Cyclohexane lipidoids for nucleic acid transfection and use thereof

Lipidoids of general formula (I)

• wherein
• X is selected from the group comprising —C(═O)NH—, —C(═O)O—, —C(═S)O—, —C(═O)S—, —C(═S)S—, —C(═O)NHNH—, —CH2—, —O—, —OC(═O)—, —S—, —SC(═O)—, —NH—, —NHNH—, —NHC(═O)—, —NHNHC(═O)—, —C≡C—, —CH═CH—, a five-membered heterocycle containing at least 2 nitrogen atoms, —CH2C(═O)NH—, —CH2C(═O)O—, —CH2C(═S)O—, —CH2C(═S)S—, —CH2C(═O)NHNH—, —N═CH—, —CH═N—, —NH—N═CH—, and —CH═N—NH—;
• Y is selected from the group consisting of C2-C10 alkylene chains, wherein the alkylene chain, one or more —CH2— groups may optionally be replaced with one or more O and/or S atoms;
• R1 are the same or different from each other, each R1 being independently selected from the group consisting of C1-C46 alkyl, C2-C46 alkenyl, C2-C46 alkynyl, wherein the alkyl, alkenyl or alkynyl may be linear or branched, and wherein in the alkyl, alkenyl or alkynyl, one or more —CH2— groups may be replaced with CH(OH), —OC(═O)—, —C(═O)O—, —S—S—, —C(═O)NH—, —NHC(═O)—, —O—, and —S—;
• wherein if R1 is C1-C4 alkyl, then one hydrogen from the terminal —CH3 group may be substituted with Z;
• with the proviso that at least one R1 contains at least 8 carbon atoms;
• Z are the same or different from each other, each Z being independently selected from the group comprising hydrogen, —OH, —CH3, —CH2OH, —NH2, —C(═O)NH2, —CONH(CH2)2OH, —CON[(CH2)2OH]2, —CONHCH(CH2OH)2, —CONHCH2CH(—OH)CH2OH, —CONH(CH2)2C(═O)NH2, —CON[CH2C(═O)NH2]2, —CONHCH[C(═O)NH2]2, —CONH(CH2)2NHC(═O)NH2, —CONH(CH2)3—N+(CH3)2—(CH2)2—SO3−, —CONH(CH2)3—N+(CH3)2—(CH2)3—SO3−, —CONH(CH2)3—N+(CH3)2—(CH2)2—COO−, —COO(CH2)2—O—P(═O)(O−)—O(CH2)2—N+(CH3)3, —N+(CH3)2—(CH2)3—SO3−, —N+(CH3)2—(CH2)2—COO−,
• wherein
• R2 is independently selected from hydrogen and —CH3;
• E is independently selected from O and S atoms;
• n is an integer within the range of from 1 to 5;
• and T are the same or different from each other, each T being independently selected from the group comprising —X—Y—N(R1)2, —C(═O)O(C1-C3 alkyl), —C(═O)OCH2CH2OH, —C(═O)NH2,
• —C(═O)OH, —CONH(CH2)2OH, —CON[(CH2)2OH]2, —CONHCH(CH2OH)2, —CONHCH2CH(—OH)CH2OH, —CONH(CH2)2C(═O)NH2, —CON[CH2C(═O)NH2]2, —CONHCH[C(═O)NH2]2, —CONH(CH2)2NHC(═O)NH2, —CONH(CH2)3—N+(CH3)2—(CH2)2—SO3−, —CONH(CH2)3—N+(CH3)2—(CH2)3—SO3−, —CONH(CH2)3—N+(CH3)2—(CH2)2—COO−, —COO(CH2)2—O—P(═O)(O—)—O(CH2)2—N+(CH3)3,
• —OH, —O(C1-C3 alkyl), —NH2, —NHC(═O)CH3, —NHS(═O)2CH3, —NHC(═O)N(CH3)2, —NHC(═O)NH(CH3), —NHC(═S)N(CH3)2, —NHC(═S)NH(CH3), —NHC(═N—CN)NH2, —NHC(═N—CN)NH(CH3), —NHC(═N—CN)N(CH3)2, —NHC[═N—S(═O)2NH2]NH2, —N+(CH3)2—(CH2)3—SO3−, —N+(CH3)2—(CH2)2—COO−, and
• wherein R2, E and n are as defined above;
• and/or if Z is —OH or —CH2OH, and T is —C(═O)OH, then Z together with T and three carbon atoms between them may form a cyclic lactone containing 4 to 5 carbon atoms;
• and pharmaceutically acceptable salts, addition salts and solvates thereof.