New antiherpetic 1,3-phenylene derivatives, inhibitors of the interaction of the HSV-1 origin binding protein (OBP) with DNA.
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.
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Medicinal Chemistry, Centro de Investigación en Farmacobiología, Aplicada, Universidad de Navarra, Pamplona, Spain.
Sanmartín
C
C
Alonso
M L
ML
Gracia
L
L
Losa
M J
MJ
Marquiegui
B
B
Merino
I
I
Nadal
E
E
Ruiz
I
I
Monge
A
A
Bengoechea
M T
MT
Cabodevilla
F
F
Elena
S
S
Martinez-Irujo
J J
JJ
Odriozola
L
L
Peñuelas
I
I
Santiago
E
E
Homa
F
F
Wathen
M W
MW
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D015195:Drug Design; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D008958:Models, Molecular; D010655:Phenylenediamines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014764:Viral Proteins / Q000187:drug effects / Q000378:metabolism*
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D010655:Phenylenediamines; D014764:Viral Proteins; C064565:UL9 protein, Human herpesvirus 1; D004247:DNA