2-乙酰基-1,2,3,4-四氢异喹啉-3-甲酸 | 143767-54-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 2-乙酰基-1,2,3,4-四氢异喹啉-3-甲酸
• 中文别名: 2-乙酰基-1,2,3,4-四氢-3-异喹啉羧酸
• 英文名称: (+/-)-2-acetyl-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid
• 英文别名: (R,S)-2-acetyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid；2-acetyl-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid；2-Acetyl-1,2,3,4-tetrahydro-isochinolin-3-carbonsaeure；2-acetyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid；2-acetyl-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 143767-54-8
• 化学式: C₁₂H₁₃NO₃
• mdl: MFCD00718847
• 分子量: 219.24
• InChiKey: CNBQGXOEOOVTPA-UHFFFAOYSA-N

物化性质

• 熔点：
  170-171 °C
• 沸点：
  465.2±45.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933499090
• 储存条件：
  室温且干燥

反应信息

• 作为反应物：
  描述：

  2-乙酰基-1,2,3,4-四氢异喹啉-3-甲酸 在 盐酸 、 sodium hydroxide 、 对甲苯磺酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 40.0h， 生成 (R)-(+)-1,2,3,4-四氢异喹啉-3-羧酸
  参考文献：
  名称：

  Efficient Synthesis of Racemic and Enantiomerically Pure 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid and Esters

  摘要：

  在碱催化下，1,2-双（卤甲基）苯 1 a 或 b 与 2-（乙酰氨基）丙二酸二乙酯（2）发生环化反应，随后发生脱羧反应和酰胺裂解反应，制备出了外消旋和光学纯的 1,2,3,4-四氢异喹啉-3-羧酸及酯。对映体的分解是通过与(-)-薄荷醇酯化，然后柱层析分离非对映异构体混合物，或通过与扁桃酸分离苄酯的双酯盐，以及碱催化两种酯的皂化反应来实现的。

  DOI：

  10.1055/s-1992-26325
• 作为产物：
  描述：

  邻二氯苄 在 盐酸 、 氢氧化钾 、 sodium methylate 作用下， 反应 8.0h， 生成 2-乙酰基-1,2,3,4-四氢异喹啉-3-甲酸
  参考文献：
  名称：

  Efficient Synthesis of Racemic and Enantiomerically Pure 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid and Esters

  摘要：

  在碱催化下，1,2-双（卤甲基）苯 1 a 或 b 与 2-（乙酰氨基）丙二酸二乙酯（2）发生环化反应，随后发生脱羧反应和酰胺裂解反应，制备出了外消旋和光学纯的 1,2,3,4-四氢异喹啉-3-羧酸及酯。对映体的分解是通过与(-)-薄荷醇酯化，然后柱层析分离非对映异构体混合物，或通过与扁桃酸分离苄酯的双酯盐，以及碱催化两种酯的皂化反应来实现的。

  DOI：

  10.1055/s-1992-26325

文献信息

• SYNTHESIS OF 8H-3A-AZA-CYCLOPENTA[A]INDENES AND 5,10-DIHYDROPYRROLO[1,2-B]ISOQUINOLINES DERIVATIVES AND THEIR USE AS ANTITUMOR THERAPEUTIC AGENTS
  申请人：Su Tsann-Long

  公开号：US20090117125A1

  公开（公告）日：2009-05-07

  The present disclosure relates to a series of bis(hydroxymethyl) and its bis(carbamate) of 8H-3a-azacyclopenta[a]indene-1-yl and 5,10-dihydropyrrolo-[1,2-b]isoquinolines derivatives (Formula I-Formula IV) as DNA di-alkylating agents. The preliminary antitumor studies indicated that compounds disclosed herein could exhibit potent cytotoxicity in vitro and antitumor therapeutic efficacy in human tumor xenografts and could have little or no cross-resistance to either Taxol or Vinblastine. The results demonstrated that compounds disclosed herein possess potent antitumor therapeutic efficacy and are expected to have potential for clinical applications.

  本公开涉及一系列8H-3a-氮杂环戊二烯-1-基和5,10-二氢吡咯并[1,2-b]异喹啉衍生物的双(羟甲基)和其双(氨基甲酸酯)（公式I-公式IV），作为DNA双烷基化剂。初步的抗肿瘤研究表明，本公开的化合物在体外可能表现出强大的细胞毒性，并在人类肿瘤移植物模型中表现出抗肿瘤治疗效果，并且可能几乎不会对紫杉醇或长春碱产生交叉耐药性。结果表明，本公开的化合物具有强大的抗肿瘤治疗效果，并有望在临床应用中发挥潜力。
• The intramolecular 1,3-dipolar cyclisation of mesoionic species generated by the thermolysis of the mixed anhydrides of acetic and N-alkynoyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids
  作者：Malcolm Sainsbury、Rosalind H. Strange、Peter R. Woodward、Paul A. Barsanti

  DOI：10.1016/s0040-4020(01)86306-7

  日期：1993.3

  The intramolecular cyclisations of mesoionic intermediates formed by heating N-alkynoyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids [alkylnoyl side chains: RCC-(CH2)2CO, where n = 3 or 4] with acetic anhydride, have been investigated. The final products are octahydropentaleno[2,3-a]isoquinolines and hexahydroindeno[2,3-a]isoquinolines respectively, formed by the expulsion of carbon dioxide from

  通过加热N-炔基-1,2,3,4-四氢异喹啉-3-羧酸[烷酰基侧链：RCC-（CH 2）2 CO，其中n = 3或4]形成的介电中间体的分子内环化用乙酸酐进行研究。最终产品是octahydropentaleno [2,3-一个]异喹啉和hexahydroindeno [2,3-一个]异喹啉分别由二氧化碳的从最初的加合物驱逐形成。还研究了分子间形式的环加成反应中烯烃和炔烃作为亲二烯体的行为。带有吸电子基团的炔烃提供吡咯并[1,2- b异喹啉，但除非使用烯烃，如亚苄基亚甲基苯二腈（首先形成的加合物可在失去CO 2之前消除HCN），否则反应将失败。
• ORGANIC COMPOUNDS AND THEIR USES
  申请人：Brandl Trixl

  公开号：US20100204159A1

  公开（公告）日：2010-08-12

  The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of human diseases.

  本申请描述了对人类疾病的治疗、预防和/或改善有用的有机化合物。
• Synthesis of 8H-3A-aza-cyclopenta [A ]indenes and 5,10-dihydropyrrolo[1,2-B]isoquinolines derivatives and their use as antitumor therapeutic agents
  申请人：Su Tsann-Long

  公开号：US08410130B2

  公开（公告）日：2013-04-02

  The present disclosure relates to a series of bis(hydroxymethyl) and its bis(carbamate) of 8H-3a-azacyclopenta[a]indene-1-yl and 5,10-dihydropyrrolo-[1,2-b]isoquinolines derivatives (Formula I-Formula IV) as DNA di-alkylating agents. The preliminary antitumor studies indicated that compounds disclosed herein could exhibit potent cytotoxicity in vitro and antitumor therapeutic efficacy in human tumor xenografts and could have little or no cross-resistance to either Taxol or Vinblastine. The results demonstrated that compounds disclosed herein possess potent antitumor therapeutic efficacy and are expected to have potential for clinical applications.

  本公开涉及一系列8H-3a-氮杂环五环[1]吲哚-1-基和5,10-二氢吡咯并[1,2-b]异喹啉衍生物的双(羟甲基)和其双(氨基甲酸酯) (公式I-公式IV)，作为DNA二烷基化剂。初步的抗肿瘤研究表明，本公开的化合物在体外可能表现出强烈的细胞毒性和人类肿瘤异种移植物的抗肿瘤治疗效果，并且可能没有对紫杉醇或长春新碱的交叉耐药性。结果表明，本公开的化合物具有强大的抗肿瘤治疗效果，并有望在临床应用中发挥潜力。
• Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores
  作者：Bin Ho、A Michael Crider、James P Stables

  DOI：10.1016/s0223-5234(00)01206-x

  日期：2001.3

  Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha -methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl-2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha -methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg(-1), TD50 = 36.4 mg kg(-1), PI = 6.3). Replacement of the piperidine ring of I by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man. (C) 2001 Editions scientifiques et medicales Elsevier SAS.