D-1,2,3,4-四氢正哈尔满碱-3-羧酸 | 72002-54-1

• 物质功能分类: 有机原料 - 杂环化合物
• 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
• 中文名称: D-1,2,3,4-四氢正哈尔满碱-3-羧酸
• 中文别名: (R)-2,3,4,9-四氢-9H-吡啶并[3,4-B]吲哚-3-甲酸
• 英文名称: (3R)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid
• 英文别名: (R)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid；(3R)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid；THCA；(3R)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-3-carboxylate
• CAS: 72002-54-1
• 化学式: C₁₂H₁₂N₂O₂
• mdl: MFCD04117830
• 分子量: 216.239
• InChiKey: FSNCEEGOMTYXKY-SNVBAGLBSA-N

物化性质

• 密度：
  1.377

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.1
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  D-1,2,3,4-四氢正哈尔满碱-3-羧酸 在 磺酰氯 作用下， 以 甲醇 为溶剂， 反应 17.0h， 以86%的产率得到(R)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect

  摘要：

  Based on our previous studies and predictive docking results, furans and thiophenes were introduced to the privileged tetrahydro-beta-carboline scaffold to generate more potent and selective PDE5 inhibitors. A total of 66 novel furyl/thienyl tetrahydro-beta-carboline derivatives were designed, synthesized and evaluated for PDE5 inhibition. Tetrahydro-beta-carboline-piperazinedione 19f and tetrahydro-beta-carboline-hydantoin 26b with optimized pendant 5-ethylfuran/5-ethylthiophene were identified as the most potent PDE5 inhibitors, and showed high selectivity towards PDE5 versus other PDE isozymes, especially PDE6 and PDE11. Further vasorelaxant activity assessments revealed that these PDE5 inhibitors also exhibited significant angiectasis on the norepinephrine-precontracted 3rd-order mesenteric arteries (110-150 mu m) via NO-sGC-cGMP pathway, implying their further application for the treatment of vascular diseases. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.028
• 作为产物：
  描述：

  (R)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 D-1,2,3,4-四氢正哈尔满碱-3-羧酸
  参考文献：
  名称：

  （R / S）-BINOL-α-磷酸乙内酰胺氨基甲酸酯和（R / S）-钛（IV）双酚酸酯-催化的对映选择性分子内Heck / Aza-Diels-Alder环加成（IHADA）：一种简便的方法

  摘要：

  的（R / S） -钛（IV）BINOLate催化对映选择性高分子内的Heck /氮杂狄尔斯-阿尔德环加成（IHADA）级联的开发是为了从制备tetrahydropyridoindoles（THPS）和octahydropyrazinopyridoindoles（oHPPs）原位生成的（- [R /小号一锅中的BINOLα-磷酰氧基氨基甲酸酯（αPPC2）。观察到（R / S）-αPPC2与（R / S）-钛（IV）BINOLate之间的手性协同作用，并成功地用于构建各种t​​HP（7个实例）和oHPP（17个实例）。

  DOI：

  10.1002/adsc.201300522

文献信息

• Synthesis of 1,2,3,4-tetrahydro-.BETA.-carboline derivatives as hepatoprotective agents. II. Alkyl 1,2,3,4-tetrahydro-.BETA.-carboline-2-carbodithioates.
  作者：YUTAKA SAIGA、IKUO IIJIMA、AKIHIKO ISHIDA、TOSHIKAZU MIYAGISHIMA、KEISUKE SHIGEZANE、TOKURO OH-ISHI、MAMORU MATSUMOTO、YUZO MATSUOKA

  DOI：10.1248/cpb.35.3262

  日期：——

  A large number of alkyl 1, 2, 3, 4-tetrahydro-β-carboline-2-carbodithioates (2 and 5) with 3-hydroxycarbonyl and 3-hydroxymethyl groups were synthesized and tested for hepatoprotective activity against CCl4-induced liver damage in mice. Structure-activity relationships were investigated. Lengthening of the alkyl group in 2 and 5 tends to adversely affect the activity. Both enantiomers of the methyl derivatives (2a and 5a), the most potent compounds in this series, were synthesized, and no difference in hepatoprotective activity was observed. Apparent neighboring group participation was observed in the treatment of 5a with base or acid, giving the cyclized product (6) or the rearranged products (7, 8, and 9).

  合成了大量含有3-羟基羰基和3-羟甲基的烷基1,2,3,4-四氢-β-咔啉-2-二硫代碳酸盐（2和5），并测试了它们对CCl4诱导的小鼠肝损伤的肝保护活性。研究了结构-活性关系。2和5中烷基链的延长往往会不利地影响活性。合成了这一系列中最强的化合物——甲基衍生物（2a和5a）的两种对映体，并观察到它们在肝保护活性上没有差异。用碱或酸处理5a时，可以观察到明显的邻位基团参与作用，生成了环化产物（6）或重排产物（7、8和9）。
• Tetrahydro-.beta.-carboline derivatives and treatment of liver diseases
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US04628057A1

  公开（公告）日：1986-12-09

  Novel tetrahydro-.beta.-carboline derivatives of the formula: ##STR1## wherein R.sup.1 is carboxyl, a lower alkoxycarbonyl, carbamoyl, an N,N-di-lower alkylcarbamoyl, an N-(phenyl-substituted lower alkylidenamino)carbamoyl, a [N,N-di(lower alkyl)amino]-lower alkyl, or a nitrogen-containing monocyclic heterocyclic group; R.sup.2 is hydrogen atom, a lower alkyl, or a hydroxy-lower alkyl group, or R.sup.2 is combined with R.sup.1 to form a group: --CO--O--CH.sub.2 --; R.sup.3 is hydrogen atom, a lower alkyl, a phenyl-lower alkyl, or a group: --CSS--R.sup.4 ; R.sup.4 is hydrogen atom, an alkyl, or a group: --(CH.sub.2).sub.n Y.sup.1 ; n is 0, 1 or 2, Y.sup.1 is a lower alkenyl, a phenyl-substituted lower alkenyl, an N,N-di(lower alkyl)amino, a lower alkylmercapto, a lower alkoxycarbonyl, benzoyl, naphthyl, a cycloalkyl, a monocyclic heterocyclic group, or a substituted or unsubstituted phenyl, which have excellent activities for alleviating, curing and preventing hepatic damages and are useful as a therapeutic or prophylactic agent for hepatic diseases, and processes for the preparation thereof, and a pharmaceutical composition containing the above compound as an active ingredient.

  该专利描述了一种新型的四氢-β-咔啉衍生物，其化学式为：##STR1## 其中R.sup.1为羧基、较低的烷氧羰基、氨基甲酰基、N,N-二较低烷基氨基甲酰基、N-(苯基取代的较低烷基亚氨基)甲酰基、[N,N-二(较低烷基)氨基]-较低烷基，或含氮的单环杂环基团；R.sup.2为氢原子、较低的烷基，或羟基较低烷基基团，或R.sup.2与R.sup.1结合形成一个基团：--CO--O--CH.sub.2 --；R.sup.3为氢原子、较低的烷基、苯基较低烷基，或一个基团：--CSS--R.sup.4；R.sup.4为氢原子、烷基，或一个基团：--(CH.sub.2).sub.n Y.sup.1；n为0、1或2，Y.sup.1为较低烯基、苯基取代的较低烯基、N,N-二(较低烷基)氨基、较低烷基硫醇基、较低的烷氧羰基、苯甲酰基、萘基、环烷基、单环杂环基团，或取代或未取代的苯基，这些化合物对缓解、治愈和预防肝损伤具有出色的活性，并可用作治疗或预防肝病的药物，以及其制备方法和含有上述化合物作为活性成分的药物组合物。
• Design, synthesis, and anti-proliferative evaluation of 1<i>H</i>-1,2,3-triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates in estrogen responsive and triple negative breast cancer cells
  作者：Bharvi Sharma、Liang Gu、Ruvesh Pascal Pillay、Nosipho Cele、Paul Awolade、Parvesh Singh、Mandeep Kaur、Vipan Kumar

  DOI：10.1039/d0nj00879f

  日期：——

  A series of 1H-1,2,3 triazole grafted tetrahydro-β-carboline-chalcone/ferrocenylchalcone conjugates were synthesized and in vitro evaluated against estrogen responsive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. Comparative analysis revealed the improvement of selectivity towards the estrogen responsive cells with the inclusion of a ferrocene core. The most potent compounds of the

  合成了一系列1 H -1,2,3三唑接枝的四氢-β-咔啉-查耳酮/二茂铁基查耳酮共轭物，并在体外评估了其对雌激素反应性（MCF-7）和三阴性（MDA-MB-231）乳腺癌细胞的作用。对比分析显示，通过加入二茂铁核心，提高了对雌激素反应性细胞的选择性。该系列中最有效的化合物为13l（R = 4-F，n = 3），对MCF-7的IC 50值为10.33μM，比标准药物他莫昔芬的效力高约5倍，而13d（ R = 2,3,4-三甲氧基，n = 5）的IC 50MDA-MB-231细胞的最大抗药性值为21.99μM，比他莫昔芬的效价高约3倍。ERα配体结合域中的分子对接研究进一步支持了实验结果，并且更大的结合亲和力归因于能量上有利的拟合以及ERα活性位点中疏水和亲水相互作用之间的平衡。
• RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：The Johns Hopkins University

  公开号：US20210094933A1

  公开（公告）日：2021-04-01

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受免疫蛋白配体家族FK506和雷帕霉素天然产物启发的大环化合物。生成包含FK506和雷帕霉素结合结构域的Rapafucin大环化合物库，应具有作为治疗疾病新药的潜力。
• Diastereoselective approach to rationally design tetrahydro-β-carboline–isatin conjugates as potential SERMs against breast cancer
  作者：Bharvi Sharma、Amandeep Singh、Liang Gu、Sourav Taru Saha、Ashona Singh-Pillay、Nosipho Cele、Parvesh Singh、Mandeep Kaur、Vipan Kumar

  DOI：10.1039/c9ra00744j

  日期：——

  A series of tetrahydro-β-carboline–isatin conjugates was prepared and assayed for anti-proliferative activities on Estrogen Responsive ER(+) and non-responsive ER(−ve) cell-lines.

  一系列四氢-β-咔啉-异喹啉共轭物被制备并用于对雌激素受体 ER(+) 和非响应性 ER(−ve) 细胞系的抗增殖活性进行测试。