Novel HIV-1 non-nucleoside reverse transcriptase inhibitors: a patent review (2011-2014)

There is a continuous need for next-generation non-nucleoside RT inhibitors (NNRTIs) with different resistance profiles, improved safety, excellent tolerability, and favorable physicochemical properties.

In this review we intend to narrate a general and cutting-edge overview of current state of NNRTI patents during the 2011-2014 (June) period and future perspectives. Particular focus is placed on the highlighting of some emerging medicinal chemistry principles and insights in the discovery and development of NNRTIs.

The development of effective NNRTIs is moving on from trial-and-error approaches to sophisticated subconscious strategies. Several newly emerging structure-based virtual screening methodologies (such as Monte Carlo free energy perturbation calculations) or new drug design insights, such as taking full use of the specific noncovalent reverse transcriptase/NNRTIs interactions, stereochemical diversity-oriented conformational restriction, novel strategies to enhance solubility and early absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment, will continue to evolve to complement the classical NNRTIs discovery approaches (structure-based core-refining and substituents-decorating).