Substituted 3,5-diphenyl-1,2,4-triazoles and their use as pharmaceutical metal chelators

• US 6,596,750 B2
• Filed: 09/23/2002
• Issued: 07/22/2003
• Est. Priority Date: 06/25/1996
• Status: Expired due to Term

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Lattmann, René, Acklin, Pierre
• Primary Examiner(s): KRASS, FREDERICK F
• Application Number:
  US10/252,899
• Publication Number:
  US 20030069273A1
• Time in Patent Office: 302 Days
• Field of Search: 514/383, 514/836, 514/235.8, 514/236.2, 514/236.5, 514/253.09, 514/255.05, 514/255.06, 514/256, 514/326, 514/340, 514/381, 514/382
• US Class Current: 514/383
• 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 39/04 Chelating agents
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The use is described of 3,5-diphenyl-1,2,4-triazoles of the formula I

in which R₁-R₅ are as defined in the description. The compounds have useful pharmaceutical properties and are particularly active as iron chelators. They can be used for the treatment of iron overload in warm-blooded animals.

Claims

1. A method of treating diseases which cause an excess of metal in a human or animal body or are caused by an excess of metal in a human or animal body comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula I

in which

R₁ and R₅ simultaneously or independently of one another are hydrogen, halogen, hydroxyl, lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, carboxyl, carbamoyl, N-lower alkylcarbamoyl, N,N-di-lower alkylcarbamoyl or nitrile;

R₂ and R₄ simultaneously or independently of one another are hydrogen, unsubstituted or substituted lower alkanoyl or aroyl, or a protective group;

R₃ is hydrogen, lower alkyl, hydroxy-lower alkyl, halo-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, R₆R₇N—

C(O)-lower alkyl, unsubstituted or substituted aryl or aryl-lower alkyl, or unsubstituted or substituted heteroaryl or heteroaralkyl;

R₆ and R₇ simultaneously or independently of one another are hydrogen, lower alkyl, hydroxy-lower alkyl, alkoxy-lower alkyl, hydroxyalkoxy-lower alkyl, amino-lower alkyl, N-lower alkylamino-lower alkyl, N,N-di-lower alkylamino-lower alkyl, N-(hydroxy-lower alkyl)amino-lower alkyl, N,N-di(hydroxy-lower alkyl)amino-lower alkyl or, together with the nitrogen atom to which they are bonded, form an azaalicyclic ring;

or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1 wherein the metal is iron.

3. A method of treating diseases which cause an excess of metal in a human or animal body or are caused by an excess of metal in a human or animal body comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula (II)

wherein

each of R₁ and R₅, independently, is hydrogen;

halogen;

lower alkyl;

halo-lower alkyl;

lower alkoxy;

halo-lower alkoxy;

carboxyl;

carbamoyl;

N-lower alkylcarbamoyl;

N,N-di-lower alkylcarbamoyl;

or nitrile;

each of R₂ and R₄, independently, is hydrogen;

unsubstituted or substituted lower alkanoyl or aroyl;

or a protective group;

R₃ is R₆R₇N—

C(O)-lower alkyl;

unsubstituted or substituted aryl;

aryl-lower alkyl substituted by N-lower alkylamino, N,N-di-lower alkylamino or pyrrolidino;

or unsubstituted or substituted heteroaryl or heteroaralkyl, with the proviso that R₃ is not phenyl or phenyl substituted by halogen, nitro, nitrile, hydroxyl, lower alkyl, halo-lower alkyl, lower alkoxy or lower alkoxycarbonyl if R₂ and R₄ are hydrogen, and R₁ and R₅ are hydrogen, halogen, lower alkyl, halo-lower alkyl, lower alkoxy or nitrile; and

each of R₆ and R₇, independently, is hydrogen;

lower alkyl;

hydroxy-lower alkyl;

alkoxy-lower alkyl;

hydroxyalkoxy-lower alkyl;

amino-lower alkyl;

N-lower alkylamino-lower alkyl;

N,N-di-lower alkylamino-lower alkyl;

N-(hydroxy-lower alkyl)amino-lower alkyl;

N,N-di(hydroxy-lower alkyl)amino-lower alkyl or, together with the nitrogen atom to which they are bonded, form an azaalicyclic ring;

or a pharmaceutically acceptable salt thereof.

4. The method according to claim 3 wherein a compound of formula (II) is administered in each of R₁ and R₅, independently, is hydrogen;

halogen;

lower alkyl;

halo-lower alkyl;

lower alkoxy;

or halo-lower alkoxy;

each of R₂ and R₄, independently, is hydrogen;

or a protective group;

R₃ is R₆R₇N—

C(O)-lower alkyl;

substituted aryl;

aryl-lower alkyl substituted by N-lower alkylamino, N,N-di-lower alkyl amino or pyrrolidino;

or unsubstituted or substituted heteroaryl or heteroaralkyl with the proviso that R₃ is not phenyl or phenyl substituted by halogen, nitro, nitrile, hydroxyl, lower alkyl, halo-lower alkyl, lower alkoxy or lower alkoxycarbonyl if R₂ and R₄ are hydrogen, and R₁ and R₅ are hydrogen, halogen, lower alkyl, halo-lower alkyl or lower alkoxy or nitrile; and

each of R₆ and R₇, independently, is hydrogen;

lower alkyl;

hydroxy-lower alkyl;

alkoxy-lower alkyl;

hydroxyalkoxy-lower alkyl;

amino-lower alkyl;

N-lower alkylamino-lower alkyl;

N,N-di-lower alkylamino-lower alkyl;

N-(hydroxy-lower alkyl)amino-lower alkyl;

N,N-di(hydroxy-lower alkyl)amino-lower alkyl or, together with the nitrogen atom to which they are bonded, form an azaalicyclic ring;

or a pharmaceutically acceptable salt thereof.

5. The method according to claim 3 wherein a compound of formula (II) is administered in which

each of R₁ and R₅, independently, is hydrogen;

halogen;

or lower alkyl;

R₂ and R₄ are hydrogen;

R₃ is R₆R₇N—

C(O)-lower alkyl;

aryl substituted by carboxyl or R₈R₉N—

C(O)—

;

aryl-lower alkyl substituted by N-lower alkylamino, N,N-di-lower alkylamino or pyrrolidino;

or unsubstituted or substituted heteroaralkyl;

each of R₆ and R₇, independently, is hydrogen;

lower alkyl;

hydroxy-lower alkyl;

alkoxy-lower alkyl;

hydroxyalkoxy-lower alkyl;

amino-lower alkyl;

N-lower alkylamino-lower alkyl;

N,N-di-lower alkylamino-lower alkyl;

N-(hydroxy-lower alkyl)amino-lower alkyl;

N,N-di(hydroxy-lower alkyl)amino-lower alkyl or, together with the nitrogen atom to which they are bonded, form an azaalicyclic ring;

each of R₈ and R₉, independently, is hydrogen;

lower alkyl or, together with the nitrogen atom to which they are bonded, form an azaalicyclic ring;

or a pharmaceutically acceptable salt thereof.

7. The method according to claim 3 wherein the metal is iron.

8. A method of treating iron overload comprising administering a subject in need of such treatment a therapeutically effective amount of a compound of claim 3, or a pharmaceutically acceptable salt thereof.

6. A method of treating diseases which cause an excess of metal in a human or animal body or are caused by an excess of metal in a human or animal body comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound selected from the group consisting of:

{4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]phenyl}-(4-methylpiperazin-1-yl)methanone;

{4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]phenyl}morpholin-4-ylmethanone;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-1-(4-methylpiperazin-1-yl)ethanone;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-1-morpholin-4-yl-ethanone;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N,N-bis(2-hydroxyethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-1-N,N-dimethylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2,3-dihydroxypropyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-dimethylaminoethyl)-N-methylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-hydroxy-1-hydroxymethylethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-hydroxyethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-hydroxyethyl)-N-methylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-methoxyethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-morpholin-4-yl-ethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-[2-(2-hydroxyethoxy)ethyl]acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-[2-(4-methylpiperazin-1-yl)ethyl]acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-methylacetamide;

2-[3,5-bis(5-chloro-2-hydroxyphenyl)-[1,2,4]triazole-1-yl]-N-(2-morpholin-4-yl-ethyl)acetamide;

3,5-bis(2-hydroxyphenyl)-1-(4-diethylaminobenzyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-(4-pyrrolidin-1-ylbenzyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-(pyridin-3-ylmethyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-(pyridin-4-ylmethyl)-1H-[1,2,4]triazole;

3,5-bis(5-chloro-2-hydroxyphenyl)-1-(4-dimethylaminobenzyl)-1H-[1,2,4]triazole;

3,5-bis(5-chloro-2-hydroxyphenyl)-1-(pyridin-2-ylmethyl)-1H-[1,2,4]triazole;

4-[3,5-bis(2-hydroxy-5-methylphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

4-[3,5-bis(5-chloro-2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

4-[3,5-bis(5-fluoro-2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

N-{2-[bis(2-hydroxyethyl)amino]ethyl}-2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]acetamide; and

N-benzyl-2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-methylacetamide;

or a pharmaceutically acceptable salt thereof.

9. A method of treating diseases which cause an excess of metal in a human or animal body or are caused by an excess of metal in a human or animal body comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula (II)

wherein

each of R₁ and R₅, independently, is hydrogen;

halogen;

lower alkyl;

halo-lower alkyl;

lower alkoxy;

halo-lower alkoxy;

carboxyl;

carbamoyl;

N-lower alkylcarbamoyl;

N,N-di-lower-alkylcarbamoyl;

or nitrile;

each of R₂ and R₄, independently, is hydrogen;

unsubstituted lower alkanoyl;

lower alkanoyl substituted by halogen, hydroxyl, lower alkoxy, trifluoromethyl, cyclo-lower alkyl or phenyl;

unsubstituted aroyl;

or aroyl substituted by one or two substituents selected from lower alkyl, lower alkoxy, hydroxyl, nitro, halogen, trifluoromethyl, carboxyl, lower alkoxycarbonyl, amino, N-lower alkylamino, N,N-di-lower alkylamino, aminocarbonyl, lower alkylaminocarbonyl, di-lower alkylaminocarbonyl and nitrile;

R₃ is R₆R₇N—

C(O)-lower alkyl;

aryl substituted by one or two substituents selected from lower alkyl, lower alkoxy, hydroxyl, nitro, halogen, trifluoromethyl, carboxyl, lower alkoxycarbonyl, amino, N-lower alkylamino, N,N-di-lower alkylamino, aminocarbonyl, lower alkylaminocarbonyl, di-lower alkylaminocarbonyl and nitrile;

or aryl-lower alkyl substituted by N-lower alkylamino or N,N-di-lower alkylamino;

with the proviso that

R₃ is not phenyl substituted by halogen, nitro, nitrile, hydroxyl, lower alkyl, trifluoromethyl, lower alkoxy or lower alkoxycarbonyl if R₂ and R₄ are hydrogen, and R₁ and R₅ are hydrogen, halogen, lower alkyl, halo-lower alkyl, lower alkoxy or nitrile; and

each of R₆ and R₇, independently, is hydrogen;

lower alkyl;

hydroxy-lower alkyl;

alkoxy-lower alkyl;

hydroxyalkoxy-lower alkyl;

amino-lower alkyl;

N-lower alkylamino-lower alkyl;

N,N-di-lower alkylamino-lower alkyl;

N-(hydroxy-lower alkyl)amino-lower alkyl;

or N,N-di(hydroxy-lower alkyl)amino-lower alkyl;

or a pharmaceutically acceptable salt thereof.

10. The method of claim 9 wherein a compound of formula (II) is administered in which

each of R₁ and R₅, independently, is hydrogen; halogen;

lower alkyl;

halo-lower alkyl;

lower alkoxy;

or halo-lower alkoxy;

each of R₂ and R₄ is hydrogen;

R₃ is R₆R₇N—

C(O)-lower alkyl;

aryl substituted by one or two substituents selected from lower alkyl, lower alkoxy, hydroxyl, nitro, halogen, trifluoromethyl, carboxyl, lower alkoxycarbonyl, amino, N-lower alkylamino, N,N-di-lower alkylamino, aminocarbonyl, lower alkylaminocarbonyl, di-lower alkylaminocarbonyl and nitrile;

or aryl-lower alkyl substituted by N-lower alkylamino or N,N-di-lower alkylamino;

with the proviso that

R₃ is not phenyl substituted by halogen, nitro, nitrile, hydroxyl, lower alkyl, trifluoromethyl, lower alkoxy or lower alkoxycarbonyl if R₁ and R₅ are hydrogen, halogen, lower alkyl, halo-lower alkyl or lower alkoxy; and

each of R₆ and R₇, independently, is hydrogen;

lower alkyl;

hydroxy-lower alkyl;

alkoxy-lower alkyl;

hydroxyalkoxy-lower alkyl;

amino-lower alkyl;

N-lower alkylamino-lower alkyl;

N,N-di-lower alkylamino-lower alkyl;

N-(hydroxy-lower alkyl)amino-lower alkyl;

or N,N-di(hydroxy-lower alkyl)amino-lower alkyl;

or a pharmaceutically acceptable salt thereof.

11. The method according to claim 9 wherein a compound of formula (II) is administered in which

each of R₁ and R₅, independently, is hydrogen;

halogen;

or lower alkyl;

each of R₂ and R₄ is hydrogen;

R₃ is R₆R₇N—

C(O)-lower alkyl;

aryl substituted by carboxyl or R₈R₉N—

C(O)—

;

or aryl-lower alkyl substituted by N-lower alkylamino or N,N-di-lower alkylamino;

each of R₆ and R₇, independently, is hydrogen;

lower alkyl;

hydroxy-lower alkyl;

alkoxy-lower alkyl;

hydroxyalkoxy-lower alkyl;

amino-lower alkyl;

N-lower alkylamino-lower alkyl;

N,N-di-lower alkylamino-lower alkyl;

N-(hydroxy-lower alkyl)amino-lower alkyl;

or N,N-di(hydroxy-lower alkyl)amino-lower alkyl; and

each of R₈ and R₉, independently, is hydrogen or lower alkyl;

or a pharmaceutically acceptable salt thereof.

12. The method according to claim 9 wherein the compound which is administered is selected from the group consisting of:

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N,N-bis(2-hydroxyethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N,N-dimethylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2,3-dihydroxypropyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-dimethylaminoethyl)-N-methylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-hydroxy-1-hydroxymethylethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-hydroxyethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-hydroxyethyl)-N-methylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-methoxyethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-[2-(2-hydroxyethoxy)ethyl]acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-methylacetamide;

3,5-bis(2-hydroxyphenyl)-1-(4-diethylaminobenzyl)-1H-[1,2,4]triazole;

3,5-bis(5-chloro-2-hydroxyphenyl)-1-(4-dimethylaminobenzyl)-1H-[1,2,4]triazole;

4-[3,5-bis(2-hydroxy-5-methylphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

4-[3,5-bis(5-chloro-2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

4-[3,5-bis(5-fluoro-2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

N-{2-[bis(2-hydroxyethyl)amino]ethyl}-2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]acetamide; and

N-benzyl-2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-methylacetamide;

or a pharmaceutically acceptable salt thereof.

13. The method according to claim 9 wherein the compound which is administered is 4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid, or a pharmaceutically acceptable salt thereof.

14. The method according to claim 9 wherein the compound which is administered is 2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid, or a pharmaceutically acceptable salt thereof.

15. The method according to claim 9 wherein the metal is iron.

16. A method of treating iron overload comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula II, as claimed in claim 9, or a pharmaceutically acceptable salt thereof.

17. The method according to claim 16 wherein the compound which is administered is 4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid, or a pharmaceutically acceptable salt thereof.

18. A method of treating diseases which cause an excess of metal in a human or animal body or are caused by an excess of metal in a human or animal body comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound selected from the group consisting of:

3,5-bis(2-hydroxyphenyl)-1-(2-hydroxyethyl)-1H-[1,2,4]triazole;

ethyl[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]acetate;

3,5-bis(2-hydroxyphenyl)-1-(2,2,2-trifluoroethyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-(4-nitrophenyl)-1H-[1,2,4]triazole;

4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

{4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-phenyl}morpholin-4-yl-methanone;

{4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-phenyl}-(4-methylpiperazin-1-yl)-methanone;

3,5-bis(2-hydroxyphenyl)-1-(4-methoxyphenyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-(2,4-difluorophenyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-benzyl-1H-[1,2,4]triazole;

4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-ylmethyl]benzonitrile;

3,5-bis(2-hydroxyphenyl)-1-(4-diethylaminobenzyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-(4-pyrrolidin-1-ylbenzyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-(pyridin-4-ylmethyl)-1H-[1,2,4]triazole;

3,5-bis(2-hydroxyphenyl)-1-(pyridin-3-ylmethyl)-1H-[1,2,4]triazole;

3,5-bis(5-chloro-2-hydroxyphenyl)-1-(2-hydroxyethyl)-1H-[1,2,4]triazole;

4-[3,5-bis(5-chloro-2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

3,5-bis(5-chloro-2-hydroxyphenyl)-1-(pyridin-2-ylmethyl)-1H-[1,2,4]triazole;

3,5-bis(5-chloro-2-hydroxyphenyl)-1-(4-dimethylaminobenzyl)-1H-[1,2,4]triazole;

4-[3,5-bis(5-fluoro-2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

4-[3,5-bis(2-hydroxy-5-methylphenyl)-[1,2,4]triazol-1-yl]benzoic acid;

[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]acetic acid;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-methylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-hydroxyethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-methoxyethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2,3-di-hydroxypropyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-morpholin-4-yl-ethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-hydroxyethyl)-N-methylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-[2-(2-hydroxyethoxy)ethyl]-acetamide;

N-{2-[bis(2-hydroxyethyl)amino]ethyl}-2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-[2-hydroxy-1-hydroxymethylethyl)acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-[2-(4-methylpiperazin-1-yl)-ethyl]acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N,N-di-methylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-1-morpholin-4-ylethanone;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-1-(4-methylpiperazin-1-yl)-ethanone;

N-benzyl-2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-methylacetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N,N-bis(2-hydroxyethyl)-acetamide;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-dimethylaminoethyl)-N-methylacetamide;

2-[3,5-bis(5-chloro-2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-N-(2-morpholin-4-yl-ethyl)acetamide;

ethyl[3,5-bis(5-chloro-2-hydroxyphenyl)-[1,2,4]triazol-1-yl]acetate;

2-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-benzoic acid; and

ethyl-4-(3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]benzoate;

or a pharmaceutically acceptable salt thereof.