Identification of spirocyclic or phosphate substituted quinolizine derivatives as novel HIV-1 integrase inhibitors: a patent evaluation of WO2016094197A1, WO2016094198A1 and WO2016154527A1. (2nd November 2017)

• Record Type: Journal Article
• Authors: Cheng, Xiqiang; Gao, Ping; Sun, Lin; Tian, Ye; Zhan, Peng; Liu, Xinyong
• Is Part Of: Expert opinion on therapeutic patents. Volume 27:Number 11(2017:Nov.)
• Page Start: 1277
• Page End: 1286
• Publication Date: 2017-11-02
• Subjects: AIDS -- HIV-1 -- IN inhibitors -- prodrug -- privileged structure -- drug design; Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1080/13543776.2017.1360283
• Languages: English
• ISSNs: 1354-3776

Abstract

ABSTRACT: Introduction : Highly active antiretroviral therapy (HAART) has been widely adopted to control the HIV-1 infection successfully. HIV-1 integrase (IN) inhibitors are primary drugs in HAART regimens targeting integration step in the HIV-1 life cycle. However, due to the emergence of viral resistance and cross-resistance amongst drugs, there is a pressing need for new and potent IN inhibitors. This review covers the three patents describing spirocyclic and phosphate substituted quinolizine derivatives as novel HIV-1 IN inhibitors for the discovery of new anti-HIV-1 drug candidates. Areas covered : This review is focused on spirocyclic and phosphate substituted quinolizine derivatives bearing the same metal chelation scaffold as novel HIV-1 IN inhibitors. Expert opinion : Generally, privileged structure-based optimizations have emerged as an effective approach to discover newly antiviral agents. More generally, due to the similar Mg 2+ catalytic active centers of endoribonucleases, some divalent metal ion chelators were found to be versatile binders targeting multiple metalloenzymes. Therefore, privileged structure-based scaffold re-evolution is an important tactic to identify new chemotypes, to explore unknown biological activities, or to provide effective ligands for multiple targets by modifying the existing active compounds.