A matched molecular pair analysis of in vitro human microsomal metabolic stability measurements for methylene substitution or replacements - identification of those transforms more likely to have beneficial effects

被引:11
作者
Dossetter, Alexander G. [1 ]
机构
[1] AstraZeneca PLC, Alderley Pk, Mereside SK10 4TG, Cheshire, England
关键词
MEDICINAL CHEMISTRY; DERIVATIVES; PARAMETERS;
D O I
10.1039/c2md20226c
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A matched molecular pair analysis (MMPA) was used to study the classic medicinal chemistry transformations of a methylene (-CH2-) into metabolic blocking groups. 1826 matched pairs were identified for 24 transforms and in vitro human microsomal stability analysed. Of these, 4 transforms have shown significant beneficial increase in stability, suggesting these transforms as preferred changes during compound optimisation.
引用
收藏
页码:1518 / 1525
页数:8
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