1,2,3,4-Tetrahydro-2-(triphenylmethyl)-7-isoquinolinecarbonitrile | 200137-82-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1,2,3,4-Tetrahydro-2-(triphenylmethyl)-7-isoquinolinecarbonitrile
• 英文别名: 2-trityl-3,4-dihydro-1H-isoquinoline-7-carbonitrile
• CAS: 200137-82-2
• 化学式: C₂₉H₂₄N₂
• 分子量: 400.523
• InChiKey: RTJPFWDAIAEFJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.91
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  27.03
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1,2,3,4-Tetrahydro-2-(triphenylmethyl)-7-isoquinolinecarbonitrile 在 硼烷四氢呋喃络合物 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 N-(2-Trityl-1,2,3,4-tetrahydro-isoquinolin-7-ylmethyl)-methanesulfonamide
  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：

  7-氨基-1,2,3,4-四氢异喹啉 在 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 、 O₄S^(2-)*2Ni⁽¹⁺⁾ 、 三乙胺 、 sodium nitrite 作用下， 以 二氯甲烷 为溶剂， 反应 17.25h， 生成 1,2,3,4-Tetrahydro-2-(triphenylmethyl)-7-isoquinolinecarbonitrile
  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

• 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.