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Last Updated: March 29, 2024

Claims for Patent: 6,110,953


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Summary for Patent: 6,110,953
Title: Pharmaceutical composition for inhibiting the growth of cancers
Abstract:A pharmaceutical composition that inhibits the growth of tumors and cancers in mammals that comprises a 1H-1,2,4-triazole derivative along with a safe and effective amount of a chemotherapeutic agent. Potentiators can be used to enhance the effectiveness of the drugs. The triazoles and potentiators compounds can also be used to treat viral infections.
Inventor(s): Camden; James Berger (West Chester, OH)
Assignee: The Procter & Gamble Company (Cincinnati, OH)
Application Number:09/245,520
Patent Claims:1. A pharmaceutical composition for treating cancers comprising a pharmaceutically acceptable carrier and a safe and effective amount of a chemotherapeutic agent and a safe and effective amount of a triazole or the formula: ##STR3## wherein Z is an alkylene selected from the group consisting of CH.sub.2 --CH.sub.2 --,--CH.sub.2 --CH.sub.2 --CH.sub.2 --, --CH(CH.sub.3)--CH(CH.sub.3)-- and --CH.sub.2 --CH(alkyl) wherein said alkyl has from 1 to about 10 carbon atoms; and Ar is a member selected from the group consisting of phenyl, substituted phenyl, thienyl, halothienyl, naphthyl and fluorenyl.

2. A pharmaceutical composition according to claim 1 comprising a pharmaceutically acceptable carrier and a safe and effective amount of a 1H-1,2,4-triazole selected from the group-consisting of:

1-[2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole;

1-[2-(2,4-dichlorophenyl)-4-methyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazo le,

1-[2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazol e,

1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazo le,

1-[2-(2,4-dichlorophenyl)-4-pentyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazo le, and the therapeutically active acid addition salts thereof.

3. A pharmaceutical composition according to claim 2 wherein said pharmaceutical acceptable acid addition salts are selected from the group consisting of chlorides, bromides, sulfates, nitrates, phosphates, sulfonates, formates, tartrates, maleates, malates, citrates, benzoates, salicylates, ascorbates and mixtures thereof.

4. A pharmaceutical composition according to claim 2 wherein said chemotherapeutic agent is selected from the group consisting of alkylating agents, DNA strand-breaking agents, intercalating topoisomerase II inhibitors, nonintercalating topoisomerase II inhibitors, DNA minor groove binders, Antimetabolites, Tubulin-binding Agents that when bound to tubulin prevent formation of microtubules, hormones, Asparaginase and hydroxyurea.

5. A pharmaceutical composition according to claim 4 wherein said chemotherapeutic agent is selected from the group consisting of Asparaginase, hydroxyurea, Cisplatin, Cyclophosphamide, Altretamine, Bleomycin, Dactinomycin, Doxorubicin, Etoposide, Teniposide, and Plicamycin.

6. A pharmaceutical composition according to claim 4 wherein said chemotherapeutic agent is selected from the group consisting of Methotrexate, Fluorouracil, Fluorodeoxyuridine, CB3717, Azacitidine, Cytarabine, Floxuridine, Mercaptopurine, 6-Thioguanine, Fludarabine, Pentostatin, Cyctrabine, and Fludarabine.

7. A method of treating cancer in warm blooded mammals comprising administering a safe and effective amount of a chemotherapeutic agent and a safe and effective amount of a 1H-1,2,4-triazole derivative of the formula: ##STR4## wherein Z is an alkylene selected from the group consisting of --CH.sub.2 --CH.sub.2 --,--CH.sub.2 --CH.sub.2 --CH.sub.2 --, --CH(CH.sub.3)--CH(CH.sub.3)-- and --CH.sub.2 --CH(alkyl) wherein said alkyl has from 1 to about 10 carbon atoms; and Ar is a member selected from the group consisting of phenyl, substituted phenyl, thienyl, halothienyl, naphthyl and fluorenyl.

8. A method according to claim 7 wherein from about 2 mg/kg body weight to about 400 mg/kg of said 1H-1,2,4-triazole is administered and from 0.5 mg/kg body weight to about 40 mg/kg body weight of said chemotherapeutic agent is administered.

9. A method according to claim 8 wherein said 1H-1,2,4-triazole is administered orally or enterically, intravenously, peritoneally, parenterally or by injection into the tumor.

10. A method according to claim 7 wherein said 1H-1,2,4-triazole is administered in a solid form, liquid form or as a liposome.

11. A method according to claim 7 wherein said 1H-1,2,4-triazole is selected from the group consisting of:

1-[2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole;

1-[2-(2,4-dichlorophenyl)-4-methyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazo le,

1-[2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazol e,

1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazo le,

1-[2-(2,4-dichlorophenyl)-4-pentyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazo le, and the therapeutically active acid addition salts thereof.

12. A method according to claim 11 wherein said pharmaceutically acceptable acid addition salts are selected from the group consisting of chlorides, bromides, sulfates, nitrates, phosphates, sulfonates, formates, tartrates, maleates, malates, citrates, benzoates, salicylates, ascorbates and mixtures thereof.

13. A method according to claim 7 wherein said chemotherapeutic agent is selected from the group consisting of alkylating agents, DNA strand-breaking agents, intercalating topoisomerase II inhibitors, nonintercalating topoisomerase II inhibitors, DNA minor groove binders, Antimetabolites, Tubulin-binding Agents that when bound to tubulin prevent formation of microtubules, hormones, Asparaginase and hydroxyurea.

14. A method according to claim 13 wherein said chemotherapeutic agent is selected from the group consisting of Asparaginase, hydroxyurea, Cisplatin, Cyclophosphamide, Altretamine, Bleomycin, Dactinomycin, Doxorubicin, Etoposide, Teniposide, and Plicamycin.

15. A method according to claim 13 wherein said chemotherapeutic agent is selected from the group consisting of Methotrexate, Fluorouracil, Fluorodeoxyuridine, CB3717, Azacitidine, Cytarabine, Floxuridine, Mercaptopurine, 6-Thioguanine, Fludarabine, Pentostatin, Cyctrabine, and Fludarabine.

16. A method of treating viral infections in warm blooded mammals comprising administering a safe and effective amount of a 1H-1,2,4-triazole derivative of the formula: ##STR5## wherein Z is an alkylene selected from the group consisting of CH.sub.2 --CH.sub.2 --,--CH.sub.2 --CH.sub.2 --CH.sub.2 --, --CH(CH.sub.3)--CH(CH.sub.3)-- and --CH.sub.2 --CH(alkyl) wherein said alkyl has from 1 to about 10 carbon atoms; and Ar is a member selected from the group consisting of phenyl, substituted phenyl, thienyl, halothienyl, naphthyl and fluorenyl and a potentiator.

17. A method according to claim 16 wherein said potentiator is procodazole.

18. The method of claim 7 wherein the cancer is colon cancer.

19. The method of claim 7 wherein the cancer is non small cell lung cancer.

20. The method of claim 7 wherein the cancer is melanoma cancer.

21. The method of claim 7 wherein the cancer is ovarian cancer.

22. The method of claim 16 wherein the viral infection is an influenza virus infection.

23. The method of claim 16 wherein the viral infection is a rhinovirus infection.

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