Investigation of the alkenyldiarylmethane non-nucleoside reverse transcriptase inhibitors as potential cAMP phosphodiesterase-4B2 inhibitors.
Investigation of the alkenyldiarylmethane non-nucleoside reverse transcriptase inhibitors as potential cAMP phosphodiesterase-4B2 inhibitors.
复制标题
研究烯基二芳基甲烷非核苷逆转录酶抑制剂作为潜在的 cAMP 磷酸二酯酶 4B2 抑制剂。
DOI：
10.1016/j.bmcl.2007.12.015
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发表时间：
2008
影响因子：
2.7
通讯作者：
Cushman,Mark
中科院分区：
文献类型：
--
作者：
Cullen,MatthewD;Cheung,York-Fong;Houslay,MilesD;Hartman,TracyL;Watson,KarenM;BuckheitJr,RobertW;Pannecouque,Christophe;DeClercq,Erik;Cushman,Mark
The alkenyldiarylmethanes (ADAMs) are currently being investigated as non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) of potential value in the treatment of HIV infection and AIDS. During the course of these studies, a number of ADAM analogues have been identified that protect HIV-infected cells from the cytopathic effects of the virus by an unknown, HIV-1 RT-independent mechanism. Since the phosphodiesterase 4 family is required for HIV infection, the effect of various ADAMs on the activity of PDE4B2 was investigated in an effort to determine if the ADAMs could possibly be targeting phosphodiesterases. Six compounds representative of the ADAM class were tested for inhibition of cAMP hydrolysis by PDE4B2 enzymatic activity. Four ADAMs were found to be weak inhibitors of PDE4B2 and two of them were inactive. The experimental results are consistent with an antiviral mechanism that does not include inhibition of PDE4 isoforms.
