General Papers ARKIVOC 2014 (v) 384-398 Page 384 © ARKAT-USA, Inc Synthesis of substituted isoindolo[2,1-a]quinoxalin-6-yl–amino and 6-imino-5-yl thiourea derivatives Barbara Parrino, Cristina Ciancimino, Chandrakant Sarwade, Virginia Spanò, Alessandra Montalbano, Paola Barraja, Girolamo Cirrincione, Patrizia Diana, and Anna Carbone* Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy E-mail: anna.carbone@unipa.it DOI: http://dx.doi.org/10.3998/ark.5550190.p008.582 Abstract A series of substituted 1-(5-bromopyridin-2-yl)-3-[2-(isoindolo[2,1-a]quinoxalin-6- ylamino)ethyl]thiourea and 1-(5-bromopyridin-2-yl)-3-[2-(6-iminoisoindolo[2,1-a]quinoxalin- 5(6H)-yl)ethyl]thiourea derivatives were prepared in good yields (63-85%) by reaction between the corresponding amino compounds with 5-bromo-2-isothiocyanatopyridine. All thiourea derivatives, tested for inhibition of HIV-1 RT, showed no significant antiviral activity. Keywords: AIDS, NNRTIs, isoindolo-quinoxalines, quinoxalinylethylpyridylthioureas, antiviral activity Introduction Human immunodeficiency virus (HIV) is a retrovirus responsible for transmission and development of the acquired immune deficiency syndrome (AIDS). It is characterized by the presence of a viral reverse transcriptase (RT) that is able to synthesize DNA from the viral RNA genoma. Due to its important role in the viral life cycle, this enzyme is considered an excellent target in the chemotherapy against AIDS. In the current treatment strategy, called highly active antiretroviral therapy (HAART), HIV-1 RT inhibitors are used in combination with HIV-1 protease inhibitors. 1-3 There are two classes of HIV-1 RT inhibitors: nucleoside analogues (NRTIs), for example AZT, ddI, ddC, d4T and non-nucleoside analogues (NNRTIs), for example nevirapine, efavirenz, delarvidine. NRTIs are competitive inhibitors that act at the catalytic site of the enzyme by interrupting DNA synthesis. 4 NNRTIs are non-competitive inhibitors, structurally diverse, that bind to a hydrophobic pocket located approximately 10 Å away from the catalytic