Synthesis and Structure−Activity Relationships of Fused Imidazopyridines: A New Series of Benzodiazepine Receptor Ligands
Synthesis and Structure−Activity Relationships of Fused Imidazopyridines: A New Series of Benzodiazepine Receptor Ligands
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稠合咪唑并吡啶的合成及构效关系：一系列新的苯二氮卓受体配体
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
A. Matsushita
中科院分区：
文献类型：
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作者：
S. Takada;T. Sasatani;N. Chomei;M. Adachi;T. Fujishita;M. Eigyo;S. Murata;K. Kawasaki;A. Matsushita
合成了 2-芳基咪唑并[4,5-c]喹啉和类似的稠合咪唑并吡啶，并作为苯二氮卓受体配体进行了评估。与 CGS-9896 等吡唑并喹啉类化合物相比，2 位芳基的体积对受体的亲和力影响很大。 2-位具有异恶唑部分的衍生物表现出高结合亲和力和体内活性。在咪唑并[4,5-c]喹啉系列中，6-位的取代降低或消除了活性。大多数具有未取代的异恶唑基的衍生物都表现出拮抗剂或反向激动剂活性，但7-卤代类似物除外，其表现出激动剂活性。另一方面，5-甲基异恶唑-3-基或3-甲基异恶唑-5-基衍生物通常表现出激动剂活性。在与非芳香环稠合的咪唑并吡啶中观察到对异恶唑部分的类似取代效应。从详细的药理评价来看，S-8510, 2-(3-异恶唑基)-3,6,7,9-四氢咪唑并[4,5-d]吡喃并[4,3-b...
2-Arylimidazo[4,5-c]quinolines and analogous fused imidazopyridines were synthesized and evaluated as benzodiazepine receptor ligands. Affinity to the receptors was greatly affected by the bulkiness of the aryl group at the 2-position, compared to the pyrazoloquinolines such as CGS-9896. Derivatives with an isoxazole moiety at the 2-position showed high binding affinity and in vivo activity. In the imidazo[4,5-c]quinoline series, substitution at the 6-position decreased or abolished activity. Most derivatives with an unsubstituted isoxazolyl group showed antagonist or inverse agonist activity except for the 7-halo analogues, which exhibited agonist activity. On the other hand, 5-methylisoxazol-3-yl or 3-methylisoxazol-5-yl derivatives generally exhibited agonist activity. A similar substitution effect on the isoxazole moiety was observed in the imidazopyridines fused with a nonaromatic ring. From the detailed pharmacological evaluation, S-8510, 2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano[4,3-b...