title: Inhibitors of HIV-1 attachment. Part 4: A study of the effect of piperazine substitution patterns on antiviral potency in the context of indole-based derivatives.
abstract: 4-Fluoro- and 4-methoxy-1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (2 and 3, respectively) have been characterized as potent inhibitors of HIV-1 attachment that interfere with the interaction of viral gp120 with the host cell receptor CD4. As part of an effort to understand fundamental aspects of this pharmacophore, discovered originally using a high throughput cell-based screen, modification and substitution of the piperazine ring was examined in the context of compounds 6a-ah. The piperazine ring was shown to be a critical element of the HIV-1 attachment inhibiting pharmacophore, acting as a scaffold to deploy the indole glyoxamide and benzamide in a topographical relationship that complements the binding site on gp120.
authors: Department of Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. Tao.Wang@bms.com
authors: Tao
authors: T
authors: Wang
authors: John F
authors: JF
authors: Kadow
authors: Zhongxing
authors: Z
authors: Zhang
authors: Zhiwei
authors: Z
authors: Yin
authors: Qi
authors: Q
authors: Gao
authors: Dedong
authors: D
authors: Wu
authors: Dawn DiGiugno
authors: DD
authors: Parker
authors: Zheng
authors: Z
authors: Yang
authors: Lisa
authors: L
authors: Zadjura
authors: Brett A
authors: BA
authors: Robinson
authors: Yi-Fei
authors: YF
authors: Gong
authors: Timothy P
authors: TP
authors: Spicer
authors: Wade S
authors: WS
authors: Blair
authors: Pei-Yong
authors: PY
authors: Shi
authors: Gregory
authors: G
authors: Yamanaka
authors: Pin-Fang
authors: PF
authors: Lin
authors: Nicholas A
authors: NA
authors: Meanwell
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D053585:Virus Attachment / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D007211:Indoles; D010879:Piperazines; C514793:gp120 protein, Human immunodeficiency virus 1