Phosphonylmethoxyalkylpurines and -pyrimidines as inhibitors of African swine fever virus replication in vitro.

Several phosphonylmethoxyalkylpurine and -pyrimidine derivatives related to (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated as inhibitors of African swine fever virus (ASFV) replication in Vero cells. (S)-HPMPA has previously been shown to inhibit ASFV replication at a minimum inhibitory concentration (MIC) of 0.01 microgram/ml with a selectivity index of 15000. Of the new compounds tested, the following emerged as the most potent and selective inhibitors of ASFV replication: the cyclic phosphonate of (S)-HPMPA [(S)-cHPMPA] with an MIC of 0.2 microgram/ml and a selectivity index of 2500, the 2,6-diaminopurine analogue of (S)-HPMPA [(S)-HPMPDAP] with an MIC of 0.5 microgram/ml and a selectivity index of 1400, and the cytosine [(S)-HPMPC] and guanine [(RS)-HPMPG] analogues with an MIC of 1 microgram/ml and a selectivity index of 600-700.