3-Substituted Piperidine-2, 6-Diones and Non-Covalent Complexes with Albumin

A compound according to Formula (II):

• or a pharmaceutically acceptable salt thereof,
• wherein
• A is a covalent bond, O or NR1;
• each RA is H, or both RA taken together is oxo;
• L is alkyl, alkyl-O-alkyl, alkenyl, alkynyl, carbocyclyl, carbocyclylalkyl, aryl, alkaryl,
• or a linker comprising a —S—S— bond, each of which is optionally substituted with 1-3 substituents independently selected from the group consisting of halo, —NO2, amine, amide, hydroxyl, O-lower alkyl and —COOH, provided that there be no covalent bonds between oxygen atoms;
• W is
• R1 is H, lower alkyl, or alkaryl, wherein the alkyl or alkaryl is optionally substituted with 1-3 substituents independently selected from the group consisting of:
• halo, NO2, amine, amide, hydroxyl, O-lower alkyl and —COOH;
• R2 is independently in each instance H, OH, NO2, NH2, SH or a branched or unbranched C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl, wherein the C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl is optionally substituted with 1-2 substituents independently selected from the group consisting of halo, OH, NO2, NH2, SH and ═O, and wherein the C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl optionally has 1-2 heteroatoms independently selected from O, S and NH wherein each heteroatom replaces a CH2, with the proviso that no O, S or N atom in the C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl is covalently bonded to another O, S or N atom;
• R3 is independently in each instance H, alkyl, alkenyl, alkynyl, alkyl-O-alkyl, alkyl-O-aryl, phenyl, or alkaryl, wherein the alkyl, alkenyl, alkynyl, alkyl-O-alkyl, alkyl-O-aryl, phenyl, or alkaryl is optionally substituted with 1-3 substituents independently selected from the group consisting of:
• halo, —NO2, —CF3, amido, sulfonamide, aryl, —OH, alkyl, —O-lower alkyl, —O-alkaryl, and —O-aryl;
• R4 is independently in each instance H, OH, NO2, NH2, SH or a branched or unbranched C1-10 alkyl, C2-10 alkenyl or C2-10 alkynyl, wherein the C1-10 alkyl, C2-10 alkenyl or C2-10 alkynyl is optionally substituted with 1-2 substituents independently selected from the group consisting of halo, OH, NO2, NH2, SH and ═O, and wherein the C1-10 alkyl, C2-10 alkenyl or C2-10 alkynyl optionally has 1-2 heteroatoms independently selected from O, S and NH wherein each heteroatom replaces a CH2, with the proviso that no O, S or N atom in the C1-10 alkyl, C2-10 alkenyl or C2-10 alkynyl is covalently bonded to another O, S or N atom;
• R5 is H, alkyl, alkenyl, alkynyl, alkyl-O-alkyl, alkyl-O-aryl, phenyl, or alkaryl, wherein the alkyl, alkenyl, alkynyl, alkyl-O-alkyl, alkyl-O-aryl, phenyl, or alkaryl is optionally substituted with 1-3 substituents independently selected from the group consisting of:
• halo, —NO2, —CF3, amido, sulfonamide, aryl, —OH, alkyl, —O-lower alkyl, —O-alkaryl, and —O-aryl;
• R6 and R7 is each independently H or lower alkyl, optionally substituted with 1-3 substituents independently selected from the group consisting of halo, nitro, amine, amide, hydroxyl, O-lower alkyl and carboxy;
• B is a covalent bond, O or NR1;
• p is 1, 2, 3, 4, 5, or 6;
• n is 1, 2, 3, 4, 5, or 6;
• and
• r is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.