Nitriles: an attractive approach to the development of covalent inhibitors.

Nitriles have broad applications in medicinal chemistry, with more than 60 small molecule drugs on the market containing the cyano functional group. In addition to the well-known noncovalent interactions that nitriles can perform with macromolecular targets, they are also known to improve drug candidates' pharmacokinetic profiles. Moreover, the cyano group can be used as an electrophilic warhead to covalently bind an inhibitor to a target of interest, forming a covalent adduct, a strategy that can present benefits over noncovalent inhibitors.

A patent review on cathepsin K inhibitors to treat osteoporosis (2011 - 2021).

Introduction: Cathepsin K (CatK) is a lysosomal cysteine protease and the predominant cathepsin expressed in osteoclasts, where it degrades the bone matrix. Hence, CatK is an attractive therapeutic target related to diseases characterized by bone resorption, like osteoporosis.

Areas Covered: This review summarizes the patent literature from 2011 to 2021 on CatK inhibitors and their potential use as new treatments for osteoporosis.

Nitrile-based peptoids as cysteine protease inhibitors.

Peptidomimetics of the class of dipeptidyl nitrile analog peptoids were synthesized as inhibitors of mammalian cysteine proteases of the papain superfamily. The dipeptidyl nitrile side chains were attached to the peptide backbone's nitrogen atom, not to the α-carbons. Synthesized nitrile-based peptoid analogs that lack the hydrogen amide at P2-P3 are responsible for many of the secondary structure elements in peptides and proteins, making them resistant to proteolysis.