC(S)N(R1b)–.Attorney Docket No.277A002WO01 34. The compound of any one of claims 1 to 22, 26, 27, and 33, wherein A4is –OC(S)N(H)–.

35. The compound of any one of claims 1, 2, 10, 26, and 27, having the structure of Formula (VIII): or an enantiomer, a of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

36. The compound of any one of claims 1, 2, 10, 26, and 27, having the structure of Formula (IX): or an enantiomer, aof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

37. The compound of any one of claims 1, 2, 10, 26, and 27, having the structure of Formula (X):Attorney Docket No.277A002WO01 or an enantiomer, a of two or morediastereomers, a a or more or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

38. The compound of any one of claims 1, 2, 10, 26, and 27, having the structure of Formula (XI): or an enantiomer, aof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

39. The compound of any one of claims 1, 2, 10, and 26 to 28, having the structure of Formula (XII): or an enantiomer, aof two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; orAttorney Docket No.277A002WO01 a pharmaceutically acceptable salt, solvate, or hydrate thereof.

40. The compound of any one of claims 26 to 39, wherein R4ais (i) hydrogen; or (ii) C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, C1-20alkoxy, or C2-20alkenoxy, each optionally substituted with one or more substituents Q.

41. The compound of any one of claims 26 to 40, wherein R4ais (i) hydrogen; or (ii) C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, or C1-20alkoxy, each optionally substituted with one or more substituents Q.

42. The compound of any one of claims 26 to 41, wherein R4ais hydrogen, ethyl, but- 1-yl, hex-1-yl, oct-1-yl, non-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, tridec-1-yl, (Z)- non-2-en-1-yl, (Z)-dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8- en-1-yl, octadec-9-en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or n-octoxy.

43. The compound of any one of claims 26 to 42, wherein R4bis C1-20alkyl, C1-20heteroalkyl, C2-20 alkenyl, C1-20 alkoxy, or C2-20 alkenoxy, each optionally substituted with one or more substituents Q, each optionally substituted with one or more substituents Q.

44. The compound of any one of claims 26 to 43, wherein R4bis C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, or C1-20alkoxy, each optionally substituted with one or more substituents Q.

45. The compound of any one of claims 26 to 44, wherein R4bis but-1-yl, hex-1-yl, oct-1-yl, non-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, tridec-1-yl, (Z)-non-2-en-1-yl, (Z)- dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9- en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)- heptadec-8,11,14-trien-1-yl, or n-octoxy.

46. The compound of any one of claims 26 to 45, wherein L4is (i) a bond; or (ii) C1-20 alkylene, C1-20 heteroalkylene, or C2-20 alkenylene, each optionally substituted with one or more substituents Q.

47. The compound of any one of claims 26 to 46, wherein L4is (i) a bond or (ii) C1-10Attorney Docket No.277A002WO01 alkylene or C1-10 heteroalkylene, each optionally substituted with one or more substituents Q.

48. The compound of any one of claims 26 to 47, wherein L4is a bond, ethane-1,2-yl, –(CH2)4C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, or –(CH2)2O(CH2)2OC(O)–.

49. The compound of any one of claims 26 to 48, wherein Z is N.

50. The compound of any one of claims 26 to 49, wherein Z is C(H).

51. The compound of any one of claims 1 to 22, wherein R4is hydrogen.

52. The compound of any one of claims 1 to 51, wherein R1is N-containing heterocyclyl, optionally substituted with one or more substituents Q.

53. The compound of any one of claims 1 to 52, wherein R1is an ionizable group.

54. The compound of any one of claims 1 to 53, wherein R1is monocyclic heterocyclyl, optionally substituted with one or more substituents Q.

55. The compound of any one of claims 1 to 54, wherein R1is 3-, 4-, 5-, 6-, or 7- membered heterocyclyl, each optionally substituted with one or more substituents Q.

56. The compound of any one of claims 1 to 55, wherein R1is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl, each optionally substituted with one or more substituents Q.

57. The compound of any one of claims 1 to 56, wherein R1is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl, each optionally substituted with one or more substituents, wherein each substituent is independently (i) C1-6alkyl, C1-6heteroalkyl, C3-10cycloalkyl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (ii) –OR1aor –C(O)NR1bR1c.

58. The compound of any one of claims 1 to 57, wherein R1is aziridin-1-yl, azetidin- 1-yl, azetidin-3-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholino, or piperazin-1-yl, each optionally substituted with one or more substituents, wherein each substituent is independently methyl, ethyl, isopropyl, fluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoro-Attorney Docket No.277A002WO01 propyl, 3,3,3-trifluoropropyl, 3-fluoro-2-(fluoromethyl)propyl, 2-hydroxyethyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan-3-yl, tetrahydropyran-4-yl, hydroxy, methoxy, hydroxymethyl, (dimethylamino)methyl, or (2-hydroxyethyl)carbamoyl 59. The compound of any one of claims 1 to 58, wherein R1is aziridin-1-yl, 2- methylaziridin-1-yl, 2-ethylaziridin-1-yl, azetidin-1-yl, 1-methylazetidin-3-yl, 1-ethylazetidin-3- yl, 1-isopropyl-azetidin-3-yl, 3-methylazetidin-1-yl, 3-ethylazetidin-1-yl, 1-isopropylazetidin-3- yl, 3-(fluoromethyl)azetidin-1-yl, 1-(2-fluoroethyl)azetidin-3-yl, 1-(2,2-difluoroethyl)azetidin-3- yl, 1-(2,2,2-trifluoroethyl)azetidin-3-yl, 1-(3-fluoropropyl)azetidin-3-yl, 1-(3,3,3-trifluoro- propyl)azetidin-3-yl, 1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl, 1,3-dimethylazetidin-3- yl, 1-(2-hydroxyethyl)azetidin-3-yl, 1-cyclobutylazetidin-3-yl, 1-cyclopentylazetidin-3-yl, 1- cyclohexylazetidin-3-yl, 1-(oxetan-3-yl)azetidin-3-yl, 1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl, 3-hydroxyazetidin-1-yl, 3-methoxyazetidin-1-yl, 3-(hydroxymethyl)azetidin-1-yl, 3-((dimethyl- amino)methyl)-azetidin-1-yl, 3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl, pyrrolidin-1-yl, 2- methylpyrrolidin-1-yl, 3-methylpyrrolidin-1-yl, 3,4-dimethylpyrrolidin-1-yl, piperidin-1-yl, morpholino, 4-methyl-piperazin-1-yl, or 4-(2-hydroxyethyl)piperazin-1-yl.

60. The compound of any one of claims 1 to 59, wherein R1or; wherein:each R5is independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6alkyl, C1-6heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) –C(O)R1a, –C(O)OR1a, –C(O)NR1bR1c, –C(O)SR1a, –C(NR1a)NR1bR1c, –C(S)R1a, –C(S)OR1a, –C(S)NR1bR1c, –OR1a, –OC(O)R1a, –OC(O)OR1a, –OC(O)NR1bR1c, –OC(O)SR1a, –OC(NR1a)NR1bR1c, –OC(S)R1a, –OC(S)OR1a, –OC(S)NR1bR1c, –OS(O)R1a, –OS(O)2R1a, –OS(O)NR1bR1c, –OS(O)2NR1bR1c, –NR1bR1c, –NR1aC(O)R1d, –NR1aC(O)OR1d, –NR1aC(O)NR1bR1c, –NR1aC(O)SR1d, –NR1aC(NR1d)NR1bR1c, –NR1aC(S)R1d, –NR1aC(S)OR1d, –NR1aC(S)NR1bR1c, –NR1aS(O)R1d, –NR1aS(O)2R1d, –NR1aS(O)NR1bR1c, or –NR1aS(O)2NR1bR1c; or two R5together with the carbon atom to which they are attached formAttorney Docket No.277A002WO01 oxo; R6is (i) hydrogen, deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-10cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) –C(O)R1a, –C(O)OR1a, –C(O)NR1bR1c, –C(O)SR1a, –C(NR1a)NR1bR1c, –C(S)R1a, –C(S)OR1a, –C(S)NR1bR1c, –OR1a, –OC(O)R1a, –OC(O)OR1a, –OC(O)NR1bR1c, –OC(O)SR1a, –OC(NR1a)NR1bR1c, –OC(S)R1a, –OC(S)OR1a, –OC(S)NR1bR1c, –OS(O)R1a, –OS(O)2R1a, –OS(O)NR1bR1c, –OS(O)2NR1bR1c, –NR1bR1c, –NR1aC(O)R1d, –NR1aC(O)OR1d, –NR1aC(O)NR1bR1c, –NR1aC(O)SR1d, –NR1aC(NR1d)NR1bR1c, –NR1aC(S)R1d, –NR1aC(S)OR1d, –NR1aC(S)NR1bR1c, –NR1aS(O)R1d, –NR1aS(O)2R1d, –NR1aS(O)NR1bR1c, or –NR1aS(O)2NR1bR1c; R7is (i) hydrogen; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14aryl, C7-15aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) –C(O)R1a, –C(O)OR1a, –C(O)NR1bR1c, –C(O)SR1a, –C(NR1a)NR1bR1c, –C(S)R1a, –C(S)OR1a, –C(S)NR1bR1c, –S(O)R1a, –S(O)2R1a, –S(O)NR1bR1c, or –S(O)2NR1bR1c; each R1a, R1b, R1c, and R1dis independently hydrogen, deuterium, C1-6alkyl, C1-6heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; p and q are each independently an integer of 0, 1, or 2; and each r is independently an integer of 0, 1, 2, 3, 4, 5, or 6.

61. The compound of claim 60, wherein R1.

62. The compound of claim 60 or 61, wherein p is an integer of 0.

63. The compound of claim 60 or 61, wherein p is an integer of 1.

64. The compound of claim 60 or 61, wherein p is an integer of 2.

65. The compound of any one of claims 60 to 64, wherein r is an integer of 0 or 1.Attorney Docket No.277A002WO01 66. The compound of any one of claims 60 to 65, wherein R5is C1-6 alkyl or C1-6 heteroalkyl, each optionally substituted with one or more substituents Q.

67. The compound of any one of claims 60 to 66, wherein R5is methyl.

68. The compound of any one of claims 60 to 67, wherein R6is (i) hydrogen; (ii) C1-6 alkyl or C1-6 heteroalkyl, each optionally substituted with one or more substituents Q; or (iii) –C(O)NR1bR1cor –OR1a.

69. The compound of any one of claims 60 to 68, wherein R6is methyl, ethyl, fluoro- methyl, hydroxymethyl, dimethylaminomethyl, 2-hydroxyethylcarbamoyl, hydroxyl, or methoxy.

70. The compound of claim 57, wherein R1.

71. The compound of claim 60 or 70, of 0.

72. The compound of claim 60 or 70, wherein q is an integer of 1.

73. The compound of claim 60 or 70, wherein q is an integer of 2.

74. The compound of any one of claims 60 and 70 to 73, wherein r is an integer of 0 or 1.

75. The compound of any one of claims 60 and 70 to 74, wherein R5is C1-6alkyl or C1-6 heteroalkyl, each optionally substituted with one or more substituents Q.

76. The compound of any one of claims 60 and 70 to 75, wherein R5is methyl.

77. The compound of any one of claims 60 and 70 to 76, wherein R7is C1-6alkyl, C1-6heteroalkyl, C3-10 cycloalkyl, or heterocyclyl, each optionally substituted with one or more substituents Q.

78. The compound of any one of claims 60 and 70 to 77, wherein R7is methyl, ethyl,Attorney Docket No.277A002WO01 isopropyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3,3-trifluoro- propyl, 3-fluoro-2-(fluoromethyl)propyl, 2-hydroxyethyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan-3-yl, or tetrahydropyran-4-yl.

79. The compound of any one of claims 1 to 78, wherein A1is –C(O)O–, –OC(O)O–, –C(O)N(R1b)–, –O–, –N(R1b)–, –N(R1a)C(O)N(R1d)–, or –N(R1a)C(S)N(R1d)–.

80. The compound of any one of claims 1 to 79, wherein A1is –C(O)O–.

81. The compound of any one of claims 1 to 79, wherein A1is –C(O)N(R1b)–.

82. The compound of any one of claims 1 to 79 and 81, wherein A1is –C(O)N(H)– or –C(O)N(CH3)–.

83. The compound of any one of claims 1 to 79, wherein A1is –O–.

84. The compound of any one of claims 1 to 79, wherein A1is –N(R1b)–.

85. The compound of any one of claims 1 to 79 and 84, wherein A1is –N(H)– or –N(CH3)–.

86. The compound of any one of claims 1 to 79, wherein A1is –N(R1a)C(O)N(R1d)–.

87. The compound of any one of claims 1 to 79 and 86, wherein A1is –N(H)C(O)N(H)– 88. The compound of any one of claims 1 to 79, wherein A1is –N(R1a)C(S)N(R1d)–.

89. The compound of any one of claims 1 to 79 and 88, wherein A1is –N(H)C(S)N(H)–.

90. The compound of any one of claims 1 to 89, wherein L1is (i) a bond; or (ii) C1-20alkylene, C1-20 heteroalkylene, or C2-20 alkenylene, each optionally substituted with one or more substituents Q.

91. The compound of any one of claims 1 to 90, wherein L1is (i) a bond or (ii) C1-10alkylene or C1-10 heteroalkylene, each optionally substituted with one or more substituents Q.Attorney Docket No.277A002WO01 92. The compound of any one of claims 1 to 91, wherein L1is a bond, ethane-1,2-yl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, or –(CH2)2O(CH2)2O(CH2)2–.

93. The compound of any one of claims 1 to 92, wherein R2ais (i) hydrogen; or (ii) C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C1-20 alkoxy, or C2-20 alkenoxy, each optionally substituted with one or more substituents Q.

94. The compound of any one of claims 1 to 93, wherein R2ais (i) hydrogen; or (ii) C1-20alkyl, C1-20heteroalkyl, C2-20alkenyl, or C1-20alkoxy, each optionally substituted with one or more substituents Q.

95. The compound of any one of claims 1 to 94, wherein R2ais hydrogen, ethyl, but- 1-yl, hex-1-yl, oct-1-yl, non-1-yl, tridec-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, (Z)- non-2-en-1-yl, (Z)-dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8- en-1-yl, octadec-9-en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or n-octoxy.

96. The compound of any one of claims 1 to 95, wherein R2bis C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C1-20 alkoxy, or C2-20 alkenoxy, each optionally substituted with one or more substituents Q, each optionally substituted with one or more substituents Q.

97. The compound of any one of claims 1 to 96, wherein R2bis C1-20alkyl, C1-20heteroalkyl, C2-20 alkenyl, or C1-20 alkoxy, each optionally substituted with one or more substituents Q.

98. The compound of any one of claims 1 to 97, wherein R2bis but-1-yl, hex-1-yl, oct-1-yl, non-1-yl, tridec-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, (Z)-non-2-en-1-yl, (Z)- dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9- en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)- heptadec-8,11,14-trien-1-yl, or n-octoxy.

99. The compound of any one of claims 1 to 98, wherein L2is (i) a bond; or (ii) C1-20 alkylene, C1-20heteroalkylene, or C2-20alkenylene, each optionally substituted with one or more substituents Q.Attorney Docket No.277A002WO01 100. The compound of any one of claims 1 to 99, wherein L2is (i) a bond or (ii) C1-10 alkylene or C1-10 heteroalkylene, each optionally substituted with one or more substituents Q.

101. The compound of any one of claims 1 to 100, wherein L2is a bond, ethane-1,2-yl, –(CH2)4C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, or –(CH2)2O(CH2)2OC(O)–.

102. The compound of any one of claims 1 to 101, wherein X is N.

103. The compound of any one of claims 1 to 102, wherein X is C(H).

104. The compound of any one of claims 1 to 103, wherein R3ais (i) hydrogen; or (ii) C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, C1-20 alkoxy, or C2-20 alkenoxy, each optionally substituted with one or more substituents Q.

105. The compound of any one of claims 1 to 104, wherein R3ais (i) hydrogen; or (ii) C1-20 alkyl, C1-20 heteroalkyl, C2-20 alkenyl, or C1-20 alkoxy, each optionally substituted with one or more substituents Q.

106. The compound of any one of claims 1 to 105, wherein R3ais hydrogen, ethyl, but- 1-yl, hex-1-yl, oct-1-yl, non-1-yl, tridec-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, (Z)- non-2-en-1-yl, (Z)-dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8- en-1-yl, octadec-9-en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)-heptadec-8,11,14-trien-1-yl, or n-octoxy.

107. The compound of any one of claims 1 to 106, wherein R3bis C1-20 alkyl, C1-20 heteroalkyl, C2-20alkenyl, C1-20alkoxy, or C2-20alkenoxy, each optionally substituted with one or more substituents Q, each optionally substituted with one or more substituents Q.

108. The compound of any one of claims 1 to 107, wherein R3bis C1-20 alkyl, C1-20 heteroalkyl, C2-20alkenyl, or C1-20alkoxy, each optionally substituted with one or more substituents Q.

109. The compound of any one of claims 1 to 108, wherein R3bis but-1-yl, hex-1-yl, oct-1-yl, non-1-yl, tridec-1-yl, pentadec-1-yl, heptadec-1-yl, octadec-1-yl, (Z)-non-2-en-1-yl, (Z)- dec-4-en-1-yl, (Z)-tridec-8-en-1-yl, (Z)-pentadec-8-en-1-yl, (Z)-heptadec-8-en-1-yl, octadec-9-Attorney Docket No.277A002WO01 en-1-yl, (8Z,11Z)-hexadec-8,11-dien-1-yl, (8Z,11Z)-heptadec-8,11-dien-1-yl, (8Z,11Z,14Z)- heptadec-8,11,14-trien-1-yl, or n-octoxy.

110. The compound of any one of claims 1 to 109, wherein L3is (i) a bond; or (ii) C1-20alkylene, C1-20 heteroalkylene, or C2-20 alkenylene, each optionally substituted with one or more substituents Q.

111. The compound of any one of claims 1 to 110, wherein L3is (i) a bond or (ii) C1-10alkylene or C1-10heteroalkylene, each optionally substituted with one or more substituents Q.

112. The compound of any one of claims 1 to 111, wherein L3is a bond, ethane-1,2-yl, –(CH2)4C(O)O–, –(CH2)6C(O)O–, –(CH2)7C(O)O–, or –(CH2)2O(CH2)2OC(O)–.

113. The compound of any one of claims 1 to 112, wherein Y is N.

114. The compound of any one of claims 1 to 113, wherein Y is C(H).

115. The compound of any one of claims 1 to 114, wherein m is an integer of 0.

116. The compound of any one of claims 1 to 114, wherein m is an integer of 1.

117. The compound of any one of claims 1 to 114, wherein n is an integer of 0.

118. The compound of any one of claims 1 to 114, wherein n is an integer of 1.

119. A compound of: 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane-1,3- diyl dioleate A001; 2-((oleoyloxy)methyl)-2-(((4-(pyrrolidin-1-yl)butanoyl)oxy)methyl)propane-1,3- diyl dioleate A002; 2-(((5-(dimethylamino)pentanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane- 1,3-diyl dioleate A003; 2-((oleoyloxy)methyl)-2-(((5-(piperidin-1-yl)pentanoyl)oxy)methyl)propane-1,3- diyl dioleate A004; 2-(((5-morpholinopentanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane-1,3-diylAttorney Docket No.277A002WO01 dioleate A005; 2-(((5-(4-methylpiperazin-1-yl)pentanoyl)oxy)methyl)-2- ((oleoyloxy)methyl)propane-1,3-diyl dioleate A006; 2-(((3-(dimethylamino)propyl)amino)methyl)-2-((oleoyloxy)methyl)propane-1,3- diyl dioleate A007; 2-((oleoyloxy)methyl)-2-(((3-(pyrrolidin-1-yl)propanoyl)oxy)methyl)propane- 1,3-diyl dioleate A008; 2-(((3-(dimethylamino)propanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane- 1,3-diyl dioleate A009; 2-(((3-morpholinopropanoyl)oxy)methyl)-2-((oleoyloxy)methyl)propane-1,3-diyl dioleate A010; 2-(((3-(4-methylpiperazin-1-yl)propanoyl)oxy)methyl)-2-((oleoyloxy)methyl)- propane-1,3-diyl dioleate A011; 2-(((5-(dimethylamino)pentanoyl)oxy)methyl)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) A012; 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9’Z,12Z,12’Z)-bis(octadeca-9,12-dienoate) A013; 2-(((3-(dimethylamino)propanoyl)oxy)methyl)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A014; 2-(((4-(dimethyl-amino)butanoyl)oxy)methyl)-2-((((4Z,7Z,10Z,13Z,16Z,19Z)- docosa-4,7,10,13,16,19-hexaenoyl)-oxy)methyl)propane-1,3-diyl (4Z,4'Z,7Z,7'Z,10Z,10'Z,13Z,13'Z,16Z,16'Z,19Z,19'Z)-bis(docosa-4,7,10,13,16,19-hexaenoate) A015; 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-(hydroxymethyl)propane-1,3-diyl dioleate A051; 2-(((4-(dimethylamino)butanoyl)oxy)methyl)-2-(hydroxymethyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A052; 7-hydroxy-7-(4-((1-methylpiperidine-4-carbonyl)oxy)butyl)tridecane-1,13-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A061; 7-hydroxy-7-(4-((1-methylpiperidine-4-carbonyl)oxy)butyl)tridecane-1,13-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) A062;Attorney Docket No.277A002WO01 (Z)-11-(hexadec-9-enoyloxy)-5-(6-((2-hexyldecanoyl)oxy)hexyl)-5-hydroxy- undecyl 1-methylpiperidine-4-carboxylate A063; 7-(4-(dimethylamino)butyl)-7-hydroxytridecane-1,13-diyl (9Z,9'Z)-bis(hexadec-9- enoate) A064; 7-(4-(dimethylamino)butyl)-7-hydroxytridecane-1,13-diyl (9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate) A065; 2-(3-(dimethylamino)propanamido)-2-((((Z)-hexadec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A101; 2-(3-(dimethylamino)propanamido)-2-(((octadecylcarbamoyl)oxy)methyl)- propane-1,3-diyl bis(octadecylcarbamate) A102; O,O'-(2-(3-(dimethylamino)propanamido)-2-(((octadecylcarbamothioyl)oxy)- methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A103; N-(1,3-bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(dimethylamino)propanamide A104; 2-(3-(3-(dimethylamino)propyl)ureido)-2-((((Z)-hexadec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A105; 2-(3-(3-(dimethylamino)propyl)ureido)-2-(((octadecylcarbamoyl)oxy)methyl)- propane-1,3-diyl bis(octadecylcarbamate) A106; O,O'-(2-(3-(3-(dimethylamino)propyl)ureido)-2-(((octadecylcarbamothioyl)oxy)- methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A107; 1-(1,3-bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(3-(dimethylamino)propyl)urea A108; 2-(3-(3-(dimethylamino)propyl)thioureido)-2-((((Z)-hexadec-9-enoyl)oxy)- methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) A109; 2-(3-(3-(dimethylamino)propyl)thioureido)-2-(((octadecylcarbamoyl)oxy)- methyl)propane-1,3-diyl bis(octadecylcarbamate) A110; O,O'-(2-(3-(3-(dimethylamino)propyl)thioureido)-2-(((octadecylcarbamothioyl)- oxy)methyl)propane-1,3-diyl) bis(octadecylcarbamothioate) A111; 1-(1,3-bis(((Z)-octadec-9-en-1-yl)oxy)-2-((((Z)-octadec-9-en-1-yl)oxy)methyl)- propan-2-yl)-3-(3-(dimethylamino)propyl)thiourea A112; 3-(dimethylamino)propyl (3-(octadecyloxy)-2,2-bis((octadecyl-oxy)methyl)-Attorney Docket No.277A002WO01 propyl) carbonate A151; 2-(azetidin-1-ylmethyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A201; 2-(aziridin-1-ylmethyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A202; 2-((2-methylaziridin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane- 1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A203; 2-((2-ethylaziridin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane- 1,3-diyl (9Z,9’Z)-bis(tetradic-9-enoate) A204; 2-(aziridin-1-ylmethyl)-2-((decanoyloxy)methyl)propane-1,3-diyl bis(decanoate) A205; 2-(aziridin-1-ylmethyl)-2-((palmitoyloxy)methyl)propane-1,3-diyl dipalmitate A206; 2-(((2-(aziridin-1-yl)ethyl)amino)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A207; 2-((3-methylazetidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane- 1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A208; 2-((3-methoxyazetidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A209; 2-((3-(fluoromethyl)azetidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A210; 2-(azetidin-1-ylmethyl)-2-((decanoyloxy)methyl)propane-1,3-diyl bis(decanoate) A211; 2-(azetidin-1-ylmethyl)-2-((palmitoyloxy)methyl)propane-1,3-diyl dipalmitate A212; 2-(((2-(azetidin-1-yl)ethyl)(methyl)amino)methyl)-2-((((Z)-tetradec-9-enoyl)- oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A213; 2-(((2-(azetidin-1-yl)ethyl)(methyl)amino)methyl)-2-((decanoyloxy)methyl)- propane-1,3-diyl bis(decanoate) A214; 2-(((2-(azetidin-1-yl)ethyl)(methyl)amino)methyl)-2-((palmitoyloxy)methyl)- propane-1,3-diyl dipalmitate A215;Attorney Docket No.277A002WO01 2-(pyrrolidin-1-ylmethyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A216; 2-((2-methylpyrrolidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A217; 2-((3-methylpyrrolidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A218; 2-((3,4-dimethylpyrrolidin-1-yl)methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A219; 2-((decanoyloxy)methyl)-2-(pyrrolidin-1-ylmethyl)propane-1,3-diyl bis(decanoate) A220; 2-((palmitoyloxy)methyl)-2-(pyrrolidin-1-ylmethyl)propane-1,3-diyl dipalmitate A221; 2-((methyl(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-2-((((Z)-tetradec-9-enoyl)- oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A222; 2-((decanoyloxy)methyl)-2-((methyl(2-(pyrrolidin-1-yl)ethyl)amino)methyl)- propane-1,3-diyl bis(decanoate) A223; 2-((methyl(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-2-((palmitoyloxy)methyl)- propane-1,3-diyl dipalmitate A224; 2-(((3-(dimethylamino)propyl)(methyl)amino)methyl)-2-((oleoyloxy)methyl)- propane-1,3-diyl dioleate A225; 2-((4-methylpiperazin-1-yl)methyl)-2-((oleoyloxy)methyl)propane-1,3-diyl dioleate A226; 2-((2-(aziridin-1-yl)ethoxy)-methyl)-2-((((Z)-tetradec-9-enoyl)oxy)methyl)- propane-1,3-diyl (9Z,9'Z)-bis(tetradec-9-enoate) A301; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B001; 1-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2- yl oleate B002; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B003; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitateAttorney Docket No.277A002WO01 B004; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B005; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B006; 1-(((1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B007; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B008; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B009; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B010; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-2-(oleoyloxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B011; 1-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)- propan-2-yl oleate B012; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl distearate B013; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B014; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B015; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)-octadeca- 9,12-dienoate B016; 1-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B017; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B018; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B019; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B020; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B021; 1-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B022;Attorney Docket No.277A002WO01 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B023; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B024; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B025; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B026; 1-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B027; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl distearate B028; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B029; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B030; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B031; 1-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B032; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B033; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B034; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B035; 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B036; 1-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B037; 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B038; 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B039; 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate)Attorney Docket No.277A002WO01 B040; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B041; 1-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2- yl oleate B042; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl distearate B043; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B044; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B045; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B046; 1-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan-2-yl oleate B047; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B048; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B049; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B050; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B051; 1-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propan- 2-yl oleate B052; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B053; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B054; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B055;Attorney Docket No.277A002WO01 2-(oleoyloxy)-3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B056; 1-(palmitoyloxy)-3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)- propan-2-yl oleate B057; 3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B058; 3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B059; 3-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B060; 3-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyl- oxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B061; 1-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-3- (palmitoyloxy)propan-2-yl oleate B062; 3-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,2-diyl distearate B063; 3-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,2-diyl dipalmitate B064; 3-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,2-diyl bis(decanoate) B065; 3-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-2-(oleoyloxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B066; 1-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyl- oxy)propan-2-yl oleate B067; 3-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl distearate B068; 3-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B069; 3-(((1-(3-fluoropropyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B070; 3-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)-2-(oleoyloxy)-Attorney Docket No.277A002WO01 propyl (9Z,12Z)-octadeca-9,12-dienoate B071; 1-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyl- oxy)propan-2-yl oleate B072; 3-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl distearate B073; 3-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl dipalmitate B074; 3-((methyl(1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,2-diyl bis(decanoate) B075; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B101; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B102; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B103; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B104; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B105; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B106; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B107; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B108; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B109; 2-(((1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B110; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B111; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B112; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B113;Attorney Docket No.277A002WO01 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B114; 2-(((1-ethylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B115; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B116; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B117; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B118; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B119; 2-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B120; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B121; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)- octadeca-9,12-dienoate B122; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B123; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B124; 2-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B125; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B126; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B127; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B128; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B129; 2-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B130; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B131; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)propylAttorney Docket No.277A002WO01 (9Z,12Z)-octadeca-9,12-dienoate B132; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B133; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,3-diyl distearate B134; 2-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B135; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(((9Z,12Z)- octadeca-9,12-dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B136; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B137; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-3-(palmitoyloxy)- propyl oleate B138; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,3-diyl distearate B139; 2-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B140; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B141; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B142; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B143; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B144; 2-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B145; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B146; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B147;Attorney Docket No.277A002WO01 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B148; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B149; 2-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B150; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-(((1-(2,2,2-trifluoroethyl)azetidin-3- yl)carbamoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B151; 3-(palmitoyloxy)-2-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B152; 3-(palmitoyloxy)-2-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propyl oleate B153; 2-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B154; 2-(((1-(2,2,2-trifluoroethyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B155; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B156; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B157; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)-3-(palmitoyloxy)propyl oleate B158; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B159; 2-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B160; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-(((1-(3,3,3-trifluoropropyl)azetidin-3- yl)carbamoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B161; 3-(palmitoyloxy)-2-(((1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)- propyl (9Z,12Z)-octadeca-9,12-dienoate B162; 3-(palmitoyloxy)-2-(((1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)-Attorney Docket No.277A002WO01 propyl oleate B163; 2-(((1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl distearate B164; 2-(((1-(3,3,3-trifluoropropyl)azetidin-3-yl)carbamoyl)oxy)propane-1,3-diyl dipalmitate B165; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-3- (((9Z,12Z)-octadeca-9,12-dienoyl)oxy)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B166; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-3- (palmitoyloxy)propyl (9Z,12Z)-octadeca-9,12-dienoate B167; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)-3- (palmitoyloxy)propyl oleate B168; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,3-diyl distearate B169; 2-(((1-(3-fluoro-2-(fluoromethyl)propyl)azetidin-3-yl)carbamoyl)oxy)propane- 1,3-diyl dipalmitate B170; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B201; 3-(((1-ethyl-2-oxoazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B202; 3-(((1-methylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B203; 3-(((1-ethylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B204; 3-(((1-isopropylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B205; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-((((1-(2,2,2-trifluoroethyl)azetidin-3- yl)carbamoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B206; 3-(((1-(2,2-difluoroethyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B207; 3-(((1-(2-fluoroethyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B208;Attorney Docket No.277A002WO01 3-(((1-(3-fluoropropyl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B209; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-((((1-(3,3,3-trifluoropropyl)azetidin- 3-yl)carbamoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B210; 3-(((1-(1,3-difluoropropan-2-yl)azetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)- octadeca-9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B211; 3-(((1,3-dimethylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B212; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-((((1-(oxetan-3-yl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B213; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-((((1-(tetrahydro-2H-pyran-4-yl)- azetidin-3-yl)carbamoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B214; 3-(((1-cyclohexylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B215; 3-(((1-cyclopentylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B216; 3-(((1-cyclobutylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B217; 3-((methyl(1-methylazetidin-3-yl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B218; 3-(((1-(2-hydroxyethyl)azetidin-3-yl)(methyl)carbamoyl)oxy)-2-((((9Z,12Z)- octadeca-9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B219; 3-(((1-isopropylazetidin-3-yl)(methyl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca- 9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B220; 3-((methyl(1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl)carbamoyl)oxy)-2- ((((9Z,12Z)-octadeca-9,12-dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B221; 3-(((1-ethylazetidin-3-yl)(methyl)carbamoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12- dienoyl)oxy)methyl)propyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate B222; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2-hydroxyethyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B223;Attorney Docket No.277A002WO01 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-ethyl-2-oxoazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B224; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-methylazetidin-3-yl)carbamoyl)oxy)- methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B225; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-ethylazetidin-3-yl)carbamoyl)oxy)- methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B226; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-isopropylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B227; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2,2,2-trifluoroethyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B228; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2,2-difluoroethyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B229; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2-fluoroethyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B230; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(3-fluoropropyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B231; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(3,3,3-trifluoropropyl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B232; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(1,3-difluoropropan-2-yl)azetidin-3- yl)carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B233; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1,3-dimethylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B234; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(oxetan-3-yl)azetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B235; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(tetrahydro-2H-pyran-4-yl)azetidin-3- yl)carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B236; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-cyclohexylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B237; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-cyclopentylazetidin-3-yl)carbamoyl)- oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B238; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-cyclobutylazetidin-3-yl)carbamoyl)-Attorney Docket No.277A002WO01 oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B239; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-(((methyl(1-methylazetidin-3-yl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B240; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-(2-hydroxyethyl)azetidin-3-yl)- (methyl)carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B241; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-isopropylazetidin-3-yl)(methyl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B242; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-(((methyl(1-(tetrahydro-2H-pyran-4-yl)- azetidin-3-yl)carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B243; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((1-ethylazetidin-3-yl)(methyl)- carbamoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B244; 3-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-2-(oleoyloxy)propyl 3-((dimethyl- amino)methyl)azetidine-1-carboxylate B301; 2-(oleoyloxy)-3-(palmitoyloxy)propyl 3-((dimethylamino)methyl)azetidine-1- carboxylate B302; 3-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,2-diyl distearate B303; 3-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,2-diyl dipalmitate B304; 3-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,2-diyl bis(decanoate) B305; 1-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-3-(((9Z,12Z)-octadeca-9,12- dienoyl)oxy)propan-2-yl 3-((dimethylamino)methyl)azetidine-1-carboxylate B306; 1-(((9Z,12Z)-octadeca-9,12-dienoyl)oxy)-3-(palmitoyloxy)propan-2-yl 3- ((dimethylamino)methyl)azetidine-1-carboxylate B307; 1-(oleoyloxy)-3-(palmitoyloxy)propan-2-yl 3-((dimethylamino)methyl)azetidine- 1-carboxylate B308; 2-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,3-diyl distearate B309; 2-((3-((dimethylamino)methyl)azetidine-1-carbonyl)oxy)propane-1,3-diyl dipalmitate B310;Attorney Docket No.277A002WO01 3-(((9Z,12Z)-heptadeca-9,12-dienoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-dienoyl)- oxy)methyl)propyl 3-((dimethylamino)methyl)azetidine-1-carboxylate B311; 3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((9Z,12Z)-octadeca-9,12-dienoyl)oxy)- methyl)propyl 3-((dimethylamino)methyl)azetidine-1-carboxylate B312; 2-(((3-(dimethylamino)propyl)amino)methyl)-2-((oleoyloxy)methyl)propane-1,3- diyl dioleate B401; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) B402; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)-bis(octadeca-9,12-dienoate) B403; 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2- hexyldecanoate) B404; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyldecanoate) B405; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B406; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B407; 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B408; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl ditetradecanoate B409; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) B410; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec- 9-enoate) B411; 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)- bis(hexadec-9-enoate) B412; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z)-bis(hexadec-9-enoate) B413; 2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diylAttorney Docket No.277A002WO01 dioleate B414; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B415; di(heptadecan-9-yl) O,O'-(2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)- oxy)methyl)propane-1,3-diyl) diadipate B416; di(heptadecan-9-yl) O,O'-(2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)- oxy)methyl)propane-1,3-diyl) diadipate B417; O,O'-(2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl) di(heptadecan-9-yl) diadipate B418; di(heptadecan-9-yl) O,O'-(2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)- propane-1,3-diyl) diadipate B419; 2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyldecanoate) B420; 2-(((6-(3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl)hexanoyl)oxy)methyl)- propane-1,3-diyl bis(2-hexyldecanoate) B421; O,O'-(2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3- diyl) di(pentadecan-7-yl) diadipate B422; O,O'-(2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane- 1,3-diyl) di(pentadecan-7-yl) diadipate B423; O,O'-(2-(((6-(3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl)hexanoyl)oxy)- methyl)propane-1,3-diyl) di(pentadecan-7-yl) diadipate B424; 2-(((3-(2-(2-(3-(hydroxymethyl)azetidin-1-yl)ethoxy)ethoxy)propanoyl)oxy)- methyl)propane-1,3-diyl bis(2-hexyldecanoate) B425; 2-(((3-(2-(2-(4-(2-hydroxyethyl)piperazin-1-yl)ethoxy)ethoxy)propanoyl)oxy)- methyl)propane-1,3-diyl bis(2-hexyldecanoate) B426; 2-(((3-(2-(2-(3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl)ethoxy)ethoxy)- propanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyldecanoate) B427; di((Z)-non-2-en-1-yl) 9-((4-(3-(hydroxymethyl)azetidin-1-yl)butanoyl)oxy)- heptadecanedioate B428; di((Z)-non-2-en-1-yl) 9-((4-(4-(2-hydroxyethyl)piperazin-1-yl)butanoyl)oxy)- heptadecanedioate B429;Attorney Docket No.277A002WO01 di((Z)-non-2-en-1-yl) 9-((4-(3-((2-hydroxyethyl)carbamoyl)azetidin-1-yl)- butanoyl)oxy)heptadecanedioate B430; 8-(4-(3-(hydroxymethyl)azetidin-1-yl)butanamido)-3,6,10,13-tetraoxapenta- decane-1,15-diyl bis(2-hexyldecanoate) B431; 2-((2-(2-(2-(3-(hydroxymethyl)azetidin-1-yl)ethoxy)ethoxy)ethoxy)methyl)- propane-1,3-diyl bis(2-hexyldecanoate) B432; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl (9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate) B433; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl bis(2-hexyl- decanoate) B434; 2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B435; 2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl dioleate B436; O,O’-(2-(((6-(4-(2-hydroxyethyl)piperazin-1-yl)hexanoyl)oxy)methyl)propane- 1,3-diyl) di(undecan-3-yl) diadipate B437; O,O’-(2-(((6-(azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl) di(undecan-3- yl) diadipate B438; O,O’-(2-(((6-(3-hydroxyazetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3-diyl) di(undecan-3-yl) diadipate B439; O,O’-(2-(((6-(3-(hydroxymethyl)azetidin-1-yl)hexanoyl)oxy)methyl)propane-1,3- diyl) di(undecan-3-yl) diadipate B440; 2-(((4-(4-(2-hydroxyethyl)piperazin-1-yl)butanoyl)oxy)methyl)propane-1,3-diyl dioleate B441; 2-(((4-(3-hydroxyazetidin-1-yl)butanoyl)oxy)methyl)propane-1,3-diyl dioleate B442; 2-(((4-(3-(hydroxymethyl)azetidin-1-yl)butanoyl)oxy)methyl)propane-1,3-diyl dioleate B443; 2-((3-(azetidin-1-yl)propanoyl)oxy)propane-1,3-diyl dioleate B444; 3-((2-hexyldecanoyl)oxy)-2-(((4-(4-(2-hydroxyethyl)piperazin-1-yl)butanoyl)- oxy)methyl)propyl oleate B445; 3-((4-(azetidin-1-yl)butanoyl)oxy)-2-(((2-hexyldecanoyl)oxy)methyl)propyl oleateAttorney Docket No.277A002WO01 B446; 3-((2-hexyldecanoyl)oxy)-2-(((4-(3-hydroxyazetidin-1-yl)butanoyl)oxy)methyl)- propyl oleate B447; 3-((2-hexyldecanoyl)oxy)-2-(((4-(3-(hydroxymethyl)azetidin-1-yl)butanoyl)oxy)- methyl)propyl oleate B448; 3-((2-hexyldecanoyl)oxy)-2-(((4-(4-(2-hydroxyethyl)piperazin-1-yl)butanoyl)- oxy)methyl)propyl nonyl adipate B449; 3-((4-(azetidin-1-yl)butanoyl)oxy)-2-(((2-hexyldecanoyl)oxy)methyl)propyl nonyl adipate B450; 3-((2-hexyldecanoyl)oxy)-2-(((4-(3-hydroxyazetidin-1-yl)butanoyl)oxy)methyl)- propyl nonyl adipate B451; 3-((2-hexyldecanoyl)oxy)-2-(((4-(3-(hydroxymethyl)azetidin-1-yl)butanoyl)oxy)- methyl)propyl nonyl adipate B452; 3-((2-hexyldecanoyl)oxy)-2-(((3-(4-(2-hydroxyethyl)piperazin-1-yl)propanoyl)- oxy)methyl)propyl nonyl adipate B453; 3-((3-(azetidin-1-yl)propanoyl)oxy)-2-(((2-hexyldecanoyl)oxy)methyl)propyl nonyl adipate B454; 3-((2-hexyldecanoyl)oxy)-2-(((3-(3-hydroxyazetidin-1-yl)propanoyl)oxy)- methyl)propyl nonyl adipate B455; 3-((2-hexyldecanoyl)oxy)-2-(((3-(3-(hydroxymethyl)azetidin-1-yl)propanoyl)- oxy)methyl)propyl 6-oxohexadecanoate B456; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(4-(2-hydroxyethyl)- piperazin-1-yl)pentanoate B501; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(3-hydroxyazetidin-1- yl)pentanoate B502; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(azetidin-1-yl)- pentanoate B503; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 3-(azetidin-1-yl)- propanoate B504; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 3-(pyrrolidin-1-yl)- propanoate B505;Attorney Docket No.277A002WO01 (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 3-(piperidin-1-yl)- propanoate B506; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 4-(azetidin-1-yl)- butanoate B507; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 4-(pyrrolidin-1-yl)- butanoate B508; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 4-(piperidin-1-yl)- butanoate B509; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(azetidin-1-yl)- pentanoate B510; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(3-(hydroxymethyl)- azetidin-1-yl)pentanoate B511; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(3-((2-hydroxyethyl)- carbamoyl)azetidin-1-yl)pentanoate B512; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(pyrrolidin-1-yl)- pentanoate B513; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(piperidin-1-yl)- pentanoate B514; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-morpholinopentanoate B515; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-(4-(2-hydroxyethyl)- piperazin-1-yl)pentanoate B516; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl 5-((1-methylazetidin-3- yl)amino)pentanoate B517; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(pyrrolidin-1-yl)- propyl)carbamate B521; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(piperidin-1-yl)- propyl)carbamate B522; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-morpholinopropyl)- carbamate B523; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(4-methylpiperazin-1-Attorney Docket No.277A002WO01 yl)propyl)carbamate B524; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(pyrrolidin-1- yl)butyl)carbamate B525; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(azetidin-1-yl)propyl)- carbamothioate B531; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(pyrrolidin-1-yl)- propyl)carbamothioate B532; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(piperidin-1-yl)- propyl)carbamothioate B533; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(pyrrolidin-1-yl)- butyl)carbamothioate B534; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(piperidin-1-yl)butyl)- carbamothioate B535; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (3-(1-methylazetidin-3- yl)propyl)carbamothioate B536; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(dimethylamino)- butyl)carbamothioate B537; (6Z,16Z)-12-((Z)-dec-4-en-1-yl)docosa-6,16-dien-11-yl (4-(dimethylamino)butyl) carbonate B541; bis(2-butyloctyl) 10-(N-(3-(azetidin-1-yl)propyl)nonanamido)nonadecanedioate B601; (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-((1-methylazetidin-3- yl)amino)butanoate B602; N-(2,3-bis(((9Z,12Z)-octadeca-9,12-dien-1-yl)oxy)propyl)-1-methylazetidin-3- amine B603; bis(2-butyloctyl) 10-(N-(3-((1-methylazetidin-3-yl)amino)propyl)nonanamido)- nonadecanedioate B604; 2-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)propane-1,3-diyl dioleate B701; 2-(azetidin-1-ylmethyl)propane-1,3-diyl dioleate B702; 2-((3-hydroxyazetidin-1-yl)methyl)propane-1,3-diyl dioleate B703; 2-((dimethylamino)methyl)propane-1,3-diyl dioleate B704;Attorney Docket No.277A002WO01 3-(((3-(diethylamino)propoxy)carbonyl)oxy)-2-(((15-methylhexadecanoyl)oxy)- methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B711; 3-(((3-(diethylamino)propoxy)carbonyl)oxy)-2-(((8-(2-hexylcyclopropyl)- octanoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B712; 3-(((3-(diethylamino)propoxy)carbonyl)oxy)-2-(((8-(2-((2-pentylcyclopropyl)- methyl)cyclopropyl)octanoyl)oxy)methyl)propyl (9Z,12Z)-octadeca-9,12-dienoate B713; 2-((((9Z,12Z)-octadeca-9,12-dienoyl)oxy)methyl)propane-1,3-diyl bis(15-methyl- hexadecanoate) B714; or 2-((((9Z,12Z)-octadeca-9,12-dienoyl)oxy)methyl)propane-1,3-diyl bis(8-(2- hexylcyclopropyl)octanoate) B715; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

120. A lipid nanoparticle comprising a compound of any one of claims 1 to 119.

121. A pharmaceutical composition comprising a lipid nanoparticle and a pharmaceutically acceptable excipient; wherein the lipid nanoparticle comprises (i) nucleic acid; (ii) a compound of any one of claims 1 to 119, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; (iii) a phospholipid; and (iv) cholesterol.

122. The pharmaceutical composition of claim 121, further comprising a conjugated lipid.

123. The pharmaceutical composition of claim 122, wherein the conjugated lipid comprises a polyethylene glycol-conjugated lipid.

124. The pharmaceutical composition of any one of claims 121 to 123, wherein the nucleic acid is an mRNA.

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