Huprines — an insight into the synthesis and biological properties

Abstract

The overlapping of tacrine and (–)-huperzine A templates yielded a family of highly potent cholinesterase inhibitors, so-called huprines. A relatively easy access to these compounds led to the development of dozens of huprine derivatives allowing to draw structure – activity relationship mainly for acetylcholinesterase and butyrylcholinesterase enzymes, but also with application to other biological targets of interest. An extension of their pharmacological profile is commonly associated with huprine scaffold binding to some other pharmacophores that yield high-molecular-weight heterodimers. The main purpose in developing the huprine family is related to Alzheimer’s disease therapy. However, these compounds are also interesting lead structures in the treatment of other disorders, such as Myasthenia gravis, African trypanosomiasis, malaria, and prion diseases. The present review provides a rationale behind the development of huprines, detailed synthetic routes leading to different classes of huprines, and a thorough discussion of their potential pharmacological applications. The bibliography includes 174 references.