Discovery of (2S)-N-(6-Cyano-5-(Trifluoromethyl)Pyridin-3-Yl)-3-(6-(4-Cyanophenyl)-3,6-Diazabicyclo[3.1.1]Heptan-3-Yl)-2-Hydroxy-2-Methylpropanamide as a Highly Potent and Selective Topical Androgen Receptor Antagonist for Androgenetic Alopecia Treatment

The document discusses the development of a topical Androgen Receptor (AR) antagonist, compound 30a, for the treatment of Androgenetic Alopecia (AGA), a common hair loss disorder. The overactivation of the AR signaling pathway in dermal papilla cells is a key factor in AGA. The researchers identified compound 30a as a potent and selective AR antagonist with good pharmacokinetic properties, leading to high skin exposure and low plasma exposure after topical application. In hair-growth and AGA mouse models, compound 30a demonstrated strong hair-growth-promoting effects without noticeable toxicity, suggesting its potential as a topical treatment for AGA.