text: After the discovery of HEPT and TIBO, compounds screening methods were used to develop BI-RG-587, the first NNRTI commonly known as nevirapine. Like HEPT and TIBO, nevirapine blocked viral RT activity by non-competitive inhibition (with respect to dNTP binding). This reinforced the idea that the new class of anti-HIV inhibitors was inhibiting the activity of RT but not at the active site. Several molecular families of NNRTIs have emerged following screening and evolution of many molecules.
  Three NNRTI compounds of the first generation have been approved by the FDA for treating HIV-1 infection. Nevirapine was approved in 1996, delavirdine in 1997 and efavirenz in 1998 (table 1). Two of these drugs, nevirapine and efavirenz, are cornerstones of first line HAART while delavirdine is hardly used nowadays. The structure of these three drugs show the wide array of rings, substituents, and bonds that allow activity against HIV-1 RT. This diversity demonstrates why so many non-nucleosides have been synthesised but doesn't explain why only three drugs have reached the market. The main problem has been the potency of these compounds to develop resistance.