Substituted heterocyclic compounds for treating multidrug resistance

• US 7,304,053 B2
• Filed: 12/19/2003
• Issued: 12/04/2007
• Est. Priority Date: 10/17/2000
• Status: Expired due to Fees

• Current Assignee: H Lee Moffitt Cancer Center & Research Institute (State University System of Florida)
• Original Assignee: H Lee Moffitt Cancer Center & Research Institute (State University System of Florida)
• Inventors: Degenhardt, Charles Raymond, Eickhoff, David Joseph
• Primary Examiner(s): Richter; Johann
• Assistant Examiner(s): Sackey; Ebenezer
• Application Number:
  US10/741,270
• Publication Number:
  US 20040132722A1
• Time in Patent Office: 1,446 Days
• Field of Search: 514/210.18, 514/218, 514/253.07, 514/309
• US Class Current: 514/218
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 211/27 having amino groups linked to the six-membered aromatic ring by saturated carbon chains
• CPC Class Codes: C07C 237/06 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 237/24 having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07C 51/06 from carboxylic acid amides
• CPC Class Codes: C07C 57/38 polycyclic
• CPC Class Codes: C07D 207/16 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 211/60 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/62 attached in position 4
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C07D 213/56 : Amides
• CPC Class Codes: C07D 213/78 : Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 215/20 : Oxygen atoms
• CPC Class Codes: C07D 215/233 : only one oxygen atom which is attached in position 4
• CPC Class Codes: C07D 239/06 : having one double bond between ring members or between a ring member and a non-ring member
• CPC Class Codes: C07D 263/06 : with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 263/12 : with radicals containing only hydrogen and carbon atoms
• CPC Class Codes: C07D 295/15 : to an acyclic saturated chain
• CPC Class Codes: C07D 295/205 : Radicals derived from carbonic acid
• CPC Class Codes: C07D 401/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links

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:

Claims

1. A composition comprising:

(A) a therapeutic agent; and

,

(B) a compound selected from the group consisting of a structure;

2. The composition of claim 1 wherein said therapeutic agent is selected from the group consisting of (i) cancer therapeutic agents, (ii) antibacterial agents, (iii) antiviral agents, (iv) antifungal agents, and combinations thereof.

3. The composition of claim 2 wherein said cancer therapeutic agents are selected from the group consisting of chemotherapeutic agents, chemosensitizing agents and combinations thereof.

4. The composition of claim 3, wherein said chemotherapeutic agents are selected from the group consisting of antinomycin D, adriyamycin, amsacrine, colchicine daunorubicin, docetaxel, doxorubicin, etoposide, mitoxantrone, mytomycin C, paclitaxel, tenipaside, vinblastine, vincristine, and combinations thereof.

5. The composition of claim 3, wherein said chemosensitizing agents are selected from the group consisting of calcium channel blockers, calmodulin, antagonists, cyclic peptides, cyclosporins and their analogs, phenothiazines, quinidine, reserpine, steroids, thioxantheres, transflupentixol, trifluoperazine, and combinations thereof.

6. The composition of claim 2, wherein said antibacterial agents are selected from the group consisiting of quinolones, fluoroquinolones, .beta.-lactam antibiotics, aminoglycosides, macrolides, glycopeptides, tetracyclines, and combinations thereof.

7. The composition of claim 2, wherein said antiviral agents are selected from the group consisting of protease inhibitors, DNA synthase inhibitors, reverse transcription inhibitors, and combinations thereof.

8. The composition of claim 2, wherein said antifungal agents are selected from the group consisting of ketoconazole, fluconazole, itraconazole, and combinations thereof.

9. The composition of claim 1, wherein said therapeutic agent and said compound are part of a single pharmaceutical composition for administration.

10. The composition of claim 1 further comprising a pharmaceutically acceptable carrier.

11. A method of treating multidrug resistant cancer comprising administering to a mammal in need of such treatment the composition in accordance with claim 1.

12. A method of treating multidrug resistant cancer comprising administering to a mammal in need of such treatment the composition in accordance with claim 10.

13. A method of treating a bacterial, viral, fungal or protozoal infection comprising administering to a mammal in need of such treatment a composition according to claim 1.

16. A method of concentration of a therapeutic agent in a cell exhibiting MRP1- or Pgp-mediated multidrug resistance comprising contacting the cell with the composition of claim 1.

17. The method of claim 16, wherein the cell is in a subject.

18. The method of claim 17, wherein the cell is contacted by administering the composition to the subject.

14. A composition comprising:

(A) a therapeutic agent; and

,

(B) a compound selected from the group consisting of a structure;

15. A composition comprising:

(A) a therapeutic agent; and

,

(B) a compound selected from the group consisting of a structure;