7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics.: 2.: Pharmacological profile of 7-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (Abaperidone, FI-8602)
7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics.: 2.: Pharmacological profile of 7-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (Abaperidone, FI-8602)
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DOI：
10.1021/jm9810396
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发表时间：
1998-12-31
影响因子：
7.3
通讯作者：
Ortiz, JA
中科院分区：
文献类型：
--
作者：
Bolós, J;Anglada, L;Ortiz, JA
合成了一系列新型 7-[3-(1-哌啶基)丙氧基]色酮，并在多项体外和体内试验中作为潜在的抗精神病药进行了测试。这些化合物对 Dp 受体具有良好的亲和力，并且对 5-HT2 受体具有更大的亲和力，这一特性已被提议作为非典型抗精神病药的模型。几种药物在口服给药的攀爬小鼠试验中也显示出高效力，表明与参考标准相比具有有效的抗精神病作用。选择化合物23进行进一步的药理学评价。强直性昏迷的诱导和刻板抑制的作用弱于标准，以及血清催乳素水平的较低增加，表明该化合物具有潜在的非典型特征。根据这些结果，7-[3-[4-(6-氟-1,2-苯并异恶唑-3-基)哌啶-1-基]丙氧基]-3-(羟甲基)色烯-4-酮(23，阿巴哌酮)已被提议作为潜在的非典型抗精神病药用于人类临床评估。
A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vivo assays. The compounds possessed good affinity for Dp receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypical antipsychotics. Several agents also displayed a high potency in the climbing mice assay on oral administration, suggesting a potent antipsychotic effect as compared to reference standards. Compound 23 was selected for fur ther pharmacological evaluation. induction of catalepsy and inhibition of stereotypies weaker than standards, along with a lower increase in serum prolactin levels, were indicative of a potential atypical profile for this compound. From these results, 7-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (23, abaperidone) has been proposed for clinical evaluation in humans as a potential atypical antipsychotic.