1364597-70-5Relevant academic research and scientific papers
Discovery and Optimization of Novel Pyrazolopyrimidines as Potent and Orally Bioavailable Allosteric HIV-1 Integrase Inhibitors
Li, Guo,Meanwell, Nicholas A.,Krystal, Mark R.,Langley, David R.,Naidu, B. Narasimhulu,Sivaprakasam, Prasanna,Lewis, Hal,Kish, Kevin,Khan, Javed A.,Ng, Alicia,Trainor, George L.,Cianci, Christopher,Dicker, Ira B.,Walker, Michael A.,Lin, Zeyu,Protack, Tricia,Discotto, Linda,Jenkins, Susan,Gerritz, Samuel W.,Pendri, Annapurna
, p. 2620 - 2637 (2020/03/05)
The standard of care for HIV-1 infection, highly active antiretroviral therapy (HAART), combines two or more drugs from at least two classes. Even with the success of HAART, new drugs with novel mechanisms are needed to combat viral resistance, improve adherence, and mitigate toxicities. Active site inhibitors of HIV-1 integrase are clinically validated for the treatment of HIV-1 infection. Here we describe allosteric inhibitors of HIV-1 integrase that bind to the LEDGF/p75 interaction site and disrupt the structure of the integrase multimer that is required for the HIV-1 maturation. A series of pyrazolopyrimidine-based inhibitors was developed with a vector in the 2-position that was optimized by structure-guided compound design. This resulted in the discovery of pyrazolopyrimidine 3, which was optimized at the 2- and 7-positions to afford 26 and 29 as potent allosteric inhibitors of HIV-1 integrase that exhibited low nanomolar antiviral potency in cell culture and encouraging PK properties.
INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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, (2012/03/27)
The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
