Design, Synthesis and Evaluation of Novel Substituted (5-methyl-1H-pyrazol-3-yl)- 1,3,4-oxadiazole as Potent Androgen Receptor Antagonist.

Background: Androgen Receptor (AR) is one of the highly explored targets for the treatment of prostate cancer. The emergence of point mutation in the Ligand Binding Domain (LBD) of AR has resulted in the development of resistance against AR antagonist. The point mutation T877A, W741L and F876L confer resistance to flutamide, bicalutamide and enzalutamide respectively.

Synthetic methodology for the preparation of N-hydroxysulfamides.

A convenient synthesis of a variety of substituted N-hydroxysulfamides from chlorosulfonyl isocyanate is reported. Alkyl groups can be introduced selectively on the N-Boc nitrogen of key intermediates 1a or 1b using the Mitsunobu reaction with alcohols. Subsequently the nitrogen carrying the silyloxy group can be alkylated under traditional conditions.