Pigini M, Quaglia W, Gentili F, Marucci G, Cantalamessa F, Franchini S, Sorbi C, Brasili L
Dipartimento di Scienze Chimiche, Università degli Studi di Camerino, Italy.
Bioorg Med Chem. 2000 May;8(5):883-8. doi: 10.1016/s0968-0896(00)00030-4.
Several analogues of cirazoline (2), a selective alpha1-adrenoreceptor agonist, were prepared and their pharmacological profiles studied. Although at the alpha1-adrenoreceptor all the compounds displayed a significant agonist activity, at the alpha2-adrenoreceptor they showed either agonist or antagonist activity depending on the nature of the phenyl substituent. The qualitative structure-activity relationship led us to the conclusion that the oxygen atom in the side-chain is essential for alpha1-agonist activity, while the cyclopropyl ring is not, and may be replaced by several groups. Of the groups studied, isopropoxy appears to be the best. Instead, the same substitution (i.e., isopropoxy for the cyclopropyl ring) at alpha2-adrenoreceptors causes a reversal of activity. On the other hand, the cyclopropyl ring seems to be important for alpha1-selectivity. Compound 20 is the most potent alpha1-agonist of the series, being equiactive with cirazoline on rat vas deferens and in pithed rat.
制备了选择性α1-肾上腺素受体激动剂西拉唑啉（2）的几种类似物，并研究了它们的药理学特性。尽管在α1-肾上腺素受体上所有化合物均表现出显著的激动剂活性，但在α2-肾上腺素受体上，根据苯基取代基的性质，它们表现出激动剂或拮抗剂活性。定性构效关系使我们得出结论，侧链中的氧原子对于α1-激动剂活性至关重要，而环丙基环则不是，并且可以被几个基团取代。在所研究的基团中，异丙氧基似乎是最佳的。相反，在α2-肾上腺素受体上进行相同的取代（即用异丙氧基取代环丙基环）会导致活性逆转。另一方面，环丙基环似乎对α1-选择性很重要。化合物20是该系列中最有效的α1-激动剂，在大鼠输精管和去脑大鼠中与西拉唑啉具有同等活性。
