(S)-(+)-3-甲基-1,2,3,4-四氢异喹啉-1-酮 | 24292-48-6

• 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
• 中文名称: (S)-(+)-3-甲基-1,2,3,4-四氢异喹啉-1-酮
• 英文名称: (S)-(+)-3-methyl-1,2,3,4-tetrahydroisoquinolin-1-one
• 英文别名: (S)-(+)-3,4-dihydro-3-methylisoquinolin-1-(2H)-one；Cambridge id 5100424；(3S)-3-methyl-3,4-dihydro-2H-isoquinolin-1-one
• CAS: 24292-48-6
• 化学式: C₁₀H₁₁NO
• 分子量: 161.203
• InChiKey: BWWCBNZSMWMIKH-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-(+)-3-甲基-1,2,3,4-四氢异喹啉-1-酮 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以74.5%的产率得到(S)-(+)-3-methyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Diener, Wolfgang; Frelek, Jadwiga; Snatzke, Guenther, Collection of Czechoslovak Chemical Communications, 1991, vol. 56, # 5, p. 954 - 965

  摘要：

  DOI：
• 作为产物：
  描述：

  (S)-(-)-2-ethoxycarbonylamino-1-phenylpropane 在 PPA 作用下， 以93%的产率得到(S)-(+)-3-甲基-1,2,3,4-四氢异喹啉-1-酮
  参考文献：
  名称：

  Diener, Wolfgang; Frelek, Jadwiga; Snatzke, Guenther, Collection of Czechoslovak Chemical Communications, 1991, vol. 56, # 5, p. 954 - 965

  摘要：

  DOI：

文献信息

• 3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines Display Remarkable Potency and Selectivity as Inhibitors of Phenylethanolamine <i>N-</i>Methyltransferase versus the α₂-Adrenoceptor^1a
  作者：Gary L. Grunewald、Vilas H. Dahanukar、Bee Teoh、Kevin R. Criscione

  DOI：10.1021/jm9807252

  日期：1999.6.1

  3-Hydroxymethyl-1,2,3,4-tetrahydroisoquinoline (4) is a more selective inhibitor (PNMT K-i = 1.1 mu M, alpha(2) K-i = 6.6 mu M, selectivity (alpha(2) K-i/PNMT K-i) = 6.0) of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), with respect to its az-adrenoceptor affinity, than is 3-methyl-1,2,3,4-tetrahydroisoquinoline (2; PNMT K-i = 2.1 mu M, alpha 2 K-i = 0.76 mu M, selectivity = 0.36) or 1,2,3,4-tetrahydroisoquinoline (1, THIQ; PNMT K-i = 9.7 mu M, alpha 2 K-i = 0.35 mu M, selectivity = 0.036). Evaluation of the O-methyl ether derivative of 4 suggested that the 3-hydroxymethyl substituent might be involved in a hydrogen-bond donor-type of interaction at a sterically compact region in the PNMT active site. The directionality of the steric bulk tolerance at both the PNMT active site and the alpha(2)-adrenoceptor appears to be the same. Since the presence of a hydrophilic electron-withdrawing substituent (such as NO2, SO2CH3, or SO2NH2) at the 7-position of THIQ reduced the binding affinity toward the alpha(2)-adrenoceptor, we investigated the combination of both a hydrophilic electron-withdrawing 7-substituent and a S-alkyl substituent on a THIQ nucleus. A synergistic effect in increasing the PNMT-inhibitory potency of the THIQ nucleus and reducing the affinity toward the alpha(2)-adrenoceptor was observed with this 3,7-disubstitution. Remarkably, 7-aminosulfonyl-3-hydroxymethyl-THIQ (12; PNMT K-i = 0.34 mu M, alpha 2 K-i = 1400 mu M, selectivity = 4100) displayed a 23-680-fold enhanced selectivity over the parent compounds 27 (SK&F 29661; PNMT K-i = 0.55 mu M, alpha 2 K-i = 100 mu M, selectivity = 180) and 4 (selectivity = 6.0) and is thus the most selective PNMT inhibitor yet reported.
• Diener, Wolfgang; Frelek, Jadwiga; Snatzke, Guenther, Collection of Czechoslovak Chemical Communications, 1991, vol. 56, # 5, p. 954 - 965
  作者：Diener, Wolfgang、Frelek, Jadwiga、Snatzke, Guenther

  DOI：——

  日期：——