2017
DOI: 10.1021/acsmedchemlett.7b00386
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Design and Synthesis of Piperazine Sulfonamide Cores Leading to Highly Potent HIV-1 Protease Inhibitors

Abstract: Using the HIV-1 protease binding mode of and as inspiration, a novel aspartate binding bicyclic piperazine sulfonamide core was designed and synthesized. The resulting HIV-1 protease inhibitor containing this core showed an 60-fold increase in enzyme binding affinity and a 10-fold increase in antiviral activity relative to .

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Cited by 42 publications
(30 citation statements)
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“…Although these compounds have received some attention in the previous reviews (especially in the papers by Majumdar and Mondal, as well as Sokolov and co‐workers cited above), they have never been at the central focus of the discussion. Meanwhile, they have great potential for medicinal chemistry projects, which is confirmed by discoveries of highly potent γ‐secretase inhibitor 1 , casein kinase II inhibitor 2 , protease‐activated receptor 1 (PAR‐1) antagonist 3 , retinoic acid receptor‐related orphan receptor γ (RORγ) antagonist 4 , or human immunodeficiency virus (HIV)‐1 protease inhibitor 5 (Figure ). Unlike in most previous reviews, we have categorized the literature data on saturated bicyclic sultams by their structural subtype (i.e.…”
Section: Introductionmentioning
confidence: 99%
“…Although these compounds have received some attention in the previous reviews (especially in the papers by Majumdar and Mondal, as well as Sokolov and co‐workers cited above), they have never been at the central focus of the discussion. Meanwhile, they have great potential for medicinal chemistry projects, which is confirmed by discoveries of highly potent γ‐secretase inhibitor 1 , casein kinase II inhibitor 2 , protease‐activated receptor 1 (PAR‐1) antagonist 3 , retinoic acid receptor‐related orphan receptor γ (RORγ) antagonist 4 , or human immunodeficiency virus (HIV)‐1 protease inhibitor 5 (Figure ). Unlike in most previous reviews, we have categorized the literature data on saturated bicyclic sultams by their structural subtype (i.e.…”
Section: Introductionmentioning
confidence: 99%
“…Recently, Bungard and colleagues reported an outstanding optimization of HIV‐1 protease inhibitor by Introduction of 2‐thia‐1,6‐diazabicyclo[3.2.1]octane 2,2‐dioxide core into 2 . This modification had significant impact on compounds potency, making it comparable to that of marketed Atazanavir and Darunavir antivirals.…”
Section: Introductionmentioning
confidence: 99%
“…Efforts to improve potency, pharmacokinetics, and resistance profiles of HIV-1 PIs have led to the discovery of exceptionally potent compounds exhibiting a wide range of properties. 5,[10][11][12][13][14] In recent years, these efforts have focused mainly on exploring DRV analogues with similar sulfonamide-based dipeptide isosteres and P2/P2 moieties. Many analogues of DRV with modifications at P1/P1…”
Section: Introductionmentioning
confidence: 99%