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

Summary 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 μg/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 μg/ml and a selectivity index of 2500, the 2,6-diaminopurine analogue of ( S )-HPMPA [( S )-HPMPDAP] with an MIC of 0.5 μg/ml and a selectivity index of 1400, and the cytosine [( S )-HPMPC] and guanine [( S )-HPMPG] analogues with an MIC of 1 μg/ml and a selectivity index of 600–700.