## 1 Introduction  
Despite ongoing prevention efforts the number of HIV-infected individuals is still increasing mainly in the developing world. For a long time, there have been only two HIV targets for blocking viral replication, reverse transcriptase and protease. Following an initial breakthrough with the design of the fusion inhibitor, Enfuvirtide (Fuzeon(r)) [1], newer generations of antiretroviral drugs have emerged to complement existing treatment regimens [2]. Small molecules capable of blocking the CCR5 chemokine receptor raised considerable hope [3], nevertheless the most promising novel class of antiretrovirals is probably the integrase inhibitors [4].  
The HIV-1 integrase (IN) is a key enzyme in the replication cycle of the retrovirus since it catalyzes the integration of the reverse transcribed viral DNA into the chromosomal DNA. Integration of the HIV-1 DNA ensures stable maintenance of the viral genome and perpetuation of the virus in the host organism, therefore making integrase an attractive target for antiviral chemotherapy. The integration process requires two distinct catalytic steps. During the first one, named 3'-processing, the integrase specifically removes two nucleotides from each 3'-end of the linear viral DNA. The second step consists in a strand transfer following the translocation of the viral DNA into the nucleus of the infected cells. During this step, IN transfers both extremities of the viral DNA into the target DNA by a one-step transesterification reaction, resulting in full-site integration (Figure 1) [5].  
Since the early 90's, many compounds that inhibit one of the two steps were identified. However, only strand transfer inhibitors (also known as INSTIs) have been shown to be potent antiviral compounds. One such compound, Raltegravir (Isentress(r)), which was developed based on early studies by [PERSON] _et al_., was approved for clinical use in autumn 2007 as the first antiretroviral drug targeting the viral integrase [6]. Other compounds such as Elvitegravir or GSK1349572 and GSK1265744, are currently in advanced clinical trials [7]. Unfortunately drug-resistance variants have emerged [8]. Moreover, INSTIs differ from the other classes of antiretrovirals in that they lead to the accumulation of reverse transcribed genomes in the form of two LTRs DNA circles. Such accumulation may cause immune signals whose effects are not known [9]. INSTIs may also interfere with endogenous retroelements which replication involves an integration step, with poorly evaluated consequences [9]. Altogether, these observations have prompted not only the search for novel INSTIs but also a reassessment of the potential inhibitory activity of 3'-processing inhibitors. From this  
Figure 1: Schematic representation of the two integrase catalytic reactions (3’-processing and strand transfer).  
viewpoint, styrylquinolines are a family of compounds that were found to be potent inhibitors of 3'-processing with a significant inhibitory activity against viral replication in cell cultures. In this review, we recapitulate the different steps of the development of this series and the data obtained _in vitro_ and _ex vivo_ that shed light on their mechanism of action.