Indazole carboxylic acids in male contraception
Cheng, C.Yan.; Mo, M.yun.; Grima, J.; Saso, L.; Tita, B.; Mruk, D.; Silvestrini, B.
Contraception 65(4): 265-268
2002
ISSN/ISBN: 0010-7824 PMID: 12020774 DOI: 10.1016/s0010-7824(01)00318-3Document Number: 258961
Two new chemical entities, 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide and 1-(2,4-dichlorobenzyl)-indazole-3-acrylic acid, were synthesized based on the core structure of lonidamine (1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid). These compounds apparently exert their effects in the testis by perturbing the Sertoli-germ cell adherens junctions causing germ cell loss from the seminiferous epithelium. Recently completed studies in the rat have demonstrated the efficacy, reversibility, and potential use of these two compounds as oral contraceptives for men. Neither compound affected the hypothalamus-pituitary-testicular axis, and both compounds were neither hepatotoxic nor nephrotoxic. These results suggest that these two compounds are safe for further development.