Inhibitors of HIV-1 attachment: The discovery and structure–activity relationships of tetrahydroisoquinolines as replacements for the piperazine benzamide in the 3-glyoxylyl 6-azaindole pharmacophore. Issue 1 (1st January 2016)

• Record Type: Journal Article
• Authors: Swidorski, Jacob J.; Liu, Zheng; Yin, Zhiwei; Wang, Tao; Carini, David J.; Rahematpura, Sandhya; Zheng, Ming; Johnson, Kim; Zhang, Sharon; Lin, Pin-Fang; Parker, Dawn D.; Li, Wenying; Meanwell, Nicholas A.; Hamann, Lawrence G.; Regueiro-Ren, Alicia
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 1(2016)
• Page Start: 160
• Page End: 167
• Publication Date: 2016-01-01
• Subjects: HIV-1 -- Entry -- Attachment -- Tetrahydroisoquinoline -- Tetrahydropyrido[3, 4-d]pyrimidines -- BMS-663068; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.11.009
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 6, 6-Fused ring systems including tetrahydroisoquinolines and tetrahydropyrido[3, 4- d ]pyrimidines have been explored as possible replacements for the piperazine benzamide portion of the HIV-1 attachment inhibitor BMS-663068. In initial studies, the tetrahydroisoquinoline compounds demonstrate sub-nanomolar activity in a HIV-1 pseudotype viral infection assay used as the initial screen for inhibitory activity. Analysis of SARs and approaches to optimization for an improved drug-like profile are examined herein.