title: Novel non-steroidal/non-anilide type androgen antagonists: discovery of 4-substituted pyrrole-2-carboxamides as a new scaffold for androgen receptor ligands.
abstract: We designed and synthesized novel pyrrole-2-carboxamide derivatives as androgen antagonists. Compounds 10 and 13 bearing benzylamine or aniline at the 4-position of the pyrrole ring showed moderate androgen antagonistic activity, and inhibited the androgen-dependent growth of Shionogi carcinoma cells (SC-3). Study of the structure-activity relationships of compound 13 led to a potent androgen antagonist 36, which has higher affinity than flutamide (4) for androgen nuclear receptor (AR). Thus, pyrrole-2-carboxamide is a new scaffold for developing AR antagonists.
authors.affiliation: Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Aya
authors.initials: A
authors.lastname: Tanatani
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005485:Flutamide / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D008024:Ligands; D011758:Pyrroles; D005485:Flutamide