methyl 1-(4-hydroxy)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylate | 799822-03-0

• 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: methyl 1-(4-hydroxy)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylate
• 英文别名: methyl (3S)-1-(4-hydroxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 799822-03-0
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: IRELGTNBKRWOMX-BHWOMJMDSA-N

物化性质

• 沸点：
  541.5±50.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 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：

  methyl 1-(4-hydroxy)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylate 在 N-甲基吗啉 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 (S)-N-(1-(benzylamino)-5-(2-chloroacetimidamido)-1-oxopentan-2-yl)-1-(4-hydroxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide
  参考文献：
  名称：

  A β-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer

  摘要：

  DOI：

  10.1021/acs.jmedchem.4c00030
• 作为产物：
  描述：

  L-色氨酸 在 硫酸 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 96.0h， 生成 methyl 1-(4-hydroxy)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylate
  参考文献：
  名称：

  Synthesis and Evaluation of New β-Carboline-3-(4-benzylidene)-4H-oxazol-5-one Derivatives as Antitumor Agents

  摘要：

  在本研究中，我们报道了一系列新的1-取代-β-咔啉衍生物的合成及其体外抗癌和抗微生物活性评估。这些衍生物在C-3位点上具有4-苄叉基-4H-噁唑-5-酮结构。化合物2-[1-(4-甲氧基苯基)-9H-β-咔啉-3-基]-4-(苄叉基)-4H-噁唑-5-酮（11）是最活跃的衍生物，对胶质瘤（U251）、前列腺癌（PC-3）和卵巢癌（OVCAR-03）细胞系表现出强效的细胞毒活性，IC50值分别为0.48、1.50和1.07 µM。此外，还对新合成的β-咔啉衍生物的ADME特性进行了计算机模拟研究。

  DOI：

  10.3390/molecules17056100

文献信息

• [EN] COMPOUNDS FOR TREATMENT OF METABOLIC SYNDROME<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DU SYNDROME MÉTABOLIQUE
  申请人：SJT MOLECULAR RES S L

  公开号：WO2012130912A1

  公开（公告）日：2012-10-04

  Present invention refers to new compounds of formula I or II, its synthesis and its use in the treatment of metabolic syndrome, particularly for the treatment of type I or type II diabetes and/or metabolic syndrome or metabolic disease or metabolic disorders.

  本发明涉及公式I或II的新化合物，其合成以及在治疗代谢综合征中的应用，特别是用于治疗I型或II型糖尿病和/或代谢综合征或代谢疾病或代谢紊乱。
• Synthesis and antiviral activity of β-carboline derivatives bearing a substituted carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1)
  作者：Anelise S. Nazari Formagio、Patricia R. Santos、Karine Zanoli、Tania Ueda-Nakamura、Lilian T. Düsman Tonin、Celso V. Nakamura、Maria Helena Sarragiotto

  DOI：10.1016/j.ejmech.2009.07.005

  日期：2009.11

  Several novel 1,3-disubstituted β-carboline derivatives bearing a substituted carbohydrazide group at C-3 were synthesized and evaluated for their antiviral activity against vaccinal poliovirus (VP) and herpes simplex virus type 1 (HSV-1). The cytotoxicity and selectivity index of the active compounds were also evaluated. Among the synthesized derivatives, compounds 10 and 11 displayed potent activity

  合成了几种新颖的在C-3带有一个取代的碳酰肼基团的1,3-二取代的β-咔啉衍生物，并评估了它们对疫苗脊髓灰质炎病毒（VP）和1型单纯疱疹病毒（HSV-1）的抗病毒活性。还评估了活性化合物的细胞毒性和选择性指数。在合成的衍生物中，化合物10和11对疫苗的脊髓灰质炎病毒和HSV-1病毒均显示出有效的活性。化合物10表现出对HSV-1病毒的最高选择性指数（SI = 2446.8）和低细胞毒性（CC 50  = 1150.0±67.3μM）。病毒产量抑制试验表明化合物10能够在病毒吸附之前和期间抑制HSV-1斑块的形成。在化合物处理过的细胞中观察到的特征性小噬斑图案表明，化合物10抑制了病毒向邻近细胞的传播。通过使用Lipinski规则确定亲脂性，拓扑极性表面积（TPSA），吸收率（％ABS）和简单分子描述符，对预测新型合成β-咔啉衍生物的ADME性质进行了计算研究。
• Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted β-carboline derivatives
  作者：Rihui Cao、Wenlie Peng、Hongsheng Chen、Xuerui Hou、Huaji Guan、Qi Chen、Yan Ma、Anlong Xu

  DOI：10.1016/j.ejmech.2004.11.005

  日期：2005.3

  A series of novel 1,3-bisubstituted and 1, 3,9-trisubstituted beta-carboline derivatives was synthesized from the starting material L-tryptophan. Cytotoxic activities of these compounds were investigated in vitro. The results showed that 1,3,9-trisubstituted beta-carboline derivatives had higher cytotoxic activities in vitro than the corresponding 1,3-bisubstituted compounds. Among all the synthesized 1,3,9-trisubstituted P-carboline derivatives, the compounds with a methyl substituent at position-1 displayed more potent cytotoxic activities, furthermore compound 5e having an ethoxycarbonyl substituent at position-3 and a pentafluorobenzyl at position-9, respectively, was found to be the most potent compounds of this series with IC50 value of 4 uM against BGC-823 cell lines. These data suggested that (1) the cytotoxic potencies of beta-carboline derivatives were enhanced by the introduction of appropriate substituents into position-1 and position-9 in beta-carboline; (2) the beta-carboline structure might be an important basis for the design and synthesis of new antitumor drugs; (3) the methyl substituent at position-1, the pentafluorobenzyl group at position-9 and the ethoxycarbonyl substituent at position-3 were the optimal combination for the improvement of cytotoxic activity of the P-carboline derivatives. (c) 2004 Elsevier SAS. All rights reserved.
• Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) β-carboline derivatives
  作者：Anelise S. Nazari Formagio、Lilian T. Düsman Tonin、Mary Ann Foglio、Christiana Madjarof、João Ernesto de Carvalho、Willian Ferreira da Costa、Flávia P. Cardoso、Maria Helena Sarragiotto

  DOI：10.1016/j.bmc.2008.10.008

  日期：2008.11

  Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50) < 100 mu M) for all eight different types of human cancer cell lines tested. The b-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI50 values lying in the nanomolar concentration range (GI(50) = 10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50) = 0.06 mu M), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents. (C) 2008 Elsevier Ltd. All rights reserved.