Conjugate based systems for controlled insulin delivery

A conjugate or a pharmaceutically acceptable salt thereof, represented by structural formulas selected from the group consisting of (I), (II), (III), and (IV):

• wherein
• each occurrence of
• represents a potential branch within the conjugate;
• each occurrence of
• represents a potential repeat within branch of the conjugate;
• each occurrence of is independently a covalent bond, a carbon atom, a heteroatom, or an optionally substituted group selected from the group consisting of acyl, aliphatic, heteroaliphatic, aryl, heteroaryl, and heterocyclic;
• each occurrence of T is independently a covalent bond or a bivalent, straight or branched, saturated or unsaturated, optionally substituted C1-30 hydrocarbon chain wherein one or more methylene units of T are optionally and independently replaced by —O—, —S—, —N(R)—, —C(O)—, —C(O)O—, —OC(O)—, —N(R)C(O)—, —C(O)N(R)—, —S(O)—, —S(O)2—, —N(R)SO2—, —SO2N(R)—, a heterocyclic group, an aryl group, or a heteroaryl group;
• each occurrence of T′ is independently selected from hydrogen, a bond, T, and Rp;
• each occurrence of R is independently hydrogen, a suitable protecting group, or an acyl moiety, arylalkyl moiety, aliphatic moiety, aryl moiety, heteroaryl moiety, or heteroaliphatic moiety, said moieties, where possible, optionally substituted with 1 to 3 groups of OH or COOH or interrupted with a —CO— or —CONH— group;
• Rp is a straight or branched, saturated or unsaturated, optionally substituted C10-40 hydrocarbon chain wherein one or more methylene units of RP are optionally and independently substituted or replaced by —O—, —S—, —N(R)—, —C(O)—, C(O)O—, —OC(O)—, —N(R)C(O)—, —C(O)N(R)—, —S(O)—, —S(O)2—, —N(R)SO2—, SO2N(R)—, a heterocyclic group, an aryl group, or a heteroaryl group, wherein the hydrocarbon chain comprises a C8-30 fatty chain that is uninterrupted by —O—, —S—, —N(R)—, —C(O)—, C(O)O—, OC(O)—, —N(R)C(O)—, —C(O)N(R)—, —S(O)—, —S(O)2—, —N(R)SO2—, SO2N(R)—, a heterocyclic group, an aryl group, or a heteroaryl group;
• Rp′ is independently selected from hydrogen and Rp;
• —B is -T-LB-X;
• each occurrence of X is independently a ligand that includes a saccharide;
• each occurrence of LB is independently a covalent bond or a group derived from the covalent conjugation of a T with an X;
• -D is -T-LD-WI;
• each occurrence of WI is independently an insulin molecule;
• each occurrence of LD is independently a covalent bond or a group derived from the covalent conjugation of a T with a WI;
• n is an integer from 0 to 5, inclusive, as valency permits, wherein when n is 0, B is present and linked to T or D;
• each occurrence of m is independently an integer from 1 to 5, inclusive;
• and each occurrence of v is independently an integer from 1 to 5, inclusive, as valency permits, wherein the substituents are selected from the group consisting of halo, hydroxy, oxo (e.g., an annular —CH— substituted with oxo is —C(O)—), nitro, halohydrocarbyl, hydrocarbyl, aryl, aralkyl, alkoxy, aryloxy, amino, acylamino, alkylcarbamoyl, arylcarbamoyl, aminoalkyl, acyl, carboxy, hydroxyalkyl, alkanesulfonyl, arenesulfonyl, alkanesulfonamido, arenesulfonamido, aralkylsulfonamido, alkylcarbonyl, acyloxy, cyano, and ureido.