GABA-UPTAKE INHIBITORS - CONSTRUCTION OF A GENERAL PHARMACOPHORE MODEL AND SUCCESSFUL PREDICTION OF A NEW REPRESENTATIVE
GABA-UPTAKE INHIBITORS - CONSTRUCTION OF A GENERAL PHARMACOPHORE MODEL AND SUCCESSFUL PREDICTION OF A NEW REPRESENTATIVE
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DOI：
10.1021/jm00112a032
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发表时间：
1991-08-01
影响因子：
7.3
通讯作者：
WERMUTH, CG
中科院分区：
文献类型：
--
作者：
NGOKA, V;SCHLEWER, G;WERMUTH, CG
利用已发表的结构-活性数据和分子模型建立了gaba摄取抑制剂药效团模型。该模型考虑了不同种类的gaba摄取抑制剂的活性。为了证实该模型，合成了取代位置6的guvacine类似物。6-（3,3-二苯丙基）guvacine （30f）与药效团吻合良好，体外IC50为0.1 mu- m。这个值与目前已知的最好的gaba摄取抑制剂一样好。
A model for the pharmacophore of GABA-uptake inhibitors was established using published structure-activity data and molecular modeling. The model accounted for the activities of different classes of GABA-uptake inhibitors. Analogues of guvacine substituted at position 6 were synthesized in order to confirm the model. 6-(3,3-Diphenylpropyl)guvacine (30f), which fit well with the pharmacophore, had an in vitro IC50 of 0.1-mu-M. This value is as good as those of the best GABA-uptake inhibitors known today.