dorzolamide and Prostatic-Neoplasms

We report herein the design, synthesis, and pharmacological characterization of a library of novel aryl pyrazol-1-yl-propanamides as selective androgen receptor degraders (SARDs) and pan-antagonists that exert broad-scope AR antagonism. Pharmacological evaluation demonstrated that introducing a pyrazole moiety as the B-ring structural element in the common A-ring-linkage-B-ring nonsteroidal antiandrogens' general pharmacophore allowed the development of a new scaffold of small molecules with unique SARD and pan-antagonist activities even compared to our recently published AF-1 binding SARDs such as UT-155 (

Topics: Androgen Receptor Antagonists; Animals; Antineoplastic Agents; Benzamides; Cell Line, Tumor; Cell Proliferation; Drug Design; Drug Resistance, Neoplasm; Half-Life; Humans; Male; Mice; Microsomes, Liver; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Androgen; Structure-Activity Relationship; Xenograft Model Antitumor Assays