865300-49-8Relevant articles and documents
Discovery of 2-Pyridinone Aminals: A Prodrug Strategy to Advance a Second Generation of HIV-1 Integrase Strand Transfer Inhibitors
Raheem, Izzat T.,Walji, Abbas M.,Klein, Daniel,Sanders, John M.,Powell, David A.,Abeywickrema, Pravien,Barbe, Guillaume,Bennet, Amrith,Clas, Sophie-Dorothee,Dubost, David,Embrey, Mark,Grobler, Jay,Hafey, Michael J.,Hartingh, Timothy J.,Hazuda, Daria J.,Miller, Michael D.,Moore, Keith P.,Pajkovic, Natasa,Patel, Sangita,Rada, Vanessa,Rearden, Paul,Schreier, John D.,Sisko, John,Steele, Thomas G.,Truchon, Jean-Fran?ois,Wai, John,Xu, Min,Coleman, Paul J.
supporting information, p. 8154 - 8165 (2015/11/09)
The search for new molecular constructs that resemble the critical two-metal binding pharmacophore required for HIV integrase strand transfer inhibition represents a vibrant area of research within drug discovery. Here we present the discovery of a new class of HIV integrase strand transfer inhibitors based on the 2-pyridinone core of MK-0536. These efforts led to the identification of two lead compounds with excellent antiviral activity and preclinical pharmacokinetic profiles to support a once-daily human dose prediction. Dose escalating PK studies in dog revealed significant issues with limited oral absorption and required an innovative prodrug strategy to enhance the high-dose plasma exposures of the parent molecules.
HIV INTEGRASE INHIBITORS
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Page/Page column 18-19, (2008/12/05)
Stereoisomers of compounds of Formula I are disclosed: wherein V1,V2, R5a, R5b, R5c, R8 and R9b are defined herein and wherein the stereoisomer contains 2 chiral centers in the 8-membered ring and one of the chiral centers is due to the presence of a chiral ring carbon. The isomers are inhibitors of HIV integrase and inhibitors of HIV replication, and are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset or progression of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
HIV INTEGRASE INHIBITORS
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Page/Page column 50-51, (2008/06/13)
Tricyclic compounds of Formula (I) are inhibitors of HIV integrase and inhibitors of HIV replication: wherein bond a, ring A, Rl, R2 and R3 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
