New antiherpetic 1,3-phenylene derivatives, inhibitors of the interaction of the HSV-1 origin binding protein (OBP) with DNA
Font M, Sanmartín C, Alonso ML, Gracia L, Losa MJ, Marquiegui B, Merino I, Nadal E, Ruiz I, Monge A, Bengoechea MT, Cabodevilla F, Elena S, Martinez-Irujo JJ, Odriozola L, Peñuelas I, Santiago E, Homa F, Wathen MW.
Medicinal Chemistry, Centro de Investigación en Farmacobiología, Aplicada, Universidad de Navarra, Pamplona, Spain
The synthesis of new 1,3-phenylene derivatives and their preliminary evaluation as antivirals (Herpes simplex 1, HSV-1) whose antiherpetic activity can be related with the inhibition of the interaction of the origin binding protein (OBP) with the DNA are presented.
The new compounds are adjusted to a previously defined common structural model, consisting of a central aromatic system, which presents two side chains of different lengths in relative position 1, 3; these chains are made up of atomic groups characterized by the alternation of positive and negative centers, situating differently substituted rings, preferably aromatic, at the ends of both chains. Some of these derivatives, such as N,N''-(4-methoxy-1,3-phenylene)bis[N'-(4-nitrophenyl)urea] (2c) or (1,3-phenylene)bis[N-(p-tolyl)aminosulfonyl] (11b), show antiherpetic activity related to the proposed mechanism.
CITATION Drug Des Discov. 2000;16(4):295-315