title: Indazole carboxylic acids in male contraception.
abstract: 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.
authors.affiliation: The Population Council, Center for Biomedical Research, 1230 York Avenue, New York, NY, USA. yan@popcbr.rockefeller.edu
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
authors.forename: Meng yun
authors.initials: My
authors.lastname: Mo
authors.forename: Josephine
authors.initials: J
authors.lastname: Grima
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.forename: Beatrice
authors.initials: B
authors.lastname: Tita
authors.forename: Dolores
authors.initials: D
authors.lastname: Mruk
authors.forename: Bruno
authors.initials: B
authors.lastname: Silvestrini
mesh_terms: 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
chemical_list: 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