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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 MK-8718 and PL-100 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 MK-8718.

SUBMITTER: Bungard CJ

PROVIDER: S-EPMC5733263 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Design and Synthesis of Piperazine Sulfonamide Cores Leading to Highly Potent HIV-1 Protease Inhibitors.

Bungard Christopher J CJ Williams Peter D PD Schulz Jurgen J Wiscount Catherine M CM Holloway M Katharine MK Loughran H Marie HM Manikowski Jesse J JJ Su Hua-Poo HP Bennett David J DJ Chang Lehua L Chu Xin-Jie XJ Crespo Alejandro A Dwyer Michael P MP Keertikar Kartik K Morriello Gregori J GJ Stamford Andrew W AW Waddell Sherman T ST Zhong Bin B Hu Bin B Ji Tao T Diamond Tracy L TL Bahnck-Teets Carolyn C Carroll Steven S SS Fay John F JF Min Xu X Morris William W Ballard Jeanine E JE Miller Michael D MD McCauley John A JA

ACS medicinal chemistry letters 20171113 12

Using the HIV-1 protease binding mode of MK-8718 and PL-100 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 MK-8718. ...[more]

PMID: 29259750

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