title: Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors.
abstract: A macrocycle provides diverse functionality and stereochemical complexity in a conformationally preorganized ring structure, and it occupies a unique chemical space in drug discovery. However, the synthetic challenge to access this structural class is high and hinders the exploration of macrocycles. In this study, efficient synthetic routes to macrocyclized betulin derivatives have been established. The macrocycle containing compounds showed equal potency compared to bevirimat in multiple HIV-1 antiviral assays. The synthesis and biological evaluation of this novel series of HIV-1 maturation inhibitors will be discussed.
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Jeffery
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Miranda
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: Cristin M
authors.initials: CM
authors.lastname: Galardi
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Irlbeck
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Brown
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: Charlene B
authors.initials: CB
authors.lastname: McDanal
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Nianhe
authors.initials: N
authors.lastname: Han
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Daxin
authors.initials: D
authors.lastname: Gao
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Caiming
authors.initials: C
authors.lastname: Xi
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Yang
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Jin
authors.affiliation: ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China.
authors.forename: Erjuan
authors.initials: E
authors.lastname: Wang
authors.affiliation: GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Johns
keywords: Betulin derivative; HIV; macrocyclization; maturation inhibitor