1345733-98-3Relevant academic research and scientific papers
Naphthyridinone (NTD) integrase inhibitors 4. Investigating N1 acetamide substituent effects with C3 amide groups
Johns, Brian A.,Kawasuji, Takashi,Weatherhead, Jason G.,Boros, Eric E.,Thompson, James B.,Koble, Cecilia S.,Garvey, Edward P.,Foster, Scott A.,Jeffrey, Jerry L.,Fujiwara, Tamio
, p. 3104 - 3107 (2015/02/19)
A series of N1 acetamide substituted naphthyridinone HIV-1 integrase inhibitors have been explored to understand structure-activity relationships (SAR) with various C3 amide groups. Investigations were evaluated using integrase enzyme inhibition, antiviral activity and protein binding effects to optimize the sub-structures. Lipophilicity was also incorporated to understand ligand lipophilic efficiency as a function of the structural modifications. Three representative analogs were further examined in a peripheral blood mononuclear cell (PBMC) antiviral assay as well as in vitro and in vivo drug metabolism and pharmacokinetic studies.
Combining symmetry elements results in potent naphthyridinone (NTD) HIV-1integrase inhibitors
Johns, Brian A.,Kawasuji, Takashi,Weatherhead, Jason G.,Boros, Eric C.,Thompson, James B.,Garvey, Edward P.,Foster, Scott A.,Jeffrey, Jerry L.,Miller, Wayne H.,Kurose, Noriyuki,Matsumura, Kenichi,Fujiwara, Tamio
scheme or table, p. 6461 - 6464 (2011/12/02)
A series of naphthyridinone HIV-1 integrase strand-transfer inhibitors have been designed based on a psdeudo-C2 symmetry element present in the two-metal chelation pharmacophore. A combination of two distinct inhibitor binding modes resulted in potent inhibition of the integrase strand-transfer reaction in the low nM range. Effects of aryl and N1 substitutions are disclosed including the impact on protein binding adjusted antiviral activity.
