Rouot B, Leclerc G, Wermuth C G
J Med Chem. 1976 Aug;19(8):1049-54. doi: 10.1021/jm00230a014.
Twenty-two structural derivatives of clonidine [2-(2,6-dichlorophenylimino)imidazolidine] have been synthesized and their main physicochemical parameters (log P, deltaRM, pKa) determined. Quantitative correlations between the peripheral alpha-mimetic action (pithed rats) and physicochemical parameters pointed out the critical role of the steric effect in the ortho positions. On the other hand, attempted quantitative correlations between physicochemical parameters and central hypotensive activity were unsuccessful. These results are discussed in the light of the postulated mechanism of action of clonidine.
已合成了二十二种可乐定[2-(2,6-二氯苯基亚氨基)咪唑烷]的结构衍生物，并测定了它们的主要物理化学参数（log P、δRM、pKa）。外周α-拟交感神经作用（脊髓麻醉大鼠）与物理化学参数之间的定量相关性表明了邻位空间效应的关键作用。另一方面，物理化学参数与中枢降压活性之间的定量相关性尝试未成功。根据可乐定假定的作用机制对这些结果进行了讨论。
