Some new 4-arylthio-pyridinones which are related to non-nucleoside RT inhibitors of HIV-1 exhibited significant antiviral activities in cell culture. They have been synthesized from different β-keto esters.The reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) has been, up to date, one of the main target aimed to search for drugs that may be useful for chemotherapeutic intervention in acquired immunodeficiency syndrome (AIDS). 1 The currently approved antiretroviral compounds (AZT, ddI, ddC, D4T) are nucleoside analogs which all inhibit competitively RT enzyme leading to chain termination during the process of reverse transcription. Unfortunately, the clinical usefulness of these drugs is limited by side effects, toxicities and drug resistance. 2 Several specific non-nucleoside reverse transcriptase inhibitors (NNRTIs), first discovered by random screening (HEPT, TIBO, αAPA, nevirapine, BHAP...) have also been evaluated in monotherapy protocols in clinical trials. However, these trials had to be discontinued due to the rapid emergence of viral resistance.2, 3 Yet, at the present time and to our knowledge, it is generally considered that the use of the NNRTIs in combination with other agents (nucleosides, protease inhibitors...) remains a viable alternative in AIDS chemotherapy. 3Recently we have discovered in our laboratory 4 a new family of pyridinone NNRTIs 1 which retain some of the structural features of HEPT 5 on one hand and of pyridinones developed by the Merck Research Laboratories 6 on the other hand.The synthesis of pyridinones 1 has been described previously. 4 The present paper presents an alternative route to this type of compounds allowing a convenient access to new modifications at positions 5 (R2) and 6 (R3) as well as preliminary anti HIV activities in vitro.