8-methoxy-1,2,3,4-tetrahydroisobenzo[h]quinoline | 223915-65-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 8-methoxy-1,2,3,4-tetrahydroisobenzo[h]quinoline
• 英文别名: 8-Methoxy-1,2,3,4-tetrahydrobenzo[h]isoquinoline
• CAS: 223915-65-9
• 化学式: C₁₄H₁₅NO
• 分子量: 213.279
• InChiKey: LTVUTAZPBISUIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-methoxy-1,2,3,4-tetrahydroisobenzo[h]quinoline 在 氢溴酸 作用下， 反应 5.0h， 以68%的产率得到1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol; hydrobromide
  参考文献：
  名称：

  Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) Toward Inhibition of Phenylethanolamine N-Methyltransferase vs the α₂-Adrenoceptor^1a

  摘要：

  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.

  DOI：

  10.1021/jm960235e
• 作为产物：
  描述：

  3-(6-methoxynaphthalen-2-yl)propanoic acid 在 sodium azide 、 草酰氯 、 dimethyl sulfide borane 、 三氟化硼乙醚 作用下， 以 四氢呋喃 为溶剂， 反应 32.0h， 生成 8-methoxy-1,2,3,4-tetrahydroisobenzo[h]quinoline
  参考文献：
  名称：

  Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) Toward Inhibition of Phenylethanolamine N-Methyltransferase vs the α₂-Adrenoceptor^1a

  摘要：

  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.

  DOI：

  10.1021/jm960235e

文献信息

• ISOQUINOLINE AND BENZO[H]ISOQUINOLINE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF AS ANTAGONISTS OF THE HISTAMINE H3 RECEPTOR
  申请人：DIAZ MARTIN Juan Antonio

  公开号：US20080269199A1

  公开（公告）日：2008-10-30

  The invention concerns a compound of formula (I): Wherein A, l, m, n, R1 and R2 are as defined herein. The compounds of this invention are useful as medicaments, particularly, in the treatment of disorders improved by modulation of the histamine H 3 receptor.

  这项发明涉及一种化合物，其化学式为（I）：其中A、l、m、n、R1和R2如本文所定义。本发明的化合物可用作药物，特别是在通过调节组胺H3受体改善的疾病治疗中。
• 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.