Phenylpiperazine derivatives: a patent review (2006 - present)

The N-phenylpiperazine subunit represents one of the most versatile scaffolds used in the medicinal chemistry field. Recently, some N-phenylpiperazine derivatives have reached late stage clinical trials for the treatment of CNS disorders, thus, this is clearly a molecular template that already has proven its "druglikeness," However, this scaffold is still strictly seen as a "CNS structure" by great part of the scientific community. The aim of this review is to draw a contemporary profile of the patents regarding N-phenylpiperazine derivatives and, them, suggest new research fields to be explored.

The site of the World Intellectual Property Organization (WIPO) was used as the main source in order to perform the research of the patents containing N-phenylpiperazine compounds with therapeutic uses. This review highlights some examples to show that this heterocyclic moiety can successfully yield new classes of hits and prototypes for many other therapeutic fields through appropriate substitution of the molecular skeleton.

The patent research concerning N-phenylpiperazine derivatives indicated for therapeutic uses from 2006 to present date resulted in thirty three documents. It is a low number if one considers the several compounds bearing the N-phenylpiperazine nucleus that reached the market and/or clinical trials. Therefore, this subunit seems to be much underrated at the moment. The adequate use of the N-phenylpiperazine moiety, through modulation of its basicity and substitution pattern of the aromatic ring, can yield pharmacokinetic and pharmacodynamic improvements that are certainly useful in several therapeutic areas, thus, being able to diversify the application and utility of this scaffold. We expect and strongly suggest the growth of this diversification.