Structure-activity relationship of diphenylthiourea antivirals.

The dependence between chemical structure and antiviral activity of N,N'-diphenylthioureas is studied by synthesis and testing of model compounds and use of conformational data. The analysis revealed a number of structural features as essential for the antiviral effect: (1) the presence of an intact -NHC(==S)NH- grouping; (2) the presence of a substituent of the XH type (X = O, NH) in the aromatic ring; (3) the distance between these substituents and the sulfur atom in the 6.68-6.75 A range for the active compounds: (4) a trans conformation of the -C(==S)NH-group bound to the substituted phenyl ring. The directed synthesis of compounds satisfying the above requirements yielded the derivative N-phenyl-N'-(m-aminophenyl)thiourea exhibiting a very high antipicornavirus activity in vitro and several other active analogues (four out of seven synthesized). The possible mechanism of interaction between the active diphenylthiourea derivatives and the viral target is discussed.