Cationic Lipids and Uses Thereof

A cationic lipid having

• wherein Y1 is C1-C6 alkylene;
• Y2 is CH2, NH or O;
• Y3 is a bond or C(O);
• Y4 is a bond or C(O);
• Y5 is CH2, NH or O;
• Y6 is a bond or C1-C6 alkylene;
• R1 and R2 are independently H, cycloalkyl, cycloalkenyl or R5;
• or
• R1 and R2, together with the nitrogen to which they are attached, are heterocycloalkyl or heteroaryl;
• one of R3 and R4 is H, and the other is C14-C20-alkenyl, or C14-C20-alkyl;
• or
• R3 and R4 independently selected C14-C20-alkenyl, or C14-C20-alkyl;
• or
• R3 and R4 to ether CR20R21, wherein R20 is H and R21 is C14-C20-alkenyl, C14-C20-alkyl, or CH2O—C14-C20-alkenyl;
• or R20 and R21 are independently selected C14-C20-alkenyl, C14-C20-alkyl, or CH2O—C14-C20-alkenyl;
• R5 is alkyl, which is unsubstituted or substituted with one or more R6, OR6, SR6, S(O)R6, SO2R6, C(O)R6, CO(O)R6, OC(O)R6, OC(O)OR6, NH2, NHR6, N(R6)2, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)NHR6, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR6, C(N)N(R6)2, CNOH, CNOCH3, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;
• R6 is R7, R8, R9, or R10;
• R7 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene;
• R8 is heteroaryl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene;
• R9 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene;
• R10 is alkyl, alkenyl or alkynyl;
• wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or more R11, OR11, SR11, S(O)R11, SO2R11, C(O)R11, CO(O)R11, OC(O)R11, OC(O)OR11, NH2, NHR11, N(R11)2, NHC(O)R11, NR11C(O)R11, NHS(O)2R11, NR11S(O)2R11, NHC(O)OR11, NR11C(O)OR11, NHC(O)NH2, NHC(O)NHR11, NHC(O)N(R11)2, NR11C(O)NHR11, NR11C(O)N(R11)2, C(O)NH2, C(O)NHR11, C(O)N(R11)2, C(O)NHOH, C(O)NHOR11, C(O)NHSO2R11, C(O)NR11SO2R11, SO2NH2, SO2NHR11, SO2N(R11)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR11, C(N)N(R11)2, CNOH, CNOCH3, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;
• R11 is R12, R13, R14, or R15;
• R12 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene;
• R13 is heteroaryl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene;
• R14 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene;
• R15 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected R16, OR16E, SR16, S(O)2R16, C(O)OH, NH2, NHR16N(R16)2, C(O)R16, C(O)NH2, C(O)NHR16, C(O)N(R16)2, NHC(O)R16, NR16C(O)R16, NHC(O)OR16, NR16C(O)OR16, OH, F, Cl, Br or I;
• R16 is alkyl, alkenyl, alkynyl, or R17;
• R17 is phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;
• wherein R12, R13, R14, and R17 are independently unsubstituted or substituted with one or more R18, OR18, SR18, S(O)R18, SO2R18, C(O)R18, CO(O)R18, OC(O)R18, OC(O)OR18, NH2, NHR18, N(R18)2, NHC(O)R18, NR18C(O)R18, NHS(O)2R18, NR18S(O)2R18, NHC(O)OR18, NR18C(O)OR18, NHC(O)NH2, NHC(O)NHR18, NHC(O)N(R18)2, NR18C(O)NHR18, NR18C(O)N(R18)2, C(O)NH2, C(O)NHR18, C(O)N(R18)2, C(O)NHOH, C(O)NHOR18, C(O)NHSO2R18, C(O)NR18SO2R18, SO2NH2, SO2NHR18, SO2N(R18)2, C(O)H, C(O)OH, C(N)NH2, C(N)NHR18, C(N)N(R18)2, CNOH, CNOCH3, OH, (O), CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br or I;
• and
• R18 is alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl.