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US 2002/0119979 A1Published application
Acyclic compounds and methods for treating multidrug resistance
OwnerCharles Raymond Degenhardt, David Joseph Eickhoffinventors
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Abstract
Substituted acyclic compounds are disclosed. The compounds are useful for treating multidrug resistance. The compounds can be formulated in compositions with a carrier and, optionally, a therapeutic agent. One suitable substituted acyclic compound has the formula: 1
Claims23
An active compound having a structure selected from the group consisting of structures (I), (II), and (III), and an optical isomer, a diastereomer, an enantiomer, a pharmaceutically-acceptable salt, a biohydrolyzable amide, a biohydrolyzable ester, and a biohydrolyzable imide of structures (I), (II), and (III), and combinations thereof, wherein structure (I) is:
- 67
- wherein a is 0 to about 10, b is 0 to about 10, c is 0 to about 10, and d is 0 or 1,
- each R1 is independently 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 structure,
- R4 is selected from the group consisting of a hydrogen atom, a hydrocarbon group, and a group of the formula
- 68
- wherein denotes a point of attachment,
- each R5 is independently 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
- R6 is selected from the group consisting of —C(O)—and —SO2—;
- structure (II) is
- 69
- wherein f is 0 to about 10, g is 0 to about 10, and his 0 or 1,
- R8 is selected from the group consisting of a 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,
- R9 is selected from the group consisting of a substituted hydrocarbon group and a substituted heterogenous group, wherein R9 is substituted with a group selected from the group consisting of an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
- and structure (III) is
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- wherein R13 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,
- R14 is selected from the group consisting of a hydrogen atom and R13, and with the proviso that optionally, R13 and R14 may be bonded together thereby forming a ring selected from the group consisting of heterocyclic groups and substituted heterocyclic groups,
- R15 is selected from the group consisting of a hydrogen atom, a hydrocarbon group, and a group having the structure
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17 more elements
A composition for treating multidrug resistance comprising:
- (A) an active compound having a structure selected from the group consisting of structures (I), (II), and (III), and an optical isomer, a diastereomer, an enantiomer, a pharmaceutically-acceptable salt, a biohydrolyzable amide, a biohydrolyzable ester, and a biohydrolyzable imide of structures (I), (II), and (III) wherein structure (I) is:
- 83
- wherein a is 0 to about 10, b is 0 to about 10, c is 0 to about 10, and d is 0 or 1,
- each R1 is independently 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 structure,
- R4 is selected from the group consisting of a hydrogen atom, a hydrocarbon group, and a group of the formula
- 84
- wherein denotes a point of attachment,
- each R5 is independently 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
- R6 is selected from the group consisting of —C(O)— and —SO2—;
- structure (II) is
- 85
- wherein f is 0 to about 10, g is 0 to about 10, and his 0 or 1,
- R8 is selected from the group consisting of a 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,
- R9 is selected from the group consisting of a substituted hydrocarbon group and a substituted heterogenous group, wherein R9 is substituted with a group selected from the group consisting of an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
- and structure (III) is
- 86
- wherein R13 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,
- R14 is selected from the group consisting of a hydrogen atom and R13, and with the proviso that optionally, R13 and R14 may be bonded together thereby forming a ring selected from the group consisting of heterocyclic groups and substituted heterocyclic groups,
- R15 is selected from the group consisting of a hydrogen atom, a hydrocarbon group, and a group having the structure
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- and
- (B) a carrier.
20 more elements
A method for inhibiting transport protein activity comprising administering, to a subject:
- (A) an active compound having a structure selected from the group consisting of structures (I), (II), and (III), and an optical isomer, a diastereomer, an enantiomer, a pharmaceutically-acceptable salt, a biohydrolyzable amide, a biohydrolyzable ester, and a biohydrolyzable imide of structures (I), (II), and (III), and combinanations thereof, wherein
- structure (I) is:
- 88
- wherein a is 0 to about 10, b is 0 to about 10, c is 0 to about 10, and d is 0 or 1,
- each R1 is independently 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 structure,
- R4 is selected from the group consisting of a hydrogen atom, a hydrocarbon group, and a group of the formula
- 89
- wherein denotes a point of attachment,
- each R5 is independently 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
- R6 is selected from the group consisting of —C(O)—and —SO2—;
- structure (II) is
- 90
- wherein f is 0 to about 10, g is 0 to about 10, and h is 0 or 1,
- R8 is selected from the group consisting of a 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,
- R9 is selected from the group consisting of a substituted hydrocarbon group and a substituted heterogenous group, wherein R9 is substituted with a group selected from the group consisting of an aromatic group, a substituted aromatic group, a heteroaromatic group, and a substituted heteroaromatic group;
- and structure (III) is
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- wherein R13 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,
- R14 is selected from the group consisting of a hydrogen atom and R13, and with the proviso that optionally, R13 and R14 may be bonded together thereby forming a ring selected from the group consisting of heterocyclic groups and substituted heterocyclic groups,
- R15 is selected from the group consisting of a hydrogen atom, a hydrocarbon group, and a group having the structure
- 92
19 more elements
Dependencies are inferred from the claim text.