Nonnucleoside inhibitors of reverse transcriptase for the...

C - Chemistry – Metallurgy – 07 – D

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C07D 213/75 (2006.01) A61K 31/44 (2006.01) A61K 31/505 (2006.01) C07D 239/46 (2006.01)

Patent

CA 2323418

Novel compounds that are potent inhibitors of HIV reverse transcriptase (RT) are described in the invention. These novel compounds also inhibit replication of a retrovirus, such as human immunodeficiency virus-1 (HIV-1). The novel compounds of the invention include analogs and derivatives of phenethylthiazolylthiourea (PETT), of dihydroalkoxybenzy-loxopyrimidine (DABO), and of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The invention additionally provides a composite HIV reverse-transcriptase (RT) nonnucleoside inhibitor (NNI) binding pocket constructed from a composite of multiple NNI-RT complexes. The composite RT-NNI binding pocket provides a unique and useful tool for designing and identifying novel, potent inhibitors of reverse transcriptase.

La présente invention concerne de nouveaux composés qui constituent de puissants inhibiteurs de la transcriptase inverse (RT) du VIH. Ces nouveaux composés inhibent également la réplication d'un rétrovirus, tel que le virus de l'immunodéficience humaine 1 (VIH-1). Ces nouveaux composés renferment des analogues et des dérivés de phénéthylthiazolylthio-urée (PETT), de dihydroalcoxybenzy-loxopyrimidine (DABO), et de 1-[(2-hydroxyéthoxy)méthyl]-6-(phénylthio)thymine (HEPT). Par ailleurs, cette invention concerne une poche de liaison composite d'inhibiteur non nucléosidique (NNI) de transcriptase inverse (RT) du VIH, fabriquée avec un composite de complexes NNI-RT multiples. La poche de liaison RT-NNI constitue un outil unique et utile pour l'élaboration et l'identification de nouveaux inhibiteurs puissants de transcriptase inverse.

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