1-Halobenzyl-1H-indazole-3-carboxylic acids. A new class of antispermatogenic agents.

ABSTRACT

The synthesis of a series of halogenated 1-benzylindazole-3-carboxylic acids and related derivatives is described. These compounds were studied for their effect on testicular weight and on the inhibition of spermatogenesis. Many of the derivatives, but in particular 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid (11), 1-(2,4-dibromobenzyl)-1H-indazole-3-carboxylic acid (13), 1-(4-chloro-2-methylbenzyl)-1H-indazole-3-carboxylic acid (27), and their glycerol esters, showed potent antispermatogenic activity.

ABSTRACT

PIP The synthesis of 1-halobenzyl-1H-indazole-3-carboxylic acids is described and the effects of these compounds on testicular weight and inhibition of spermatogenesis are reported. Histologically, the antispermatogenic activity of all the active derivatives was similar. Rat testis showed disorganization of the seminiferous tubules consisting mainly of lesion and loss of spermatocytes and spermatids while the spermatogonia and interstitial tissue appeared normal. 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid, 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid, 1-(4-chloro-2-methylbenzyl)-1H-indazole-3-carboxylic acid and their glycerol esters showed the most potent antispermatogenic activity.