3,4-Dihydro-8-methoxybenz[h]isoquinolin-1(2H)-one | 126157-40-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3,4-Dihydro-8-methoxybenz[h]isoquinolin-1(2H)-one
• 英文别名: 8-methoxy-3,4-dihydro-2H-benzo[h]isoquinolin-1-one
• CAS: 126157-40-2
• 化学式: C₁₄H₁₃NO₂
• 分子量: 227.263
• InChiKey: CUIFGUORTZDDCS-UHFFFAOYSA-N

物化性质

• 熔点：
  170-172 °C
• 沸点：
  513.3±39.0 °C(predicted)
• 密度：
  1.215±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-Dihydro-8-methoxybenz[h]isoquinolin-1(2H)-one 在 硫酸 、 碘 、 碘酸 、 铜 、 lithium hexamethyldisilazane 作用下， 以 溶剂黄146 为溶剂， 反应 33.67h， 生成 3,4-Dihydro-7-(trifluoromethyl)-8-methoxy-1-oxo-2H-benzisoquinoline-2-acetic acid methyl ester
  参考文献：
  名称：

  Conformationally rigid analogs of aldose reductase inhibitor, tolrestat. Novel syntheses of naphthalene-fused .gamma.-, .delta.-, and .epsilon.-lactams

  摘要：

  DOI：

  10.1021/jo00296a028
• 作为产物：
  描述：

  6-Methoxy-2-<2-<(methoxycarbonyl)amino>ethyl>-1-naphthalenecarboxylic acid methyl ester 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以95%的产率得到3,4-Dihydro-8-methoxybenz[h]isoquinolin-1(2H)-one
  参考文献：
  名称：

  Conformationally rigid analogs of aldose reductase inhibitor, tolrestat. Novel syntheses of naphthalene-fused .gamma.-, .delta.-, and .epsilon.-lactams

  摘要：

  DOI：

  10.1021/jo00296a028

文献信息

• Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&amp;F 29661) Toward Inhibition of Phenylethanolamine <i>N</i>-Methyltransferase <i>vs</i> the α₂-Adrenoceptor^1a
  作者：Gary L. Grunewald、Vilas H. Dahanukar、Timothy M. Caldwell、Kevin R. Criscione

  DOI：10.1021/jm960235e

  日期：1997.12.1

  7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661, 1) is a potent inhibitor of the enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), In contrast to other inhibitors of PNMT, it is also highly selective toward PNMT in comparison with its affinity toward the alpha(2)-adrenoceptor (PNMT K-i = 0.55 mu M, alpha(2) K-i = 100 mu M, selectivity [alpha(2) K-i/PNMT K-i] = 180). A diverse set of compounds was synthesized and evaluated to probe the role of the acidic hydrogen of the aminosulfonyl group of 1 in imparting this selectivity. Compounds were designed to investigate the effect on selectivity of the acidity of the NH group [the 7-N-methyl (compound 5) and 7-N-(p-chlorophenyl) (compound 4) derivatives of 1], the relative spatial position of the acidic hydrogen [7-(N-(methylsulfonyl)amino)-1,2,3,4-tetrahydroisoquinoline (6) and 7-((N-(methylsulfonyl)amino)methyl)-1,2,3,4-tetrahydroisoquinoline (8)], or the effect of the substitution of an acidic phenolic group for the aminosulfonyl moiety [1-(aminomethyl)-6-hydroxynaphthalene (23) and 8-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline (9)]. All of the compounds studied displayed lower affinity for PNMT than I, and nine of the eleven compounds studied showed increased, rather than the desired decreased, affinity for the alpha(2)-adrenoceptor. Specifically, compound 4, in which the aminosulfonyl NH group is more acidic than that in 1, showed greatly reduced selectivity on account of increased alpha(2)-adrenoceptor affinity as compared to 1 (PNMT K-i = 2.6 mu M, alpha(2) K-i = 6.3 mu M, selectivity = 2.4). Compound 8, in which the acidic NH group is in the same region of space as that in 1, although the aminosulfonyl group is reversed with respect to the aromatic ring, showed poor PNMT affinity and modest alpha(2)-adrenoceptor affinity (PNMT K-i = 330 mu M, alpha(2) K-i = 18 mu M, selectivity = 0.055). Compound 9, in which a phenolic group is in the same region of space as the acidic NH of 1, exhibited the best alpha(2)-adrenoceptor affinity of any of the compounds studied (PNMT K-i = 0.98 mu M, alpha(2) K-i = 0.078 mu M, selectivity = 0.080). Results from this study suggest that the selectivity of 1 is not solely due to the presence of an acidic hydrogen on the 7-aminosulfonyl group of 1 but is likely also dependent on some other property (e.g.electron-withdrawing character) of the aminosulfonyl group.
• WROBEL, JAY;DIETRICH, ARLENE;GORHAM, BEVERLY J.;SESTANJ, KAZIMIR, J. ORG. CHEM., 55,(1990) N, C. 2694-2702
  作者：WROBEL, JAY、DIETRICH, ARLENE、GORHAM, BEVERLY J.、SESTANJ, KAZIMIR

  DOI：——

  日期：——
• Conformationally rigid analogs of aldose reductase inhibitor, tolrestat. Novel syntheses of naphthalene-fused .gamma.-, .delta.-, and .epsilon.-lactams
  作者：Jay Wrobel、Arlene Dietrich、Beverly J. Gorham、Kazimir Sestanj

  DOI：10.1021/jo00296a028

  日期：1990.4