Indazole carboxylic acids in male contraception.
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.
Cheng
C Yan
CY
The Population Council, Center for Biomedical Research, 1230 York Avenue, New York, NY, USA. yan@popcbr.rockefeller.edu
Mo
Meng yun
My
Grima
Josephine
J
Saso
Luciano
L
Tita
Beatrice
B
Mruk
Dolores
D
Silvestrini
Bruno
B
D000818:Animals; D000988:Antispermatogenic Agents / Q000494:pharmacology; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D003272:Contraceptive Agents, Male / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage / Q000494:pharmacology; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology; D007365:Intercellular Junctions / Q000187:drug effects; D008297:Male; D012708:Sertoli Cells / Q000187:drug effects / Q000648:ultrastructure; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure
C415442:1-(2,4-dichlorobenzyl)indazole-3-acrylic acid; C432482:1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; D000988:Antispermatogenic Agents; D001593:Benzyl Compounds; D003272:Contraceptive Agents, Male; D006834:Hydrazines; D007191:Indazoles