1. Synthesis and evaluation of C2-carbon-linked heterocyclic-5-hydroxy-6-oxo-dihydropyrimidine-4-carboxamides as HIV-1 integrase inhibitors.
- Author
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Naidu BN, Sorenson ME, Patel M, Ueda Y, Banville J, Beaulieu F, Bollini S, Dicker IB, Higley H, Lin Z, Pajor L, Parker DD, Terry BJ, Zheng M, Martel A, Meanwell NA, Krystal M, and Walker MA
- Subjects
- Amides chemical synthesis, Amides pharmacokinetics, Animals, HIV Integrase metabolism, HIV Integrase Inhibitors chemistry, HIV Integrase Inhibitors pharmacokinetics, HIV-1 drug effects, Half-Life, Heterocyclic Compounds chemistry, Humans, Male, Pyrimidines chemistry, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Amides chemistry, HIV Integrase chemistry, HIV Integrase Inhibitors chemical synthesis, HIV-1 enzymology
- Abstract
Integration of viral DNA into the host cell genome is an obligatory process for successful replication of HIV-1. Integrase catalyzes the insertion of viral DNA into the target DNA and is a validated target for drug discovery. Herein, we report the synthesis, antiviral activity and pharmacokinetic profiles of several C2-carbon-linked heterocyclic pyrimidinone-4-carboxamides that inhibit the strand transfer step of the integration process., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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