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

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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).

Keywords::

• AIDS
• drug design
• HIV-1
• inhibitor
• medicinal chemistry
• non-nucleoside RT inhibitors
• patent
• reverse transcriptase

Notes

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