Inhibitors of HIV-1 attachment. Part 3: A preliminary survey of the effect of structural variation of the benzamide moiety on antiviral activity

• Published in: Bioorganic & medicinal chemistry letters 2009-09, Vol.19 (17), p.5136-5139
• Main Authors: Meanwell, Nicholas A., Wallace, Owen B., Wang, Henry, Deshpande, Milind, Pearce, Bradley C., Trehan, Ashok, Yeung, Kap-Sun, Qiu, Zhilei, Wright, J.J. Kim, Robinson, Brett A., Gong, Yi-Fei, Wang, Hwei-Gene Heidi, Blair, Wade S., Shi, Pei-Yong, Lin, Pin-fang
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral; Antiviral agents; Benzamides - chemical synthesis; Benzamides - chemistry; Benzamides - pharmacology; Biological and medical sciences; Cell Line; HIV attachment inhibitor; HIV Envelope Protein gp120 - antagonists & inhibitors; HIV Envelope Protein gp120 - metabolism; HIV Fusion Inhibitors - chemical synthesis; HIV Fusion Inhibitors - chemistry; HIV Fusion Inhibitors - pharmacology; HIV inhibitor; Human immunodeficiency virus 1; Humans; Indole glyoxamide; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Medical sciences; Pharmacology. Drug treatments; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Structure-Activity Relationship; Virus Attachment - drug effects
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.07.027

1-(4-Benzoylpiperazin-1-yl)-2-(1 H-indol-3-yl)ethane-1,2-dione ( 1a) has been characterized as an inhibitor of HIV-1 attachment that interferes with the interaction of viral gp120 with the host cell receptor CD4. In previous studies, the effect of indole substitution pattern on antiviral activity was probed. In this Letter, the effect of structural variation of the benzamide moiety is described, a study that reveals the potential or the phenyl moiety to be replaced by five-membered heterocyclic rings and a restricted tolerance for the introduction of substituents to the phenyl ring. 1-(4-Benzoylpiperazin-1-yl)-2-(1 H-indol-3-yl)ethane-1,2-dione ( 1a) has been characterized as an inhibitor of HIV-1 attachment that interferes with the interaction of viral gp120 with the host cell receptor CD4. In previous studies, the effect of indole substitution pattern on antiviral activity was probed. In this Letter, the effect of structural variation of the benzamide moiety is described, a study that reveals the potential or the phenyl moiety to be replaced by five-membered heterocyclic rings and a restricted tolerance for the introduction of substituents to the phenyl ring.