1-(2-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide | 223691-13-2

• 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: 1-(2-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide
• CAS: 223691-13-2
• 化学式: C₁₈H₁₃ClN₄O
• 分子量: 336.78
• InChiKey: GEDPLCOUYFKRRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide 在 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 反应 49.0h， 生成 N'-[4,6-bis(isopropylamino)-1,3,5-triazin-2-yl]-1-(2-chlorophenyl)-β-carboline-3-carbohydrazide
  参考文献：
  名称：

  Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids

  摘要：

  A series of novel hybrids beta-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC50 values less than 8 mu M. Compounds 9e and 1611) were also active against amastigote forms, displaying IC50 values of 1.0 +/- 0.1 mu M and 1.2 +/- 0.51 mu M, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of beta-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.014
• 作为产物：
  描述：

  L-色氨酸 在 硫酸 、 sulfur 、 一水合肼 、 三氟乙酸 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 二氯甲烷 为溶剂， 反应 147.0h， 生成 1-(2-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide
  参考文献：
  名称：

  新型杂种β-咔啉-4-噻唑烷酮类化合物的合成和评价作为潜在的抗肿瘤和抗病毒药

  摘要：

  合成了一系列新颖的杂种β-咔啉-4-噻唑烷酮，并评估了其对人癌细胞的体外抗肿瘤活性以及对单纯疱疹病毒1型（HSV-1）的抗病毒活性。从N' - （咪唑烷-2-亚基-4-噻唑烷酮） - β咔啉-3-碳酰肼系列（9-11），Ç ompounds 9C和11d中是最活跃的，表现出生长抑制50％（GI 50）的值小于对于所有测试的细胞系，均大于5μM 化合物9c中，轴承4 -二甲氨基苯基在C-1 β选择-咔啉来进行有关细胞死亡和细胞周期图的进一步研究，重点是人肾腺癌细胞系786-0。用25μM的化合物9c处理在处理15小时后会诱导细胞死亡，其特征在于磷脂酰丝氨酸的暴露和膜完整性的丧失。此外，用12.5μM的处理可促进亚G1阻滞，这表明细胞死亡。N-（2-取代-芳基-4-噻唑烷酮）-β-咔啉-3-羧酰胺系列（18-23）的衍生物显示出对神经胶质瘤（U251）和卵巢癌（OVCAR-3）的强活性和高选择

  DOI：

  10.1016/j.ejmech.2016.10.018

文献信息

• Design, Synthesis and Bioactivity Evaluation of Novel β-carboline 1,3,4-oxadiazole Derivatives
  作者：Zhi-Jun Zhang、Jing-Jing Zhang、Zhi-Yan Jiang、Guo-Hua Zhong

  DOI：10.3390/molecules22111811

  日期：——

  A series of novel β-carboline 1,3,4-oxadiazole derivatives were designed and synthesized, and the in vitro cytotoxic activity against Sf9 cells and growth inhibitory activity against Spodoptera litura were evaluated. Bioassay results showed that most of these compounds exhibited excellent in vitro cytotoxic activity. Especially, compound 37 displayed the best efficacy in vitro (IC50 = 3.93 μM), and

  设计并合成了一系列新型β-咔啉1,3,4-恶二唑衍生物，并评估了其体外对Sf9细胞的细胞毒活性和对斜纹夜蛾的生长抑制活性。生物测定结果表明，这些化合物中的大多数表现出优异的体外细胞毒活性。特别是，化合物 37 在体外表现出最佳功效（IC50 = 3.93 μM），并且比喜树碱（CPT）（IC50 = 18.95 μM）强五倍。此外，化合物 5 和 37 可以诱导细胞凋亡和细胞周期停滞并刺激 Sf9 细胞中的 Sf-caspase-1 活化。体内生物测定还表明，化合物5和37可以显着抑制斜纹夜蛾幼虫的生长，降低幼虫和蛹的重量。根据这些生物测定结果，
• Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents
  作者：Chen、Guo、Ma、Chen、Fan、Zhang

  DOI：10.3390/molecules24162950

  日期：——

  Utilizing a pharmacophore hybridization approach, we have designed and synthesized a novel series of 28 new heterobivalent β-carbolines. The in vitro cytotoxic potential of each compound was evaluated against the five cancer cell lines (LLC, BGC-823, CT-26, Bel-7402, and MCF-7) of different origin—murine and human, with the aim of determining the potency and selectivity of the compounds. Compound 8z

  利用药效团杂交方法，我们设计并合成了一系列新的 28 种新型异二价 β-咔啉。评估了每种化合物对不同来源（鼠类和人）的五种癌细胞系（LLC、BGC-823、CT-26、Bel-7402 和 MCF-7）的体外细胞毒性潜力，目的是确定化合物的效力和选择性。化合物 8z 显示出抗肿瘤活性，半数最大抑制浓度 (IC50) 值为 9.9 ± 0.9、8.6 ± 1.4、6.2 ± 2.5、9.9 ± 0.5 和 5.7 ± 1.2 µM，对测试的五种癌细胞系。此外，使用鸡绒毛尿囊膜 (CAM) 体内模型研究了化合物 8z 对血管生成过程的影响。在 5 μM 的浓度下，化合物 8z 显示出对血管生成的积极影响。
• Synthesis and antitumor activity of β-carboline 3-(substituted-carbohydrazide) derivatives
  作者：Valéria Aquilino Barbosa、Anelise S. Nazari Formagio、Franciele Cristina Savariz、Mary Ann Foglio、Humberto Moreira Spindola、João Ernesto de Carvalho、Emerson Meyer、Maria Helena Sarragiotto

  DOI：10.1016/j.bmc.2011.08.059

  日期：2011.11

  synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The β-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N9-methylation of β-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the b

  合成了一系列在C-3处带有取代的碳酰肼部分的β-咔啉衍生物，并评估了其对八种人类癌细胞系的抗肿瘤活性。通常，β-咔啉N-（取代的亚苄基）碳酰肼显示出比其N-（亚烷基）碳酰肼类似物更大的抗肿瘤活性。β-咔啉N-（取代的亚苄基）碳酰肼的N 9甲基化导致抗肿瘤活性降低。在所测试的化合物中，苄基碳酰肼3，4，11，13，16，21和22是最活跃的，具有IC对于八种肿瘤细胞系中的六种，有50种小于10μM。衍生物4对所有测试的细胞系表现出最显着的活性，对肾脏（786-0）细胞系具有显着的细胞毒性（IC 50  = 0.04μM）。在Ehrlich实体癌测定中测定化合物4的体内抗肿瘤活性。
• Synthesis and antitumor activity of novel 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines and their Mannich bases
  作者：Franciele Cristina Savariz、Mary Ann Foglio、Ana Lucia T. Goes Ruiz、Willian Ferreira da Costa、Marina de Magalhães Silva、Josué Carinhanha Caldas Santos、Isis Martins Figueiredo、Emerson Meyer、João Ernesto de Carvalho、Maria Helena Sarragiotto

  DOI：10.1016/j.bmc.2014.10.031

  日期：2014.12

  for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a–e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15 μM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67–3.20 μM. A high selectivity and potent activity were observed for some

  一系列新型的1-（取代的苯基）-3-（2-氧代-1,3,4-恶二唑-5-基）β-咔啉（4a – e）和相应的曼尼希碱5 – 9（a – c合成）并评估其对七种人类癌细胞系的体外抗肿瘤活性。4a – e系列化合物显示出广泛的抗肿瘤活性，五个细胞系的GI 50值低于15μM。在C-1处具有N，N-二甲基氨基苯基的衍生物4b在GI 50下表现出最高的活性在0.67–3.20μM的范围内。观察到某些Mannich碱基具有较高的选择性和强活性，特别是对耐药卵巢（NCI-ADR / RES）细胞系（5a，5b，6a，6c和9b）和卵巢（OVCAR-03）细胞系（5b，图6a，6c，9a，9b和9c）。另外，通过使用UV和荧光光谱分析研究了化合物4b与DNA的相互作用。这些研究表明4b通过插入结合与ctDNA相互作用。
• 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.