Pyridopyrimidinone inhibitors of HIV-1 RNase H.

Velthuisen, Emile J; Johns, Brian A; Gerondelis, Peter; Chen, Yan; Li, Ming; Mou, Ke; Zhang, Wenwen; Seal, John W; Hightower, Kendra E; Miranda, Sonia R; Brown, Kevin; Leesnitzer, Lisa

Velthuisen, Emile J; Johns, Brian A; Gerondelis, Peter; Chen, Yan; Li, Ming; Mou, Ke; Zhang, Wenwen; Seal, John W; Hightower, Kendra E; Miranda, Sonia R; Brown, Kevin; Leesnitzer, Lisa.

Afiliação

Velthuisen EJ; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States. Electronic address: emile.j.velthuisen@gsk.com.
Johns BA; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Gerondelis P; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Chen Y; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Li M; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Mou K; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Zhang W; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Seal JW; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Hightower KE; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Miranda SR; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Brown K; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.
Leesnitzer L; GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, United States.

Eur J Med Chem ; 83: 609-16, 2014 Aug 18.

Article em En | MEDLINE | ID: mdl-24997293

ABSTRACT

ABSTRACT

Using a structure based pharmacophore design, a weak inhibitor of RNase H, identified from a small library of two metal binding HIV-1 integrase inhibitors, was optimized for potency and physicochemical properties. This manuscript describes the SAR and in vivo DMPK for the pyridopyrimidinone class of inhibitors.

Assuntos

HIV-1/enzimologia; Pirimidinonas/química; Pirimidinonas/farmacologia; Inibidores da Transcriptase Reversa/química; Inibidores da Transcriptase Reversa/farmacologia; Ribonuclease H do Vírus da Imunodeficiência Humana/antagonistas & inibidores; Animais; Masculino; Pirimidinonas/farmacocinética; Ratos; Ratos Sprague-Dawley; Inibidores da Transcriptase Reversa/farmacocinética; Relação Estrutura-Atividade

Palavras-chave

AIDS; Endonuclease; HIV; Integrase; Reverse transcriptase; Two-metal binder

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirimidinonas / HIV-1 / Inibidores da Transcriptase Reversa / Ribonuclease H do Vírus da Imunodeficiência Humana Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

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