Substituted heterocyclic compounds for treating multidrug resistance
First Claim
Patent Images
1. A composition comprising:
- (A) a therapeutic agent; and
, (B) a compound selected from the group consisting of a structure;
or an optical isomer, diastereomer, enantiomer, or pharmaceutically-acceptable salt thereof, wherein;
(i) s is an integer from about 1 to about 3;
(ii) A is selected from the group consisting of A1 and A3 (iii) A1 is a group of the formula;
wherein, (a) 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;
(b) x is 0 to about 10;
(c) R2 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;
(d) D1 and D2 are each independently selected from the group consisting of —
C(O)— and
—
NR3—
;
(e) R3 is selected from the group consisting of a hydrogen atom and R2, and with the proviso that optionally, R2 and R3 may be bonded together thereby forming a ring selected from the group consisting of heterocyclic groups and substituted heterocyclic groups;
(f) y is 0 or 1 and z is 0 or 1, with the provisos that when y is 0, z is 1 and when y is 1, z is 0, when y is 0 and D1 is —
NR3—
, then D is —
C(O)—
, when y is 0 and D is —
NR3—
, then D1 is —
C(O)—
, and when x is 0, D1 is —
C(O)—
, y is 0, D2 is —
NR3—
, and D3 is —
C(O)—
or —
S(O)2—
, then R2 is selected from the group consisting of a hydrocarbon group and a substituted hydrocarbon group, wherein the substituted hydrocarbon group is substituted with an aromatic group; and
(iv) A2 is a group of the formula;
wherein, (a) u is 0 to about 10;
(b) p is 0 to about 10;
(c) v is 0 or 1;
(d) D3 is selected from the group consisting of —
S(O)2—
, —
C(O)—
, and —
CR1(OH)—
, with the provisos that when D3 is —
S(O)2—
, then D1 is —
C(O)—
, D2 is —
NR3—
, and R2 and R3 are bonded together to form the ring structure, and when D3 is —
C(O)—
, v is 0, and R5 contains a —
C(O)—
group, then p is not 0;
(e) R5 is selected from the group consisting of a substituted hydrocarbon group of at least 2 carbon atoms and substituted heterogeneous groups of at least 2 member atoms, wherein R5 is substituted with at least one group selected from the group consisting of aromatic groups, heteroaromatic groups, substituted aromatic groups, and substituted heteroaromatic groups;
(v) A3 has the formula
wherein, (a) t is about 1 to about 6;
(b) D4 is selected from the group consisting of —
C(O)— and
—
CHR1—
;
(c) D5 is selected from the group consisting of —
NR6(R7), —
OrR6, and —
C(O)R6, wherein r is 0 or 1;
(d) 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
, (e) R7 is selected from the group consisting of a hydrogen atom and R6, with the proviso that when u is 0, D3 and D4 are not both —
C(O)—
.
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Accused Products
Abstract
Substituted heterocyclic compounds for treating multidrug resistance are disclosed. Compositions and methods of use for the substituted heterocyclic compounds are disclosed. Suitable substituted heterocyclic compounds include:
66 Citations
17 Claims
-
1. A composition comprising:
-
(A) a therapeutic agent; and
,(B) a compound selected from the group consisting of a structure;
or an optical isomer, diastereomer, enantiomer, or pharmaceutically-acceptable salt thereof, wherein;
(i) s is an integer from about 1 to about 3;
(ii) A is selected from the group consisting of A1 and A3 (iii) A1 is a group of the formula;
wherein, (a) 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;
(b) x is 0 to about 10;
(c) R2 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;
(d) D1 and D2 are each independently selected from the group consisting of —
C(O)— and
—
NR3—
;
(e) R3 is selected from the group consisting of a hydrogen atom and R2, and with the proviso that optionally, R2 and R3 may be bonded together thereby forming a ring selected from the group consisting of heterocyclic groups and substituted heterocyclic groups;
(f) y is 0 or 1 and z is 0 or 1, with the provisos that when y is 0, z is 1 and when y is 1, z is 0, when y is 0 and D1 is —
NR3—
, then D is —
C(O)—
, when y is 0 and D is —
NR3—
, then D1 is —
C(O)—
, and when x is 0, D1 is —
C(O)—
, y is 0, D2 is —
NR3—
, and D3 is —
C(O)—
or —
S(O)2—
, then R2 is selected from the group consisting of a hydrocarbon group and a substituted hydrocarbon group, wherein the substituted hydrocarbon group is substituted with an aromatic group; and
(iv) A2 is a group of the formula;
wherein,(a) u is 0 to about 10;
(b) p is 0 to about 10;
(c) v is 0 or 1;
(d) D3 is selected from the group consisting of —
S(O)2—
, —
C(O)—
, and —
CR1(OH)—
, with the provisos that when D3 is —
S(O)2—
, then D1 is —
C(O)—
, D2 is —
NR3—
, and R2 and R3 are bonded together to form the ring structure, and when D3 is —
C(O)—
, v is 0, and R5 contains a —
C(O)—
group, then p is not 0;
(e) R5 is selected from the group consisting of a substituted hydrocarbon group of at least 2 carbon atoms and substituted heterogeneous groups of at least 2 member atoms, wherein R5 is substituted with at least one group selected from the group consisting of aromatic groups, heteroaromatic groups, substituted aromatic groups, and substituted heteroaromatic groups;
(v) A3 has the formula
wherein,(a) t is about 1 to about 6;
(b) D4 is selected from the group consisting of —
C(O)— and
—
CHR1—
;
(c) D5 is selected from the group consisting of —
NR6(R7), —
OrR6, and —
C(O)R6, wherein r is 0 or 1;
(d) 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
,(e) R7 is selected from the group consisting of a hydrogen atom and R6, with the proviso that when u is 0, D3 and D4 are not both —
C(O)—
. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method for inhibiting transport protein activity comprising administering, to a subject, a composition comprising:
-
(A) a therapeutic agent; and
,(B) a compound selected from the group consisting of a structure;
or an optical isomer, diastereomer, enantiomer, or pharmaceutically-acceptable salt thereof, wherein;
(i) s is an integer from about 1 to about 3;
(ii) A is selected from the group consisting of A1 and A3;
(iii) A1 is a group of the formula;
wherein,(a) 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;
(b) x is 0 to about 10;
(c) R2 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;
(d) D1 and D2 are each independently selected from the group consisting of —
C(O)— and
—
NR3—
;
(e) R3 is selected from the group consisting of a hydrogen atom and R2, and with the proviso that optionally, R2 and R3 may be bonded together thereby forming a ring selected from the group consisting of heterocyclic groups and substituted heterocyclic groups;
(f) y is 0 or 1 and z is 0 or 1, with the provisos that when y is 0, z is 1 and when y is 1, z is 0, when y is 0 and D1 is —
NR3—
, then D2 is —
C(O)—
, when y is 0 and D2 is —
NR3—
, then D1 is —
C(O)—
, andwhen x is 0, D1 is —
C(O)—
, y is 0, D2 is —
NR3—
, and D3 is —
C(O)—
or —
S(O)2—
, then R2 is selected from the group consisting of a hydrocarbon group and a substituted hydrocarbon group, wherein the substituted hydrocarbon group is substituted with an aromatic group;
(iii) A2 is a group of the formula;
wherein,(a) u is 0 to about 10;
(b) p is 0 to about 10;
(c) v is 0 or 1;
(d) D3 is selected from the group consisting of —
S(O)2—
, —
C(O)—
, and —
CR1(OH)—
, with the provisos that when D3 is —
S(O)2—
, then D1 is —
C(O)—
, D is —
NR3-, and R2 and R3 are bonded together to form the ring structure, and when D3 is —
C(O)—
, v is 0, and R5 contains a —
C(O)—
group, then p is not 0;
(e) R5 is selected from the group consisting of a substituted hydrocarbon groups of at least 2 carbon atoms and substituted heterogeneous groups of at least 2 member atoms, wherein R5 is substituted with at least one group selected from the group consisting of aromatic groups, heteroaromatic groups, substituted aromatic groups, and substituted heteroaromatic groups;
(iv) A3 has the formula
wherein,(a) t is about 1 to about 6;
(b) D4 is selected from the group consisting of —
C(O)— and
—
CHR1—
;
(c) D5 is selected from the group consisting of —
NR6(R7), —
OrR6, and —
C(O)R6, wherein r is 0 or 1;
(d) 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
,(e) R is selected from the group consisting of a hydrogen atom and R6, with the proviso that when u is 0, D3 and D4 are not both —
C(O)—
. - View Dependent Claims (16, 17)
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Specification