Carroll F I, Abraham P, Mascarella S W, Singh P, Moreland C G, Sankar S S, Kwon Y W, Triggle D J
Chemistry and Life Sciences, Research Triangle Institute, North Carolina 27709.
J Med Chem. 1991 Apr;34(4):1436-40. doi: 10.1021/jm00108a030.
The structure of azaprophen, which was originally assigned by 1H NMR analysis, was confirmed by X-ray crystallography. A comparison of 13C NMR isotropic chemical shift data for azaprophen in the solid state and in CDCl3 and DMSO-d6 solution was used to correlate solution and solid-state conformation as determined by the X-ray data. The data suggested that the solid-state and solution conformation of azaprophen were similar. The observed solid-state structure was also compared to low-energy conformations identified by molecular-mechanics calculations. A comparison of azaprophen and atropine radioligand binding in guinea pig ileum, rat heart, rat brain, and in CHO cells expressing transfected m1 and m3 receptors was conducted. Azaprophen is more active than atropine in all preparations except the m3 receptor expressed in CHO cells. However, like atropine, it does not provide major discrimination among the muscarinic receptor subtypes.
阿扎丙宗的结构最初是通过1H NMR分析确定的，后经X射线晶体学证实。通过比较阿扎丙宗在固态、CDCl3和DMSO-d6溶液中的13C NMR各向同性化学位移数据，来关联由X射线数据确定的溶液和固态构象。数据表明，阿扎丙宗的固态和溶液构象相似。还将观察到的固态结构与通过分子力学计算确定的低能构象进行了比较。对阿扎丙宗和阿托品在豚鼠回肠、大鼠心脏、大鼠脑以及表达转染m1和m3受体的CHO细胞中的放射性配体结合进行了比较。除了在CHO细胞中表达的m3受体外，阿扎丙宗在所有制剂中都比阿托品更具活性。然而，与阿托品一样，它在毒蕈碱受体亚型之间没有明显的区分作用。
