2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2016 Jan 1;26(1):160-7. doi: 10.1016/j.bmcl.2015.11.009.
Jacob J Swidorski 1,  Zheng Liu 1,  Zhiwei Yin 1,  Tao Wang 1,  David J Carini 1,  Sandhya Rahematpura 2,  Ming Zheng 2,  Kim Johnson 2,  Sharon Zhang 3,  Pin-Fang Lin 3,  Dawn D Parker 2,  Wenying Li 2,  Nicholas A Meanwell 1,  Lawrence G Hamann 1,  Alicia Regueiro-Ren 1
Affiliations

Affiliations

  • 1 Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
  • 2 Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
  • 3 Department of Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
PMID: 26584882 DOI: 10.1016/j.bmcl.2015.11.009
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.

Keywords

Attachment; BMS-663068; Entry; HIV-1; Tetrahydroisoquinoline; Tetrahydropyrido[3,4-d]pyrimidines.

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