One-Pot Synthesis of Substituted 2-Amino Isonicotinic Acids: Reminiscent of the Guareschi-Thorpe Condensation.

This work describes a concise manner to make a wide variety of mono- or disubstituted 2-amino isonicotinic acids via the corresponding 2,4-dioxo-carboxylic acid ethyl esters and ethyl 3-amino-3-iminopropionate hydrochloride. The reaction likely proceeds through an in situ decarboxylation process and is reminiscent of the Guareschi-Thorpe Condensation.

Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II.

A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These type II inhibitors were optimized using a cellular Lck-dependent proliferation assay and are capable of inhibiting Lck at single-digit nanomolar concentrations. This scaffold is likely to serve a valuable template for developing potent inhibitors of a number of SFKs.