Anti-AIDS agents. Part 62: anti-HIV activity of 2'-substituted 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs.
Four 4-methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2'-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 2'-Methyl-2'-ethyl-4-methyl DCK (7b) was more potent (EC(50)=0.22 microM, TI>175) than the other three compounds (7a, 7c, and 7d), but significantly less potent than 4-methyl DCK (2, EC(50)=0.0059 microM, TI>6600). The bioassay results indicated that the 2'-substituents had a strong effect on the anti-HIV activity, and gem-dimethyl substitution at the 2'-position was greatly preferable to larger alkyl substituents or hydrogen atoms.
Zhang
Qian
Q
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 200032, China.
Chen
Ying
Y
Xia
Peng
P
Xia
Yi
Y
Yang
Zheng-Yu
ZY
Yu
Donglei
D
Morris-Natschke
Susan L
SL
Lee
Kuo-Hsiung
KH
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D002164:Camphor / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans
D019380:Anti-HIV Agents; D002164:Camphor