Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 19; pp. 5831 - 5834
• Main Authors: Liu, Hong-Shan, Xu, Shi-Qing, Cheng, Ming, Chen, Ying, Xia, Peng, Qian, Keduo, Xia, Yi, Yang, Zheng-Yu, Chen, Chin-Ho, Morris-Natschke, Susan L., Lee, Kuo-Hsiung
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.10.2011; Elsevier
• Subjects: 2-Ethyl-1′-thia-DCP; 2′-Monomethyl-1′-oxa-DCP; 2′-Monomethyl-1′-thia-DCP; 4-Methyl-1′-thia-DCK; Anti-HIV activity; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; antiviral properties; Biological and medical sciences; Camphor - analogs & derivatives; Camphor - chemical synthesis; Camphor - chemistry; Camphor - pharmacology; Cell Line; Chromones - chemical synthesis; Chromones - chemistry; Chromones - metabolism; Chromones - pharmacology; coumarins; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - metabolism; Coumarins - pharmacology; Drug Design; Drug Evaluation, Preclinical; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Hydroxylation; Inhibitory Concentration 50; Lymphocytes - metabolism; Lymphocytes - virology; Medical sciences; Pharmacology. Drug treatments; Stereoisomerism; Structure-Activity Relationship; virus replication; Virus Replication - drug effects; Virus Replication - physiology; 2-Ethyl-1′-thia-DCP; Anti-HIV activity; 2′-Monomethyl-1′-oxa-DCP; 2′-Monomethyl-1′-thia-DCP; 4-Methyl-1′-thia-DCK; 2'-Monomethyl-1'-thia-DCP; Terpenoid; Coumarine derivatives; 2-Ethyl-1'-thia-DCP; Retroviridae; Lactone; 2'-Monomethyl-1'-oxa-DCP; Lentivirus; In vitro; Biological activity; Virus; Antiviral; Monoterpene; Human immunodeficiency virus; Chemical synthesis; 4-Methyl-1'-thia-DCK
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.07.105

Six 3′ R,4′ R-di- O-( S)-camphanoyl-2′,2′-dimethyldihydropyrano[2,3- f]chromone (DCP) and two 3′ R,4′ R-di- O-( S)-camphanoyl-(+)- cis-khellactone (DCK) derivatives were designed, synthesized, and evaluated for inhibition of HIV-1 NL4-3 replication in TZM-bl cells. 2-Ethyl-2′-monomethyl-1′-oxa- and -1′-thia-DCP ( 5a, 6a), as well as 2-ethyl-1′-thia-DCP ( 7a) exhibited potent anti-HIV activity with EC 50 values of 30, 38 and 54 nM and therapeutic indexes of 152.6, 48.0 and 100.0, respectively, which were better than or comparable to those of the lead compound 2-ethyl-DCP in the same assay. 4-Methyl-1′-thia-DCK ( 8a) also showed significant inhibitory activity with an EC 50 of 128 nM and TI of 237.9.