A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.
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Major role of dolutegravir in the emergence of the S147G integrase resistance mutation.
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Department of Virology, Sorbonne Université, INSERM, UMR-S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, 83 Boulevard de l'Hôpital 39, F-75013 Paris, France.
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Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon.
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