Substituted piperidine amides and methods of their use

A composition for treating multidrug resistance comprising:

• (A) an active compound selected from the group consisting of a structure
• 59
• wherein w is 0 to about 6, x is 0 to about 10, and t is 0 to about 6;
• A is a substituted heterocyclic group having about 4 to about 9 members;
• R1 is selected from the group consisting of a hydrogen atom, a hydroxyl group, a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group,
• R2 and R3 are bonded together to form a substituted heterocyclic group having about 4 to about 9 members, with the proviso that the substituted heterocyclic group optionally contains 1 or more members selected from the group consisting of O, and NR10, wherein R10 is selected from the group consisting of hydrogen atom, a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
• R4 is selected from the group consisting of —S(O)2—,—C(O)—, —C(O)—C(O)—, and —CH(R1)—;
• R5 is selected from the group consisting of —NR6(R7)' and —OrR6—,
• wherein r is 0 or 1;
• R6 is selected from the group consisting of a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
• and
• R7 is selected from the group consisting of a hydrogen atom and R6;
• R8 is selected from the group consisting of a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
• R9 is selected from the group consisting of a hydrogen atom and a hydrocarbon group;
• and
• an optical isomer, a diastereomer, an enantiomer, a pharmaceutically-acceptable salt, a biohydrolyzable amide, a biohydrolyzable ester, and a biohydrolyzable imide of the structure, and combinations thereof;
• and (B) a carrier.

A method for inhibiting transport protein activity comprising administering, to a subject, a compound selected from the group consisting of a structure:

• 60
• wherein w is 0 to about 6, x is 0 to about 10, and t is 0 to about 6;
• A is a substituted heterocyclic group having about 4 to about 9 members;
• R1 is selected from the group consisting of a hydrogen atom, a hydroxyl group, a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group,
• R2 and R3 are bonded together to form a substituted heterocyclic group having about 4 to about 9 members, with the proviso that the substituted heterocyclic group optionally contains 1 or more members selected from the group consisting of O, and NR10, wherein R10 is selected from the group consisting of hydrogen atom, a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
• R4 is selected from the group consisting of —S(O)2—,—C(O)—, —C(O)—C(O)—, and —CH(R1)—;
• R5 is selected from the group consisting of 'NR6(R7)— and —OrR6—,
• wherein r is 0 or 1;
• R6 is selected from the group consisting of a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
• and
• R7 is selected from the group consisting of a hydrogen atom and R6;
• R8 is selected from the group consisting of a hydrocarbon group, a substituted hydrocarbon group, a heterogeneous group, a substituted heterogeneous group, a carbocyclic group, a substituted carbocyclic group, a heterocyclic group, a substituted heterocyclic group, an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
• R9 is selected from the group consisting of a hydrogen atom and a hydrocarbon group;
• an optical isomer, a diastereomer, an enantiomer, a pharmaceutically-acceptable salt, a biohydrolyzable amide, a biohydrolyzable ester, and a biohydrolyzable imide of the structure;
• and combinations thereof.