REGIOISOMERIC 3-AMINOMETHYL, 4-AMINOMETHYL AND 5-AMINOMETHYL ISOXAZOLES - SYNTHESIS AND MUSCARINIC ACTIVITY
REGIOISOMERIC 3-AMINOMETHYL, 4-AMINOMETHYL AND 5-AMINOMETHYL ISOXAZOLES - SYNTHESIS AND MUSCARINIC ACTIVITY
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DOI：
10.1016/0223-5234(96)88303-6
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发表时间：
1995-01-01
影响因子：
6.7
通讯作者：
STRIEGEL, HG
中科院分区：
文献类型：
--
作者：
DANNHARDT, G;KIEFER, W;STRIEGEL, HG
合成了一系列3-、4-和5-氨甲基异恶唑和杂环上有一个或两个额外甲基的异恶唑，以研究结构要求，即杂环部分、区域化学和氨烷基单元的长度对毒蕈碱活性的影响。在离体兔输精管（M（1）受体亚型）和离体豚鼠心房（M（2）受体亚型）和回肠（M（3）受体亚型）上进行了测定。测试的异恶唑比呋喃或恶二唑衍生物的活性低一到三个数量级，除了杂环之外具有相似的结构特征。因此，分子点电荷和电荷分布的差异有助于这些化合物的毒蕈碱活性超过分子形状和构象能的小差异。
A series of 3-, 4- and 5-aminomethyl isoxazoles and isoxazoles with one or two additional methyl groups at the heterocycle were synthesized in order to investigate the structural requirements, ie heterocyclic moiety, regiochemistry and length of an aminoalkyl unit, for muscarinic activity. This was assayed on isolated rabbit vas deferens (M(1) receptor subtype) and isolated guinea-pig atrium (M(2) receptor subtype) and ileum (M(3) receptor subtype). The isoxazoles tested are one to three orders of magnitude less active than furane or oxadiazole derivatives, having similar structural characteristics except for the heterocycle. Thus, the differences in molecular point charges and charge distribution contribute to the muscarinic activity of these compounds more than small differences in molecular shape and conformational energies.