Takeuchi N, Kasama T, Aida Y, Oki J, Maruyama I, Watanabe K, Tobinaga S
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Chem Pharm Bull (Tokyo). 1991 Jun;39(6):1415-21. doi: 10.1248/cpb.39.1415.
In connection with the chemical structure of coumarin 1 (a mixture of acetylangeloylkhellactone and acetyltigloylkhellactone), a compound isolated from Peucedanum japonicum THUNB., we synthesized eight coumarin compounds (3-10) and performed pharmacological studies on these nine compounds, as well as on another coumarin, praeruptorin A (= Pd-Ia) (2), a compound isolated from Peucedanum praeruptorum DUNN. We studied the effects of compounds 1-5 on isolated smooth muscle and of compounds 1-10 on the cardiovascular system. These compounds showed dose-related antagonistic effects on histamine- and Ca(2+)-induced contractions in smooth muscle and the potencies were in the order 2 greater than 1 greater than seselin (3) greater than xanthyletin (4) = 2.2.10-trimethyl-2H,8H-benzo[1,2-b: 3,4-b']dipyran-8-one (5). All the compounds except 7-geranyloxy-4-methylcoumarin (10) produced a dose-related increase in vertebral, carotid and femoral blood flow. Compounds 1, 5, and 4-methyl-7-(3-methyl-2-butenyloxy)coumarin (8) caused an increase in blood pressure, but 3 and 4 caused a slight decrease. Compounds 2, 3, 4, 5, and 8 increased heart rate. Jatamansinone (6) and jatamansinol (7) caused only slight changes in blood pressure. All the compounds except 10 increased heart rate. Compound 1 also increased blood flow in the cerebral cortex. Thus, compound 1 was confirmed to have an inhibitory effect on contraction in isolated smooth muscle and an action increasing arterial blood flow. Among the compounds tested in this study, 3, as well as 6 and 7 synthesized on the basis of 3, showed actions similar to those of Ca2+ blockers and some compounds had papaverine-like activities.(ABSTRACT TRUNCATED AT 250 WORDS)
关于从日本前胡（Peucedanum japonicum THUNB.）中分离得到的香豆素1（乙酰当归酰基凯刺内酯和乙酰惕各酰基凯刺内酯的混合物）的化学结构，我们合成了8种香豆素化合物（3 - 10），并对这9种化合物以及另一种从白花前胡（Peucedanum praeruptorum DUNN.）中分离得到的香豆素——白花前胡素A（= Pd - Ia）（2）进行了药理研究。我们研究了化合物1 - 5对离体平滑肌的作用以及化合物1 - 10对心血管系统的作用。这些化合物对组胺和Ca(2+)诱导的平滑肌收缩表现出剂量相关的拮抗作用，其效力顺序为2大于1大于蛇床子素（3）大于花椒毒素（4）= 2,2,10 - 三甲基 - 2H,8H - 苯并[1,2 - b:3,4 - b']二吡喃 - 8 - 酮（5）。除7 - 香叶氧基 - 4 - 甲基香豆素（10）外，所有化合物均使椎动脉、颈动脉和股动脉血流量呈剂量相关增加。化合物1、5和4 - 甲基 - 7 -（3 - 甲基 - 2 - 丁烯氧基）香豆素（8）导致血压升高，但3和4导致血压略有下降。化合物2、3、4、5和8使心率增加。紫花前胡酮（6）和紫花前胡醇（7）仅引起血压轻微变化。除10外，所有化合物均使心率增加。化合物1还增加了大脑皮质的血流量。因此，证实化合物1对离体平滑肌收缩有抑制作用且具有增加动脉血流量的作用。在本研究测试的化合物中，3以及基于3合成的6和7表现出与Ca2+阻滞剂类似的作用，一些化合物具有罂粟碱样活性。（摘要截于250字）
