(R)-2-(methylsuccinimido)benzoic acid | 474902-30-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-2-(methylsuccinimido)benzoic acid
• 英文别名: (R)-2-methyllycactonic acid；(R)-2-(3-Methyl-2,5-dioxopyrrolidin-1-yl)benzoic acid；2-[(3R)-3-methyl-2,5-dioxopyrrolidin-1-yl]benzoic acid
• CAS: 474902-30-2
• 化学式: C₁₂H₁₁NO₄
• 分子量: 233.224
• InChiKey: OMRMFMYVQMSRLZ-SSDOTTSWSA-N

物化性质

• 熔点：
  117-119 °C
• 沸点：
  507.0±33.0 °C(Predicted)
• 密度：
  1.376±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  lycoctonine 、 (R)-2-(methylsuccinimido)benzoic acid 在 吡啶 、 对甲苯磺酰氯 作用下， 反应 25.0h， 以45%的产率得到(R)-methyllycaconitine
  参考文献：
  名称：

  Synthesis, nicotinic acetylcholine receptor binding, antinociceptive and seizure properties of methyllycaconitine analogs

  摘要：

  A series of methyllycaconitine (la, MLA) analogs was synthesized where the (S)-2-methylsuccinimidobenzoyl group in MLA was replaced with a (R)-2-methyl, 2,2-dimethyl-, 2,3-dimethyl, 2-phenyl-, and 2-cyclohexylsuccinimidobenzoyl (1b-f) group. The analogs 1b-f were evaluated for their inhibition of [I-125]iodo-MLA binding at rat brain alpha 7 nicotinic acetylcholine receptors (nAChR). In order to determine selectivity, MLA and the analogs 1b-f were evaluated for inhibition of binding to rat brain alpha,beta nAChR using [H-3]epibatidine. At the alpha 7 nAChR, MLA showed a K-i value of 0.87 nM, analogs 1b-e possessed Ki values of 1.67-2.16 nM, and If showed a K-i value of 26.8 nM. Surprisingly, the analog le containing the large phenyl substituent (K-i = 1.67 nM) possessed the highest affinity. None of the compounds possessed appreciable affinity for alpha,beta nAChRs. MLA antagonized nicotine-induced seizures with an AD(50) = 2 mg/kg. None of the MLA analogs were as potent as MLA in this assay. MLA and all of the MLA analogs, with the exception of 1b, antagonized nicotine's antinociceptive effects in the tail-flick assay. Compound 1c (K-i = 1.78 nM at alpha 7 nAChR) with an AD(50) value of 1.8 mg/kg was 6.7 times more potent than MLA (AD(50) = 12 mg/kg) in antagonizing nicotine's antinociceptive effects but was 5-fold less potent than MLA in blocking nicotine-induced seizures. Since MLA has been reported to show neuroprotection against beta-amyloid(1-42), these new analogs which have high alpha 7 nAChR affinity and good selectivity relative to alpha,beta nAChRs will be useful biological tools for studying the effects of alpha 7 nAChR antagonist and neuroprotection. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.061
• 作为产物：
  描述：

  (R)-(+)-甲基丁二酸 在 吡啶 、 乙酸酐 作用下， 以 氯仿 为溶剂， 反应 12.5h， 生成 (R)-2-(methylsuccinimido)benzoic acid
  参考文献：
  名称：

  Synthesis, nicotinic acetylcholine receptor binding, antinociceptive and seizure properties of methyllycaconitine analogs

  摘要：

  A series of methyllycaconitine (la, MLA) analogs was synthesized where the (S)-2-methylsuccinimidobenzoyl group in MLA was replaced with a (R)-2-methyl, 2,2-dimethyl-, 2,3-dimethyl, 2-phenyl-, and 2-cyclohexylsuccinimidobenzoyl (1b-f) group. The analogs 1b-f were evaluated for their inhibition of [I-125]iodo-MLA binding at rat brain alpha 7 nicotinic acetylcholine receptors (nAChR). In order to determine selectivity, MLA and the analogs 1b-f were evaluated for inhibition of binding to rat brain alpha,beta nAChR using [H-3]epibatidine. At the alpha 7 nAChR, MLA showed a K-i value of 0.87 nM, analogs 1b-e possessed Ki values of 1.67-2.16 nM, and If showed a K-i value of 26.8 nM. Surprisingly, the analog le containing the large phenyl substituent (K-i = 1.67 nM) possessed the highest affinity. None of the compounds possessed appreciable affinity for alpha,beta nAChRs. MLA antagonized nicotine-induced seizures with an AD(50) = 2 mg/kg. None of the MLA analogs were as potent as MLA in this assay. MLA and all of the MLA analogs, with the exception of 1b, antagonized nicotine's antinociceptive effects in the tail-flick assay. Compound 1c (K-i = 1.78 nM at alpha 7 nAChR) with an AD(50) value of 1.8 mg/kg was 6.7 times more potent than MLA (AD(50) = 12 mg/kg) in antagonizing nicotine's antinociceptive effects but was 5-fold less potent than MLA in blocking nicotine-induced seizures. Since MLA has been reported to show neuroprotection against beta-amyloid(1-42), these new analogs which have high alpha 7 nAChR affinity and good selectivity relative to alpha,beta nAChRs will be useful biological tools for studying the effects of alpha 7 nAChR antagonist and neuroprotection. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.061

文献信息

• Structure–activity studies with ring E analogues of methyllycaconitine. Synthesis and evaluation of enantiopure isomers of selective antagonist at the α3 nicotinic receptor
  作者：K.A Ismail、S.C Bergmeier

  DOI：10.1016/s0223-5234(02)01353-3

  日期：2002.6

  The four diastereomers 4a-d of methyllycaconitine (MLA) analogue 3 (R = (CH2)(3)Ph, R' = CH3) have been synthesized in enantiomerically pure form by coupling both (S)- and (R)-2-(methylsuccinimido)benzoic acid (5a and 5b) with both (S)- and (R)-3-hydroxymethyl-N-(3-phenyl) propylpiperidine (6a and 6b) using TBTU. These compounds were assayed for potency as nicotinic acetylcholine receptor (nAChRs) antagonist. All the four diastereomers showed the same potency at both the alpha3 and alpha7 receptors as racemic compound 3. This indicates that the binding at nicotine acetylcholine receptors (nAchRs) is probably non-stereospecific. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
• Synthesis, nicotinic acetylcholine receptor binding, antinociceptive and seizure properties of methyllycaconitine analogs
  作者：F. Ivy Carroll、Wei Ma、Hernán A. Navarro、Philip Abraham、Scott A. Wolckenhauer、M.I. Damaj、Billy R. Martin

  DOI：10.1016/j.bmc.2006.10.061

  日期：2007.1

  A series of methyllycaconitine (la, MLA) analogs was synthesized where the (S)-2-methylsuccinimidobenzoyl group in MLA was replaced with a (R)-2-methyl, 2,2-dimethyl-, 2,3-dimethyl, 2-phenyl-, and 2-cyclohexylsuccinimidobenzoyl (1b-f) group. The analogs 1b-f were evaluated for their inhibition of [I-125]iodo-MLA binding at rat brain alpha 7 nicotinic acetylcholine receptors (nAChR). In order to determine selectivity, MLA and the analogs 1b-f were evaluated for inhibition of binding to rat brain alpha,beta nAChR using [H-3]epibatidine. At the alpha 7 nAChR, MLA showed a K-i value of 0.87 nM, analogs 1b-e possessed Ki values of 1.67-2.16 nM, and If showed a K-i value of 26.8 nM. Surprisingly, the analog le containing the large phenyl substituent (K-i = 1.67 nM) possessed the highest affinity. None of the compounds possessed appreciable affinity for alpha,beta nAChRs. MLA antagonized nicotine-induced seizures with an AD(50) = 2 mg/kg. None of the MLA analogs were as potent as MLA in this assay. MLA and all of the MLA analogs, with the exception of 1b, antagonized nicotine's antinociceptive effects in the tail-flick assay. Compound 1c (K-i = 1.78 nM at alpha 7 nAChR) with an AD(50) value of 1.8 mg/kg was 6.7 times more potent than MLA (AD(50) = 12 mg/kg) in antagonizing nicotine's antinociceptive effects but was 5-fold less potent than MLA in blocking nicotine-induced seizures. Since MLA has been reported to show neuroprotection against beta-amyloid(1-42), these new analogs which have high alpha 7 nAChR affinity and good selectivity relative to alpha,beta nAChRs will be useful biological tools for studying the effects of alpha 7 nAChR antagonist and neuroprotection. (c) 2006 Elsevier Ltd. All rights reserved.