Synthesis and biological evaluation of macrocyclized betulin derivatives as a novel class of anti-HIV-1 maturation inhibitors

Open Medicinal Chemistry Journal

Volumn 8, Issue , 2014, Pages 23-27

  Tang, Jun ^a   Jones, Stacey A ^a   Jeffery, Jerry L ^a   Miranda, Sonia R ^a   Galardi, Cristin M ^a   Irlbeck, David M ^a   Brown, Kevin W ^a   McDanal, Charlene B ^a   Han, Nianhe ^b   Gao, Daxin ^b   Wu, Yongyong ^b   Shen, Bin ^b   Liu, Chunyu ^b   Xi, Caiming ^b   Yang, Heping ^b   Li, Rui ^b   Yu, Yajun ^b   Sun, Yufei ^b   Jin, Zhimin ^b   Wang, Erjuan ^b   Johns, Brian A ^a   more..

^a GLAXOSMITHKLINE   (United States)

^b ShangPharma   (China)

Author keywords

Betulin derivative; HIV; Macrocyclization; Maturation inhibitor

Indexed keywords

ALKENE; BETULIN; BEVIRIMAT; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; MACROCYCLIC COMPOUND;

ARTICLE; DNA POLYMORPHISM; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; PRIORITY JOURNAL;

EID: 84926480151     PISSN: None     EISSN: 18741045     Source Type: Journal    
DOI: 10.2174/1874104501408010023     Document Type: Article

References (14)

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13. The antiviral activity was determined in a two cell co-culture HIV lifecycle assay. In this assay, Jurkat T-lymphocytes that were chronically infected with HIV-1 HxB2 were co-cultured with indicator HOS cells that harbor a modified HIV-1 LTR-luciferase reporter. The description of this assay can be found: Gao, D.; Han, N; Jin, Z.; Ning, F.; Tang, J.; Wu, Y.; Yang, H. Derivatives of be-tulin. WO2,011,100,308, August 18, 2011.
14. The description of this PBMC assay can be found: Hatcher, A. M.; Johns, A. B.; Martin, T. M.; Tabet, A. E.; Tang, J. Derivatives of betulin. WO2,013,090,664, June 20, 2013. Cellular stability has been evaluated with exemplar compounds. Observed half-lives in human microsomes were less than 20 minutes. The cellular toxicity of these compounds have been measured in the MT4 lymphocytic cell line with CC50s greater than 10 uM.