Benzylguanidines and Other Galegine Analogues Inducing Weight Loss in Mice
Benzylguanidines and Other Galegine Analogues Inducing Weight Loss in Mice
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DOI：
10.1021/jm8011933
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发表时间：
2009-06-11
影响因子：
7.3
通讯作者：
Waigh, Roger D.
中科院分区：
文献类型：
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作者：
Coxon, Geoffrey D.;Furman, Brian L.;Waigh, Roger D.
二甲基烯丙基胍，也称为galegine，分离自Galega officinalis，已显示具有体内减肥特性。当在BALB/c小鼠中评价时，用N-氰基取代胍基和用脒、嘧啶、吡啶或咪唑部分取代胍可消除体重减轻特性。然而，保留胍和用一系列官能化苄基取代基取代二甲基烯丙基显示出，并且在某些情况下显著改善了这些分子在BALB/c、ob/ob和饮食诱导的肥胖（DIO）小鼠模型中的减肥特性。在所有模型中鉴定的先导化合物为1-（4-氯苄基）胍半硫酸盐，其在BALB/c、ob/ob和DIO模型中的平均每日体重差异（与时间匹配对照的%; +/- SEM）分别为-19.7 +/- 1.0、-11.0 +/- 0.7和-7.3 +/- 0.8。
Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing properties when evaluated in BALB/c mice. However, retention of the guanidine and replacement of the dimethylallyl group by a series of functionalized benzyl substituents was shown to exhibit, and in some cases significantly improve, the weight reducing properties of these molecules in BALB/c, ob/ob, and diet induced obesity (DIO) mice models. The lead compound identified, across all models, was 1-(4-chlorobenzyl)guanidine hemisulfate, which gave an average daily weight difference (% from time-matched controls; +/- SEM) of -19.7 +/- 1.0, -11.0 +/- 0.7, and -7.3 +/- 0.8 in BALB/c, ob/ob, and DIO models, respectively.