Ionizable lipids for use in lipid nanoparticles

Abstract

The present invention relates to ionizable lipids for use in lipid nanoparticles, lipid nanoparticle formulations comprising these ionizable lipids, alone or in combination with other lipids and / or polymers. The lipid nanoparticles formulations may be formulated with nucleic acids for their delivery to target tissues after administration, in particular after parenteral administration such as intravenous, intramuscular, subcutaneous or intratumoral administration.

Description

Ionizable Lipids for Use in Lipid NanoparticlesThe present invention relates to ionizable lipids for use in lipid nanoparticles, lipid nanoparticle formulations comprising these ionizable lipids, alone or in combination with other lipids and / or polymers. The lipid nanoparticles formulations may be formulated with nucleic acids for their delivery to target tissues after administration, in particular after parenteral administration such as intravenous, intramuscular, subcutaneous or intratumoral administration.Background of the inventionNucleic acids represent a new and promising class of therapeutics. Rather than treating conditions by dosing small molecules or proteins, DNA or RNA is administered to patients, whose cells then produce the desired pharmaceutically relevant protein from these “blueprints.” As nucleic acids are much more stable and easier to produce and modify than fully translated proteins, there is enormous potential for these drugs to treat disease, with applications ranging from cancerto chronic conditions like cystic fibrosis and even neurological disorders. Recently, nucleic acid therapeutics have come into the public eye in the form of mRNA vaccines against the SARS-CoV-2 virus.Although nucleic acids alone are fairly stable, mRNA therapeutics generally employ polymeric or lipid nanoparticles (LNPs) to deliver the mRNA, which, while excellent delivery carriers, rapidly aggregate in solution, losing 20% of their activity in just one week at standard refrigerator temperatures. This aggregation unfortunately makes it infeasible for patients to store these therapeutics at home, limiting their potential for clinical translation.These concerns apply not only to vaccinating but also to many other applications of mRNA therapeutics, especially chronic conditions like cystic fibrosis, for which a patient-centric home-stable and self- administrable therapeutic is desirable. For cystic fibrosis in particular, which is an excellent RNA therapy candidate due to its single-gene-mutation nature, it is also desirable to have local delivery to the lungs, which cannot be trivially accomplished using conventional LNP solutions. Despite lipid nanoparticles are promising mRNA delivery vehicles to target cells in vivo, effective mRNA delivery requires circumventing RNAse-mediated degradation, cellular entry, and endosomal escape. Lipid nanoparticles created from ionizable lipids combined with other lipid components, including neutral lipids, cholesterol, and PEGylated lipids, have been utilized to safeguard nucleic acids from degradation and enhance their cellular uptake. While lipid nanoparticle-based vehicles containing ionizable lipids have shown promising results in terms of encapsulation, stability, and localization, there is still a significant need for improvements in these delivery systems. There is a demand for enhanced ionizable lipids that exhibit better pharmacokinetic properties and can effectively deliver various types of nucleic acids to a wide range of cell types and tissues with greater efficiency. Additionally, there is a need for innovative ionizable lipids that have reduced toxicity and can efficiently transport encapsulated nucleic acids to targeted cells, tissues, and organs. The development of novel ionizable lipids that can be easily eliminated in vivo after administration and have lower toxicity is also necessary. Additionally, there is a requirement for biodegradable ionizable lipids. Enhanced ionizable lipids and lipid nanoparticles for nucleic acid delivery should optimize nucleic acid / lipid ratios, protect nucleic acids from degradation and clearance in serum, be suitable for both systemic and local delivery, and ensure intracellular delivery of the nucleic acid. Furthermore, the lipidnucleic acid particles need to be well-tolerated and provide an adequate therapeutic index, ensuring thateffective doses of the nucleic acid do not carry unacceptable toxicity or risk for patients. Moreover, the lipid-nucleic acid particles should remain stable as liquid formulations when stored at certain temperatures for extended periods in a pharmaceutically acceptable buffer.Accordingly, new ionizable lipids addressing all, some or individual mentioned needs are needed.Summary of the inventionIn one aspect, the present disclosure relates to compounds of formula (I)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R1, R2, R3, R4, Xi, X2, Z and Y are as defined herein, and methods fortheir preparation.In another aspect, the present disclosure relates to compounds of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R1, R2, R3, R4, X, Z and Y are as defined herein, and methods for their preparation.Compositions comprising one or more of the foregoing compounds of formula (I) or (la) and a therapeutic agent are also provided.In some embodiments, the compositions further comprise one or more components selected from neutral lipids, charged lipids, steroids and polymer conjugated lipids. Such compositions are useful for formation of lipid nanoparticles for the delivery of the therapeutic agent.In other embodiments, the present invention provides a method for administering a therapeutic agent to a patient in need thereof, the method comprising preparing a composition of lipid nanoparticles comprising the compound of formula (I) or (la) and a therapeutic agent and delivering the composition to the patient.The compounds of formula (I) and (la) are cationic or cationically ionizable lipids and are referred to as lipids or ionizable lipids. They can be used forthe development of lipid nanoparticle (LNP) based therapies such as protein replacement therapies, vaccines and gene editing.A further use of the compounds of formula (I) or (la) can be the combination of those compounds with deep learning methods. Implementation of machine learning techniques along with novel structures of ionizable lipids should facilitate in silico design of novel lipid libraries with improved properties.When using the compounds of the present invention for preparing lipid nanoparticles, the lipid nanoparticles comprising a compound of formula (I) or (la) result in an optimal pKa for mRNA delivery and / or mediated expression of respective proteins.The lipid nanoparticles comprising a compound of formula (I) or (la) also show high expression when administered via different routes, low toxicity and thus overcome the known drawbacks.Lipid nanoparticles comprising a compound of formula (I) or (la) result in suitable properties for administration in vivo, demonstrate potent and selective delivery of the payload via different administration routes and / or mediate comparative secretion of AST and ALT levels indicating a low toxicity profile and / or do not result in increased levels of terminal complex of complement pathway, indicating a possible safe profile. Hence, the advantageous characteristics of the compounds of the present invention will allow the effective, and safe use of the compounds of formula (I) or (la) for making lipid nanoparticles, lipid nanoparticle formulations comprising these ionizable lipids, alone or in combination with other lipids and / or polymers.Brief description of the FiguresFigure 1 . COSY spectrum of lipid 191 : Structure assignment Figure 2. COSY spectrum of lipid 314: Structure assignmentDetailed description of the inventionThe present invention relates to a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1and R2are independently from each other hydrogen, a linear alkyl, branched alkyl, cycloalkyl, aryl, heteroaryl, or polycyclic structure, whereby the polycyclic motifs can be fused aliphatic polycycles, fused aromatic polycycles, aliphatic spirocycles, aliphatic bridged cycles, wherein each individual ring optionally is containing up to three heteroatoms selected from N, O and S, optionally substituted with one or more groups independently selected from hydroxy, halogen, heterocycle, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, - NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, - CN, alkyl, -ORX, heterocycle, -NRxRy, -NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle;- R3and R4are independently from each other a branched or unbranched C4 to C48 alkyl; branched or unbranched C4 to C48 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C48 alkynyl each containing up to 6 triple bonds that is optionally substituted with one or more of the following functionalities: sulfides -S-Rx; mono-, bi-, tri- or tetracyclic subunits (carbocycles); aromatic or heteroaromatic rings; halogen atoms; tertiary, secondary or primary -OH groups; ether -O-Rx; -NRxRy, - NRxC(=O)Ry, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -OSiRsawith Rabeing independently of each other either aliphatic or aromatic residues; thioamides -C(=S)NHRX, -NH(C=S)RX, -C(=S)NRxRy, -NRy(C=S)Rx, wherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds; optionally fused polyaromatic or heteroaromatic rings; monocyclic or polycyclic structures with up to 6 cyclic motifs of 3 to 8-membered rings, such as cholesteryl or cyclohexyl residues, optionally substituted by one or more groups independently selected from hydroxy, halogen, heterocycle, -Rx, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX”, heterocycle, -NRX”Ry”, -NRX”C(=O)Ry", -NRXSOnRy, -C(=O)RX”, -C(=O)ORX, -C(=O)ORX, -C(=O)NRX”Ry”, -SOn’Rx”, -SOnNRx”Ry”, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle;- X is absent or C0-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.As used herein, the term “fatty tail” (lipophilic residues) shall refer to the residues R3and R4. Fatty tail R3and R4may be branched, unbranched or cyclic C4 to C48 alkyl; branched, unbranched or cyclic C4 to C48 alkynyl; branched, unbranched or cyclic C4 to C48 alkenyl that is optionally substituted with one or more of the following functionalities:- ester group -C(=O)ORXor -Rx(=Q)OC- (both directions)- peptide bond -C(=O)NHRXor -C(=Q)NRxRY(both directions)- cyclic or non-cyclic amine groups -NRxRy- thioether -S-Rx- mono-, bi-, tri- or tetracyclic subunits (carbocycles)- aromatic or heteroaromatic rings- branched or non-branched disulfide bonds Rx-S-S-Ry- thioester functionality (both directions) -C(=O)SRX- 1 or more double bonds- 1 or more triple bonds- 1 or more halogen atoms- 1 or more -OH groups (tertiary, secondary or primary)- ether -O-Rx- OSiRsawith Rabeing either aliphatic or aromatic residues- thioamide -C(=S)NRxRy- fused polyaromatic or heteroaromatic rings- monocyclic or polycyclic structures with up to 6 cyclic motifs (e.g. cholesteryl, cyclohexyl etc.): These polycyclic motifs can be fused ring structures, spirocycles, bridged rings but also fused with one or two aromatic rings. Each individual ring size can vary from 3 to 7, with the following substituents possible at any position of the ring: one or more groups independently selected from hydroxy, halogen, heterocycle, -Rx-CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, - SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, -NRxC(=O)Ry, - NRXSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRXRy, -SOnRx’, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.Each ring can be either carbocycle or also a heterocycle containing one or more of the following heteroatom functionalities: -N(RX)-, -O-, -S-, -S(O)-, -S(O2)-, -O(C=O)O- with Rxbeing hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, - NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx’, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.Possible examples of fatty tails R3and R4in this embodiment are, but not limited to:In some embodiment fatty tails R3and R4are independently from each other a branched or unbranched C4 to C48 alkyl; branched or unbranched C4 to C48 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C48 alkynyl each containing up to 6 triple bonds that are optionally substituted with one or more of the following functionalities: Sulfides -S-Rx; mono-, bi-, tri- or tetracyclic subunits (carbocycles); aromatic or heteroaromatic rings; halogen atoms; tertiary, secondary or primary -OH groups; ether -O-Rx; -NRxRy, -NRxC(=O)Ry, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -OSiR3awith Rabeing independently of each other either aliphatic or aromatic residues; thioamides -C(=S)NHRX, -NH(C=S)RX, -C(=S)NRxRy, -NRy(C=S)Rx, wherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 doublebonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds. Residues R3and R4can be optionally fused polyaromatic or heteroaromatic rings; monocyclic or polycyclic structures with up to 6 cyclic motifs of 3 to 8-membered rings (e.g. cholesteryl or cyclohexyl residues etc.) optionally substituted by one or more groups independently selected from hydroxy, halogen, heterocycle, -Rx, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx’, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX”, heterocycle, -NRX"Ry”, -NRX"C(=O)Ry”, -NRX”SOnRy”, - C(=O)RX”, -C(=O)ORX”, -C(=O)ORX”, -C(=O)NRX”Ry”, -SOnRx”, -SOnNRx”Ry", wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.In some further embodiment fatty tails R3and R4are independently from each other a branched or unbranched C4 to C48 alkyl; branched or unbranched C4 to C48 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C48 alkynyl each containing up to 6 triple bonds that are optionally substituted with one or more of the following functionalities: esters -C(=O)ORX, -O(C=O)RX; disulfide bonds -S-SRX; amides -C(=O)NHRX, -NH(C=O)RX, -C(=O)NRxRy, -NRy(C=O)Rx; acetals -CH(ORx)(ORy); thioacetals -CH(SRx)(SRy); thioesters -C(=O)SRX, -S(C=O)RXand amines -NRxRywherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds. Fatty tails R3and R4can optionally be substituted by one of the following groups -C(=O)ORX, -C(=O)NHRX, -C(=O)NRxRy, -CH(ORx)(ORy), -CH(SRx)(SRy) wherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds.In some embodiment, the fatty tails R3and R4are independent of each other saturated alkyl fatty tails consisting of 9 to 18 carbon atoms.Possible examples of the fatty tails R3and R4in this embodiment are, but not limited to:n = 8 to 17In a further embodiment, the fatty tails R3and R4are independent of each other unsaturated C9 to Cis alkenyl, containing one or two double bonds, having the double bonds an E or Z configurations or a combination of both.Possible examples of the fatty tails R3and R4in this embodiment are, but not limited to:E or Z configuration E:E, Z:Z, E:Z, or Z:E configurations n = 0 to 7 k = 0 to 7 m = 0 to 6 I = 0 to 4In a further embodiment, the fatty tails R3and R4are independent of each other branched or non-branched alkyl or alkenyl chains consisting of 9 to 18 carbon atoms containing at least one ester functionality. Possible examples of the fatty tails R3and R4in this embodiment are, but not limited to:E E, Z:Z or mixutre of both all double bonds having E, Z configurations or various mixtures of E-Z isomers m = 0 to 9 r = 0 to 7 m = 0 to 9 s = 0 to 6 t = 0 to 7 u = 0 to 4In a further embodiment, the fatty tails R3and R4are independent of each other branched alkyl or alkenyl chains consisting of 9 to 18 carbon atoms containing at least one ester functionality.Possible examples of the fatty tails R3and R4in this embodiment are, but not limited to:With Rnbeing the following branched or non-branched residues:E E, Z Z or mixutre of both all double bonds having E, Z configurations or various mixtures of E-Z isomers r = 0 to 7 s = 0 to 6 t = 0 to 7 u = 0 to 4As used herein, the term “core” shall refer to the motif that connects the residues “head groups” R1and R2with the “fatty tails” R3and R4. The “core” motif always contains an N-acylurea functionality with the “head groups” R1and R2attached to its nitrogen atoms.As used herein, the groups X, Z and Y are connected by single bonds or a double bond.In some embodiment, the groups X, Z and Y are connected by a single bond.In some embodiment, the groups X, Z and Y are connected by a single bond, Z is CH2, a carbonyl group (C=O), a part of an ester group (-C(O)O-) or an amide group (-C(O)NH-), and the branching point Y that connects two fatty tails R3and R4is a nitrogen atom N or methine group (CH).Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:In some further embodiment the groups X, Z and Y are connected by a single bond and X is a methylene group -(CH2)n- with n = 1 , 2, 3 or 4.Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:In some even further embodiment, the groups X, Z and Y are connected by a single bond, X is a methylene group -(CH2)n- with n = 1 , 2, 3 or 4, Z is a carbonyl group (C=O), a part of an ester group (-C(O)O-) or an amide group (-C(O)NH-), and the branching point Y that connects two fatty tails R3and R4is a nitrogen atom N or methine group (CH).Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:n = 1 , 2, 3, 4 n = 1 , 2, 3, 4In an even further embodiment X is absent (Co), having connected Z directly to the N-acylurea functionality and the groups Z and Y are connected by a single bond.In an even further embodiment X is absent (Co), having connected Z directly to the N-acylurea functionality and the groups Z and Y are connected by a single bond, Z is a methylene group -(CH2)n- with n = 1 , 2, 3 or 4, and the branching point Y that connects two fatty tails R3and R4is a nitrogen atom N or methine group (CH).Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:n = 1 , 2, 3, 4 n = 1 , 2, 3, 4In an even further embodiment X and Z are both absent (Co), having connected Y directly to the N- acylurea functionality.In an even further embodiment X and Z are both absent (Co), having connected Y directly to the N- acylurea functionality, and the branching point Y that connects two fatty tails R3and R4is a nitrogen atom N or methine group (CH).Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:In some further embodiment, Z is absent (Co), having connected X directly to the N-acylurea functionality and the groups X and Y are connected by a double bond.In an even further embodiment, Z is absent (Co), having connected X directly to the N-acylurea functionality, the groups X and Y are connected by a double bond, and X is a methine group (CH) or a carbon atom substituted with a methyl group or ethyl group.Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:In an even further embodiment, Z is absent (Co), having connected X directly to the N-acylurea functionality, the groups X and Y are connected by a double bond, X is a methine group (CH) or a carbon atom substituted with a methyl group or ethyl group, and Y is an olefin carbon atom attached to the fatty tails R3and R4.Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:In a preferred embodiment X, Y and Z are branched alkyl and alkenyl chains.Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:In a most preferred embodiment X, Y and Z are branched alkyl chains, esters, amides and tertiary amines.Possible examples of the groups X, Z and Y in this embodiment are, but not limited to:As used herein, the term “head group” shall refer to the residues R1and R2. “Head groups” can be either a “non-basic head group” or a “basic head group”. As used herein, the term “non-basic head group” R1and R2shall refer to a hydrogen atom, linear or branched Ci to C40 alkyl, alkenyl, alkinyl, cycloalkyl, aryl, heteroaryl or polycyclic structures such as fused aliphatic polycycles, fused aromatic polycycles, aliphatic spirocycles, aliphatic bridged cycles, as well as various heterocyclic structures, optionally containing up to three heteroatoms selected from N, O and S, optionally substituted with one or more groups independently selected from hydroxy, halogen, heterocycle, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, -NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRXRy, -SOnRx’, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.Possible examples of non-basic head groups R1and R2in this embodiment are, but not limited to:In a further embodiment, the term “non-basic head group” R1and R2shall refer to Ci to C40 alkyl, alkenyl, alkinyl chains, especially methyl, ethyl and longer related homologous groups, optionally containing one or more linear or branched ester groups.Possible examples of non-basic head groups R1and R2in this embodiment are, but not limited to:In an even further embodiment, the term “non-basic head group” R1and R2shall refer to non-branched Ci to Ca hydroxyalkyl chains.Possible examples of non-basic head groups R1and R2in this embodiment are, but not limited to:As used herein, the term “basic head group” R1and R2shall refer to C2 to Ca alkyl, C2 to Ca alkenyl, C2 to Ca alkynyl, aromate, heteroaromate or a 3 to 8-membered carbocycle or cyclic amine optionally containing up to three heteroatoms selected from N, O and S, optionally substituted with one or more groups independently selected from hydroxy, halogen, heterocycle, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, - CN, alkyl, -ORX, heterocycle, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In some further embodiment, the term “basic head group” R1and R2shall refer to C2 to Ca alkyl, C2 to Ca alkenyl, C2 to Ca alkynyl that carries one tertiary amino group.Possible examples of basic head groups R1and R2in this embodiment are, but not limited to:In yet a further embodiment, the term “basic head group” R1and R2shall refer to C2 to Ca alkyl, C2 to Ca alkenyl, C2 to Ca alkynyl that carries at any position in the C2 to Ca alkyl, C2 to Ca alkenyl, C2 to Ca alkynyl chain an aromatic ring, a heteroaromatic ring, a saturated or a non-saturated carbocycle.Possible examples of basic head groups R1and R2in this embodiment are, but not limited to:In an even further embodiment, the term “basic head group” R1and R2shall refer to C2to Ca alkyl, C2toCa alkenyl, C2 to Ca alkynyl substituted by an N-heteroaromatic residue. N-heteroaromate can be optionally substituted at any position of the ring with one or more groups independently selected from hydroxy, halogen, heterocycle, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSO2Ry, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, - NRx’C(=O)Ry’, -NRxSO2Ry, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.Possible examples of basic head groups R1and R2in this embodiment are, but not limited to:In some further embodiment, the term “basic head group” R1and R2shall refer to C2to Ca alkyl, C2to Ca alkenyl, C2to Ca alkynyl substituted by or containing an amino group at any position in an acyclic and / or cyclic ring with up to 7-ring size. Cyclic amines can be either a monocyclic structure, but also bi- ortricyclic structure: These polycyclic motifs can be fused ring structures, spirocycles, bridged rings but also fused with one or two aromatic rings. Each individual ring size can vary from 3 to 7, with the following substituents possible at any position of the ring: one or more groups independently selected from hydroxy, halogen, heterocycle, -Rx-CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with oneor more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRx’Ry’, - NRx’C(=O)Ry’, -NRxSO2Ry, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.Each ring can be either carbocycle or also a heterocycle containing at any position of the ring one or more of the following heteroatom functionalities: -N(RX)-, -O-, -S-, -S(O)-, -S(O2)-, -O(C=O)O- with Rxbeing hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, - NRxRy, -NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, - SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle. Possible examples of basic head groups R1and R2in this embodiment are, but not limited to:In some further embodiment, the term “basic head group” R1and R2shall refer to C2to Ca alkyl, C2to Ca alkenyl, C2to Ca alkynyl substituted at any position by an amino group where the acyclic amines are substituted with one or two cyclic residues at the basic N atom. Cyclic residues at the amino groups can be either a monocyclic structure, but also bi- or tricyclic structure: These polycyclic motifs can be fused ring structures, spirocycles, bridged rings but also fused with one or two aromatic rings. Each individual ring size can vary from 3 to 7, with the following substituents possible at any position of the ring: one or more groups independently selected from hydroxy, halogen, heterocycle, -Rx-CN, -ORX, -NRxRy, - NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, -NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, - C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.Each ring can be either carbacycle or also a heterocycle containing at any position of the ring one or more of the following heteroatom functionalities: -N(RX)-, -O-, -S-, -S(O)-, -S(O2)-, -O(C=O)O- with Rxbeing hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substitutedwith one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, - NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx’, - SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle. Possible examples of basic head groups R1and R2in this embodiment are, but not limited to:In a most preferred embodiment basic head group R1and R2is a linear C2 to C7 alkyl chain, unsubstituted or optionally substituted with a tertiary amine with two equal non-branched alkyl chains up to 4 carbon atoms.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:In a further most preferred embodiment basic head group R1and R2is a linear C2 to C7 alkyl chain that contains one tertiary amine with two non-branched alkyl chains up to 4 carbon atoms. These tertiary amines can contain two equal alkyl C1-C4 chains.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:n = 1 to 6In a further most preferred embodiment basic head group R1and R2is a linear C2 to C7 alkyl chain that contains one tertiary amine with two non-branched alkyl chains up to 4 carbon atoms. These tertiary amines can contain two non-equivalent C1-C4 alkyl chains.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:n = 1 to 6In a further most preferred embodiment basic head group R1and R2is a linear C2 to C7 alkyl chain that contains one tertiary amine with two non-branched alkyl chains up to 4 carbon atoms. These tertiary amines can contain hydroxyethyl or methoxyethyl groups as the preferred functionalized residue.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:In a further preferred embodiment basic head group R1and R2is a linear C2 to Ca alkyl substituted at any position by an amino group in a ring with up to 8-ring size.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:n = 1 to 6In a further preferred embodiment basic head group R1and R2is a linear C2 to Ca alkyl substituted at any position by an amino group in a saturated 4 to 8 membered ring size.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:n = 1 to 6In an even further embodiment basic head group R1and R2saturated 4 to 8 membered ring size substituted at any position by an amino group in a linear C2 to Ca alkyl substituted are N-methyl azetidine (substituted at C-3 position), N-methyl pyrrolidine (substituted at C-3 position), and N-methyl piperidine (substituted at C-4 position). Even further preferred these moieties are attached to the core motif by a Co- C5 alkyl chain.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:n = 0 to 5In an even further embodiment basic head group R1and R2is a linear C2 to Ca alkyl substituted at any position by an amino group in a 6-ring size.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:In a further embodiment basic head group R1and R2is a C2 to Ca alkenyl, C2 to Ca alkynyl, aromatic or heteroaromatic ring substituted at any position by an amino group in a ring with up to 7-ring size where the acyclic mines can be substituted with one or two cyclic residues.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:In a further embodiment basic head group R1and R2is a C2 to Ca alkyl substituted by an up to 7-ring size heteroaromatic ring, substituted at any position by Rx, wherein Rxis hydrogen, alkyl or heterocycle, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:n = 1 to 6In a further embodiment basic head group R1and R2is a C2 to Ca alkyl substituted by an aromatic ring, preferably phenyl and pyridinyl, optionally substituted at any position by Rx, wherein Rxis hydrogen, alkyl or heterocycle, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, -NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:n = 0 to 3 m = 0 to 3In an even further embodiment basic head group R1and R2is a C2 to Ca alkyl substituted by an aromatic or saturated cyclic or heterocyclic substituent attached to the basic amino group.Possible examples of basic head groups R1and R2in this preferred embodiment are, but not limited to:In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1is a linear alkyl, branched alkyl, cycloalkyl, aryl, heteroaryl, or polycyclic structure, whereby the polycyclic motifs can be fused aliphatic polycycles, fused aromatic polycycles, aliphatic spirocycles, aliphatic bridged cycles, wherein each individual ring optionally is containing up to three heteroatoms selected from N, O and S, optionally substituted with one or more groups independently selected from hydroxy, halogen, heterocycle, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, - NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle with the proviso that R1contains at least one basic nitrogen atom;- R2is hydrogen, a linear alkyl, branched alkyl, cycloalkyl, aryl, heteroaryl, or polycyclic structure, whereby the polycyclic motifs can be fused aliphatic polycycles, fused aromatic polycycles, aliphatic spirocycles, aliphatic bridged cycles, wherein each individual ring optionally is containing up to three heteroatoms selected from N, O and S, optionally substituted with one or more groups independently selected from hydroxy, halogen, heterocycle, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, - NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle;- R3and R4are independently from each other a branched or unbranched C4 to C48 alkyl; branched or unbranched C4 to C48 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C48 alkynyl each containing up to 6 triple bonds that is optionally substituted with one or more of the following functionalities: sulfides -S-Rx; mono-, bi-, tri- or tetracyclic subunits (carbocycles); aromatic or heteroaromatic rings; halogen atoms; tertiary, secondary or primary -OH groups; ether -O-Rx; -NRxRy, - NRxC(=O)Ry, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -OSiRsawith Rabeing independently of each other either aliphatic or aromatic residues; thioamides -C(=S)NHRX, -NH(C=S)RX, -C(=S)NRxRy, -NRy(C=S)Rx, wherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds; optionally fused polyaromatic or heteroaromatic rings; monocyclic or polycyclic structures with up to 6 cyclic motifs of 3 to 8-membered rings, such as cholesteryl or cyclohexyl residues, optionally substituted by one or more groups independently selected from hydroxy, halogen, heterocycle, -Rx, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX”, heterocycle, -NRXRy, -NRx”C(=O)Ry", -NRXSOnRy, -C(=O)RX", -C(=O)ORX, -C(=O)ORX, -C(=O)NRX”Ry”,-SOnRx”, -SOnNRx”Ry”, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond.In a further preferred embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1is hydrogen, a linear alkyl, branched alkyl, cycloalkyl, aryl, heteroaryl, or polycyclic structure, whereby the polycyclic motifs can be fused aliphatic polycycles, fused aromatic polycycles, aliphatic spirocycles, aliphatic bridged cycles, wherein each individual ring optionally is containing up to three heteroatoms selected from N, O and S, optionally substituted with one or more groups independently selected from hydroxy, halogen, heterocycle, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, - NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle;- R2is a linear alkyl, branched alkyl, cycloalkyl, aryl, heteroaryl, or polycyclic structure, whereby the polycyclic motifs can be fused aliphatic polycycles, fused aromatic polycycles, aliphatic spirocycles, aliphatic bridged cycles, wherein each individual ring optionally is containing up to three heteroatoms selected from N, O and S, optionally substituted with one or more groups independently selected from hydroxy, halogen, heterocycle, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX, heterocycle, -NRxRy, - NRx’C(=O)Ry’, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle with the proviso that R2contains at least one basic nitrogen atom;- R3and R4are independently from each other a branched or unbranched C4 to C48 alkyl; branched or unbranched C4 to C48 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C48 alkynyl each containing up to 6 triple bonds that is optionally substituted with one or more of the following functionalities: sulfides -S-Rx; mono-, bi-, tri- or tetracyclic subunits (carbocycles); aromatic or heteroaromatic rings; tertiary, secondary or primary -OH groups; ether -O-Rx; -NRxRy, -NRxC(=O)Ry, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -OSiR3awith Rabeing independently of each other either aliphatic or aromatic residues; thioamides -C(=S)NHRX, -NH(C=S)RX, -C(=S)NRxRy, -NRy(C=S)Rx, wherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds; optionally fused polyaromatic or heteroaromatic rings; monocyclic or polycyclic structures with up to 6 cyclic motifs of 3 to 8-membered rings, such as cholesteryl or cyclohexyl residues, optionally substituted by one or more groups independently selected from hydroxy, halogen, heterocycle, -Rx, -CN, -ORX, -NRxRy', -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX”, heterocycle, -NRX”Ry”, - NRx”C(=O)Ry”, -NRXSOnRy”, -C(=O)RX”, -C(=O)ORX, -C(=O)ORX, -C(=O)NRx"Ry”, -SOnRx”, -SOnNRxRy, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond.In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1and R2are independently from each other Ci to C40 alkyl, simple non-branched Ci to Cs hydroxyalkyl chains, C2 to C7 alkyl chains containing one tertiary amine substituted with two non-branched Ci to C4 alkyl chains which optionally are substituted by one additional secondary amine, ether, thioether, sulfone, or ester functionality, a saturated nitrogen containing 4 to 8 membered ring attached to Co to C7 alkyl;- R3and R4are independently from each other a branched or unbranched C4 to C48 alkyl; branched or unbranched C4 to C48 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C48 alkynyl each containing up to 6 triple bonds that is optionally substituted with one or more of the following functionalities: sulfides -S-Rx; mono-, bi-, tri- or tetracyclic subunits (carbocycles); aromatic or heteroaromatic rings; halogen atoms; tertiary, secondary or primary -OH groups; ether -O-Rx; -NRxRy, - NRxC(=O)Ry, -C(=O)RX, -C(=O)ORX, -C(=O)NRxRy, -OSiR3awith Rabeing independently of each other either aliphatic or aromatic residues; thioamides -C(=S)NHRX, -NH(C=S)RX, -C(=S)NRxRy, -NRy(C=S)Rx, wherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds; optionally fused polyaromatic or heteroaromatic rings; monocyclic or polycyclic structures with up to 6 cyclic motifs of 3 to 8-membered rings, such as cholesteryl or cyclohexyl residues, optionally substituted by one or more groups independently selected from hydroxy,halogen, heterocycle, -Rx, -CN, -ORX, -NRxRy, -NRxC(=O)Ry, -NRxSOnRy, -C(=O)RX, -C(=O)ORX, - C(=O)NRxRy, -SOnRx, -SOnNRxRy, wherein n is 0, 1 , or 2 and Rxand Ryare each independently hydrogen, alkyl or heterocycle, wherein each alkyl and heterocycle of Rxand Rymay be further substituted with one or more groups independently selected from oxo, halogen, -OH, -CN, alkyl, -ORX”, heterocycle, -NRX”Ry”, -NRx”C(=O)Ry", -NRXSOnRy, -C(=O)RX", -C(=O)ORX, -C(=O)ORX, -C(=O)NRx”Ry”,-SOn Rx”, -SOnNRx”Ry”, wherein n’ is 0, 1 , or 2, and Rxand Ryare each independently hydrogen, alkyl, or heterocycle;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C; - Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1and R2are independently from each other Ci to C40 alkyl, simple non-branched Ci to Cs hydroxyalkyl chains, C2 to C7 alkyl chains containing one tertiary amine substituted with two non-branched Ci to C4 alkyl chains which optionally are substituted by one additional secondary amine, ether, thioether, sulfone, or ester functionality, a saturated nitrogen containing 4 to 8 membered ring attached to Co to C7 alkyl;- R3and R4are independently from each other a branched or unbranched C4 to C48 alkyl; branched or unbranched C4 to C48 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C48 alkynyl each containing up to 6 triple bonds that is optionally substituted with one or more of the following functionalities: esters -C(=O)ORX, -O(C=O)RX; disulfide bonds -S-SRX; amides -C(=O)NHRX, -NH(C=O)RX, -C(=O)NRxRy, -NRy(C=O)Rx; acetals -CH(ORx)(ORy); thioacetals -CH(SRx)(SRy); thioesters -C(=O)SRX, - S(C=O)RXand amines -NRxRywherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds. Fatty tails R3and R4can optionally be substituted by one of the following groups -C(=O)ORX, -C(=O)NHRX, -C(=O)NRxRy, - CH(ORx)(ORy), -CH(SRx)(SRy) wherein Rxand Ryare each independently hydrogen, branched or unbranched C4 to C40 alkyl; branched or unbranched C4 to C40 alkenyl each containing up to 6 double bonds; branched or unbranched C4 to C40 alkynyl each containing up to 6 triple bonds;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1and R2are independently from each other Ci to C40 alkyl, simple non-branched Ci to Ca hydroxyalkyl chains, C2 to C7 alkyl chains containing one tertiary amine substituted with two non-branched Ci to C4 alkyl chains which optionally are substituted by one additional secondary amine, ether, thioether, sulfone, or ester functionality, a saturated nitrogen containing 4 to 8 membered ring attached to Co to C7 alkyl;- R3and R4are independently from each other saturated C9 to C18 alkyl, unsaturated C9 to C18 alkenyl, optionally containing at least one ester functionality;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1and R2are independently from each other hydrogen, a linear C2 to C40 alkyl chain, unsubstituted or optionally substituted with a hydroxy group, with a terminal NRkR’ amino group, wherein, Rkand R1are independently from each other methyl, ethyl, n-propyl, i-propyl, hydroxyethyl or form a cyclic amine group azetidine, pyrrolidine or piperidine;- R3and R4are independently from each other branched or non-branched C9 to C18 alkyl chain, branched or non-branched C9 to C18 alkenyl chain containing one or two double bonds;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1is hydrogen or a Ci to C40 alkyl, alkenyl, alkinyl chain, optionally containing a hydroxy group, and also optionally containing one or more linear or branched ester groups;- R2is a linear C2 to C7 alkyl chain, with a terminal NRkR’ amino group, wherein, Rkand R1are independently from each other methyl, ethyl, n-propyl, i-propyl, hydroxyethyl or form a cyclic amine group azetidine, pyrrolidine or piperidine; with the proviso that R2contains at least one basic nitrogen atom;- R3and R4are independently from each other branched or non-branched C9 to C18 alkyl chain, branched or non-branched C9 to C18 alkenyl chain containing one or two double bonds;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond.In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1is a linear C2 to C7 alkyl chain, with a terminal NRkR’ amino group, wherein, Rkand R1are independently from each other methyl, ethyl, n-propyl, i-propyl, hydroxyethyl or form a cyclic amine group azetidine, pyrrolidine or piperidine; with the proviso that R1contains at least one basic nitrogen atom;- R2is hydrogen or a Ci to C40 alkyl, alkenyl, alkinyl chain optionally containing a hydroxy group, and also optionally containing one or more linear or branched ester groups;- R3and R4are independently from each other branched or non-branched C9 to C18 alkyl chain, branched or nonbranched C9 to Cis alkenyl chain containing one or two double bonds;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond.In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1is methyl, ethyl and longer related homologous groups, optionally containing a hydroxy group, and also optionally containing one or more linear or branched ester groups;- R2is a linear C2 to C7 alkyl chain, with a terminal NRkR’ amino group, wherein, Rkand R1are independently from each other methyl, ethyl, n-propyl, i-propyl, hydroxyethyl or form a cyclic amine group azetidine, pyrrolidine or piperidine; with the proviso that R2contains at least one basic nitrogen atom;- R3and R4are independently from each other branched or non-branched C9 to C18 alkyl chain, branched or non-branched C9 to C18 alkenyl chain containing one or two double bonds;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond.In a further embodiment the compound is a compound of formula (la)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1is a linear C2 to C7 alkyl chain, with a terminal NRkR’ amino group, wherein, Rkand R1are independently from each other methyl, ethyl, n-propyl, i-propyl, hydroxyethyl or form a cyclic amine group azetidine, pyrrolidine or piperidine; with the proviso that R1contains at least one basic nitrogen atom;- R2is methyl, ethyl and longer related homologous groups, optionally containing a hydroxy group, and also optionally containing one or more linear or branched ester groups;- R3and R4are independently from each other branched or non-branched C9 to C18 alkyl chain, branched or non-branched C9 to C18 alkenyl chain containing one or two double bonds;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is absent or C, C=O, -C(O)O-, or -C(O)NH-; and- X-Z and Z-Y is a single or a double bond.In a further embodiment the compound is a compound of formula (II)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1and R2are independently from each other Ci to C40 alkyl, simple non-branched Ci to Cs hydroxyalkyl chains, C2 to C7 alkyl chains containing one tertiary amine substituted with two non-branched Ci to C4 alkyl chains which optionally are substituted by one additional secondary amine, ether, thioether, sulfone, or ester functionality, a saturated nitrogen containing 4 to 8 membered ring attached to Co to C7 alkyl;- R3and R4are independently from each other saturated C9 to C18 alkyl, unsaturated C9 to C18 alkenyl, optionally containing at least one ester functionality;- X is absent or C1-C4 alkyl, optionally substituted with a methyl or an ethyl group;- Y is N or C;- Z is a C, C=O, -C(O)O-, or -C(O)NH-;- X-Z is a single bond; and- Z-Y is a single bond; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the compound is a compound of formula (III)or a pharmaceutically acceptable salt, co-crystal, polymorph, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof; wherein- R1and R2are independently from each other Ci to C40 alkyl, simple non-branched Ci to Ca hydroxyalkyl chains, C2 to C7 alkyl chains containing one tertiary amine substituted with two non-branched Ci to C4 alkyl chains which optionally are substituted by one additional secondary amine, ether, thioether, sulfone, or ester functionality, a saturated nitrogen containing 4 to 8 membered ring attached to Co to C7 alkyl; - R3and R4are are independently from each other saturated C9 to C18 alkyl, unsaturated C9 to C18 alkenyl, optionally containing at least one ester functionality;- X is (CH2)n;- n is 1 , 2, 3 or 4;- Y is N or C; - Z is a C, C=O, -C(O)O-, or -C(C)NH-;- X-Z is a single bond; and- Z-Y is a single bond; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the compound is a compound of formula (IV)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof; wherein- R1and R2are independently from each other Ci to C40 alkyl, simple non-branched Ci to Ca hydroxyalkyl chains, C2 to C7 alkyl chains containing one tertiary amine substituted with two non-branched Ci to C4 alkyl chains which optionally are substituted by one additional secondary amine, ether, thioether, sulfone, or ester functionality, a saturated nitrogen containing 4 to 8 membered ring attached to Co to C7 alkyl;- R3and R4are independently from each other saturated C9 to C18 alkyl, unsaturated C9 to C18 alkenyl, optionally containing at least one ester functionality;- Y is N or C;- Z is a C, C=O, -C(O)O-, or -C(O)NH-;- Z-Y is a single bond; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the compound is a compound of formula (V)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof; wherein- R1and R2are independently from each other Ci to C40 alkyl, simple non-branched Ci to Cs hydroxyalkyl chains, C2 to C7 alkyl chains containing one tertiary amine substituted with two non-branched Ci to C4 alkyl chains which optionally are substituted by one additional secondary amine, ether, thioether, sulfone, or ester functionality, a saturated nitrogen containing 4 to 8 membered ring attached to Co to C7 alkyl;- R3and R4are independently from each other saturated C9 to C18 alkyl, unsaturated C9 to C18 alkenyl, optionally containing at least one ester functionality; and- Y is N or C; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the compound is a compound of formula (VI)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof; wherein- R1and R2are independently from each other Ci to C40 alkyl, simple non-branched Ci to Ca hydroxyalkyl chains, C2 to C7 alkyl chains containing one tertiary amine substituted with two non-branched Ci to C4 alkyl chains which optionally are substituted by one additional secondary amine, ether, thioether, sulfone, or ester functionality, a saturated nitrogen containing 4 to 8 membered ring attached to Co to C7 alkyl;- R3and R4are independently from each other saturated C9 to C18 alkyl, unsaturated C9 to C18 alkenyl, optionally containing at least one ester functionality; and- X is C, optionally substituted with a methyl or an ethyl group; and - Y is N or C; with the proviso that at least one of R1or R2contains at least one basic nitrogen atom.In a further embodiment the present invention relates to compounds of formulae(VII), (VIII), (IX), (X), (XI), (XII), (Xllla), (Xlllb), (XlVa), (XlVb), (XVa), (XVb), (XVIa), (XVIb), (XVIIa), (XVIIb), (XVIIIa), (XVIIIb), (XIXa), (XlXb), (XXa), (XXb), (XXIa), (XXIb), (XXIIa), (XXIIb), (XXIIIa), (XXIIIb), (XXIVa), (XXIVb), (XXVa), (XXVb), (XXVIa), (XXVIb), (XXVIla), (XXVIlb), (XXVIlla), (XXVHIb), (XXIXa), (XXIXb), (XXXa), (XXXb), (XXXIa), (XXXIb), (XXXIIa), (XXXIIb), (XXXIIIa), (XXXIIIb), (XXXIVa), (XXXIVb), (XXXVa), (XXXVb), (XXXVI), (XXXVIla) and (XXXVIlb) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereofFormula (X)Formula (XXVa)Formula (XXXIIIb)The present invention also relates to a compound of formula (I)wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl,Xi and X2 independently of one another are absent or optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C2-C6 heteroalkenyl or C2-Ce heteroalkynyl,Z is absent or optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl or a chemical moiety selected from the group consisting of -C(=O)-, -C(=O)O-, -C(=O)NH-, andY is N or C, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (Ila)wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl,Xi is absent or optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C2-C6 heteroalkenyl or C2-C6 heteroalkynyl,Z is absent or optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl or a chemical moiety selected from the group consisting of -C(=O)-, -C(=O)O-, -C(=O)NH-, andY is N or C, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (III)wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and / or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl,Z is absent or optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl or a chemical moiety selected from the group consisting of -C(=O)-, -C(=O)O-, -C(=O)NH-,Y is N or C, and n is an integer from 0 to 6, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (Illa)(Illa), wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl,Z is absent or optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl or a chemical moiety selected from the group consisting of -C(=O)-, -C(=O)O-, -C(=O)NH-, andY is N or C, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (lllb)wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, andZ is absent or optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl or a chemical moiety selected from the group consisting of -C(=O)-, -C(=O)O-, -C(=O)NH-,and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (lllc)(lllc), wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, 02-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, andZ is absent or optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl or a chemical moiety selected from the group consisting of -C(=O)-, -C(=O)O-, -C(=O)NH-, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (IV)wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2- C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl,Z is absent or optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl or a chemical moiety selected from the group consisting of -C(=O)-, -C(=O)O-, -C(=O)NH-, andY is N or C, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (V)wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2- C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, andY is N or C, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (Va)wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2- C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom, andR3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (Vb)wherein R1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2- C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom, andR3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl,and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein R1and R2independently of one another are C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2- Ce alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, hydroxyalkyl, alkoxy, halogen, -CN, -NO2, -N3, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, -SRa, -S-SRa, -C(=O)Ra, - CH(ORa)(ORb), -C(=O)ORa, -C(=O)SRa-, -C(=O)Ra, -OC(=O)Ra, -SC(=O)Ra, -C(=O)NRaRb, - OC(=O)NRaRb, -NRaC(=O)ORb, -NRaC(=NRb)NRcRd, -NRaC(=NRb)Rc, -C(=NRa)NRbRc, - NRaC(=O)NRbRc, -S(=O)Ra, -SO2Ra, -NRaSORb, -NRaSO2Rb, -S(=O)NRaRb, -C(=S)NRaRb, -NRaC(=S)Rb, -SO2NRaRb, and -OSO3Ra, -OPC>3RaRb, -N=NRband -OSiRaRbRc, whereinRa, Rb, Rcand Rdindependently of one another are hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl or alkoxy, wherein each C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Ra, Rb, Rcand Rdare optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo,whereinRa, Rb, Rcand Rdindependently of one another are hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl or alkoxy, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein R1and R2independently of one another are C1-C20 alkyl, C1-C20 heteroalkyl, cycloalkyl or heterocycloalkyl, optionally substituted with one or more groups independently selected from aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, halogen, -ORa, -NRaRb, -N+RaRbRc, - NRaC(=O)Rb, -C(=O)ORa, -OC(=O)Ra, -C(=O)NRaRb; whereinRa, Rband Rcindependently of one another are hydrogen, C1-C20 alkyl, C1-C20 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy, whereineach aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Ra, Rband Rcare optionally substituted with one or more groups independently selected from Ci-Ce alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, halogen, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, -C(=O)ORa, -OC(=O)Ra, - C(=O)NRaRb; whereinRa, Rband Rcindependently of one another are hydrogen, C1-C20 alkyl, C1-C20 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy; with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1and R2independently of one another are C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl, optionally substituted with one or more groups independently selected from aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, halogen, -ORa, -NRaRb, -N+RaRbRc, - NRaC(=O)Rb, -C(=O)ORa, -OC(=O)Ra, -C(=O)NRaRb; whereinRa, Rband Rcindependently of one another are hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy, wherein each aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Ra, Rband Rcare optionally substituted with one or more groups independently selected from C1-C6 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, halogen, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, -C(=O)ORa, -OC(=O)Ra, - C(=O)NRaRb; whereinRa, Rband Rcindependently of one another are hydrogen, C1-C20 alkyl, C1-C20 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy; with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1and R2independently of one another are C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl or heterocycloalkyl, optionally substituted with one or more groups independently selected from aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, halogen, -ORa, -NRaRb, -N+RaRbRc, - NRaC(=O)Rb, -C(=O)ORa, -OC(=O)Ra, -C(=O)NRaRb; whereinRa, Rband Rcindependently of one another are hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1and R2independently of one another are Ci-Ce alkyl, Ci-Ce heteroalkyl, cycloalkyl or heterocycloalkyl, optionally substituted with one or more groups independently selected from cycloalkyl, heterocycloalkyl, hydroxy, oxo, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, -C(=O)ORa, -OC(=O)Ra, -C(=O)NRaRb; wherein Ra, Rband Rcindependently of one another are hydrogen, Ci-Ce alkyl, Ci-Ce heteroalkyl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1and R2independently of one another are Ci-Ce alkyl, heterocycloalkyl, optionally substituted with one or more groups independently selected from Ci-Ce alkyl, heterocycloalkyl, -NRaRb; whereinRaand Rbindependently of one another are hydrogen or Ci-Ce alkyl, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1and R2independently of one another are Ci-Ce alkyl, pyrrolidine or piperidine, optionally substituted with one or more groups independently selected from Ci-Ce alkyl, -NRaRb, pyrrolidine or piperidine; whereinRaand Rbindependently of one another are hydrogen or Ci-Ce alkyl, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1and R2independently of one another are Ci-Ce alkyl, optionally substituted with one or more groups independently selected from -NRaRb, pyrrolidine or piperidine; whereinRaand Rbindependently of one another are hydrogen or Ci-Ce alkyl; and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1is Ci-Ce alkyl, optionally substituted with -NRaRb; whereinR2is Ci-Ce alkyl, pyrrolidine or piperidine, optionally substituted with one or more groups independently selected from C1-C6 alkyl, -NRaRb, pyrrolidine or piperidine; whereinRaand Rbindependently of one another are hydrogen or C1-C6 alkyl, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1is C1-C6 alkyl, optionally substituted with -NRaRb;R2is C1-C6 alkyl optionally substituted with one or more groups independently selected from -NRaRb, pyrrolidine or piperidine or pyrrolidine or piperidine, optionally substituted with C1-C6 alkyl; wherein Raand Rbindependently of one another are hydrogen or C1-C6 alkyl; and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1is C1-C6 alkyl, optionally substituted with -NRaRb; whereinR2is C1-C6 alkyl, optionally substituted with one or more groups independently selected from -NRaRb, pyrrolidine or piperidine; whereinRaand Rbindependently of one another are hydrogen or C1-C6 alkyl; and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR1is C1-C3 alkyl, optionally substituted with -NRaRb; whereinR2is C1-C3 alkyl, optionally substituted with one or more groups independently selected from -NRaRb, pyrrolidine or piperidine; whereinRaand Rbindependently of one another are hydrogen or C1-C2 alkyl; and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein R1and R2are identical, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein R1and I or R2are independently selected from the list consisting of:and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein R1and I or R2are independently selected from the list consisting of:and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein R1and I or R2are independently selected from the list consisting of:and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein the at least one nitrogen atom is a basic nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR3and R4independently of one another are C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2- Ce alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, hydroxyalkyl, alkoxy, halogen, -CN, -NO2, -N3, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, -SRa, -S-SRa, -C(=O)Ra, - CH(ORa)(ORb), -C(=O)ORa, -C(=O)SRa-, -C(=O)Ra, -OC(=O)Ra, -SC(=O)Ra, -C(=O)NRaRb, - OC(=O)NRaRb, -NRaC(=O)ORb, -NRaC(=NRb)NRcRd, -NRaC(=NRb)Rc, -C(=NRa)NRbRc, - NRaC(=O)NRbRc, -S(=O)Ra, -SO2Ra, -NRaSORb, -NRaSO2Rb, -S(=O)NRaRb, -C(=S)NRaRb, -NRaC(=S)Rb, -SO2NRaRb, and -OSO3Ra, -OPO3RaRb, -N=NRband -OSiRaRbRc, whereinRa, Rb, Rcand Rdindependently of one another are hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl or alkoxy, wherein each C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Ra, Rb, Rcand Rdare optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, hydroxyalkyl, alkoxy, halogen, , -CN, -NO2, -N3, -ORa, -NRaRb, -Ra, Rb, Rcand Rdindependently of one another are hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl or alkoxy, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR3and R4independently of one another are C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, optionally substituted with one or moregroups independently selected from hydroxy, oxo, thioxo, alkoxy, NRaC(=O)Rb, -SRa, -S-SRa, -C(=O)ORa, -C(=O)SRa-, -OC(=O)Ra, -SC(=O)Ra, -C(=O)NRaRb, , -C(=S)NRaRb, -OSiRaRbRc; whereinRa, Rb, and Rcindependently of one another are hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy, wherein each alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Ra, Rband Rcare optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, alkoxy, NRaC(=O)Rb, -SRa, -S-SRa, -C(=O)ORa, -C(=O)SRa, - OC(=O)Ra, -OS(=O)Ra, -C(=O)NRaRb, -C(=S)NRaRb, -OSiRaRbRc; whereinRa, Rband Rcindependently of one another are hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, whereinR3and R4independently of one another are C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, optionally substituted with one or more groups independently selected from hydroxy, oxo, -C(=O)ORa, -OC(=O)Ra; whereinRais hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl or C2-C48 heteroalkenyl, wherein each alkyl, alkenyl, heteroalkyl and Raare optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, hydroxy, oxo, -C(=O)ORa, -OC(=O)Ra; whereinRais hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl or C2-C48 heteroalkenyl, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein R3and / or R4are independently selected from the list consisting of:and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va) or (Vb) as disclosed above, wherein R3and / or R4are independently selected from the list consisting of:and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) or (Ila) as disclosed above, wherein Xi is optionally substituted Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C2-C6 heteroalkenyl or C2-C6 heteroalkynyl, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) or (Ila) as disclosed above, wherein Xi is optionally substituted C1-C6 alkyl, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) or (Ila) as disclosed above, wherein Xi is optionally substituted methylene, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) or (Ila) as disclosed above, wherein Xi is methylene, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III) or (IV) as disclosed above, whereinZ is optionally substituted aryl, heteroaryl, cycloalkyl or heterocycloalkyl, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III) or (IV) as disclosed above, whereinZ is absent, C=O, -C(=O)O-, or -C(=O)NH-, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (IV) or (V) as disclosed above, wherein Y is C, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III), (Illa), (IV) or (V) as disclosed above, whereinY is N, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinXi is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinX2 is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I), (Ila), (III) or (IV) as disclosed above, whereinZ is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinX2 and Zare absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinXi, X2 and Zare absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinXi is optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C2-C6 heteroalkenyl or C2-C6 heteroalkynyl,X2 is absent, andZ is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinXi is optionally substituted Ci-Ce alkyl,X2 is absent, andZ is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinXi is optionally substituted methylene, X2 is absent, andZ is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof. In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinXi is methylene,X2 is absent, andZ is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound of formula (I) as disclosed above, whereinXi is absent,X2 is absent, and Z is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound selected from the list of table 1 consisting of:Table 1and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.In another embodiment, the compound is a compound selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX), (LIV), (XI), (L), (LIII), (XLVIII), (XXXIVa), (XXXIX), (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In another embodiment, the compound is a compound selected from the list consisting of compound of formulas (XI), (L), (LIII), (XLVIII), (XXXIVa) and (XXXIX) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In another embodiment, the compound is a compound selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX) and (LIV) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In another embodiment, the compound is a compound selected from the list consisting of compound of formulas (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In another embodiment, the compound is any single one of the above-mentioned specific compounds of table 1 or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In one embodiment, the compound is a compound of formula (XI)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In one embodiment, the compound is a compound of formula (L)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In one embodiment, the compound is a compound of formula (LIII)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In one embodiment, the compound is a compound of formula (XLVIII)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In one embodiment, the compound is a compound of formula (XXXIVa)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In one embodiment, the compound is a compound of formula (XXXIX)or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.The terms "a", "an" and "the" and similar references used in the context of describing the present disclosure (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by the context.The term "optional" or "optionally" as used herein means that the subsequently described event, circumstance or condition may or may not occur, and that the description includes instances where said event, circumstance, or condition occurs and instances in which it does not occur.The term "cationic lipid" refers to a lipid or lipid-like material having a net positive charge. Cationic lipids bind negatively charged nucleic acid by electrostatic interaction. Generally, cationic lipids possess a lipophilic moiety, such as a sterol, an acyl chain, a diacyl or more acyl chains, and the head group of the lipid typically carries the positive charge. In some embodiments, a cationic lipid has a net positive charge only at certain pH, in particular acidic pH, while it has preferably no net positive charge, preferably has no charge, i.e., it is neutral, at a different, preferably higher pH such as physiological pH. This ionizable behavior is thought to enhance efficacy through helping with endosomal escape and reducing toxicity as compared with particles that remain cationic at physiological pH.The term "cationically ionizable lipid" refers to a lipid or lipid-like material which has a net positive charge or is neutral, i.e., which is not permanently cationic. Thus, depending on the pH of the composition in which the cationically ionizable lipid is solved, the cationically ionizable lipid is either positively charged or neutral. For purposes of the present disclosure, cationically ionizable lipids are covered by the term "cationic lipid" unless contradicted by the circumstances. According to the present invention, the terms "cationic lipid" and "ionizable lipid" are used interchangeably.In the present specification, a structural formula of a compound may represent a certain isomer of said compound. It is to be understood, however, that the present disclosure includes all isomers such as geometrical isomers, optical isomers based on an asymmetrical carbon, stereoisomers, tautomers and the like which occur structurally and isomer mixtures and is not limited to the description of the formula. Furthermore, in the present specification, a structural formula of a compound may represent a specific salt and / or solvate of said compound. It is to be understood, however, that the present disclosure includes all salts (e.g., pharmaceutically acceptable salts) and solvates (e.g., hydrates) and is not limited to the description of the specific salt and / or solvate.Isomers are compounds having the same molecular formula but differ in structure (structural isomers) or in the geometrical (spatial) positioning of the functional groups and / or atoms (stereoisomers). Enantiomers are a pair of stereoisomers which are non- superimposable mirror-images of each other. A racemic mixture or racemate contains a pair of enantiomers in equal amounts and is denoted by the prefix (plus or minus). Diastereomers are stereoisomers which are non-superimposable and which are not mirror-images of each other. "Tautomers" are structural isomers of the same chemical substance that spontaneously and reversibly interconvert into each other, even when pure, due to the migration of individual atoms or groups of atoms; i.e., the tautomers are in a dynamic chemical equilibrium with each other. An example of tautomers are the isomers of the keto-enol-tautomerism. "Conformers" are stereoisomers that can be interconverted just by rotations about formally single bonds, and include - in particular - those leading to different 3-dimentional forms of (hetero)cyclic rings, such as chair, half-chair, boat, and twist-boat forms of cyclohexane.The term "polymorph" refers to a crystalline form of a compound (or a salt, hydrate, or solvate thereof). All polymorphs have the same elemental composition. Different crystalline forms usually have different X- ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability, and solubility. Recrystallization solvent, rate of crystallization, storage temperature, and other factors may cause one crystal form to dominate. Various polymorphs of a compound can be prepared by crystallization under different conditions.The term "solvate" as used herein refers to an addition complex of a dissolved material in a solvent (such as an organic solvent (e.g., an aliphatic alcohol (such as methanol, ethanol, n- propanol, isopropanol), acetone, acetonitrile, ether, and the like), water or a mixture of two or more of these liquids), wherein the addition complex exists in the form of a crystal or mixed crystal. The amount of solvent contained in theaddition complex may be stoichiometric or non-stoichiometric. A hydrate is a solvate wherein the solvent is water.The term "pharmaceutically acceptable" refers to the non-toxicity of a material which does not interact with the action of the active component of the pharmaceutical composition.Pharmaceutically acceptable salts in the context of the present invention are physiologically acceptable salts of the compounds according to the invention. Salts which are not themselves suitable for pharmaceutical uses but can be used, for example, for isolation, purification or storage of the compounds according to the invention are also included.In isotopically labeled derivative of a compound of the invention, one or more atoms are replaced by a corresponding atom having the same number of protons but differing in the number of neutrons. For example, a hydrogen atom may be replaced by a deuterium or tritium atom. Exemplary isotopes which can be used in the present disclosure include deuterium, tritium,11C,13C,14C,15N,18F,32P,32S,35S,36CI, and125l.The term "basic nitrogen atom" refers to a nitrogen atom that has a lone pair of electrons, allowing it to accept protons (H+ions) and thus act as a base according to Bnansted-Lowry theory.In one embodiment, the basic nitrogen atom leads to a lipid having a pKa value of higher than 7. Direct pKa measurement of the lipids are challenging due to their non-water-soluble properties. However, simulated pKa values can be estimated with commercial chemistry software tools, e.g. ChemDraw. The following chemical groups carrying a basic nitrogen atom may be mentioned by way of example and by way of preference: Primary amine; secondary amine; tertiary amine, wherein primary amine; secondary amine; tertiary amine can be cyclic; polycyclic or non-cyclic amines, wherein the cyclic or polycyclic amines can be fully saturated, partially saturated or unsaturated. Cyclic or polycyclic amines include but are not limited to pyridine; pyrimidine; pyridazine; pyrrol; imidazole; pyrazole; indole; oxazole and benzimidazole.Alkyl in the context of the invention represents an optionally substituted straight-chain or branched alkyl radical having 1 to 50 carbon atoms.(Ci-Ce)-Alkyl in the context of the invention represents an optionally substituted straight-chain or branched alkyl radical having 1 to 6 carbon atoms. The following may be mentioned by way of example and by way of preference: methyl; ethyl; n-propyl; isopropyl; n-butyl; isobutyl; sec-butyl; tert-butyl; n-pentyl; isopentyl; and n-hexyl. (Ci-Ci5)-Alkyl in the context of the invention represents an optionally substituted straightchain or branched alkyl radical having 1 to 15 carbon atoms. The following may be mentioned by way of example and by way of preference: methyl; ethyl; n-propyl; isopropyl; n-butyl; isobutyl; sec-butyl; tertbutyl; n-pentyl; isopentyl; n-hexyl; 2-methylpentyl; n-heptyl; 2-methylhexyl; n-octyl; 2-ethylheptyl; n-nonyl; 3-methyloctyl; n-decyl; 2-propylnonyl; n-undecyl; 3-methyldecyl; n-dodecyl; 2-ethyldecyl; n-tridecyl; 3- methylundecyl; n-tetradecyl; 2-propyltridecyl; n-pentadecyl; and 3-methyltetradecyl. (Ci-C2o)-Alkyl in the context of the invention represents an optionally substituted straight-chain or branched alkyl radical having1 to 20 carbon atoms. The following may be mentioned by way of example and by way of preference: methyl; ethyl; n-propyl; isopropyl; n-butyl; isobutyl; sec-butyl; tert-butyl; n-pentyl; isopentyl; n-hexyl; 2- methylpentyl; n-heptyl; 2-methylhexyl; n-octyl; 2-ethylheptyl; n-nonyl; 3-methyloctyl; n-decyl; 2- propylnonyl; n-undecyl; 3-methyldecyl; n-dodecyl; 2-ethyldecyl; n-tridecyl; 3-methylundecyl; n-tetradecyl; 2-propyltridecyl; n-pentadecyl; 3-methyltetradecyl; n-hexadecyl; 2-ethylpentadecyl; n-heptadecyl; 3- methylhexadecyl; n-octadecyl; 2-propylheptadecyl; n-nonadecyl; and 3-methylnonadecyl; n-icosyl; 2- ethylnonadecyl; and 3-methylicosyl. (C4-C4s)-Alkyl in the context of the invention represents an optionally substituted straight-chain or branched alkyl radical having 4 to 48 carbon atoms. The following may be mentioned by way of example and by way of preference: n-butyl; isobutyl; sec-butyl; tert-butyl; n-pentyl; isopentyl; n-hexyl; 2-methylpentyl; n-heptyl; 2-methylhexyl; n-octyl; 2-ethylheptyl; n-nonyl; 3-methyloctyl; n-decyl; 2-propylnonyl; n-undecyl; 3-methyldecyl; n-dodecyl; 2-ethyldecyl; n-tridecyl; 3-methylundecyl; n- tetradecyl; 2-propyltridecyl; n-pentadecyl; and 3-methyltetradecyl; n-hexadecyl; n-heptadecyl; n- octadecyl; n-nonadecyl; n-icosyl; n-docosyl; n-tricosyl; n-tetracosyl; n-pentacosyl; n-hexacosyl; n- heptacosyl; n-octacosyl; n-nonacosyl; n-triacontyl; n-hentriacontyl; n-dotriacontyl; n-tritriacontyl; n- tetratriacontyl; and n-pentatriacontyl.Heteroalkyl in the context of the invention represents an optionally substituted straight-chain or branched alkyl radical as defined above, wherein at least one carbon atom, preferably one to five carbon atoms, are independently replaced by a heteroatom or heteroatom functionality, selected from -NH-, -N=, -O-, - S-S-, -S-, -S(=O)- or -S(=O)2.Alkenyl in the context of the invention represents an optionally substituted straight-chain or branched alkenyl radical having one to five double bonds and 2 to 50 carbon atoms. (C2-C6)-Alkenyl in the context of the invention represents an optionally substituted straight-chain or branched alkenyl radical having one or two double bonds and 2 to 6 carbon atoms. The following may be mentioned by way of example and by way of preference: vinyl; allyl; n-prop-1-en-1-yl; iso-propenyl; n-but-1-en-1-yl; n-but-2-en-1 -yl; n-but-3- en-1-yl; 2-methylprop-1-en-1-yl; 2-methylprop-2-en-1-yl; n-pent-1-en-1 -yl; and 2-methylbut-2-en-1 -yl. (C2- Ci5)-Alkenyl in the context of the invention represents an optionally substituted straight-chain or branched alkenyl radical having one to five double bonds and 2 to 15 carbon atoms. The following may be mentioned by way of example and by way of preference: vinyl; allyl; n-prop-1 -en-1-yl; iso-propenyl; n-but-1-en-1-yl; n-but-2-en-1-yl; n-but-3-en-1-yl; 2-methylprop-1-en-1-yl; 2-methylprop-2-en-1-yl; n-pent-1-en-1-yl; 2- methylbut-2-en-1-yl; n-hex-1 -en-1-yl; 3-methylpent-1 -en-1-yl; n-hept-1-en-1-yl; 2-methylhex-2-en-1-yl; n- oct-1-en-1-yl; 3-methylhept-1-en-1 -yl; n-non-1-en-1-yl; 2-methyloct-2-en-1-yl; n-dec-1-en-1-yl; 3- methylnon-1-en-1-yl; n-undec-1-en-1-yl; 2-methyldec-2-en-1-yl; n-dodec-1-en-1-yl; 3-methylundec-1-en- 1 -yl; n-tridec-1 -en-1-yl; 2-methyldodec-2-en-1-yl; n-tetradec-1-en-1-yl; 3-methyltridec-1-en-1-yl; n- pentadec-1-en-1-yl; and 2-methyl-tetradec-2-en-1-yl. (C2-C2o)-Alkenyl in the context of the invention represents an optionally substituted straight-chain or branched alkenyl radical having one to five double bonds and 2 to 20 carbon atoms. The following may be mentioned by way of example and by way of preference: vinyl; allyl; n-prop-1-en-1-yl; iso-propenyl; n-but-1-en-1-yl; n-but-2-en-1 -yl; n-but-3-en-1-yl; 2- methylprop-1 -en-1 -yl; 2-methylprop-2-en-1 -yl; n-pent-1 -en-1 -yl; 2-methylbut-2-en-1 -yl; n-hex-1 -en-1 -yl; 3- methylpent-1 -en-1-yl; n-hept-1 -en-1-yl; 2-methylhex-2-en-1-yl; n-oct-1-en-1-yl; 3-methylhept-1-en-1-yl; n-non-1 -en-1 -yl; 2-methyloct-2-en-1-yl; n-dec-1-en-1-yl; 3-methylnon-1-en-1 -yl; n-undec-1-en-1-yl; 2- methyldec-2-en-1-yl; n-dodec-1-en-1-yl; 3-methylundec-1-en-1-yl; n-tridec-1-en-1-yl; 2-methyldodec-2- en-1-yl; n-tetradec-1-en-1-yl; 3-methyltridec-1-en-1-yl; n-pentadec-1-en-1-yl; 2-methyltetradec-2-en-1-yl; n-hexadec-1-en-1-yl; 3-methylpentadec-1-en-1-yl; n-heptadec-1 -en-1-yl; 2-methylhexadec-2-en-1-yl; n- octadec-1-en-1-yl; 3-methylheptadec-1-en-1-yl; n-nonadec-1-en-1-yl; 2-methyloctadec-2-en-1 -yl; n-icos- 1-en-1 -yl; and 3-methylnonadec-1-en-1-yl. (C4-C4s)-Alkenyl in the context of the invention represents an optionally substituted straight-chain or branched alkenyl radical having one to five double bonds and 4 to 48 carbon atoms. The following may be mentioned by way of example and by way of preference: n-but- 1-en-1-yl; n-but-2-en-1-yl; n-but-3-en-1-yl; 2-methylprop-1-en-1-yl; 2-methylprop-2-en-1-yl; n-pent-1-en- 1-yl; 2-methylbut-2-en-1-yl; n-hex-1-en-1-yl; 3-methylpent-1-en-1-yl; n-hept-1-en-1-yl; 2-methylhex-2-en- 1-yl; n-oct-1-en-1-yl; 3-methylhept-1-en-1-yl; n-non-1 -en-1-yl; 2-methyloct-2-en-1-yl; n-dec-1-en-1-yl; 3- methylnon-1-en-1-yl; n-undec-1-en-1-yl; 2-methyldec-2-en-1-yl; n-dodec-1-en-1-yl; 3-methylundec-1-en- 1-yl; n-tridec-1 -en-1-yl; 2-methyldodec-2-en-1-yl; n-tetradec-1-en-1-yl; 3-methyltridec-1-en-1-yl; n- pentadec-1-en-1-yl; 2-methyl-tetradec-2-en-1-yl; n-hexadec-1-en-1-yl; n-heptadec-1-en-1-yl; n-octadec- 1-en-1-yl; n-nonadec-1-en-1-yl; n-icos-1-en-1-yl; n-docos-1-en-1-yl; n-tricos-1-en-1 -yl; n-tetracos-1-en-1- yl; n-pentacos-1-en-1-yl; n-hexacos-1 -en-1-yl; n-heptacos-1-en-1-yl; n-octacos-1 -en-1-yl; n-nonacos-1- en-1-yl; n-triacont-1-en-1 -yl; and n-hentriacont-1-en-1-yl.Heteroalkenyl in the context of the invention represents an optionally substituted straight-chain or branched alkenyl radical as defined above, wherein at least one carbon atom, preferably one to five carbon atoms, are independently replaced by a heteroatom or heteroatom functionality, selected from - NH-, -N=, -O-, -S-S-, -S-, -S(=O)- or -S(=0)2.Alkynyl in the context of the invention represents an optionally substituted straight-chain or branched alkinyl radical having one to five triple bonds and 2 to 50 carbon atoms. (C2-Ce)-Alkynyl in the context of the invention represents an optionally substituted straight-chain or branched alkinyl radical having one or two triple bonds and 2 to 6 carbon atoms. The following may be mentioned by way of example and by way of preference: ethynyl; prop-1 -yn-1-yl; 2-propynyl; n-but-1 -yn-1 -yl; 2-butynyl; and n-pent-1-yn-1-yl. (C2-Ci5)-Alkynyl in the context of the invention represents an optionally substituted straight-chain or branched alkinyl radical having one to five triple bonds and 2 to 15 carbon atoms. The following may be mentioned by way of example and by way of preference: ethynyl; prop-1 -yn-1 -yl; 2-propynyl; n-but-1-yn- 1 -yl; 2-butynyl; n-pent-1 -yn-1 -yl; 3-methylbut-1-yn-1-yl; n-hex-1-yn-1-yl; 3-methylpent-1-yn-1-yl; n-hept-1- yn-1 -yl; 2-methylhex-1-yn-1-yl; n-oct-1-yn-1-yl; 3-methylhept-1-yn-1 -yl; n-non-1-yn-1-yl; 2-methyloct-1- yn-1 -yl; n-dec-1-yn-1-yl; 3-methylnon-1-yn-1-yl; n-undec-1-yn-1-yl; 2-methyldec-1 -yn-1-yl; n-dodec-1-yn- 1 -yl; 3-methylundec-1-yn-1-yl; n-tridec-1 -yn-1 -yl; 2-methyldodec-1-yn-1-yl; n-tetradec-1-yn-1-yl; 3- methyltridec-1-yn-1-yl; n-pentadec-1-yn-1-yl; and 2-methyltetradec-1-yn-1-yl. (C2-C2o)-Alkynyl in the context of the invention represents an optionally substituted straight-chain or branched alkinyl radical having one to five triple bonds and 2 to 20 carbon atoms. The following may be mentioned by way of example and by way of preference: ethynyl; prop-1 -yn-1 -yl; 2-propynyl; n-but-1-yn-1-yl; 2-butynyl; n-pent- 1-yn-1 -yl; 3-methylbut-1 -yn-1-yl; n-hex-1-yn-1-yl; 3-methylpent-1-yn-1-yl; n-hept-1-yn-1-yl; 2-methylhex- 1 -yn-1 -yl; n-oct-1-yn-1-yl; 3-methylhept-1-yn-1-yl; n-non-1-yn-1-yl; 2-methyloct-1-yn-1 -yl; n-dec-1-yn-1-yl;3-methylnon-1-yn-1-yl; n-undec-1-yn-1-yl; 2-methyldec-1 -yn-1-yl; n-dodec-1 -yn-1-yl; 3-methylundec-1- yn-1-yl; n-tridec-1 -yn-1 -yl; 2-methyldodec-1-yn-1-yl; n-tetradec-1-yn-1-yl; 3-methyltridec-1-yn-1 -yl; n- pentadec-1-yn-1-yl; and 2-methyltetradec-1-yn-1-yl. (C4-C4s)-Alkynyl in the context of the invention represents an optionally substituted straight-chain or branched alkinyl radical having one to five triple bonds and 4 to 48 carbon atoms. The following may be mentioned by way of example and by way of preference: n-but-1-yn-1-yl; 2-butynyl; n-pent-1-yn-1-yl; 3-methylbut-1-yn-1-yl; n-hex-1-yn-1 -yl; 3- methylpent-1-yn-1-yl; n-hept-1-yn-1-yl; 2-methylhex-1-yn-1 -yl; n-oct-1-yn-1-yl; 3-methylhept-1-yn-1-yl; n- non-1-yn-1-yl; 2-methyloct-1-yn-1-yl; n-dec-1-yn-1-yl; 3-methylnon-1-yn-1-yl; n-undec-1-yn-1-yl; 2- methyldec-1-yn-1 -yl; n-dodec-1-yn-1-yl; 3-methylundec-1-yn-1-yl; n-tridec-1 -yn-1 -yl; 2-methyldodec-1- yn-1-yl; n-tetradec-1-yn-1-yl; 3-methyltridec-1-yn-1-yl; n-pentadec-1-yn-1-yl; and 2-methyltetradec-1-yn- 1-yl.Heteroalkynyl in the context of the invention represents an optionally substituted straight-chain or branched alkynyl radical as defined above, wherein at least one carbon atom, preferably one to five carbon atoms, are independently replaced by a heteroatom or heteroatom functionality, selected from - NH-, -N=, -O-, -S-S-, -S-, -S(=O)- or -S(=0)2.Aryl in the context of the invention represents an optionally substituted aromatic cycle (aromatic radical) which can be either monocyclic or polycyclic, having 3 to 8 atoms per ring. The following may be mentioned by way of example and by way of preference: phenyl; naphtyl; fluorenyl; anthraceneyl; and phenanthrenyl.Heteroaryl in the context of the invention represents an optionally substituted aromatic heterocycle (heteroaromatic radical) which can be either monocyclic or polycyclic, having 3 to 8 atoms per ring, wherein at least one ring contains at least one heteroatom or heteroatom functionality, preferably one to five heteroatoms or heteroatom functionalities, independently selected from. -NH-, -N=, -O-, -S-S-, -S-, -S(=O)- or -S(=O)2- and is attached via a ring carbon atom or a heteroatom wherein the one or more rings can have 4 to 8 ring atoms. The following may be mentioned by way of example and by way of preference: pyridyl; furanyl; thienyl; quinolinyl; isoquinolinyl; indolyl; benzofuranyl; and benzothiazolyl.Cycloalkyl in the context of the invention represents an optionally substituted saturated or partially saturated cycloalkyl group, which can be either monocyclic or polycyclic, having 3 to 8 atoms per ring, whereby the polycyclic cycloalkyl group can be fused ring structures, spirocycles, bridged rings or a cycloalkyl group fused with one or more aromatic rings. The following may be mentioned by way of example and by way of preference: cyclopropyl; cyclobutyl; cyclopentyl; cyclohexyl; cycloheptyl; cyclohexenyl; cyclopentenyl; cyclobutenyl; cycloheptenyl; cyclooctenyl; bicyclo[1 .1 ,0]butyl; bicyclo[2.2.0]hexyl; bicyclo[3.3.0]octyl; bicyclo[3.2.0]heptyl; bicyclo[2.2.0]hexenyl; bicyclo[3.3.0]octenyl; decalyl; norbornyl; cubyl; bicyclo[4.2.0]octan-7-ylidene; decahydronaphthalen-2-ylidene; bicyclo[2.2.0]hexan-2-ylidene; bicyclo[4.2.0]octa-1 (6);2;4-trien-7-ylidene; 2;3-dihydro-1 H-inden-1 -ylidene; 2;3-dihydro-1 H-inden-2- ylidene; spiro[3.3]heptan-2-ylidene; spiro[3.5]nonan-7-ylidene; spiro[3.5]nonan-2-ylidene; spiro[5.5]undecan-3-ylidene; adamantan-2-ylidene; bicyclo[3.1 ,1]heptan-3-ylidene; bicyclo[2.2.2]octan-2-ylidene; bicyclo[2.1 ,1]hexan-2-ylidene; bicyclo[2.2.1]heptan-2-ylidene; cholesteryl; cholesteryl-derivatives and adamantyl.Heterocycloalkyl in the context of the invention represents an optionally substituted saturated or partially saturated heterocyclic group, which can be either monocyclic or polycyclic, having 3 to 8 atoms per ring, wherein at least one ring contains at least one heteroatom or heteroatom functionality, preferably one to five heteroatoms or heteroatom functionalities, independently selected from -NH-, -N=, -O-, -S-S-, -S-, - S(=O)- or -S(=O)2- and is attached via a ring carbon atom or a heteroatom; whereby the polycyclic heterocycloalkyl group can be fused ring structures; spirocycles; bridged rings or a heterocycloalkyl group fused with one or more aromatic rings. The following may be mentioned by way of example and by way of preference: pyrrolidinyl; tetra hydro furanyl; oxetan-3-ylidene; oxolan-3-ylidene; oxan-4-ylidene; oxepan-4- ylidene; morpholinyl; piperidinyl; furanyl; thienyl; thiazolyl; indolinyl; quinolinyl; tetrahydroquinolinyl; isoquinolinyl; benzothiazolyl; benzofuranyl; bicyclo[2.2.1]heptyl; 2-oxo-2,3-dihydro-1 H-indol-3-ylidene; 4,5,6,7-tetrahydro-1 -benzothiophen-4-ylidene; 1 H,4H,5H,6H-cyclopenta[b]pyrrol-4-ylidene; decahydroquinolin-4-ylidene; octahydro-2H-1 -benzopyran-4-ylidene; hexahydro-1 H-cyclopenta[c]furan-5- ylidene; 2,2-dioxo-2lambda6-thiaspiro[3.3]heptan-6-ylidene; 2-thiaspiro[3.3]heptan-6-ylidene; 2- oxaspiro[3.3]heptan-6-ylidene; 2-azabicyclo[2.2.2]octan-5-ylidene and 2-oxabicyclo[2.2.2]octan-5-ylidene.Alkoxy in the context of the invention represents an optionally substituted straight-chain or branched alkoxy radical. A straight-chain or branched alkoxy radical having 1 to 6 carbon atoms is preferred. The following radicals may be mentioned by way of example and by way of preference: methoxy; ethoxy; n-propoxy; isopropoxy; n-butoxy; tert-butoxy; n-pentoxy and n-hexoxy.Hydroxyalkyl in the context of the invention represents an alkyl group as defined above that contains one or more hydroxyl (-OH) functional groups.Optionally substituted in the context of the invention means that the referenced chemical moiety may be unsubstituted or substituted with one or more chemical groups. Substituted with a chemical group in the context of the invention means that one or more hydrogen atoms are replaced by a different chemical group. In one embodiment of the invention, substituted means substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, alkoxy, halogen, -CN, -NO2, -N3, -ORa, - NRaRb, -N+RaRbRc, -NRaC(=O)Rb, -SRa, -S-SRa, -C(=O)Ra, -CH(ORa)(ORb), -C(=O)ORa, -C(=O)SRa-, - C(=O)Ra, -OC(=O)Ra, -SC(=O)Ra, -C(=O)NRaRb, -OC(=O)NRaRb, -NRaC(=O)ORb, -NRaC(=NRb)NRcRd, - NRaC(=NRb)Rc, -C(=NRa)NRbRc, -NRaC(=O)NRbRc, -S(=O)Ra, -SO2Ra, -NRaSORb, -NRaSO2Rb, - S(=O)NRaRb, -C(=S)NRaRb, -NRaC(=S)Rb, -SO2NRaRb, and -OSO3Ra, -OPO3RaRb, -N=NRb, -OSiRaRbRc; wherein Ra, Rb, Rcand Rdindependently of one another are hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, and alkoxy, and wherein each alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Ra, Rb, Rcand Rdare optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, alkoxy, halogen, -CN, -NO2, -N3, -ORa, -NRaRb, - N+RaRbRc, -NRaC(=O)Rb, -SRa’, -S-SRa, -C(=O)Ra, -CH(ORa’)(ORb), -C(=O)ORa, -C(=O)SRa, -C(=O)Ra,-OC(=O)Ra, -SC(=O)Ra, -C(=O)NRaRb, -OC(=O)NRaRb, -NHC(=O)NRaRb, -NRaC(=O)NHRb, - NRaC(=NRb)NRcRd, -NRaC(=NRb)Rc, -C(=NRa)NRbRc, -NRaC(=O)NRbRc, -S(=O)Ra, -SO2Ra, - NRaSORb, -NRaSO2Rb, -S(=O)NRa’Rb, -C(=S)NRa’Rb’, -NRa’C(=S)Rb, -SO2NRaRb, and -OSO3Ra, - OPO3RaRb, -N=NRb, -OSiRaRbRc; wherein Ra, Rb, Rcand Rdindependently of one another are hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, and alkoxy.As used herein, use of the phrase "at least one instance" refers to 1 , 2, 3, 4, or more instances, but also encompasses a range, e.g., for example, from 1 to 4, from 1 to 3, from 1 to 2, from 2 to 4, from 2 to 3, or from 3 to 4 instances, inclusive.The terms "composition" and "formulation" are used interchangeably.In another aspect, the present invention is directed to a composition comprising a compound of the invention (e.g. a compound of Formula (I) or (la)) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In one embodiment the composition additionally comprises at least one helper lipid (e.g., lipids that contribute to the stability and delivery efficiency of compositions (e.g., fatty acids or cholesteryl hemisuccinate (CHEMS)) and I or at least one phospholipid (e.g., non-cationic phospholipids), and I or at least one lipid for membrane structure (e.g., sterols), and I or at least one PEG-lipid. In certain embodiments, the composition is a pharmaceutical composition. In certain embodiments, the composition is a nanoparticle composition comprising lipids (a "lipid nanoparticle"). In certain embodiments, the composition is in the form of a particle (e.g., nanoparticle). In certain embodiments, the composition is in the form of a particle (e.g., nanoparticle) for the delivery of nucleic acids ("nucleic acid particle").For non-viral nucleic acid delivery vehicles, nanoparticle encapsulation of nucleic acids physically protects nucleic acids from degradation and, depending on the specific chemistry, can aid in cellular uptake and endosomal escape.A nucleic acid particle can be used to deliver nucleic acid to a target site of interest (e.g., cell, tissue, organ, and the like). A nucleic acid particle may be formed from lipids comprising at least one cationic or cationically ionizable lipid. Without intending to be bound by any theory, it is believed that the cationic or cationically ionizable lipid combines together with the nucleic acid to form aggregates, and this aggregation results in colloidally stable particles. In a particular embodiment, the nucleic acid particle, is an RNA particle or mRNA particle.Nucleic acid particles described herein include lipid nanoparticle (LNP)-based and lipoplex (LPX)-based compositions. A lipoplex (LPX) described herein is obtainable from mixing two aqueous phases, namely a phase comprising nucleic acid and a phase comprising a dispersion of lipids. In some embodiments, the lipid phase comprises liposomes. In some embodiments, liposomes are self-closed unilamellar or multilamellar vesicular particles wherein the lamellae comprise lipid bilayers and the encapsulated lumen comprises an aqueous phase. A prerequisite for using liposomes for nanoparticle formation is that thelipids in the mixture as required are able to form lamellar (bilayer) phases in the applied aqueous environment.The term "lipid nanoparticle" or "LNP" relates to a nano-sized particle comprising nucleic acid, especially RNA or mRNA, as described herein and at least one cationic or cationically ionizable lipid, wherein all three external dimensions of the particle are in the nanoscale, i.e., at least about 1 nm and below about 1000 nm. Preferably, the size of a particle is its diameter.In general, a lipid nanoparticle (LNP) is obtainable from direct mixing of nucleic acid in an aqueous phase with lipids in a phase comprising an organic solvent, such as ethanol. In that case, lipids or lipid mixtures can be used for particle formation, which do not form lamellar (bilayer) phases in water.In a particular embodiment, the composition is a lipid nanoparticle.In certain embodiments, the compositions (e.g. the LNPs) comprise a compound of the invention (e.g. a compound of Formula (I) or (la)) , and one or more of the following types of lipids: helper lipids (e.g., lipids that contribute to the stability and delivery efficiency of compositions (e.g., fatty acids or cholesteryl hemisuccinate (CHEMS))), phospholipids (e.g., non-cationic phospholipids), lipids for membrane structure (e.g., sterols), and PEG-lipids. In certain embodiments, the compositions comprise a compound of the invention (e.g. a compound of Formula (I) or (la)), and two or more of the following types of lipids: helper lipids (e.g., lipids that contribute to the stability and delivery efficiency of compositions (e.g., fatty acids or cholesteryl hemisuccinate (CHEMS))), phospholipids (e.g., non-cationic phospholipids), lipids for membrane structure (e.g., sterols), and PEG-lipids. In certain embodiments, the compositions comprise a compound of the invention (e.g. a compound of Formula (I) or (la)), and three or more of the following types of lipids: helper lipids (e.g., lipids that contribute to the stability and delivery efficiency of compositions (e.g., fatty acids or cholesteryl hemisuccinate (CHEMS))), phospholipids (e.g., non-cationic phospholipids), lipids for membrane structure (e.g., sterols), and PEG-lipids.In certain embodiments, the composition comprises a compound according to any one of formula (I), (la), (II), (Ila), (III), (Illa), (II lb), (lllc), (IV), (V), (Va) or (Vb) or (VI) or a pharmaceutically acceptable salt, cocrystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In certain embodiments, the composition comprises a compound selected from the list consisting of compound of formulas (VII), (VIII), (IX), (X), (XI), (XII), (Xllla), (Xlllb), (XlVa), (XlVb), (XVa), (XVb), (XVIa), (XVIb), (XVIIa), (XVIIb), (XVIIIa), (XVIIIb), (XIXa), (XlXb), (XXa), (XXb), (XXIa), (XXIb), (XXIIa), (XXIIb), (XXIIIa), (XXIIIb), (XXIVa), (XXIVb), (XXVa), (XXVb), (XXVIa), (XXVIb), (XXVIla), (XXVIlb), (XXVIlla), (XXVHIb), (XXIXa), (XXIXb), (XXXa), (XXXb), (XXXIa), (XXXIb), (XXXIIa), (XXXIIb), (XXXIIIa), (XXXIIIb), (XXXIVa), (XXXIVb), (XXXVa), (XXXVb), (XXXVI), (XXXVIla), (XXXVIlb), (XXXVIII), (XXXIX), (XL), (XLI), (XLII), (XLIII), (XLIV), (XLV), (XL VI), (XLVII), (XL VIII), (XLIX), (L), (LI), (Lil), (LIII), (LIV), (LV) or (LVI) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In a certain embodiment, the composition comprises a compound selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX), (LIV), (XI), (L), (LIII), (XLVIII), (XXXIVa),(XXXIX), (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In a certain embodiment, the composition comprises a compound selected from the list consisting of compound of formulas (XI), (L), (LIII), (XLVIII), (XXXIVa) and (XXXIX) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In a certain embodiment, the composition comprises a compound selected from the list consisting of compound of formulas XI), (XLI), (XLII), (XLVII), (LI), (XLIX) and (LIV) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In a certain embodiment, the composition comprises a compound selected from the list consisting of compound of formulas (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In a certain embodiment, the composition (e.g. the LNPs) comprises from about 20 to about 60 percent, or from about 25 percent to about 60 percent, or from about 30 percent to about 55 percent, or from about 40 percent to about 55 percent, or from about 40 percent to about 50 percent, of molar amount of lipidic compound disclosed herein, in percent relative to the total molar amount of the lipid components.In a certain embodiment, the composition (e.g. the LNPs) comprises from about 20 percent, about 25, about 30, about 35, about 40, about 45, about 50, about 55, or about 60 percent, of molar amount of lipidic compound disclosed herein, in percent relative to the total molar amount of the lipid components.LNPs comprising the compounds of the invention are showing optimal pKa for nucleic acid, preferably RNA, more preferably mRNA delivery. In one embodiment the LNPs comprising the compounds of the invention have a pKa value of 5.5 or higher, between 5.5 and 8.5, between 5.5 and 7.5, between 6 and 7.4 or between 6 and 7. The LNP pKa can be determined using TNS binding assay.LNPs comprising the compounds of the invention can be manufactured by conventional methods, e.g. microfluidic mixing, resulting in LNP with suitable properties for administration in vivo. Such properties include a particle size below 200 nm with a low polydispersity index (PDI) and a high encapsulation efficiency, indicating the robustness of the LNPs manufactured using the compound of the invention. The particle size and PDI of the lipid nanoparticles can be measured by dynamic light scattering (DLS). The RNA encapsulation efficiency and total RNA concentration can be quantified by Quant-iT RiboGreen RNA assay.LNPs comprising the compounds of the invention mediate expression of a protein of interest, e.g. firefly luciferase (Flue) or human erythropoietin (hEPO) when administered via different routes, e.g. i.v., s.c. or i.m.. In a further embodiment, the expression is mediated in at least one organ or tissue, in particular selected from liver, spleen or lung.LNPs comprising the compounds of the invention mediated acceptable secretion of aminotransferase (AST) and alanine aminotransferase (ALT) into the serum indicating a low toxicity profile, in particular for i.v. administrations. AST and ALT can be determined in in vivo experiments using Cobas® 6000 analyzer for quantification.LNPs comprising the compounds of the invention do not result in increased levels of terminal complex of complement pathway, indicating a safe profile.LNPs comprising the compounds of the invention induce pro-inflammatory cytokine MCP-1 depending on the lipids used for the LNP. The diversity of compounds according to the invention allow for immunomodulation depending on the therapeutic intent.In certain embodiments, helper lipids are lipids that contribute to the stability and delivery efficiency of compositions. In certain embodiments, the helper lipid is a fatty acid. In certain embodiments, the helper lipid is oleic acid. In certain embodiments, the helper lipid is a neutral phospholipid. In certain embodiments, the helper lipid is a phosphatidylethanolamine. In certain embodiments, the helper lipid is di oleoylphosphatidylethanolamine (DOPE). In certain embodiments, the helper lipid is 1 ,2- Distearoylphosphatidylethanolamine (DSPE). In certain embodiments, the helper lipid is a phosphatidylcholine. In certain embodiments, the helper lipid is 1 ,2-Distearoyl-sn-glycero-3- phosphocholine (DSPC). In certain embodiments, the helper lipid is l-palmitoyl-2-oleoyl-sn- glycero-3 - phosphocholine (POPC or GPCho). In certain embodiments, the helper lipid is 1 ,2 Dipalmitoylphosphatidylcholine (DPPC). In certain embodiments, the helper lipid is DOPE or DSPC. In certain embodiments, the helper lipid is cholesteryl hemisuccinate (CHEMS).

[0135] In some embodiments, the helper lipid is a fixed cationic lipid or salt thereof. In some embodiments, the fixed cationic lipid is l,2-dioleoyl-3 -trimethylammonium propane (DOTAP), 1 ,2-di-0-octadecenyl-3 - trimethylammonium propane (DOTMA), l,2-stearoyl-3- trimethylammonium-propane (18:0 TAP), l,2- dipalmitoyl-3 -trimethylammonium -propane (16:0 TAP), l,2-dimyristoyl-3-trimethylammonium-propane (14:0 TAP), dimethyldioctadecylammonium (18:0 DDAB), l,2-dimyristoleoyl-sn-glycero-3- ethylphosphocholine (14:1 EPC), l-palmitoyl-2-oleoyl-sn-glycero-3 -ethylphosphocholine (16:0-18:1 EPC), l,2-dioleoyl-sn-glycero-3 -ethylphosphocholine (18:1 EPC), 1 ,2- distearoyl-sn-glycero-3- ethylphosphocholine (18:0 EPC), l,2-dipalmitoyl-sn-glycero-3- ethylphosphocholine (16:0 EPC), 1, 2- dimyristoyl-sn-glycero-3-ethylphosphocholine (14:0 EPC), l,2-dilauroyl-sn-glycero-3 ethylphosphocholine (12:0 EPC), O.O’-ditetradecanoyl-N- (a-trimethylammonioacetyl)di ethanolamine (DC-6-14), or N-(2-hydroxyethyl)-N,N- dimethyl-2,3-bis(oleoyloxy)propan-l-aminium. In some embodiments, the fixed cationic lipid is l,2-dioleoyl-3 -trimethylammonium propane (DOTAP).In some embodiments, the helper lipid is a salt of a fixed cationic ligand. In certain embodiments, the salt of a fixed cationic lipid is a chloride salt, bromide salt, methyl sulfate salt, or triflate salt. In some embodiments, the salt of a fixed cationic ligand is a chloride salt.In some embodiments, the helper lipid is an ionizable lipid. In certain embodiments, the ionizable lipid is 1 ,2-distearoyl-3-dimethylammonium-propane (18:0 DAP), l,2-dipalmitoyl-3 -dimethylammonium -propane (16:0 DAP), l,2-dimyristoyl-3- dimethylammonium-propane (14:0 DAP), l,2-dioleoyl-3- dimethylammonium-propane (DODAP or 18: 1 DAP), or l,2-dioleyloxy-3 -dimethylaminopropane (DODMA).In certain embodiments, the phospholipid is a non-cationic phospholipid. In certain embodiments, the noncationic phospholipid is DSPC. In certain embodiments, the lipid for membrane structure is a sterol. In certain embodiments, the lipid for membrane structure is an animal sterol. In certain embodiments, the lipid for membrane structure is cholesterol. In certain embodiments, the PEG-lipid is a lipid that comprises polyethylene glycol (PEG). In certain embodiments, the PEG-lipid is an mPEG-comprising phospholipid. In certain embodiments, the PEG-lipid is a phospholipid comprising PEG2000 (PEG with a molecular weight of 2000 g / mol). In certain embodiments, the PEG-lipid is 1 ,2-dimyristoyl-sn-glycero- 3- phosphoethanolamine-N-[methoxy- (polyethyleneglycol)-2000] (ammonium salt) ("C14- PEG 2000"). In certain embodiments, the PEG-lipid is l,2-dipalmitoyl-sn-glycero-3- phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (ammonium salt) ("16:0 PEG2000 phospholipid"). In certain embodiments, the PEG-lipid is 1 ,2-dioleoyl-sn-glycero- 3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (ammonium salt) ("18: 1 PEG2000 phospholipid"). In certain embodiments, the PEG-lipid is 1 ,2-distearoyl-sn- glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (ammonium salt) ("18:0 PEG2000 phospholipid"). In certain embodiments, the PEG-lipid is a phospholipid comprising PEG750 (PEG with a molecular weight of 750 g / mol), PEG1000 (PEG with a molecular weight of 1000 g / mol), PEG3000 (PEG with a molecular weight of 3000 g / mol), PEG3000 (PEG with a molecular weight of 3000 g / mol), or PEG5000 (PEG with a molecular weight of 5000 g / mol).In certain embodiments, the compositions comprise a weight ratio of the lipid compounds described herein ("lipids") to the pharmaceutical agent (e.g. RNA or mRNA) of approximately 10:1 . In certain embodiments, the compositions comprise a lipid to pharmaceutical agent weight ratio of approximately 18:1 , approximately 17:1 , approximately 16:1 , approximately 15:1 , approximately 14:1 , approximately 13:1 , approximately 12:1 , approximately 1 1 :1 , approximately 10:1 , approximately 9:1 , approximately 8:1 , approximately 7:1 , approximately 6:1 , approximately 5:1 , approximately 3:1 , or approximately 2:1. In certain embodiments, the compositions comprise a lipid to pharmaceutical agent weight ratio of approximately 15:1 to approximately 5:1. In certain embodiments, the compositions comprise a lipid to pharmaceutical agent weight ratio of approximately 15:1 to approximately 10:1. In certain embodiments, the compositions comprise a lipid to pharmaceutical agent weight ratio of approximately 12:1 to approximately 8:1 , approximately 11 :1 to approximately 8:1 , approximately 11 :1 to approximately 9:1 , approximately 10:1 to approximately 8:1 , or approximately 10:1 to approximately 9:1. In certain embodiments, the compositions comprise a lipid to pharmaceutical agent weight ratio of approximately 10:1 .In certain embodiments, the compositions comprise approximately 3-30 molar percent ("mol percent ") of a helper lipid. In certain embodiments, the compositions comprise approximately 3-30 mole percent, approximately 5-30 mole percent, approximately 5-25 mole percent, approximately 5-20 mole percent, approximately 5-15 mole percent, approximately 10-15 mole percent, approximately 10-12 mole percent, approximately 12-15 mole percent, approximately 12-18 mole percent, or approximately 12-20 mole percent of a helper lipid. In certain embodiments, the compositions comprise approximately 3-30 mole percent of a helper lipid. In certain embodiments, the compositions comprise approximately 10-20 molepercent of DOPE. In certain embodiments, the compositions comprise 3-30 mole percent, approximately 5-30 mole percent, approximately 5-25 mole percent, approximately 5-20 mole percent, approximately 5- 15 mole percent, approximately 10-15 mole percent, approximately 10-12 mole percent, approximately 12-15 mole percent, approximately 12-18 mole percent, or approximately 12-20 mole percent of DOPE.In certain embodiments, the compositions comprise approximately 35-75 mole percent of lipids described herein. In certain embodiments, the compositions comprise approximately 35-75 mole percent, approximately 35-70 mole percent, approximately 35-65 mole percent, approximately 35-60 mole percent, approximately 35-55 mole percent, approximately 35-50 mole percent, approximately 35-52 mole percent, approximately 35-45 mole percent, or approximately 35-40 mole percent of lipids. In certain embodiments, the compositions comprise approximately 25-60 mole percent, approximately 30-60 mole percent, approximately 35-60 mole percent, approximately 33-60 mole percent, approximately 33-58 mole percent, approximately 33-57 mole percent, approximately 33-55 mole percent, approximately 30-45 mole percent, approximately 35-45 mole percent, or approximately 35-50 mole percent of lipids. In certain embodiments, the compositions comprise approximately 35-50 mole percent of lipids. In certain embodiments, the compositions comprise approximately 30 mole percent, approximately 31 mole percent, approximately 32 mole percent, approximately 33 mole percent, approximately 34 mole percent, approximately 35 mole percent, approximately 36 mole percent, approximately 37 mole percent, approximately 38 mole percent, approximately 39 mole percent, approximately 40 mole percent, approximately 41 mole percent, approximately 42 mole percent, approximately 43 mole percent, approximately 44 mole percent, approximately 45 mole percent, approximately 46 mole percent, approximately 47 mole percent, approximately 48 mole percent, approximately 49 mole percent, or approximately 50 mole percent of lipids.In certain embodiments, the compositions comprise approximately 0.5-3.0 mole percent of PEG-lipid. In certain embodiments, the compositions comprise approximately 0.5-3.0 mole percent, approximately 0.5- 2.5 mole percent, 1 .0-3.0 mole percent, approximately 1 .0-2.8 mole percent, approximately 1 .0- 2.5 mole percent, approximately 1 .5-2.5 mole percent, or approximately 1 .5-2.0 mole percent of PEG-lipid.In certain embodiments, the compositions comprise approximately 1.0-3.0 mole percent, approximately 1 .2-2.8 mole percent, 1 .5-2.8 mole percent, or approximately 1 .5-2.5 mole percent of PEG-lipid. In certain embodiments, the compositions comprise approximately 1.5 mole percent, approximately 1.75 mole percent, approximately 2.0 mole percent, approximately 2.25 mole percent, or approximately 2.5 mole percent of PEG-lipid. In certain embodiments, the PEG-lipid is l,2-dimyristoyl-sn-glycero-3- phosphoethanolamine-N-[methoxy- (polyethyleneglycol)-2000] (ammonium salt) ("C14-PEG 2000"), and the compositions comprise approximately 1.5 mole percent, approximately 1 .75 mole percent, approximately 2.0 mole percent, approximately 2.25 mole percent, or approximately 2.5 mole percent of PEG- lipid. In certain embodiments, the PEG-lipid is l,2-dimyristoyl-sn-glycero-3- phosphoethanolamine- N-[methoxy- (polyethyleneglycol)-2000] (ammonium salt) ("C14-PEG 2000"), and the compositions comprise approximately 1 .5-2.5 mole percent PEG-lipid.In certain embodiments, the compositions comprise a lipid to pharmaceutical agent weight ratio of approximately 10:1 ; approximately 10-20 mole percent of helper lipid; approximately 35-50 mole percent of lipid; approximately 1.5-2.5 mole percent of PEG-lipid. In certain embodiments, the compositions comprise a lipid to pharmaceutical agent weight ratio of approximately 10:1 ; approximately 10-20 mole percent of helper lipid DOPE; approximately 35-50 mole percent of lipid; or approximately 1.5-2.5 mole percent of PEG-lipid C14-PEG 2000.In certain embodiments, the compositions comprise a lipid composition weight ratio of compound of the invention (e.g. a compound of Formula (I) or (la)) / helper lipid / sterol / PEG-lipid of 45 / 15 / 45 / 2.0. In certain embodiments, the compositions comprise a lipid composition weight ratio of compound of the invention(e.g. a compound of Formula (I) or (la)) / helper lipid / sterol / PEG-lipid of 45 / 10 / 42.5 / 2.5, wherein the helper lipid is DOPE, the sterol is cholesterol, and the PEG- lipid is C14-PEG 2000. In certain embodiments, the compositions comprise a lipid composition weight ratio of compound of the invention (e.g. a compound of Formula (I) or (la)) / helper lipid / sterol / PEG-lipid of 45 / 15 / 45 / 2.0; 40 / 15 / 43 / 2.5; 35 / 12 / 43 / 2.5; 35 / 16 / 37 / 2.5; or 35 / 16 / 37 / 2.5.In certain embodiments, the compositions comprise one or more pharmaceutical agents described herein (e.g., an RNA or mRNA). In certain embodiments, the pharmaceutical agent is RNA or mRNA. In certain embodiments, the pharmaceutical agent is mRNA. In certain embodiments, the pharmaceutically agent is an mRNA vaccine.In certain embodiments, the composition comprises a compound of the invention (e.g. a compound of Formula (I) or (la)), pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or isotopically enriched derivative thereof; a polunucleotide, and one or more of a helper lipid, a PEG-lipid, and a sterol. In certain embodiments, the composition comprises a compound of the invention, pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or isotopically enriched derivative thereof; a polunucleotide, and two or more of a helper lipid, a PEG-lipid, and a sterol. In certain embodiments, the composition comprises a compound of the invention, pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or isotopically enriched derivative thereof; a helper lipid, a PEG-lipid, a sterol, and a polynucleotide. In certain embodiments, the helper lipid is DOPE, the PEG-lipid is DMG- PEG2000, the sterol is cholesterol, and the polynucleotide is mRNA. In certain embodiments, the composition further comprises a cationic lipid. In certain embodiments, the cationic lipid is DOTAP.In a certain embodiment, the composition (e.g. the LNPs) comprises DSPC / cholesterol / PEG-DMG at a molar ratio of 50:38.5:10:1 .5 mol %.In certain embodiments, the compositions selectively deliver a pharmaceutically agent to a tissue or organ in a subject (e.g., to lung, spleen, or liver tissue). In certain embodiments, the compositions selectively deliver a pharmaceutical agent to lung tissue in a subject. In certain embodiments, the compositions selectively deliver a pharmaceutical agent to spleen tissue in a subject. In certain embodiments, compositions selectively deliver a pharmaceutically agent to liver tissue in a subject.Compositions described herein can be prepared by any method known in the art. Compositions can be prepared, packaged, and / or sold in bulk, as a single unit dose, and / or as a plurality of single unit doses. A "unit dose" is a discrete amount of the composition comprising a predetermined amount of the pharmaceutical agent. The amount of the pharmaceutical agent is generally equal to the dosage of the pharmaceutical agent which would be administered to a subject and / or a convenient fraction of such a dosage, such as one-half or one-third of such a dosage.Relative amounts of the compound, excipient, pharmaceutical agent, and / or any additional ingredients in a composition described herein will vary, depending upon the identity, size, and / or condition of the subject treated and further depending upon the route by which the composition is to be administered. The composition may comprise between 0.1 percent and 100 percent (w / w) pharmaceutical agent. The composition may comprise no pharmaceutical agent.Excipients and accessory ingredients used in the manufacture of provided compositions include inert diluents, dispersing and / or granulating agents, surface active agents and / or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and / or oils. Excipients and accessory ingredients, such as cocoa butter, PEGylated lipids, phospholipids, suppository waxes, coloring agents, coating agents, sweetening, flavoring, and perfuming agents, may also be present in the composition.In certain embodiments, the compositions as described above further comprise a pharmaceutical agent and are useful for delivering said pharmaceutical agent (e.g., to a subject or cell). In certain embodiments, the compositions are pharmaceutical compositions which are useful for treating a disease in a subject in need thereof. In certain embodiments, the pharmaceutical compositions are useful for preventing a disease in a subject.In certain embodiments, the pharmaceutical agent is a small organic molecule, inorganic molecule, nucleic acid, protein, peptide, or polynucleotide. Pharmaceutical agents include therapeutically active agents. Pharmaceutical agents also include prophylactically active agents. Pharmaceutical agents include small organic or inorganic molecules such as drug compounds (e.g., compounds approved for human or veterinary use by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, polynucleotides, lipids, hormones, vitamins, vaccines, immunological agents, and cells or other biological materials. In a particular embodiment, the pharmaceutical agent is a nucleic acid.The term "nucleic acid" comprises deoxyribonucleic acid (DNA), ribonucleic acid (RNA), combinations thereof, and modified forms thereof. The term comprises genomic DNA, cDNA, mRNA, recombinantlyproduced and chemically synthesized molecules. In some embodiments, a nucleic acid is DNA. In some embodiments, a nucleic acid is RNA. In some embodiments, a nucleic acid is a mixture of DNA and RNA. A nucleic acid may be present as a single-stranded or double-stranded and linear or covalently circularly closed molecule.In one embodiment the nucleic acid is RNA. In a particular embodiment the nucleic acid is a messenger RNA (mRNA), single-stranded RNA (ssRNA), double-stranded RNA (dsRNA), small interfering RNA (siRNA), precursor messenger RNA (pre-mRNA), small hairpin RNA or short hairpin RNA (shRNA), microRNA (miRNA), guide RNA (gRNA), single guide RNA (sgRNA), transfer RNA (tRNA), antisense RNA (asRNA), heterogeneous nuclear RNA (hnRNA), coding RNA, non-coding RNA (ncRNA), long noncoding RNA (long ncRNA or IncRNA), satellite RNA, viral satellite RNA, signal recognition particle RNA, small cytoplasmic RNA, all nuclear RNA (snRNA), ribosomal RNA (rRNA), Piwi-interacting RNA (piRNA), polyinosinic acid, ribozyme, flexizyme, small nucleolar RNA (snoRNA), spliced leader RNA, viral RNA, viral satellite RNA, self-amplifying mRNA, or Trans-amplifying mRNA.aaln preferred embodiment the pharmaceutically agent is a ribonucleic acid (RNA), a small interfering RNA (siRNA), a micro RNA (miRNA), an antisense oligo nucleotides, a messenger RNA (mRNA), ribozymes, pDNA, CRISPR mRNA, gRNA or an immune stimulating nucleic acid. In a preferred embodiment the pharmaceutical agent is a messenger RNA (mRNA).In one embodiment, the pharmaceutical composition comprises a nucleic acid, preferably a RNA, more preferably an mRNA and a compound of the invention.In another embodiment the nucleic acid is DNA. In a particular embodiment the nucleic acid is pDNA.In one embodiment, the pharmaceutical composition comprises a lipid nanoparticle comprising a nucleic acid, preferably an RNA, more preferably an mRNA and a compound of the invention.In another embodiment, the pharmaceutical composition additionally comprises at least one pharmaceutically acceptable excipient. The pharmaceutically acceptable excipients may be selected from the list comprising neutral lipids such as phospholipids, a steroid such as cholesterol, and a polymer- conjugated lipid.In some embodiments, nucleic acid particles (especially mRNA particles) comprise more than one type of nucleic acid molecules, where the molecular parameters of the nucleic acid molecules may be similar or different from each other, like with respect to molar mass or fundamental structural elements such as molecular architecture, capping, coding regions or other features.In certain embodiments, the pharmaceutical agent described herein is provided in an effective amount in the composition. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount. In certain embodiments, the effective amount is an amount effective for treating a proliferative disease in a subject in need thereof.In certain embodiments, the effective amount is an amount effective for preventing a proliferative disease in a subject in need thereof. In certain embodiments, the effective amount is an amount effective for treating an autoimmune disease in a subject in need thereof. In certain embodiments, the effective amount is an amount effective for preventing an autoimmune disease in a subject in need thereof. In certain embodiments, the effective amount is an amount effective for reducing the risk of developing a disease (e.g., genetic disease, proliferative disease, hematological disease, neurological disease, painful condition, psychiatric disorder, metabolic disorder, long-term medical condition, inflammatory disease, autoinflammatory disease, liver disease, lung disease, spleen disease, familial amyloid neuropathy, cardiovascular disease, viral infection, infectious disease, fibrotic condition, or autoimmune disease) in a subject in need thereof.Compositions may be formulated into liquid dosage forms for oral and parenteral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the pharmaceutically agents, the liquid dosage forms may comprise inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3 -butylene glycol, dimethylformamide, oils (e.g., cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. In certain embodiments for parenteral administration, the particles described herein are mixed with solubilizing agents, such as Cremophor(R), alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and mixtures thereof.Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated according to the known art using suitable dispersing orwetting agents and suspending agents. The sterile injectable preparation can be a sterile injectable solution, suspension, or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1 ,3 -butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer’s solution, U.S.P., and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or di-glycerides. In addition, fatty acids, such as oleic acid, are used in the preparation of injectables.The pharmaceutical compositions provided herein can be administered by any route, including enteral (e.g., oral), parenteral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and / or drops), mucosal, nasal, bucal, sublingual; by intratracheal instillation, bronchial instillation, and / or inhalation; and / or as an oral spray, nasal spray, and / or aerosol. Specifically contemplated routes are oral administration, intravenous administration (e.g., systemic intravenous injection), regional administration via blood and / or lymph supply, and / or direct administration to an affected site. In general, the most appropriate route of administration will depend upon a variety offactors including the nature of the pharmaceutically agent (e.g., its stability in the environment of the gastrointestinal tract), and / or the condition of the subject (e.g., whether the subject is able to tolerate oral administration). In certain embodiments, the composition described herein is suitable for topical administration to the eye of a subject.In some embodiments, the percentage of the pharmaceutical composition that comprises a pharmaceutical agent is between about 1 and about 100 percent (e.g., about 1 percent, about 2 percent, about 3 percent, about 4 percent, about 5 percent, about 10 percent, about 15 percent, about 20 percent, about 30 percent, about 40 percent, about 50 percent, about 60 percent, about 70 percent, about 80 percent, about 90 percent, or about 100 percent). In some embodiments, the percentage of the pharmaceutical composition that comprises a pharmaceutical agent is less than about 50 percent, e.g., less than about 40 percent, less than about 35 percent, less than about 30 percent, less than about 25 percent, less than about 20 percent, less than about 15 percent, or less than about 10 percent. In some embodiments, the percentage of the pharmaceutical compositions that comprise a pharmaceutical agent is between about 5 percent and about 50 percent, about 5 percent and about 40 percent, about 5 percent and about 30 percent, about 5 percent and about 25 percent, or about 5 percent and about 20 percent. In some embodiments, the percentage of the pharmaceutical composition that comprises a pharmaceutical agent is between about 5 percent and 90 percent. In some embodiments, the percentage of the pharmaceutical compositions that comprise a pharmaceutical agent is between about 5 percent and about 75 percent. In the some embodiments, the percentage of pharmaceutical composition that comprises a pharmaceutical agent is between about 5 percent and about 50 percent. In the some embodiments, the percentage of the pharmaceutical composition that comprises a pharmaceutical agent is between about 10 percent and about 25 percent.In some embodiments, the total amount of the pharmaceutical agent present in the pharmaceutical composition is greater than about 5 percent (e.g., about 6 percent, about 7 percent, about 8 percent, about 9 percent, about 10 percent, about 12 percent, about 15 percent, about 20 percent, about 25 percent, about 30 percent, or more) of the total size or weight of the conjugate or pharmaceutical composition. In some embodiments, the total amount of the pharmaceutical agent present in the conjugate or pharmaceutical composition is greater than about 10 percent (e.g., about 12 percent, about 15 percent, about 20 percent, about 25 percent, about 30 percent, or more) of the total size or weight of the conjugate or pharmaceutical composition.In a further embodiment, the present invention relates to a pharmaceutical composition comprising a compound of the invention and at least one additional neutral or stealth-modified lipid.In a further embodiment, the present invention relates to a pharmaceutical composition comprising a compound of the invention and a polymer.In a further embodiment, the compound of the invention is present in the pharmaceutical composition in an amount of 10% to 70%, preferably 30% to 60 %., more preferably about 50%.In a further embodiment, the pharmaceutical composition is in the form of a particle.In a further embodiment, the pharmaceutical composition is in the form of a micelle, lipid nanoparticle (LNP), liposome, or lipoplex.In a further embodiment, the pharmaceutical composition is in the form of a nanoparticle or microparticle.In a further embodiment, the pharmaceutical composition relates to a nanoparticle comprising a compound of the invention.In another embodiment, the present invention provides inhalable dry powder compositions comprising microparticles, wherein the microparticles comprise a nucleic acid, a lipid nanoparticle, and a saccharide excipient, and wherein at least about 50% of the microparticles in the composition have an aerodynamic size of about 1 micron to about 5 microns, a physical diameter of about 3 microns to about 10 microns, or a combination thereof. In certain embodiments, the nucleic acid is encapsulated by the lipid nanoparticle.In another aspect, the present invention relates to a method for delivering a therapeutic agent to cells using the pharmaceutical composition of the invention. In one embodiment, the compounds of the invention are used for delivery of pharmaceutical agents in particulate form.The present disclosure also provides methods of using the compounds described herein, or compositions (e.g., pharmaceutical compositions) or formulations thereof, for delivering a pharmaceutically agent (e.g., a polynucleotide (e.g., RNA)). The present disclosure also provides methods of using the compounds described herein, or compositions (e.g., pharmaceutical compositions) thereof, for the treatment, prevention, or diagnosis of a disease or condition (e.g., genetic disease, proliferative disease, hematological disease, neurological disease, painful condition, psychiatric disorder, metabolic disorder, long-term medical condition, inflammatory disease, autoinflammatory disease, liver disease, lung disease, spleen disease, familial amyloid neuropathy, cardiovascular disease, viral infection, infectious disease, fibrotic condition, or autoimmune disease).The present disclosure also provides a compound of Formula (I), (la), or a pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, isotopically enriched derivative, or prodrug, or composition thereof, for use as a medicament.The present disclosure also provides a compound of Formula (I), (la), or a pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, isotopically enriched derivative, or prodrug, or composition thereof, for use in the treatment of diseases, such as genetic diseases, proliferative diseases, hematological diseases, neurological diseases, painful condition, psychiatric disorder, metabolic disorder, long-term medical condition, inflammatory diseases, autoinflammatory diseases, liver diseases, lung diseases, spleen diseases, familial amyloid neuropathy, cardiovascular diseases, viral infection, infectious diseases, fibrotic condition, or autoimmune diseases, in a subject inneed thereof. The present disclosure also provides a compound of Formula (I), (la), or a pharmaceutically acceptable salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, isotopically enriched derivative, or prodrug, or composition thereof, for use in the delivery of a pharmaceutically agent (e.g., RNA) to a tissue or organ, in a subject in need thereof. In certain embodiments, provided herein are compositions including compounds described herein for delivering a pharmaceutically agent. In certain embodiments, provided herein are compositions including compounds described herein for delivering RNA.In certain embodiments, the methods described herein include treating a disease, disorder, or condition from which a subject suffers, comprising administering to a subject in need thereof an effective amount of a composition described herein. In certain embodiments, the methods described herein include delivering an RNA agent to a tissue or cell (e.g., a liver, lung, or spleen tissue / cell), comprising administering to a subject in need thereof an effective amount of a composition described herein. In certain embodiments, the methods described herein selectively deliver an RNA agent to a tissue or organ in a subject (e.g., to lung, spleen, or liver tissue). In certain embodiments, the methods described herein selectively deliver a pharmaceutically agent to lung tissue in a subject. In certain embodiments, the methods described herein selectively deliver a pharmaceutically agent to spleen tissue in a subject. In certain embodiments, methods described herein selectively deliver a pharmaceutically agent to liver tissue in a subject. In certain embodiments, the methods described herein include implanting in a subject an effective amount of the composition described herein. In certain embodiments, the methods described herein comprise treating a disease or condition in a subject in need thereof by administering to or implanting in the subject a therapeutically effective amount of a composition. In certain embodiments, the methods described herein comprise preventing a disease or condition in a subject in need thereof by administering to or implanting in the subject a prophylactically effective amount of a composition. In certain embodiments, the methods described herein comprise diagnosing a disease or condition in a subject in need thereof by administering to or implanting in the subject a diagnostically effective amount of a composition. In certain embodiments, the disease or condition is a genetic disease, proliferative disease, hematological disease, neurological disease, painful condition, psychiatric disorder, metabolic disorder, long-term medical condition, cancer (e.g. lung cancer, large bowel cancer, pancreas cancer, biliary tract cancer, or endometrial cancer), neoplasm, angiogenesis, inflammatory disease, autoinflammatory disease, liver disease, lung disease, spleen disease, familial amyloid neuropathy, cardiovascular disease, viral infection, infectious disease, fibrotic condition, or autoimmune disease. In some embodiments, the compositions are useful in treating cancer.In a further embodiment, the present invention relates to a method of delivering a prophylactic or therapeutic agent to a mammalian cell within a mammalian subject, the method comprising administering to the mammalian subject the composition of the invention comprising the prophylactic or therapeutic agent.In a further embodiment, the present invention relates to a method of producing a polypeptide of interest in a mammalian cell, the method comprising contacting the cell with the pharmaceutical composition ofthe invention comprising an RNA, wherein the RNA encodes the polypeptide of interest, and whereby the messenger RNA (mRNA) is translated in the cell to produce the polypeptide of interest.In a further embodiment, the present invention relates to a method of treating a disease or disorder in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of the pharmaceutical composition of the invention.In another embodiment, the present invention provides methods for treating and / or preventing a disease, disorder, or condition (e.g., a genetic disease, proliferative disease, hematological disease, neurological disease, liver disease, spleen disease, lung disease, painful condition, psychiatric disorder, musculoskeletal disease, a metabolic disorder, inflammatory disease, or autoimmune disease) in a subject, comprising administering to the subject a pharmaceutical composition comprising a pharmaceutical agent and a compound selected from the list consisting of compound of formulas (I), (la), (II), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va), (Vb), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (Xllla), (Xlllb), (XlVa), (XlVb), (XVa), (XVb), (XVIa), (XVIb), (XVIIa), (XVIIb), (XVIIIa), (XVIIIb), (XIXa), (XlXb), (XXa), (XXb), (XXIa), (XXIb), (XXIIa), (XXIIb), (XXIIIa), (XXIIIb), (XXIVa), (XXIVb), (XXVa), (XXVb), (XXVIa), (XXVIb), (XXVIla), (XXVIlb), (XXVIlla), (XXVIHb), (XXIXa), (XXIXb), (XXXa), (XXXb), (XXXIa), (XXXIb), (XXXIIa), (XXXIIb), (XXXIIIa), (XXXIIIb), (XXXIVa), (XXXIVb), (XXXVa), (XXXVb), (XXXVI), (XXXVIla), (XXXVIlb), (XXXVIII), (XXXIX), (XL), (XLI), (XLII), (XLIII), (XLIV), (XLV), (XL VI), (XLVII), (XLVIII), (XLIX), (L), (LI), (Lil), (LIII), (LIV), (LV) or (LVI) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX), (LIV), (XI), (L), (LIII), (XLVIII), (XXXIVa), (XXXIX), (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (L), (LIII), (XLVIII), (XXXIVa) and (XXXIX) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX) and (LIV) or a pharmaceutically acceptable salt, co- crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the present invention provides a method of gene silencing, comprising the step of contacting a cell with a pharmaceutical composition comprising a compound of the invention. In some embodiments, the cell is a cancer cell.In another embodiment, the present invention provides methods of treating or preventing a disorder or a disease by administering to a subject in need thereof a therapeutically effective amount of an inhalable dry powder composition provided herein.In yet another embodiment, the present invention provides the use of an inhalable dry powder composition provided herein for the prophylaxis, treatment, and / or amelioration of a disorder or a disease. In certain embodiments, the disease is a genetic disease, proliferative disease, hematological disease, neurological disease, liver disease, spleen disease, lung disease, painful condition, psychiatric disorder, musculoskeletal disease, a metabolic disorder, inflammatory disease, or autoimmune disease. In certain embodiments, the disorder or disease is an allergic disease, an autoimmune disease, an infectious disease, or a cancer. In some embodiments, the disorder or disease is a lung disease, a cardiovascular disease, or a neuronal disease.In yet another embodiment the present invention provides methods of delivering a nucleic acid to a subject, comprising administering to the subject a pharmaceutical composition comprising a nucleic acid and a compound of formula (I), (la), (II), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va), (Vb), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (Xllla), (Xlllb), (XlVa), (XlVb), (XVa), (XVb), (XVIa), (XVIb), (XVIIa), (XVIIb), (XVIIIa), (XVIIIb), (XIXa), (XlXb), (XXa), (XXb), (XXIa), (XXIb), (XXIIa), (XXIIb), (XXIIIa), (XXIIIb), (XXIVa), (XXIVb), (XXVa), (XXVb), (XXVIa), (XXVIb), (XXVIla), (XXVIlb), (XXVIlla), (XXVHIb), (XXIXa), (XXIXb), (XXXa), (XXXb), (XXXIa), (XXXIb), (XXXIIa), (XXXIIb), (XXXIIIa), (XXXIIIb), (XXXIVa), (XXXIVb), (XXXVa), (XXXVb), (XXXVI), (XXXVIla), (XXXVIlb), (XXXVIII), (XXXIX), (XL), (XLI), (XLII), (XLIII), (XLIV), (XLV), (XLVI), (XL VII), (XLVIII), (XLIX), (L), (LI), (Lil), (LII I), (LIV), (LV) or (LVI) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX), (LIV), (XI), (L), (LIII), (XLVIII), (XXXIVa), (XXXIX), (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (L), (LIII), (XLVIII), (XXXIVa) and (XXXIX) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX) and (LIV) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In another embodiment, the present invention provides kits comprising a compound of formula (I), (la), (II), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va), (Vb), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (Xllla), (Xlllb),(XlVa), (XlVb), (XVa), (XVb), (XVIa), (XVIb), (XVIIa), (XVIIb), (XVIIIa), (XVIIIb), (XIXa), (XlXb), (XXa), (XXb), (XXIa), (XXIb), (XXIIa), (XXIIb), (XXIIIa), (XXIIIb), (XXIVa), (XXIVb), (XXVa), (XXVb), (XXVIa), (XXVIb), (XXVIla), (XXVIlb), (XXVIlla), (XXVHIb), (XXIXa), (XXIXb), (XXXa), (XXXb), (XXXIa), (XXXIb), (XXXIIa), (XXXIIb), (XXXIIIa), (XXXIIIb), (XXXIVa), (XXXIVb), (XXXVa), (XXXVb), (XXXVI), (XXXVIla), (XXXVIlb), (XXXVIII), (XXXIX), (XL), (XLI), (XLII), (XLIII), (XLIV), (XLV), (XLVI), (XLVII), (XLVIII), (XLIX), (L), (LI), (LII), (LIII), (LIV), (LV) or (LVI) or a pharmaceutically acceptable salt, co-crystal, polymorph,solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof; and instructions for using the compound, or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof, or pharmaceutical composition for treating and / or preventing a disease or condition in a subject or delivering a nucleic acid to a subject. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX), (LIV), (XI), (L), (LIII), (XLVIII), (XXXIVa), (XXXIX), (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (L), (LIII), (XLVIII), (XXXIVa) and (XXXIX) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX) and (LIV) or a pharmaceutically acceptable salt, cocrystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In another embodiment, the present invention provides methods of preparing a dry powder composition of a compound comprising a compound of formula (I), (la), (II), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va), (Vb), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (Xllla), (Xlllb), (XlVa), (XlVb), (XVa), (XVb), (XVIa), (XVIb),(XVIIa), (XVIIb), (XVIIIa), (XVIIIb), (XIXa), (XlXb), (XXa), (XXb), (XXIa), (XXIb), (XXIIa), (XXIIb), (XXIIIa), (XXIIIb), (XXIVa), (XXIVb), (XXVa), (XXVb), (XXVIa), (XXVIb), (XXVIla), (XXVIlb), (XXVIlla), (XXVHIb), (XXIXa), (XXIXb), (XXXa), (XXXb), (XXXIa), (XXXIb), (XXXIIa), (XXXIIb), (XXXIIIa), (XXXIIIb), (XXXIVa), (XXXIVb), (XXXVa), (XXXVb), (XXXVI), (XXXVIla), (XXXVIlb), (XXXVIII), (XXXIX), (XL), (XLI), (XLII), (XLIII), (XLIV), (XLV), (XLVI), (XLVII), (XLVIII), (XLIX), (L), (LI), (Lil), (LIII), (LIV), (LV) or (LVI) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX), (LIV), (XI), (L), (LIII), (XLVIII), (XXXIVa), (XXXIX), (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (L), (LIII), (XLVIII), (XXXIVa) and (XXXIX) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX) and (LIV) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In another embodiment, the present invention provides methods of preparing a dry powder composition, the method comprising: a) providing an aqueous mixture comprising a nucleic acid, a lipid nanoparticle comprising a compound of formula (I), (la), (II), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va), (Vb), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (Xllla), (Xlllb), (XlVa), (XlVb), (XVa), (XVb), (XVIa), (XVIb), (XVIIa), (XVIIb), (XVIIIa), (XVIIIb), (XIXa), (XlXb), (XXa), (XXb), (XXIa), (XXIb), (XXIIa), (XXIIb), (XXIIIa), (XXIIIb), (XXIVa), (XXIVb), (XXVa), (XXVb), (XXVIa), (XXVIb), (XXVIla), (XXVIlb), (XXVIlla), (XXVIHb), (XXIXa), (XXIXb), (XXXa), (XXXb), (XXXIa), (XXXIb), (XXXIIa), (XXXIIb), (XXXIIIa), (XXXIIIb), (XXXIVa), (XXXIVb), (XXXVa), (XXXVb), (XXXVI), (XXXVIla), (XXXVIlb), (XXXVIII), (XXXIX), (XL), (XLI), (XLII), (XLIII), (XLIV), (XLV), (XLVI), (XL VII), (XLVIII), (XLIX), (L), (LI), (Lil), (LIII), (LIV), (LV) or (LVI) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof, and a saccharide excipient, wherein the nucleic acid is encapsulated by the lipid nanoparticles; and b) spray freeze drying the mixture to form microparticles, wherein at least about 50% of the microparticles in the composition have an aerodynamic size of about I micron to about 5 microns, a physical diameter of about 3 microns to about 10 microns, or a combination thereof, thereby preparing the dry powder composition. In some embodiments, the lipid nanoparticle comprises a compound of formula (I), (la), (II), (Ila), (III), (Illa), (lllb), (lllc), (IV), (V), (Va), (Vb), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (Xllla), (Xlllb), (XlVa), (XlVb), (XVa), (XVb), (XVIa), (XVIb), (XVIIa), (XVIIb), (XVIIIa), (XVIIIb), (XIXa), (XlXb), (XXa), (XXb), (XXIa), (XXIb), (XXIIa), (XXIIb), (XXIIIa), (XXIIIb), (XXIVa), (XXIVb), (XXVa), (XXVb), (XXVIa), (XXVIb), (XXVIla), (XXVIlb), (XXVIlla), (XXVIHb), (XXIXa), (XXIXb), (XXXa), (XXXb), (XXXIa), (XXXIb), (XXXIIa), (XXXIIb), (XXXIIIa), (XXXIIIb), (XXXIVa), (XXXIVb), (XXXVa), (XXXVb), (XXXVI), (XXXVIla), (XXXVIlb), (XXXVIII), (XXXIX), (XL), (XLI), (XLII), (XLIII), (XLIV), (XLV), (XLVI), (XLVII), (XLVIII), (XLIX), (L), (LI), (Lil), (LIII), (LIV), (LV) or (LVI) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX), (LIV), (XI), (L), (LIII), (XLVIII), (XXXIVa), (XXXIX), (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (L), (LIII), (XLVIII), (XXXIVa) and (XXXIX) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XI), (XLI), (XLII), (XLVII), (LI), (XLIX) and (LIV) or a pharmaceutically acceptable salt, cocrystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof. In another embodiment, the compound is selected from the list consisting of compound of formulas (XII), (LV) and (LVII) or a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer, or isotopically labelled derivative thereof.In a further embodiment, the present invention relates to the use of the compounds of the invention for filling a database or training a system for the prediction of new lipids or lipid nanoparticles.In a further embodiment, the present invention relates to the use of the compounds of the invention for preparing a lipid nanoparticle. The present invention also related to a method of preparing a lipid particle using a compound according to the invention. In another aspect, the present invention is directed to a process for the preparation of the compounds of the invention by employing a reaction with a carbodiimide. In one embodiment, a carboxylic acid compound is reacted with a carbodiimide compound and the compound according to the invention is obtained after an addition reaction followed by a rearrangement reaction (O -> N acyl shift). This approach possesses a high step economy, as all functional parts of target lipids are assembled in only one synthesis step without use of any reagents or catalysts.ExamplesExample 1 : Characterization and synthesis of compoundsColumn chromatography and TLCReagents and solvents for column chromatography and TLC (MeOH, CH2CI2) were of reagent grade and acquired from Sigma-Aldrich. They were used without further purification.For column chromatography, silica gel 60 (230-400 mesh) was used. Thin layer chromatography was carried out with ready-to-use glass plates coated with silica gel from Sigma-Aldrich). Detection was done both by irradiation of the plate with UV-light at 254 nm and by application of staining reagent KMnC . The staining reagent KMnO4 was prepared by dissolving 3 g KMnC and 10 g K2CO3 in 300 mL water followed by addition of 5 mL 5% aqueous NaOH.NMRNMR spectra were recorded using Bruker 500 MHz NMR spectrometer. Calibration of the spectra was done using solvent residual peaks. Coupling constants J were given in Hz. The following abbreviations were used to describe the signals in the NMR spectra: s - singlet, d - doublet, t - triplet, q - quartet, quint - quintet, and m - complex multiplet. Abbreviation “br” is used to describe broad signals: e.g. “brs” stands for “broad singlet”. LC-MSLC MS were recorded using XEVO qTOF LCMS by Waters.Synthesis procedures of key acid intermediatesIntermediate 4: Intermediate 4 was prepared by synthesis methods analogous to the ones described for the related branched fatty acids in the literature (see the synthesis of 2-octadecylicosanoic acid WO2017099823, page 324-325):It was prepared by two-fold alkylation of dimethyl malonate with linoleyl bromide in DMF / THF in the presence of NaH (reflux), followed by ester saponification with NaOH in MeOH / FW and final decarboxylation step at 140 °C (solvent-free reaction).Intermediate 4 was isolated as a yellowish oil. It was used for the synthesis of lipid 42 and 457.1H NMR (500 MHz, CDCb) 6 0.88 - 0.95 (m, 6H), 1 .24 - 1 .42 (m, 36H), 1 .45 - 1 .53 (m, 2H), 1 .59 - 1 .68 (m, 2H), 2.02 - 2.11 (m, 8H), 2.31 - 2.42 (m, 1 H), 2.80 (t, J = 6.8 Hz, 4H), 5.31 - 5.45 (m, 8H), 10.16 (br s, 1 H).Intermediate 8:Diol 5 (150 mg, 0.93 mmol, commercially available Intermediate) was dissolved in DCM (8 mL) and esterified with the acid 6 (778 mg, 2.59 mmmol, this is a literature known compound, see its synthesis in WO2022159472, page 190-191) in the presence of 3-{[(ethylimino)methylidene]amino}-A / ,A / - dimethylpropan-1 -amine hydrochloride (585 mg, 3.05 mmol), / V, / V-dimethylpyridin-4-amine (22.6 mg, 0.19 mmol) and / V-ethyl- / V-isopropylpropan-2-amine (564 pL, 3.24 mmol) for 14 hours. Subsequently, all volatiles were removed in vacuo, the crude taken up with EtOAc (40 mL) and extracted with H2O (40 mL). The organic layer was dried over Na2SC>4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica gel (EtOAc:heptane = 1 :10 -> 4:7) to afford 7 as a colorless oil (576 mg, 0.79 mmol).1H NMR (500 MHz, CDCb) 6 0.86 - 0.93 (m, 12H), 1 .23 - 1 .36 (m, 25H), 1 .49 (s, 9H), 1 .50 - 1 .63 (m, 7H), 1 .65 - 1 .77 (m, 8H), 2.29 - 2.53 (m, 8H), 4.45 (d, J = 4.3 Hz, 2H), 4.78 - 4.88 (m, 2H), 5.21 (t, J = 4.3 Hz, 1 H). Intermediate 7 (576 mg, 0.792 mmol) was dissolved in DCM (6 mL) and TFA (4 mL) was carefully added to this solution. The resulting solution was stirred at RT for 17 hours. Subsequently all volatiles were removed in vacuo. The material was redissolved in toluene and dried in vacuo again to afford 8 as a yellowish oil. It was subjected to the synthesis of lipid 136 without further purification.1H NMR (500 MHz, CDCb) 6 0.86 - 0.94 (m, 12H), 1.28 (s, 25H), 1 .49 - 1.79 (m, 15H), 2.29 - 2.58 (m, 8H), 4.37 (dt, J = 12.2, 3.0 Hz, 1 H), 4.71 (dt, J = 12.2, 4.5 Hz, 1 H), 4.80 - 4.90 (m, 2H), 5.40 - 5.45 (m,1 H).Intermediate 10:Synthesis performed in analogy to the synthesis of 8. Intermediate 9 is described in the literature (see its synthesis in WO2023133089A1 , page 102-103). Intermediate 10 isolated as a yellowish oil and was used for the synthesis of lipid 131 .1H NMR (500 MHz, CDCb) 6 0.90 (t, J = 6.9 Hz, 12H), 1 .28 (s, 48H), 1 .48 - 1 .58 (m, 8H), 1 .62 - 1 .79 (m, 8H), 2.29 - 2.60 (m, 8H), 4.41 (dd, J = 12.2, 2.8 Hz, 1 H), 4.69 (dd, J = 12.1 , 4.4 Hz, 1 H), 4.90 (h, J = 6.1 Hz, 2H), 5.43 (dd, J = 4.4, 2.8 Hz, 1 H).Intermediate 12:Synthesis performed in analogy to the synthesis of 8. Intermediate 12 isolated as a yellowish oil and was used for the synthesis of lipid 152.1H NMR (500 MHz, CDCb) 6 0.90 (t, J = 6.9 Hz, 12H), 1 .20 - 1 .37 (m, 64H), 1 .56 - 1.81 (m, 10H), 2.28 - 2.62 (m, 8H), 3.93 - 4.08 (m, 4H), 4.37 (dd, J = 12.2, 2.6 Hz, 1 H), 4.71 (dd, J = 12.1 , 4.4 Hz, 1 H), 5.43Intermediate 18:Intermediate 16 is prepared from literature known bromide 13 (see Murata et al, Org. Let. 2014, 16, 844-847). 13 was first reacted with TosMIC followed by hydrolysis with HCI affording ketone 14 (protocol based on Dasseux et al, J. Med. Chem. 2004, 47, 6082-6099). It was subsequently subjected to the olefination with tert-butyl dimethylphosphonoacetate affording Intermediate 15 (protocol based on Sall et al, J. Med. Chem. 1997, 40, 2843-2857). For cleaving benzyl groups and reducing the double bond, Intermediate 15 was hydrogenated in EtOH in the presence of catalytic amounts of Pd / C (2.5 mol%) at 70 °C and afforded diol 16.1H NMR (500 MHz, CDCb) 6 1 .19 - 1 .43 (m, 22H), 1 .46 (s, 9H), 1 .54 - 1 .64 (m, 4H), 1 .77 - 1 .86 (m, 1 H), 2.15 (d, J = 6.9 Hz, 2H), 3.66 (t, J = 6.6 Hz, 4H).Intermediate 16 (2.0 g, 5.6 mmol) was dissolved in DCM (40 mL) and esterified with 2-hexyldecanoic acid (4.9 mL, 17.0 mmol) in the presence of 3-{[(ethylimino)methylidene]amino}-A / ,A / -dimethylpropan-1-amine hydrochloride (3.5 g, 18.0 mmol), / V, / V-dimethylpyridin-4-amine (170 mg, 1.4 mmol) and A / -ethyl- / V- isopropylpropan-2-amine (2.9 mL, 17.0 mmol) for 4.5 hours. Subsequently, all volatiles were removed in vacuo, the crude taken up with EtOAc (150 mL) and extracted with H2O (2 x 100 mL). The organic layer was dried over Na2SC>4, filtered and concentrated in vacuo. The residue was purified by column chromatography over silica gel (EtOAc: heptane = 1 :50 — > 1 :20) to afford 17 as a yellow oil (3.27 g, 3.91 mmol).1H NMR (500 MHz, CDCb) 6 0.86 - 0.94 (m, 12H), 1 .20 - 1.39 (m, 60H), 1.41 - 1.49 (m, 13H), 1.58 - 1 .67 (m, 8H), 1 .78 - 1 .85 (m, 1 H), 2.15 (d, J = 6.8 Hz, 2H), 2.28 - 2.39 (m, 2H), 4.08 (t, J = 6.7 Hz, 4H).Ester 17 (3.27 g, 3.91 mmol) was dissolved in DCM (30 mL) and TFA (10 mL) was carefully added to this solution. The resulting solution was stirred at RT for 3.5 hours. Subsequently all volatiles were removed in vacuo. The material was purified by column chromatography over silica gel (EtOAc:heptane = 1 :10 — > 1 :5) to afford 18 as a yellowish oil (3.0 g, 3.85 mmol). This acid was used for the synthesis of lipids 191 , 314, 362, 363, 364, 373, 374, 375, 378, 382, 383 and 385.1H NMR (500 MHz, CDCb) 6 0.84 - 0.94 (m, 12H), 1 .19 - 1 .40 (m, 60H), 1 .41 - 1.50 (m, 4H), 1.55 - 1.70 (m, 8H), 1 .83 - 1 .92 (m, 1 H), 2.27 - 2.39 (m, 4H), 4.09 (t, J = 6.7 Hz, 4H).Intermediate 21 :Intermediate 16 (550 mg, 1.53 mmol) was dissolved in DCM (45 mL) and esterified with 2-hexyldecanoic acid (449 pL, 1 .53 mmol) in the presence of 3-{[(ethylimino)methylidene]amino}-A / ,A / -dimethylpropan-1- amine hydrochloride (294 mg, 1.53 mmol), / V, / V-dimethylpyridin-4-amine (38 mg, 0.31 mmol) and / V-ethyl- A / -isopropylpropan-2-amine (294 pL, 1 .69 mmol) for 4.5 hours. Subsequently, all volatiles were removed in vacuo and the crude product purified by column chromatography over silica gel (EtOAc: heptane = 1 :5 —> 1 :3) to afford 19 as a colorless oil (340 mg, 0.57 mmol).1H NMR (500 MHz, CDCh) 6 0.86 - 0.93 (m, 6H), 1 .21 - 1 .41 (m, 40H), 1 .42 - 1 .50 (s, 11 H), 1 .57 - 1 .67 (m, 6H), 1 .77 - 1 .85 (m, 1 H), 2.15 (d, J = 6.9 Hz, 2H), 2.27 - 2.38 (m, 1 H), 3.62 - 3.70 (m, 2H), 4.08 (t, J = 6.7 Hz, 2H).Intermediate 19 (340 mg, 0.57 mmol) was dissolved in DCM (15 mL) and esterified with decanoic acid (174 mg, 1.01 mmol) in the presence of 3-{[(ethylimino)methylidene]amino}-A / ,A / -dimethylpropan-1-amine hydrochloride (150 mg, 0.78 mmol), / V, / V-dimethylpyridin-4-amine (24 mg, 0.2 mmol) and A / -ethyl- / V- isopropylpropan-2-amine (109 pL, 0.63 mmol) for 4.5 hours. Subsequently, all volatiles were removed in vacuo. Crude product was dissolved in EtOAc (150 mL) and extracted with water (50 mL). Organic phase was dried over Na2SO4 and all volatiles removed in vacuo. The residue was purified by column chromatography over silica gel (EtOAc: heptane = 1 :40 — > 1 :25) to afford 20 as a colorless oil (395 mg, 0.53 mmol).1H NMR (500 MHz, CDCb) 6 0.84 - 0.93 (m, 9H), 1 .21 - 1 .39 (m, 52H), 1 .42 - 1 .49 (s, 11 H), 1 .57 - 1 .67 (m, 8H), 1 .77 - 1 .86 (m, 1 H), 2.15 (d, J = 6.8 Hz, 2H), 2.28 - 2.37 (m, 3H), 4.02 - 4.12 (m, 4H).Intermediate 20 (395 mg, 0.53 mmol) was dissolved in DCM (5 mL) and TFA (1 .2 mL) was carefully added to this solution. The resulting solution was stirred at RT for 2.5 hours. Subsequently all volatiles were removed in vacuo. The material was purified by column chromatography over silica gel (EtOAc:heptane = 1 :10 —> 1 :3) to afford 21 as a yellowish oil (344 mg, 0.50 mmol). This acid was used for the synthesis of lipid 389.1H NMR (500 MHz, CDCb) 6 0.86 - 0.95 (m, 9H), 1.21 - 1 .40 (m, 52H), 1 .41 - 1 .50 (m, 2H), 1 .53 - 1 .68 (m, 8H), 1.83 - 1.91 (m, 1 H), 2.28 - 2.38 (m, 5H), 4.05 - 4.12 (m, 4H).Intermediate 24:Intermediate 22 (150 mg, 0.73 mmol, this compound is commercially available) was dissolved in DCM (5 mL) and esterified with 2-hexyldecanoic acid (537 pL, 1.84 mmol) in the presence of 3- {[(ethylimino)methylidene]amino}-A / ,A / -dimethylpropan-1-amine hydrochloride (394 mg, 2.06 mmol), N,N- dimethylpyridin-4-amine (22 mg, 0.18 mmol) and / V-ethyl- / V-isopropylpropan-2-amine (320 pL, 1 .84 mmol) for 6.5 hours. Subsequently, all volatiles were removed in vacuo. Crude product was dissolved in EtOAc (150 mL) and extracted with water (2 x 100 mL). Organic phase was dried over Na2SO4 and all volatiles removed in vacuo. The residue was purified by column chromatography over silica gel (EtOAc: heptane = 1 :40 — > 1 :15) to afford 23 as a colorless oil (370 mg, 0.53 mmol).1H NMR (500 MHz, CDCb) 6 0.90 (t, J = 6.8 Hz, 12H), 1 .28 (s, 40H), 1 .40 - 1 .50 (m, 13H), 1 .57 - 1 .66 (m, 4H), 1.76 - 1.87 (m, 2H), 1.92 - 2.05 (m, 2H), 2.28 - 2.38 (m, 2H), 2.46 - 2.57 (m, 1 H), 4.05 - 4.15 (m, 4H).Ester 23 (370 mg, 0.53 mmol) was dissolved in DCM (3 mL) and TFA (2 mL) was carefully added to this solution. The resulting solution was stirred at RT for 2 hours. Subsequently all volatiles were removed in vacuo. The material was purified by column chromatography over silica gel (EtOAc:heptane = 1 :15 — > 1 :1) to afford 24 as a yellowish oil (322 mg, 0.52 mmol). This acid was used for the synthesis of lipid 342.1H NMR (500 MHz, CDCb) 6 0.83 - 0.96 (m, 12H), 1 .22 - 1 .35 (m, 40H), 1 .41 - 1 .51 (m, 4H), 1 .54 - 1 .67 (m, 4H), 1.85 - 1.97 (m, 2H), 2.01 - 2.13 (m, 2H), 2.28 - 2.38 (m, 2H), 2.64 - 2.74 (m, 1 H), 4.16 (t, J = 6.5 Hz, 4H), 9.01 (br s, 1 H).Intermediate 29:Ketone 25 is a literature known compound and was prepared according to the known procedures (see WO2023044343, page 350-351). After esterification (analogous to the esterification of 25, described in WO2023044343, page 351), Intermediate 26 was converted to 29 following the olefination, hydrogenation and ester cleavage protocols used forthe Intermediate 18. This acid was used forthe synthesis of the lipids 343, 386, 387 and 388.1H NMR (400 MHz, CDCb) 6 0.86 (t, J = 6.6 Hz, 12H), 1 .08 - 1 .36 (m, 68H), 1 .47 - 1 .76 (m, 6H), 1 .74 - 1.91 (m, 1 H), 2.17 - 2.41 (m, 6H), 3.95 (d, J = 5.7 Hz, 4H).Intermediate 32:Glycine methyl ester hydrochloride 30 (1.84 g, 14.2 mmol) was suspended in DCM (60 mL). To this mixture were added NEts (3.88 mL, 27.7 mmol), sodium triacetoxyborohydride (9.09 g, 41.6 mmol) and linoleyl aldehyde (11.0 g, 41.6 mmol, commercially available compound). After stirring overnight, saturated aqueous solution of NaHCCh (100 mL) was added and the aqueous layer was extracted with DCM (100 mL). Combined organis were dried over MgSC and concentrated in vacuo. The residue was purified by column chromatography over silica gel (EtOAc:petroleum ether = 1 :10) to afford 31 .Intermediate 31 (6.96 g, 11 .9 mmol) was taken up with the mixture of THF (55 mL) and MeOH (27 mL). To this mixture was added a solution of NaOH (4.75 g, 119 mmol) in water (27 mL). The resulting mixture was heated to 65 for 1 h. Subsequently, the reaction mixture was acidified with aqueous HCI (37%) to pH 1 , and the aqueous phase extracted with EtOAc (2 x 100 mL). Combined organics were dried over MgSC and concentrated in vacuo. The residue was purified by column chromatography over silica gel (EtOAc:petroleum ether = 1 :10). The isolated product was dissolved in DCM and washed with an squeous NaOH solution (0.3 M) to afford the sodium salt 32. This Intermediate was used for the synthesis of lipid 419.1H NMR (400 MHz, CDCb) 6 0.88 (t, J = 6.7 Hz, 6H), 1.11 - 1.50 (m, 36H), 1.96 - 2.10 (m, 8H), 2.40 - 2.56 (m, 4H), 2.75 (t, J = 6.7 Hz, 4H), 3.00 (s, 2H), 5.25 - 5.47 (m, 8H).Synthesis procedures of key carbodiimide intermediates1 -Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-[3-(dimethylamino)propyl]-3- ethylcarbodiimide methiodide (EDC methiodide) are both commercially available compounds. Syntheses of other carbodiimides are described below.General procedure for the synthesis of Intermediates 35, 38, 40, 42, 44 and 46Carboxamides 33 and 36 are commercially available compounds. They were reacted with the diamines and converted to the respective urea compounds following the reported protocol (Batey et al, J. Org.Chem. 2022, 87, 11329-11349): Carbamoylimidazole 33 or 36 (1 .0 mmol), NEts (1.0 mmol) and amine (1 .0 mmol) were dissolved in DCM (10 mL) and stirred at RT for 20 hours. Subsequently volatiles were removed in vacuo and the obtained ureas were converted to the respective carbodiimides following the procedure described in the literature (see US6506782, page 58): The respective urea (1.0 mmol) was dissolved in DCM (10 to 20 mL) and excess NEb (4.0 mmol) was added. After subsequent addition ofTsCI (2.0 equiv.), the reacation mixture was refluxed for 4 to 8 hours. All volatiles were removed in vacuo and the carbodiimides were purified by vacuum distillation. This procedure afforded the following Intermediates: Intermediate 351H NMR (400 MHz, CDCb) 6 1.66 (p, J = 6.9 Hz, 2H), 2.16 (s, 6H), 2.27 (t, J = 7.3 Hz, 2H), 2.89 (d, J =1 .0 Hz, 3H), 3.20 (t, J = 6.8 Hz, 2H).Intermediate 381H NMR (400 MHz, CDCb) 6 1 .10 - 1 .24 (m, 3H), 1 .69 (p, J = 7.0 Hz, 2H), 2.22 (s, 3H), 2.30 - 2.52 (m, 10H), 3.10 - 3.27 (m, 4H).Intermediate 401H NMR (400 MHz, CDCb) 6 1 .12 - 1 .25 (m, 3H), 1 .64 - 1 .82 (m, 6H), 2.34 - 2.51 (m, 6H), 3.09 - 3.27(m, 4H).Intermediate 421H NMR (400 MHz, CDCb) 6 1.01 (t, J = 7.1 Hz, 6H), 1.18 - 1.28 (m, 3H), 1 .63 - 1.78 (m, 2H), 2.43 -2.57 (m, 6H), 3.15 - 3.32 (m, 4H).Intermediate 441H NMR (400 MHz, CDCb) 6 1 .12 - 1 .27 (m, 3H), 1 .32 - 1 .46 (m, 2H), 1 .50 - 1 .64 (m, 4H), 1 .67 - 1 .82(m, 2H), 2.24 - 2.46 (m, 6H), 3.12 - 3.33 (m, 4H).Intermediate 461H NMR (400 MHz, CDCb) 6 1 .23 (t, J = 7.2 Hz, 3H), 1 .57 - 1 .71 (m, 2H), 1 .83 - 1 .97 (m, 2H), 2.01 - 2.15 (m, 2H), 2.26 (s, 3H), 2.67 - 2.80 (m, 2H), 3.15 - 3.29 (m, 3H).Procedure for the synthesis of Intermediate 50Carboxamide 47 is a literature known compound and was prepared according to the known procedure (see US2014037573, page 105). Protected aminoalcohol 48 is a literature known compound as well and was prepared according to the published protocol (Turockin et al, J. Org. Chem. 2016, 81, 4516-4529). Intermediates 47 and 48 were converted to the respective urea following the reported protocol (Batey et al, J. Org. Chem. 2022, 87, 11329-11349): Carbamoylimidazole 47 (1.0 mmol), NEts (1.0 mmol) and protected aminoalcohol (1.0 mmol) were dissolved in DCM (10 mL) and stirred at RT for 20 hours. Subsequently volatiles were removed in vacuo and the obtained urea was converted to Intermediate 50following the procedure described in the literature (see analogous synthesis in US6506782, page 58): The respective urea (1 .0 mmol) was dissolved in DCM (10 to 20 mL) and excess NEts (4.0 mmol) was added. After subsequent addition of TsCI (2.0 equiv.), the reacation mixture was refluxed for 4 to 8 hours. All volatiles were removed in vacuo and Intermediate 50 was purified by column chromatography. This Intermediate was used for the synthesis of the lipid 378.Intermediate 501H NMR (400 MHz, DMSO) 6 1 .00 (s, 9H), 1 .57 (p, J = 6.8 Hz, 2H), 1 .75 (p, J = 6.3 Hz, 2H), 2.08 (s, 6H), 2.21 (t, J = 7.0 Hz, 2H), 3.14 (t, J = 6.6 Hz, 2H), 3.29 - 3.39 (m, 2H), 3.72 (t, J = 6.1 Hz, 2H), 7.39 - 7.51 (m, 6H), 7.57 - 7.67 (m, 4H).General procedures for the synthesis of ionizable and cationic lipids:To as solution of carboxylic acid (0.5 mmol) in CH2CI2 (2 mL) the respective cabodiimide is added (1.5 mmol, e.g. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide). The resulting solution is heated to 80 °C while the reaction vessel is still open: Within 30 minutes DCM typically evaporates, and the resulting neat mixture is further stirred for 12-20 hours. Subsequently, all volatiles are removed in vacuo and the residue is purified by column chromatography over silica gel using MeOH:CH2Cl2 = 1 :10 as eluent to afford the pure lipid.Compounds according to the invention prepared according to the above-described procedure can be found in table 2.Assignment of the structures of the isolated regioisomers:Mechanistically, the formation of the lipids from the acids and carbodiimides can be regarded as a two- step process: At first an isourea intermediate is formed, which subsequently rearranges to the final lipids via N— >O acyl shift. During this rearrangement two regioisomers are formed. As an example, the formation mechanism of the respective lipid 191 and 314 is presented below:Both lipid isomers can be separated by using column chromatography, as exemplified by the isomeric pair of lipids 191 and 314. The correct structure assignment of each isomer was performed by using COSY (Correlation Spectroscopy). The structure assignment was built upon the fact that the methylene H-signal located in the close proximity to both carbonyl group has a very low chemical shift due to electron pulling effect of two C=O groups: Its chemical shift was expected to be between 3.5 and 4.0 ppm. The only -C / - / 2- signals with lower chemical shifts were the ones located next to the ester groups (-C / - / 2OOC- ). Indeed, both isolated compounds showed signals at 3.79 and 3.82 ppm respectively.characteristic H signalsThe less polar fraction isolated during column chromatographic purification was shown to have a clear correlation between the signal at 3.79 ppm and signal at 1 .80 ppm. Another very characteristic correlation was observed between the C / - / 3 protons (1.19 ppm) and a methylene group at 3.30 ppm: These signals belong to the -NCH2CH3 group. These data clearly indicate that this isomer posseses structure assigned as lipid 191 . Furthermore,1H NMR spectrum shows that the signal at 3.79 ppm is a tripplett, which further supports the assigned structure of IL191 : If it possessed the structure of IL314, the signal at such low chemical shift would have to be a quartett (3J coupling with the methyl group protons -NCH2C / - / 3) or a more complex multiplett due to an additional3J couping with the NH proton. Based on these data, the structure of IL191 was assigned to the less polar fraction isolated during the column chromatography (see Figure 1).The more polar fraction isolated during column chromatographic purification was shown to have a correlation between the signal at 3.82 ppm and signal at 1.23 ppm. Signal at 1.23 ppm is largely overlapping with other aliphatic signals, but its chemical shift corresponds to the value typical for a CH3 gorup (part of the short ethyl chain -NCH2C / - / 3). Moreover,1H NMR spectrum shows that the signal at 3.82 ppm is a quartett, which further supports the assigned structure of IL314: If it possessed the structure of IL191 , the signal at such low chemical shift could not be quartett, but would rather be a tripplett (3J coupling with the methylene protons of the amino allyl residue Me2NCH2C / 2CH2-). Based on these data, the structure of IL314 was assigned to the more polar fraction isolated during the column chromatography (see Figure 2).Based on this pattern, it is possible to assign the structures of other lipids synthesized and isolated in the course of this work.Table 2Example 2: Preparation of lipid nanoparticle composition via pipetting mixing.Exemplary lipid nanoparticle compositions were prepared by dissolving a lipid mixture containing a compound of the invention / DSPC / cholesterol / PEG-DMG at a molar ratio of 50:38.5:10:1.5 mol % in ethanol. The compound of the invention as referenced by the No in table 3 is the ionizable lipid of the LNP.Flue mRNA was solubilized in 25 mM acetate buffer pH 4 at 0.15 mg / ml. Lipid nanoparticles were prepared by adding 15 pL of ethanol containing the lipid mixture at 16.4 mM to 45 pL of mRNA dissolved in 25 mM acetate buffer pH 4 at mRNA concentration of 0.15 mg / ml using a pipette and mixing up-down. Then, 40 pL of PBS was added to the formulation to reduce the amount of ethanol. The formulations were dialyzed against phosphate buffered saline (PBS) in Pierce™ Microdialysis Plates (Thermofisher, Cat. # 88260, Waltham, USA) for 3h hours with exchange of buffer. Formulations were stored at 4°C for one week.The LNP pKa was determined using the TNS binding assay. The TNS reagent was prepared as a 300 pM stock solution in DMSO. In black 96-well plate, 3.26 pL of LNP at a mRNA concentration of 0.04 mg / ml and 2 pL TNS were added to 90 pL of buffers pL of buffered solutions containing a broad range of buffers with 10 mM sodium citrate, 10 mM sodium phosphate and 10 mM sodium borate with a pH ranging from 3 to 10. The fluorescence was measured with Ex340 / Em4430 in Tecan Infinite M200 Pro Multimode Plate Reader (Tecan Reader). The fluorescence data was fitted using Sigmoidal fitting.Table 3:It can be derived that lipid nanoparticles prepared according to Example 2 containing compounds of the invention resulted in pKA above 5.5. Several ionizable lipid candidates exhibited optimal pKa for hepatic RNA delivery (6<pKa< 7.4).Example 3: Preparation of lipid nanoparticle composition via microfluidic mixing.Exemplary lipid nanoparticle compositions were prepared by dissolving a lipid mixture containing a compound of the invention / DSPC / cholesterol / PEG-DMG at a molar ratio of 50:38.5:10:1.5 mol % in ethanol. The compound of the invention as referenced by the IL No in tables 4 to 6 is the ionizable lipid of the LNP.Lipid nanoparticles were prepared by mixing an ethanol phase containing the lipid mixture with an aqueous phase containing the RNA using a microfluidic mixing device, the Ignite™ Benchtop Instrument (Precision NanoSystems, Vancouver, BC), at flow rate of 12 min / ml, and flow rate ratio of 3:1 (Aqueous:Organic phase). The resultant mixture was directly dialyzed against phosphate buffered saline (1xPBS) for 2h at RT, and then overnight at 4°C using Pur-A-Lyzer™ Maxi Dialysis Kit (12-14 kDa, MerckMillipore). If required, the formulations were then re-concentrated by ultrafiltration using Amicon® Ultra Centrifugal titers (30kDa NMWL, Merck Millipore). Formulations were stored at 4°C for one week.The particle size and polydispersity (PDI) of the lipid nanoparticles were measured by dynamic light scattering (DLS) using DynaPro plate reader II instrument from WYATT technology GmbH (Dembach, Germany). The lipid formulations were diluted in 1xPBS to a final RNA concentration of 0.0001 mg / mL, 3 sec, 15 acquisitions.The RNA encapsulation efficiency and total RNA concentration was quantified by Quant-iT RiboGreen RNA assay (Thermo Fischer Scientific). Briefly, the encapsulation efficiency was determined using the RNA binding dye RiboGreen by comparing fluorescence between samples in the presence and absence of 2% Triton X-100. In the absence of detergent, fluorescence can be measured from accessible free RNA only, whereas in the presence of detergent, fluorescence is measured from the total RNA amount. The fluorescence of samples in the presence of the detergent Triton X-100 was also used to calculate the total RNA concentration based on a calibration curve. Lipid nanoparticle samples or PBS (negative control) were diluted with IxTE buffer (Thermo Fisher Scientist) down to a mRNA concentration between 2 and 5 pg / mL. Aliquots of each diluted samples was further diluted 1 :1 in IxTE buffer (measuring accessible mRNA) or 1 :1 in IxTE buffer containing 2% Triton-X100 (measuring total mRNA, both accessible within the particle and free mRNA). Samples were prepared in duplicate. Samples were incubated 10 min at 37°C to ensure sufficient lipid dissociation. Quant-iT RiboGreen RNA reagent (1 :100 dilutions from the stock solution in TE buffer) was then added 1 :1 to each sample and the fluorescence of the dye was measured at an excitation wavelength of 485 nm and emission 535 nm (Tecan Infinite M200 Pro Multimode Plate Reader).The RNA accessibility was determined as follows: the total RNA concentration was determined using an RNA calibration curve in 1xTE buffer with 2% Triton X-100.The particle characterization for each exemplary lipid nanoparticle composition for different payloads are shown in tables 4 to 6.Table 4Table 5Table 6It can be derived that lipid nanoparticles containing exemplary compounds according to the invention prepared according to Example 3 with varied payloads resulted in suitable properties for administration in vivo, such as sub-200 nm particles, with suitable PDI (<0.3) and high encapsulation efficiency. The data indicates the robustness of the herein described ionizable lipids.Example 4: In vivo biodistribution of lipid nanoparticles containing ionizable lipids.Lipid nanoparticles prepared according to Example 3 containing compounds according to the invention, were used in this example.Mice (Balb / C mice, female, 10-15, n = 3 in each group) are anesthetized with isoflurane and lipid nanoparticles containing compounds according to the invention formulated with luciferase encoding mRNA were injected intravenously (caudal vein) or subcutaneously (right flank) with a 1-ml pre-equipped with syringe pre-equipped with a cannula of 26G in size. The mouse was observed until regaining consciousness for signs of pain, suffering, and distress.At the time of measurement (6h and 24h post-dose), mice were injected intraperitoneally with D-Luciferin- solution resulting 150 mg / kg body weight. Subsequently, mice were anesthetized with Isoflurane and placed on a heated mat (37°C) inside the BERTHOLD TECHNOLOGIES NightOwl imaging chamber with a constant supply of Isoflurane / oxygen via individual anesthesia masks. Ten minutes afterthe injection of luciferin, the detection of bioluminescence light via camera was performed. Mice were then sacrificed by exsanguination, and organs such as liver, lung, spleen, heart, and kidney, were collected and incubated in 0.3 mg / ml of luciferin forten minutes and measured again with the imaging device. The resulting images were analyzed using the Indigo software. The region of interest (ROI) were drawn around the organs to quantify the average flux of photon [ph s-1 cm-2 sr-1 ].Table 7Table 8Table 9It can be derived that the lipid nanoparticles formulated according to Example 3 containing compounds according to the invention demonstrate high mRNA expression of the payload into at least one organ via different administration routes.Example 5: Hepatic toxicity of single injection of lipid nanoparticles via intravenous injection.The exemplary lipid nanoparticles prepared according to Example 3 containing compounds according to the invention, were administered to balb / C mice (female, 10-15 weeks)( n = 3 in each group). The blood was collected at 6h and 24h after administration and the plasma was collected by centrifugation (18003g, for 10 minutes, 4°C). aminotransferase (AST) and alanine aminotransferase (ALT) in the serum were quantified in Cobas® 6000 analyzer (Roche Diagnostics).Table 10It can be derived that lipid nanoparticles formulated according to Example 3 containing compounds according to the invention mediated secretion of AST and ALT levels after intravenous administration. The typical levels of ALT and AST in healthy mice are 50-60 and 90-100 IU / L, respectivelly. In this example, several exemplary ionizable lipids mediated acceptable secretion of AST and ALT levels, indicating a low toxicity profile of exemplary ionizable lipids after IV administrations.Example 6: Activation of complement terminal complex of lipid nanoparticles containing ionizable lipids.The exemplary lipid nanoparticles prepared according to Example 3 containing compounds according to the invention, were incubated with human serum at 37°C. LNP concentrations were calculated as the nanoparticle theoretical plasma concentration, which derives from the ratio between the human dose and the human blood volume. This concentration provides a rough estimation of maximum concentration of LNP in the human blood. On average, a human with a body weight of 70 kg body weight has approximately 5.6 L of blood. Therefore, based on a human dose of 1 mg / kg, the theoretical plasma concentration (i.e., the in vitro testing concentration) is equivalent to an mRNA concentration of 12.5 pg / mL. Vehicle buffer (PBS) was used as negative controls. Concentrations of complement terminal complex C5b-9 was quantified using MicroVue SC5b 9 Plus Enzyme Immunoassay (Quidel), following the manufacturing instructions.Table 1 1It can be derived that lipid nanoparticles prepared according to Example 3 containing exemplary compounds according to the invention did not result in substantial increased levels of terminal complex of complement pathway, indicating a possible safe profile.Example 7: hEPO secretion after intravenous application of lipid nanoparticles containing ionizable lipids.The exemplary lipid nanoparticles prepared according to Example 3 containing compounds according to the invention, were administered to balb / C mice (female, 10-15 weeks)(n = 4 in each group). The blood was collected at 3, 6, 10, 24 and 48h after administration and the plasma was collected by centrifugation (1800 g, for 10 minutes, 4°C). hEPO secretion in plasma was quantified by ELISA.Table 12Example 8: Cytokine induction of lipid nanoparticles containing ionizable lipids.The exemplary lipid nanoparticles prepared according to Example 3 containing compounds according to the invention, were administered to balb / C mice (female, 10-15 weeks) (n = 4 in each group). The blood was collected at 6h after administration and the plasma was collected by centrifugation (1800 3g, for 10 minutes, 4°C). MCP-1 secretion in plasma was quantified by ELISA.Table 13It can be derived that the lipid nanoparticles prepared according to Example 3 containing exemplary compounds according to the invention induce the secretion of MCP-1 cytokine after IV administration. The secretion of MCP-1 is substantial at 6h, but it decreased to basal levels 24h-post injection. The profile of pro-inflammatory cytokine MCP-1 might depend on the ionizable lipid structure.

Claims

Claims1 . Compound of formula (I)whereinR1and R2independently of one another are optionally substituted C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, with the proviso that R1and I or R2contain at least one nitrogen atom,R3and R4independently of one another are optionally substituted C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl,Xi and X2 independently of one another are absent or optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C2-C6 heteroalkenyl or C2-C6 heteroalkynyl,Z is absent or optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl or a chemical moiety selected from the group consisting of -C(=O)-, -C(=O)O-, -C(=O)NH-, andY is N or C, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

2. Compound according to Claim 1 , whereinR1and R2independently of one another are C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, optionally substituted with one or more groups independently selected from C1- Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, hydroxyalkyl, alkoxy, halogen, -CN, -NO2, -N3, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, - SRa, -S-SRa, -C(=O)Ra, -CH(ORa)(ORb), -C(=O)ORa, -C(=O)SRa-, -C(=O)Ra, -OC(=O)Ra, - SC(=O)Ra, -C(=O)NRaRb, -OC(=O)NRaRb, -NRaC(=O)ORb, -NRaC(=NRb)NRcRd, -NRaC(=NRb)Rc, -C(=NRa)NRbRc, -NRaC(=O)NRbRc, -S(=O)Ra, -SO2Ra, -NRaSORb, -NRaSO2Rb, -S(=O)NRaRb, - C(=S)NRaRb, -NRaC(=S)Rb, -SO2NRaRb, and -OSO3Ra, -OPO3RaRb, -N=NRband -OSiRaRbRc, whereinRa, Rb, Rcand Rdindependently of one another are hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 heteroalkyl, C2-C20 heteroalkenyl, C2-C20 heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl or alkoxy, wherein each C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Ra, Rb, Rcand Rdare optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, hydroxyalkyl, alkoxy, halogen, -CN, -NO2,-N3, -ORa, -NRa’Rb’, -N+RaRbRc, -NRaC(=O)Rb, -SRa’, -S-SRa, -C(=O)Ra, -CH(ORa’)(ORb), -C(=O)ORa, -C(=O)SRa, -C(=O)Ra, -OC(=O)Ra, -SC(=O)Ra, -C(=O)NRaRb, - OC(=O)NRaRb, -NHC(=O)NRaRb, -NRaC(=O)NHRb, -NRaC(=NRb)NRcRd, NRaC(=NRb)Rc, -C(=NRa)NRbRc, -NRaC(=O)NRbRc, -S(=O)Ra, -SO2Ra, -NRaSORb, - NRaSO2Rb, -S(=O)NRaRb, -C(=S)NRa’Rb’, -NRa’C(=S)Rb’, -SO2NRaRb, and -OSO3Ra, - OPO3RaRb, -N=NRband -OSiRaRbRc, whereinRa, Rb, Rcand Rdindependently of one another are hydrogen, Ci-C2o alkyl, C2-C2o alkenyl, C2-C2o alkynyl, Ci-C2o heteroalkyl, C2-C2o heteroalkenyl, C2-C2o heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl or alkoxy, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

3. Compound according to Claim 1 or 2, whereinR1and R2independently of one another are Ci-Ce alkyl, Ci-Ce heteroalkyl, cycloalkyl or heterocycloalkyl, optionally substituted with one or more groups independently selected from cycloalkyl, heterocycloalkyl, hydroxy, oxo, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, -C(=O)ORa, -OC(=O)Ra, -C(=O)NRaRb; whereinRa, Rband Rcindependently of one another are hydrogen, Ci-Ce alkyl, Ci-Ce heteroalkyl, cycloalkyl, heterocycloalkyl, hydroxyalkyl and alkoxy, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

4. Compound according to any of Claims 1 to 3, whereinR1is Ci-C6alkyl, optionally substituted with -NRaRb; whereinR2is Ci-C6alkyl, pyrrolidine or piperidine, optionally substituted with one or more groups independently selected from Ci-Ce alkyl, -NRaRb, pyrrolidine or piperidine; wherein Raand Rbindependently of one another are hydrogen or Ci-Ce alkyl, with the proviso that R1and I or R2contain at least one nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

5. Compound according to any of Claims 1 to 4, wherein the at least one nitrogen atom is a basic nitrogen atom, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

6. Compound according to any of Claims 1 to 5, whereinR3and R4independently of one another are C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl orheterocycloalkyl, optionally substituted with one or more groups independently selected from Ci- Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, hydroxyalkyl, alkoxy, halogen, -CN, -NO2, -N3, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, - SRa, -S-SRa, -C(=O)Ra, -CH(ORa)(ORb), -C(=O)ORa, -C(=O)SRa-, -C(=O)Ra, -OC(=O)Ra, - SC(=O)Ra, -C(=O)NRaRb, -OC(=O)NRaRb, -NRaC(=O)ORb, -NRaC(=NRb)NRcRd, -NRaC(=NRb)Rc, -C(=NRa)NRbRc, -NRaC(=O)NRbRc, -S(=O)Ra, -SO2Ra, -NRaSORb, -NRaSO2Rb, -S(=O)NRaRb, - C(=S)NRaRb, -NRaC(=S)Rb, -SO2NRaRb, and -OSO3Ra, -OPO3RaRb, -N=NRband -OSiRaRbRc, whereinRa, Rb, Rcand Rdindependently of one another are hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl or alkoxy, wherein each C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Ra, Rb, Rcand Rdare optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxy, oxo, thioxo, hydroxyalkyl, alkoxy, halogen, , -CN, -NO2, -N3, -ORa, -NRaRb, -N+RaRbRc, -NRaC(=O)Rb, -SRa, -S-SRa, -C(=O)Ra, -CH(ORa)(ORb), -C(=O)ORa, -C(=O)SRa, -C(=O)Ra, -OC(=O)Ra, -SC(=O)Ra, -C(=O)NRaRb, -OC(=O)NRaRb, -NHC(=O)NRaRb, -NRaC(=O)NHRb, - NRaC(=NRb)NRcRd, -NRaC(=NRb)Rc, -C(=NRa)NRbRc, -NRaC(=O)NRbRc, -S(=O)Ra, - SO2Ra, -NRaSORb, -NRaSO2Rb, -S(=O)NRa’Rb, -C(=S)NRa’Rb, -NRa’C(=S)Rb, -SO2NRaRb, and -OSO3Ra, -OPO3RaRb, -N=NRband -OSiRaRbRc, whereinRa, Rb, Rcand Rdindependently of one another are hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C2-C48 alkynyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, C2-C48 heteroalkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, hydroxyalkyl or alkoxy, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

7. Compound according to any of Claims 1 to 6, whereinR3and R4independently of one another are C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl, C2-C48 heteroalkenyl, optionally substituted with one or more groups independently selected from hydroxy, oxo, -C(=O)ORa, -OC(=O)Ra; whereinRais hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl or C2-C48 heteroalkenyl, wherein each alkyl, alkenyl, heteroalkyl and Raare optionally substituted with one or more groups independently selected from C1-C6 alkyl, C2-C6 alkenyl, hydroxy, oxo, -C(=O)ORa, - OC(=O)Ra; whereinRais hydrogen, C1-C48 alkyl, C2-C48 alkenyl, C1-C48 heteroalkyl or C2-C48 heteroalkenyl, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

8. Compound according to any of Claims 1 to 7, whereinXi is optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C2-C6 heteroalkenyl or C2-C6 heteroalkynyl, andX2 is absent; and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

9. Compound according to any of Claims 1 to 8, whereinXi is absent or optionally substituted methylene,X2 is absent, andZ is absent, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

10. Compound according to any of Claims 1 to 9, whereinY is C, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.11 . Compound according to any of Claims 1 to 10, whereinY is N, and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

12. Compound according to any of Claims 1 to 11 , wherein the compound is of the formula,and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

13. Compound according to any of Claims 1 to 12, wherein the compound is of the formula,and a pharmaceutically acceptable salt, co-crystal, polymorph, solvate, hydrate, tautomer, stereoisomer and isotopically labeled derivative thereof.

14. Use of a compound according to any of Claims 1 to 13 for preparing a lipid nanoparticle.

15. A composition comprising a compound according to any of Claims 1 to 13.