(+)-(R)-α-methyl-1H-indole-1-acetic acid | 105074-56-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (+)-(R)-α-methyl-1H-indole-1-acetic acid
• 英文别名: (R)-1-(1-carboxyethyl)-indole；(R)-2-(Indol-1-yl)propanoic acid；(r)-2-(Indol-1-yl)propionic acid；(2R)-2-indol-1-ylpropanoic acid
• CAS: 105074-56-4
• 化学式: C₁₁H₁₁NO₂
• 分子量: 189.214
• InChiKey: ORDGYGARDALAGC-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  (+)-(R)-α-methyl-1H-indole-1-acetic acid 在 正丁基锂 、 三甲基乙酰氯 、 三乙胺 、 红铝 作用下， 以 甲苯 为溶剂， 反应 6.0h， 生成 4-[(2R)-2-(2-methylindol-1-yl)propyl]morpholine
  参考文献：
  名称：

  Antinociceptive (aminoalkyl)indoles

  摘要：

  The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays. In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) ''alpha-methylation'' caused an increase in PG inhibitory potency, (2) the (R)-alpha-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported ''active'' conformations of the aroyl and related aromatic acetic acid derivatives. The H-1 NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50. Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity. The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments. The low eudismic ratios of the alpha-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids. Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis. An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis. Yet 67 was antinociceptive in four different rodent assays. This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation. Unlike opioids, however, the inhibition was not antagonized by naloxone. A subseries of AAIs was identified, of which 67 was prototypic. These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo. Pravadoline was also inhibitory in the MVD. Its antinociceptive activity, therefore, may be a consequence of both its PG synthetase inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD. The evidence is summarized which suggests that this second antinociceptive mechanism is associated with binding to the recently characterized cannabinoid receptor.

  DOI：

  10.1021/jm00107a034
• 作为产物：
  描述：

  (S)-(-)-2-溴丙酸 、 吲哚钠盐 以 N,N-二甲基甲酰胺 为溶剂， 以48%的产率得到(+)-(R)-α-methyl-1H-indole-1-acetic acid
  参考文献：
  名称：

  Nilsson, Ingemar; Isaksson, Roland, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1985, vol. 39, # 7, p. 531 - 548

  摘要：

  DOI：

文献信息

• Heterocyclic derivatives as modulators of ion channels
  申请人：Martinborough Esther

  公开号：US20080027067A1

  公开（公告）日：2008-01-31

  The present invention relates to heterocyclic derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及用作离子通道抑制剂的杂环衍生物。该发明还提供了包括本发明化合物的药用可接受组合物，以及使用这些组合物治疗各种疾病的方法。
• Atropselective Dibrominations of a 1,1′‐Disubstituted 2,2′‐Biindolyl with Diverging Point‐to‐Axial Asymmetric Inductions. Deriving 2,2′‐Biindolyl‐3,3′‐diphosphane Ligands for Asymmetric Catalysis
  作者：Thomas Baumann、Reinhard Brückner

  DOI：10.1002/anie.201806294

  日期：2019.3.26

  atropselectively—because of point‐to‐axial asymmetric inductions—and atropdivergently, exhibiting up to 95 % (M)‐ and as much (P)‐atropselectivity. This route to atropisomerically pure biaryls is novel and should extend to other substrates and/or different functionalizations. The dibromobiindolyls (M)‐ and (P)‐18 a furnished the biindolyldiphosphanes (M)‐ and (P)‐14 without atropisomerization. These syntheses did

  在1 H NMR时标上，带有（R）配置的（1-烷氧基丙）-2-基，（1-羟基丙）-2-基或（1-甲硅烷氧基）-2-基取代基的2,2'-二吲哚基在C-1和C-1'处，在<0°C时对映异构稳定，在> 30°C时互变。此类2,2'-二吲哚基（R，R）‐17 a和非手性（！）溴化试剂可提供对映异构稳定的3,3′‐二溴二吲哚基（M）‐和/或（P）‐18 a由于点到轴的不对称感应，充其量最多只能是atropselective，而atropdivergent最多可以表现出95％（M）和同样高的（P）各向异性。这种向阻转异构的纯联芳基的途径是新颖的，并且应该扩展到其他底物和/或不同的官能化。二溴联二吲哚基（M）‐和（P）‐18 a提供了二吲哚基二膦烷（M）‐和（P）‐14，没有阻转异构化。这些合成不需要拆分外消旋混合物，这使它们与迄今为止已知的几乎所有联芳基二膦合成都不同。（M）‐和（P）‐14在催化不对
• BELL, MALCOLM R.;DAMBRA, THOMAS E.;KUMAR, VIRENDRA;EISSENSTAT, MICHAEL A.+, J. MED. CHEM., 34,(1991) N, C. 1099-1110
  作者：BELL, MALCOLM R.、DAMBRA, THOMAS E.、KUMAR, VIRENDRA、EISSENSTAT, MICHAEL A.+

  DOI：——

  日期：——
• Antinociceptive (aminoalkyl)indoles
  作者：Malcolm R. Bell、Thomas E. D'Ambra、Virendra Kumar、Michael A. Eissenstat、John L. Herrmann、Joseph R. Wetzel、David Rosi、Richard E. Philion、Sol J. Daum

  DOI：10.1021/jm00107a034

  日期：1991.3

  The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays. In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) ''alpha-methylation'' caused an increase in PG inhibitory potency, (2) the (R)-alpha-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported ''active'' conformations of the aroyl and related aromatic acetic acid derivatives. The H-1 NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50. Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity. The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments. The low eudismic ratios of the alpha-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids. Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis. An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis. Yet 67 was antinociceptive in four different rodent assays. This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation. Unlike opioids, however, the inhibition was not antagonized by naloxone. A subseries of AAIs was identified, of which 67 was prototypic. These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo. Pravadoline was also inhibitory in the MVD. Its antinociceptive activity, therefore, may be a consequence of both its PG synthetase inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD. The evidence is summarized which suggests that this second antinociceptive mechanism is associated with binding to the recently characterized cannabinoid receptor.
• Nilsson, Ingemar; Isaksson, Roland, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1985, vol. 39, # 7, p. 531 - 548
  作者：Nilsson, Ingemar、Isaksson, Roland

  DOI：——

  日期：——