Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure-Activity Relationship, Inhibition Mechanism, Metabolism, and In Vivo Studies.

Rhodesain is a major cysteine protease of , a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches.

New Cysteine Protease Inhibitors: Electrophilic (Het)arenes and Unexpected Prodrug Identification for the Protease Rhodesain.

Electrophilic (het)arenes can undergo reactions with nucleophiles yielding π- or Meisenheimer (σ-) complexes or the products of the SAr addition/elimination reactions. Such building blocks have only rarely been employed for the design of enzyme inhibitors. Herein, we demonstrate the combination of a peptidic recognition sequence with such electrophilic (het)arenes to generate highly active inhibitors of disease-relevant proteases.

Library of Azabenz-Annulated Core-Extended Perylene Derivatives with Diverse Substitution Patterns and Tunable Electronic and Optical Properties.

Here, we present a collection of different azabenz-annulated perylene derivatives. By developing new synthetic strategies and improving existing protocols, we have expanded the structural diversity of these dye molecules to a multifunctional class of ligating chromophores. The Pictet-Spengler (PS) reaction of 1-amino-perylenes with different aldehydes is used to modify the terminal substitution pattern.