Amphiphilic compounds and vesicles liposomes for organ-specified drug targeting

An amphiphilic compound capable of forming vesicles or liposomes, of the formula Ia:

• R8—R7-A4-R6-A3-R5—OC-Q2-R10-Q1-CO—R1-A1-R2-A2-R3—R4 (Ia)
• wherein:
• R1 and R5, the same or different, each is —(CH2)n;
• A1 is selected from the group consisting of —(CH2)m+2—, —CH═CH—(CH2)m—, —CH═CH—CH(Y1)—, —CH2—CH2—CH(Y1)—, (—CH2—CH(Y1)—(CH2)m—, —CH(Y1)—CH2—(CH2)m—, —CH(Y1)—CH(Y2)—(CH2)m—, wherein Y1 and Y2 each is halogen, —OH, —O—CO—(CH2)m—Y3, —NH—CO—Y3, —SH, —SR11, —NH2, and —N(R11)(R12), or Y1 and Y2 together with the carbon atoms to which they are attached form a 2,3-oxiranylene group;
• and Y3 is halogen, —OH, —SH, —NH2, or —N(R11)(R12);
• R2 and R6, the same or different, each is C1-C4 alkylene, unsubstituted or substituted by halogen, amino or hydroxy;
• A2 is —CH(R13)—, —CH2—CH(R13)—, —CH(R13)—CH2—, —CH(OH)—CH(R13) —, —CH(R13)—CH(OH)—, —CH(OH)—CH2—CH(OH)—CH(R13)—, —CH(OH)—CH2—CH(R13)—CH(OH)—, -G1-(C6-C14 arylene)-(CH2)qR14, —N(CH3)2R14, or —SR14;
• R3 and R7, the same or different, each is —(CH2)o—;
• R4 is H or CH3, and wherein the total sum of carbon atoms in the R1-A1-R2-A2-R3—R4 chain is at most 23;
• Q1 is —NH—, —O—, —S—, or —O—PO(OH)—O—;
• Q2 is —NH—, —O—, —S—, or —O—PO(OH)—O—;
• R10 is —(CH2)p—;
• —CH2(CH3)—(CH2)p—;
• —CH(CH3)—(CH2)p—CH(CH3)—;
• —(CH2—CH2—O—)p—CH2—CH2—;
• —(CH2—CH2—S—)p—CH2—CH2—;
• —(CH2—CH2—NH—)p—CH2—CH2—;
• —C6-C14 arylene-;
• —(C6-C14 arylene)-R—(C6-C14 arylene), wherein R is C1-C4 alkylene, —CCH3)2—, —O—, —S—, —NH— or —SO2—;
• A3 is as defined for A1, or is —(CH2)m, phenyl or —CH2-phenyl, wherein the phenyl ring is unsubstituted or substituted by C1-C4 alkyl, halogen or both;
• A4 is as defined for A2, or is —(CH2)m—;
• R8 is as defined for R4;
• R13 is -G1-(CH2)mR14 or -G1-CO(CH2)mR14;
• G1 is —O—, —S—, —NR″—, —CH2NR″—, —CH2S—, —CH2O—, —NH—CO—, —O—CO—NH—, —NH—CO—NH—, —C═NO—, or —C(NH2)=NO—, wherein R″ is H or C1-C18 alkyl;
• R14 is either a headgroup containing a selectively cleavable group or moiety, or is as defined for R15 or for R15 substituted by a selectively cleavable group or moiety;
• R11 and R12, the same or different, each is C1-C18 alkyl unsubstituted or substituted by halogen;
• phenyl or —CH2-phenyl, wherein the phenyl ring is unsubstituted or substituted by C1-C4-alkyl, halogen, or both, and wherein one of R11 and R12 may be H;
• R15 is —NH2;
• —NR11R12;
• —N+R11R12R16 wherein R16 is as defined for R11 and R12;
• —O—CO—(C2-C6 alkenyl);
• —O—CO—(CH2)t—NR11R12;
• —O—CO—(CH2)t—N+R11R12R16;
• —O—CO—(CH2)t—COOH;
• —O—CO—(CH2)t—SO3H;
• —O—CO—(CH2)t—O—PO(OH)2;
• —NH—(CH2)r—COOH;
• —NH—(CH2)r—SO3H;
• —NH—(CH2)r—O—PO(OH)2;
• —NH—PO(OH)2;
• —N+(CH3)2—R17;
• —O—PO(OH)—O—(CH2)2—N+R11R12R16;
• —O—PO(OH)—O—(CH2)2—NH3+;
• —O—PO(OH)—NH—PO(OH)—O—;
• —O—PO(OH)—O—CH2—CH(NH3+)—COO−;
• —CH2—CH═CH2;
• —CO—CH═CH2;
• —CO—C(CH3)═CH2;
• —(CH2)r—COOH;
• —(CH2)r—O—SO2H;
• —(CH2)r—O—PO(OH)2;
• —SR18;
• -G1-(C6-C14 arylene)-NR11R12;
• -G1-(C6-C14 arylene)-N+R11R12R16;
• -G1-(C6-C14 arylene)-COOH;
• -G1-(C6-C14 arylene)-SO3H;
• -G1-(C6-C14 arylene)-O—PO(OH)2;
• -G1-(C6-C14 arylene)-(CH2)t—NR11R12;
• -G1-(C6-C14 arylene)-(CH2)n—N+R11R12R16;
• -G1-(C6-C14 arylene)-(CH2)t—COOH;
• or -G1-(C6-C14 arylene)-(CH2)t—SO3H;
• R17 is —CH2—CH═CH2, —CO—CH═CH2, —CO—C(CH3)═CH2, —(CH2)q—N+R11R12R16, —(CH2)q—NH—(CH2)q—SO3H, —(CH2)q—NH—(CH2)q—COOH, —(CH2)q—NH—(CH2)q—O—PO(OH)2, —PO(OH)2, or —O—PO(OH)—O—(CH2)2—N+R11R12R16;
• R18 is hydrogen, C1-C18 alkyl, C2-C6 alkenyl with a terminal double bond, —CO—CH═CH2, or —CO—C(CH3)═CH—NR11R12;
• n is an integer from 5 to 10;
• m is an integer from 0 to 4;
• o is an integer from 0 to 10;
• p is an integer from 1 to 16;
• q is an integer from 0 to 3;
• r is an integer from 1 to 6;
• and t is an integer from 1 to 14,
• and salts thereof;
• wherein said amphiphilic compound of formula Ia has at least one radical R14 which is a headgroup containing a selectively cleavable group or moiety and at least one hydrogen-bonding group located within said at least one headgroup, in close proximity thereto, or within and in close proximity to said at least one headgroup;
• and said selectively cleavable group or moiety is a group or moiety that is cleaved under selective conditions selected from the group consisting of change of chemical conditions, physical conditions, biological environment and combinations thereof.