2-Benzimidazolyl-9-(chroman-4-yl)-purinone derivatives as JAK3 inhibitors.

A novel class of Janus tyrosine kinase 3 (JAK3) inhibitors based on a 2-benzimidazoylpurinone core structure is described. Through substitution of the benzimidazoyl moiety and optimization of the N-9 substituent of the purinone, compound 24 was identified incorporating a chroman-based functional group. Compound 24 shows excellent kinase activity, good oral bioavailability and demonstrates efficacy in an acute mechanistic mouse model through inhibition of interleukin-2 (IL-2) induced interferon-gamma (INF-gamma) production.

Imidazolylpyrimidine based CXCR2 chemokine receptor antagonists.

An imidazolylpyrimidine was identified in a CXCR2 chemokine receptor antagonist screen and was optimized for potency, in vitro metabolic stability, and oral bioavailability. It was found that subtle structural modification within the series affected the oral bioavailability. Potent and orally available CXCR2 antagonists are herein reported.

2-(Aminomethyl)-benzamide-based glycine transporter type-2 inhibitors.

Structure-activity studies on benzamide 1 obtained from library screening led to the discovery of a novel series of potent and selective glycine transporter type-2 inhibitors.