Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7.
Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7.
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5-[1-(2-甲氧基甲基吡咯烷基)磺酰基]靛红衍生物吡咯烷环上4-或5-取代基对其抑制caspase-3和-7活性的影响
DOI：
10.1016/j.ejmech.2013.04.011
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发表时间：
2013
影响因子：
6.7
通讯作者：
G. Haufe
中科院分区：
文献类型：
--
作者：
P. Limpachayaporn;B. Riemann;K. Kopka;O. Schober;M. Schäfers;G. Haufe
制备了一系列新的5-[1-（2-甲氧基甲基吡咯烷基）磺酰基]靛红的4-或5-取代的吡咯烷衍生物，它们在靛红氮上带有额外的正丁基或4-氟丁基，并测试了它们对半胱天冬酶-3和-7的抑制活性，已知半胱天冬酶-3和-7参与程序性细胞死亡（称为细胞凋亡）的执行。还合成了几种在吡咯烷环的4-位氟化的类似物，因为这样的抑制剂可能被开发为18F-放射性示踪剂，用于通过PET在体内对活化的半胱天冬酶进行分子成像。对映体纯的非对映体4-氟吡咯烷基衍生物抑制酶的纳摩尔级，即100 -1000倍，比相应的4-甲氧基类似物更有效。4，4-二氟化化合物显示出最好的结果，对于上述半胱天冬酶的IC 50 = 362 nM和178 nM。相比之下，4-甲氧基和4-三氟甲基类似物在μM规模下对酶的抑制效力较低，而所有4-OPEG 4（PEG 4 =四甘醇）和5-甲氧基甲基衍生物均无活性。
A series of new 4- or 5-substituted pyrrolidine derivatives of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin bearing additional n-butyl or 4-fluorobutyl groups at the isatin nitrogen were prepared and their inhibitory activities have been tested against caspases-3 and -7, which are known to participate in the execution of the programmed cell death, called apoptosis. Several analogues fluorinated at the 4-position of the pyrrolidine ring were also synthesized since such inhibitors might be developed as18F-radiotracers for molecular imaging of activated caspases in vivo by PET. Enantiomerically pure diastereomeric 4-fluoropyrrolidinyl derivatives inhibited the enzymes in the nanomolar scale, i.e.100–1000 times more efficient than the corresponding 4-methoxy analogues. The 4,4-difluorinated compound showed the best result with IC50= 362 nM and 178 nM for the aforementioned caspases. In contrast, the 4-methoxy and 4-trifluoromethyl analogues exhibited less inhibition potencies for the enzymes in the μM scale, whereas all 4-OPEG4(PEG4= tetraethyleneglycol) and 5-methoxymethyl derivatives were inactive.
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影响因子：
7.4
作者：
Baumann, Anne;Faust, Andreas;Karst, Uwe
通讯作者：
Karst, Uwe
影响因子：
3.5
作者：
Kamal, Ahmed;Rajender;Sastry, G. Narahari
通讯作者：
Sastry, G. Narahari
C2 对称反式-2,5-双(羟甲基)吡咯烷的两种对映体的合成。
影响因子：
1.8
作者：
M. Sibi;Jianliang Lu
通讯作者：
Jianliang Lu
影响因子：
2.7
作者：
Zhou, Dong;Chu, Wenhua;Mach, Robert H.
通讯作者：
Mach, Robert H.
影响因子：
4.2
作者：
Podichetty, Anil Kumar;Wagner, Stefan;Haufe, Guenter
通讯作者：
Haufe, Guenter