Design, synthesis and SAR study of novel C2-pyrazolopyrimidine amides and amide isosteres as allosteric integrase inhibitors. Issue 21 (1st November 2020)

• Record Type: Journal Article
• Authors: Patel, Manoj; Cianci, Christopher; Allard, Christopher W.; Parker, Dawn D.; Simmermacher, Jean; Jenkins, Susan; Mcauliffe, Brian; Minassian, Beatrice; Discotto, Linda; Krystal, Mark; Meanwell, Nicholas A.; Naidu, B. Narasimhulu
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 21(2020)
• Publication Date: 2020-11-01
• Subjects: HIV -- HIV-1 integrase -- LEDGF/p75 -- Allosteric integrase inhibitors -- Pyrazolopyrimidine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127516
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: The design, synthesis and structure–activity relationships associated with a series of C2-substituted pyrazolopyrimidines as potent allosteric inhibitors of HIV-1 integrase (ALLINIs) are described. Structural modifications to these molecules were made in order to examine the effect on potency and, for select compounds, pharmacokinetic properties. We examined a variety of C2-substituted pyrazolopyrimidines and found that the C2-amide derivatives demonstrated the most potent antiviral activity of this class against HIV-1 infection in cell culture. Abstract: The design, synthesis and structure–activity relationships associated with a series of C2-substituted pyrazolopyrimidines as potent allosteric inhibitors of HIV-1 integrase (ALLINIs) are described. Structural modifications to these molecules were made in order to examine the effect on potency and, for select compounds, pharmacokinetic properties. We examined a variety of C2-substituted pyrazolopyrimidines and found that the C2-amide derivatives demonstrated the most potent antiviral activity of this class against HIV-1 infection in cell culture.