Pyrazolo[1,5-a]pyrimidine based Trk inhibitors: Design, synthesis, biological activity evaluation

Tropomyosin receptor kinases (Trks), a transmembrane receptor tyrosine kinases, have attracted more and more attention as a drug target. Here we reported the structure-based synthesis and biological evaluation of novel pyrazolo[1,5-a]pyrimidine derivatives as Trk inhibitors, which exhibited potent Trk inhibitory activities. Particularly, compounds 8a, 8f, 9a, 9b and 9f (IC50 < 5 nM) showed significant inhibitory potency against Trk.

Automated summary

Novel pyrazolo[1,5-a]pyrimidine derivatives were synthesized as Trk inhibitors, showing potent inhibitory activities against Trk. Particularly, compounds 8a, 8f, 9a, 9b, and 9f exhibited significant inhibitory potency against Trk with IC50 values < 5 nM.