Diether based biodegradable cationic lipids for siRNA delivery

A cationic lipid of Formula A:

• wherein:
• R1 and R2 are independently selected from H, (C1-C6)alkyl, heterocyclyl, and polyamine, wherein said alkyl, heterocyclyl and polyamine are optionally substituted with one to three substituents selected from R1;
• or R1 and R2 can be taken together with the nitrogen to which they are attached to form a monocyclic heterocycle with 4-7 members optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, said monocyclic heterocycle is optionally substituted with one to three substituents selected from R′;
• R5 is independently selected from (C4-C8)alkylene or (C4-C8)alkenylene, said alkylene or alkenylene optionally substituted with one to three substituents selected from R′;
• R6 is (C1-C2)alkyl, said alkyl optionally substituted with one to three substituents selected from R′;
• Q2 is a bond, —OC(O)—, —C(O)O—, —SC(O)—, —C(O)S—, —OC(S)—, —S—S, —C(R″)═N—, —N═C(R″)—, —C(R″)═N—O—, —O—N═C(R″)—, —C(O)(NR″)—, —N(R″)C(O)—, —C(S)(R″)—, —(R″)C(O)—, —N(R″)C(O)N(R″)—, —OC(O)O—, OSi(R″)2O—, —C(O)(CR″2)C(O)O—, or —OC(O)(CR″2)C(O)—, with the proviso that when either Q1 or Q2 is a bond then the other is not a bond;
• each occurrence of R′ is independently selected from halogen, R″, OR″, SR″, CN, CO2R″ or CON(R″)2;
• R″ is independently selected from H and (C1-C6)alkyl, wherein said alkyl is optionally substituted with halogen and OH;
• n is 0, 1, 2, 3, 4 or 5;
• and
• -R3-Q1-R4 is selected from the group consisting of
• or a pharmaceutically acceptable salt or stereoisomer thereof.