Caliendo Giuseppe, Perissutti Elisa, Santagada Vincenzo, Fiorino Ferdinando, Severino Beatrice, Cirillo Donatella, di Villa Bianca Roberta d'Emmanuele, Lippolis Laura, Pinto Aldo, Sorrentino Raffaella
Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy.
Eur J Med Chem. 2004 Oct;39(10):815-26. doi: 10.1016/j.ejmech.2004.05.003.
An efficient, facile, and practical parallel combinatorial synthesis of substituted-benzoxazines under microwave irradiation was described. The procedure involved the use of a microwave oven especially designed for organic synthesis suitable for parallel synthesis of solution libraries. A demonstration 19-membered library of substituted N,N-dimethyl- and N-methyl-benzoxazine amide derivatives, structurally related to the potassium channel opener cromakalim, was generated by both conventional and microwave procedures, achieving a reduction from 7 h to 30-36 min in library generation time for the microwave approach. All the synthesized compounds were tested using the in vitro models of rat aorta and guinea pig trachea rings pre-contracted with phenylephrine and carbachol, respectively. All N,N-dimethyl amide derivatives showed a relaxant activity higher on guinea pig trachea rings than on rat aorta rings.
描述了一种在微波辐射下高效、简便且实用的平行组合合成取代苯并恶嗪的方法。该方法使用了专门为有机合成设计的微波炉，适用于溶液库的平行合成。通过常规方法和微波方法生成了一个由19种取代的N,N-二甲基和N-甲基苯并恶嗪酰胺衍生物组成的示范库，这些衍生物在结构上与钾通道开放剂克罗卡林相关。对于微波方法，库生成时间从7小时减少到了30 - 36分钟。所有合成的化合物分别使用用去氧肾上腺素和卡巴胆碱预收缩的大鼠主动脉和豚鼠气管环的体外模型进行了测试。所有N,N-二甲基酰胺衍生物对豚鼠气管环的舒张活性高于对大鼠主动脉环的舒张活性。
