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Combining symmetry elements results in potent naphthyridinone (NTD) HIV-1 integrase inhibitors |
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| Authors: | Johns Brian A Kawasuji Takashi Weatherhead Jason G Boros Eric E Thompson James B Garvey Edward P Foster Scott A Jeffrey Jerry L Miller Wayne H Kurose Noriyuki Matsumura Kenichi Fujiwara Tamio |
| Institution: | GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA. brian.a.johns@gsk.com |
| Abstract: | 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. |
| Keywords: | HIV Integrase Naphthyridinone Antiviral HAART |
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