Lonidamine analogues and their use in male contraception and cancer treatment
View Patent ↗Novel compounds useful for inhibiting spermatogenesis and cancer treatment, and in particular as inhibitors of heat shock proteins and/or elongation factor 1 alpha.
1. A compound selected from the group consisting of—before
3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-acrylic acid;
6-chloro-1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid hydrazide;
3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-acrylic acid;
6-chloro-1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid hydrazide;
1-(2,4-dichlorobenzyl)-6-fluoro-1H-indazole-3-carboxylic acid methyl ester;
6-fluoro-1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid hydrazide;
3-[1-(2,4-dichlorobenzyl)-6-fluoro-1H-indazol-3-yl]-acrylic acid;
3-[1-(2,4-dichlorobenzyl)-6-chloro-1H-indazol-3-yl]-acrylic acid;
3-[1-(2,4-dichlorobenzyl)-6-trifluoromethoxy-1H-indazol-3-yl] acrylic acid; and
3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-propionic acid;
and pharmaceutically acceptable salts and esters thereof.
2. A pharmaceutical composition for inhibiting spermatogenesis comprising a therapeutically-effective amount at least one of the compounds of claim 1 .
3. The pharmaceutical composition of claim 2 further comprising a pharmaceutically acceptable carrier.
4. A method for inhibiting spermatogenesis in mammals comprising administering to such mammal a therapeutically effective amount of at least one of the compounds of claim 1 .
5. The method of claim 4 further comprising administering to such mammal a pharmaceutically acceptable carrier.
6. The composition of claim 2 wherein said compound is 3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-acrylic acid and pharmaceutically acceptable salts and esters thereof.
7. The composition of 2 wherein said compound is 3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-propionic acid.
8. The compound of claim 1 which is 3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-acrylic acid and pharmaceutically acceptable salts and esters thereof.
9. The compound of claim 1 which is 3-[1-(2,4-dichlorobenzyl)-6-trifluoromethyl-1H-indazol-3-yl]-propionic acid and pharmaceutically acceptable salts and esters thereof.
10. Compounds according to the Formula:
wherein R 1 is carboxyl, acryl, or carboxylic acid hydrazide;
wherein R 2 at the 6-position and is trihaloalkyl;
wherein X and Y are the same or different from each other and are halogen or lower alkyl;
wherein Z 1 , Z 2 , Z 3 , and Z 4 are carbon;
and pharmaceutically acceptable salts and esters thereof.
11. The compounds according to claim 10 wherein R 2 is trifluoromethyl.
12. A pharmaceutical composition comprising a therapeutically-effective amount at least one of the compounds of claim 10 .
13. A pharmaceutical composition of claim 12 further comprising a pharmaceutically acceptable carrier.