Rapid Access to 10-(Cyclohexylimino)-7,9-diazaspiro[4.5]decane-6,8-dione Derivatives for HIV-1 Reverse Transcriptase Inhibition via Ruthenium-Catalyzed Ring-Closing Metathesis
Rapid Access to 10-(Cyclohexylimino)-7,9-diazaspiro[4.5]decane-6,8-dione Derivatives for HIV-1 Reverse Transcriptase Inhibition via Ruthenium-Catalyzed Ring-Closing Metathesis
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通过钌催化的闭环复分解快速获得 10-(环己基亚氨基)-7,9-二氮杂螺[4.5]癸烷-6,8-二酮衍生物以抑制 HIV-1 逆转录酶
DOI：
10.1055/s-0033-1339179
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Liu, Junyi
中科院分区：
文献类型：
--
作者：
Zhang, Zhili;Tian, Chao;Wang, Xiaowei;Liu, Junyi
Abstract HIV-1 reverse transcriptase, a multifunctional enzyme critical in the viral replication process, is an important target for suppression of virus spread. To date, there has been considerable effort to develop drugs against this enzyme with high activity and specificity, notably TNK-651 and its derivatives. In order to further improve the efficacy and to explore the structure–activity relationship, we have introduced the diazaspiro[4.5]decane-6,8-dione scaffold, with both a pyrimidine and an alicyclic ring, and have synthesized several new compounds in this class. Appreciable overall yield was achieved with minimized purification of the intermediates. Several compounds were tested against HIV-1 reverse transcriptase in vitro using nevirapine as a reference. One compound showed potent inhibitory activity, with an IC50 value (ca. 1.65 μM) comparable to that of nevirapine. Our synthetic method provides a rapid access to compounds in this class. Thus, many other similar compounds can be further studied in a timely and cost-effective manner.
通过钌催化的闭环复分解快速获得 10-(环己基亚氨基)-7,9-二氮杂螺[4.5]癸烷-6,8-二酮衍生物以抑制 HIV-1 逆转录酶
DOI：
10.1055/s-0033-1339179
发表时间：
2013-06
期刊：
Synthesis
影响因子：
--
作者：
Zhang, Zhili;Tian, Chao;Wang, Xiaowei;Liu, Junyi
通讯作者：
Liu, Junyi
DOI：
10.1002/chin.201402093
发表时间：
2013
期刊：
ChemInform
影响因子：
--
作者：
J. And
通讯作者：
J. And