(1S,3S)-1-(p-methoxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid | 519032-22-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (1S,3S)-1-(p-methoxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid
• 英文别名: cis-1-(4-methoxy)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid；(1S,3S)-1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-3-carboxylate
• CAS: 519032-22-5
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: DALGDMAVNXHKCK-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,3S)-1-(p-methoxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid 在 盐酸羟胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (1S,3S)–N-(4-(hydroxycarbamoyl)benzyl)-1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxamide
  参考文献：
  名称：

  四氢-β-咔啉衍生物作为有效的组蛋白脱乙酰酶 6 抑制剂，具有广谱抗增殖活性

  摘要：

  应用支架跳跃策略合理设计并合成了一系列基于四氢β-咔啉（TH β C）的异羟肟酸作为新型选择性HDAC6抑制剂（sHDAC6is）。几种 TH β C 类似物对 HDAC6 酶具有高效能（IC 50 < 5 nM）和选择性，并对人多发性骨髓瘤(MM) 细胞表现出良好的抗增殖活性。分子对接解释了结构活性关系（SAR）。使用 WB 测定在 RPMI-8226 细胞中证实了 HDAC6 的靶标参与。体外，(1 S , 3 R )-1-(4-氯苯基) -N -(4-(羟基氨基甲酰基)苄基)-2,3,4,9-四氢-1H-吡啶并[3, 4- b ] indole-3-carboxamide ( 14g ) 对各种肿瘤（包括白血病、结肠癌、黑色素瘤和乳腺癌细胞系）表现出有效、广泛的抗增殖活性，优于 ACY-1215。此外， 14g在小鼠口服给药中也表现出良好的药代动力学特性。

  DOI：

  10.1016/j.ejmech.2023.115776
• 作为产物：
  描述：

  (1S,3S)-1-(4-methoxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 (1S,3S)-1-(p-methoxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid
  参考文献：
  名称：

  四氢-β-咔啉衍生物作为有效的组蛋白脱乙酰酶 6 抑制剂，具有广谱抗增殖活性

  摘要：

  应用支架跳跃策略合理设计并合成了一系列基于四氢β-咔啉（TH β C）的异羟肟酸作为新型选择性HDAC6抑制剂（sHDAC6is）。几种 TH β C 类似物对 HDAC6 酶具有高效能（IC 50 < 5 nM）和选择性，并对人多发性骨髓瘤(MM) 细胞表现出良好的抗增殖活性。分子对接解释了结构活性关系（SAR）。使用 WB 测定在 RPMI-8226 细胞中证实了 HDAC6 的靶标参与。体外，(1 S , 3 R )-1-(4-氯苯基) -N -(4-(羟基氨基甲酰基)苄基)-2,3,4,9-四氢-1H-吡啶并[3, 4- b ] indole-3-carboxamide ( 14g ) 对各种肿瘤（包括白血病、结肠癌、黑色素瘤和乳腺癌细胞系）表现出有效、广泛的抗增殖活性，优于 ACY-1215。此外， 14g在小鼠口服给药中也表现出良好的药代动力学特性。

  DOI：

  10.1016/j.ejmech.2023.115776

文献信息

• A new class of β-carboline alkaloid-peptide conjugates with therapeutic efficacy in acute limb ischemia/reperfusion injury
  作者：Wei Bi、Yue Bi、Ping Xue、Yanrong Zhang、Xiang Gao、Zhibo Wang、Meng Li、Michèle Baudy-Floc’h、Nathaniel Ngerebara、K. Michael Gibson、Lanrong Bi

  DOI：10.1016/j.ejmech.2011.01.021

  日期：2011.5

  We describe a novel class of beta-carboline alkaloid-peptide conjugates that possess both free radical scavenging and thrombolytic activity. These conjugates demonstrate therapeutic efficacy in a rat arterial thrombosis assay, as well as free radical scavenging capacity as evaluated in a PC12 cell survival assay. Our results indicate that beta-carboline alkaloid-peptide conjugate 26a exerts a significant protective effect against local and remote organ injury induced by limb I/R injury in the rat. Published by Elsevier Masson SAS.
• Methyl 1-imidazolecarbodithioate as a thiocarbonyl transfer reagent: a facile one-pot, three-component synthesis of novel 2-substituted-5-aryl-1-oxo-3-thioxo-1,2,3,5,11,11a-hexahydro-6H-imidazo-[1,5-b]-β-carbolines
  作者：Balendu Singh、G.S.M. Sundaram、Nimesh C. Misra、Hiriyakkanavar Ila

  DOI：10.1016/j.tetlet.2008.11.008

  日期：2009.1

  An efficient one-pot, three-component synthesis of novel 2-substituted-5-aryl-1-oxo-3-thioxo-1,2,3,5,11,11a-hexahydro-6H-imidazo-[1,5-b]-beta-carbolines employing 1-aryl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylates, primary amines (or amino acid esters) and methyl 1-imidazolecarbodithioate as the thiocarbonyl transfer reagent is reported. (C) 2008 Elsevier Ltd. All rights reserved.
• <scp>l</scp>-Tryptophan Reacts with Naturally Occurring and Food-Occurring Phenolic Aldehydes To Give Phenolic Tetrahydro-β-carboline Alkaloids:  Activity as Antioxidants and Free Radical Scavengers
  作者：Tomas Herraiz、Juan Galisteo、Cristina Chamorro

  DOI：10.1021/jf0210066

  日期：2003.4.1

  The reaction between the essential amino acid L-tryptophan and flavoring or naturally occurring phenyl and phenolic aldehydes was studied, and the alkaloidal reaction products were characterized by NMR and HPLC-MS. Benzaldehyde, vanillin, syringaldehyde, salicylaldehyde, and anisaldehyde condensed with L-tryptophan in aqueous-acidic media affording the corresponding phenolic tetrahydro-beta-carboline-3-carboxylic acid as two diastereoisomers, 1 S,3S-cis and 1R,3S-trans. With the exception of benzaldehyde, the rest of the aldehydes needed heating conditions (70 degreesC) to significantly form tetrahydro-beta-carbolines over time with the cyclization highly favored at low pH. This suggests a likely formation of these compounds under conditions that may occur in foods, food processing, or cooking. The new phenolic tetralhydro-beta-carboline alkaloids were assayed, for the first time, for their activity as free radical scavengers and antioxidants and showed good antioxidant properties with Trolox equivalent antioxidant capacity (TEAC) values much higher than those of ascorbic acid and the water soluble vitamin E analogue, Trolox, in the 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) assay.
• Tetrahydro-β-carboline derivatives as potent histone deacetylase 6 inhibitors with broad-spectrum antiproliferative activity
  作者：Xin Chen、Jiayun Wang、Peng Zhao、Baiyun Dang、Ting Liang、Raphael R. Steimbach、Aubry K. Miller、Jia Liu、Xin Wang、Tongtong Zhang、Xiaofa Luan、Jiadong Hu、Jinming Gao

  DOI：10.1016/j.ejmech.2023.115776

  日期：2023.11

  application of scaffold hopping strategy. Several THβC analogues were highly potent (IC50 < 5 nM) and selective against HDAC6 enzyme and exhibited good antiproliferative activity against human multiple myeloma (MM) cell. Molecular docking interpreted the structure activity relationship (SAR). Target engagement of HDAC6 was confirmed in RPMI-8226 cells using the WB assay. In vitro, (1S, 3R)-1-(4-chloro

  应用支架跳跃策略合理设计并合成了一系列基于四氢β-咔啉（TH β C）的异羟肟酸作为新型选择性HDAC6抑制剂（sHDAC6is）。几种 TH β C 类似物对 HDAC6 酶具有高效能（IC 50 < 5 nM）和选择性，并对人多发性骨髓瘤(MM) 细胞表现出良好的抗增殖活性。分子对接解释了结构活性关系（SAR）。使用 WB 测定在 RPMI-8226 细胞中证实了 HDAC6 的靶标参与。体外，(1 S , 3 R )-1-(4-氯苯基) -N -(4-(羟基氨基甲酰基)苄基)-2,3,4,9-四氢-1H-吡啶并[3, 4- b ] indole-3-carboxamide ( 14g ) 对各种肿瘤（包括白血病、结肠癌、黑色素瘤和乳腺癌细胞系）表现出有效、广泛的抗增殖活性，优于 ACY-1215。此外， 14g在小鼠口服给药中也表现出良好的药代动力学特性。