6-thienyl and 6-phenylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase

被引:22
作者
Andreani, A
Rambaldi, M
Leoni, A
Morigi, R
Locatelli, A
Giorgi, G
Lenaz, G
Ghelli, A
Degli Esposti, M
机构
[1] Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy
[2] Ctr Interdipartimentale Anal & Determinaz Struttu, I-53100 Siena, Italy
[3] Dipartimento Biol ES, I-40126 Bologna, Italy
[4] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3168, Australia
关键词
imidazo[2,1-b]thiazole; mitochondrial complex I; ubiquinone; rotenone;
D O I
10.1016/S0223-5234(99)00203-2
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Starting from the potent inhibitory effect of the previously described 2 methyl-6-(2-thienyl)imidazo[2,1-b]thiazol on mitochondrial complex I, we prepared a series of derivatives in order to study the effect of a different substitution at the positions 2, 5 and 6. The replacement of the thienyl group at position 6 with a phenyl group does not modify the biological behaviour of the lead compound, whereas the shift of the methyl group from position 2 to position 5 yields a compound devoid of inhibitory effects. In both the 6-thienyl and 6-phenyl series, the lengthening of the chain at position 2 has provided useful information to outline the structural determinants of the ubiquinone antagonist action in imidazothiazole derivatives. (C) 1999 Editions scientifiques et medicales Elsevier SAS.
引用
收藏
页码:883 / 889
页数:7
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