diethyl N-(4-ethynylbenzoyl)-L-glutamate | 116387-23-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: diethyl N-(4-ethynylbenzoyl)-L-glutamate
• 英文别名: diethyl (2S)-2-[(4-ethynylbenzoyl)amino]pentanedioate
• CAS: 116387-23-6
• 化学式: C₁₈H₂₁NO₅
• 分子量: 331.368
• InChiKey: DWMCEUKMNNDCCZ-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl N-(4-ethynylbenzoyl)-L-glutamate 在 palladium on activated charcoal copper(l) iodide 、 氢气 、 三乙胺 、 三苯基膦 、 palladium dichloride 作用下， 以 乙腈 、 三氟乙酸 为溶剂， 25.0 ℃ 、365.42 kPa 条件下， 反应 27.0h， 生成 diethyl N-<4-<<2-(pivaloylamino)-4-hydroxy-5,6,7,8-tetrahydropyrido<2,3-d>pyrimidin-6-yl>ethyl>benzoyl>-L-glutamate
  参考文献：
  名称：

  Convergent and efficient palladium-effected synthesis of 5, 10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF)

  摘要：

  DOI：

  10.1021/jo00276a023
• 作为产物：
  描述：

  4-乙炔苯甲酸甲酯 在 三乙胺 、 N-苯基磷氨基氯化苯 、 三氟乙酸 作用下， 反应 8.5h， 生成 diethyl N-(4-ethynylbenzoyl)-L-glutamate
  参考文献：
  名称：

  Convergent and efficient palladium-effected synthesis of 5, 10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF)

  摘要：

  DOI：

  10.1021/jo00276a023

文献信息

• Design, Synthesis, and Biological Activities of Classical <i>N</i>-{4-[2-(2-Amino-4-ethylpyrrolo[2,3-<i>d</i>]pyrimidin-5-yl)ethyl]benzoyl}-<scp>l</scp>-glutamic Acid and Its 6-Methyl Derivative as Potential Dual Inhibitors of Thymidylate Synthase and Dihydrofolate Reductase and as Potential Antitumor Agents
  作者：Aleem Gangjee、Jianming Yu、Roy L. Kisliuk、William H. Haile、Giulia Sobrero、John J. McGuire

  DOI：10.1021/jm0203534

  日期：2003.2.1

  3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid (2) and N-[2-amino-4-ethyl-6-methyl[(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutam ic acid (4), were designed and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and as antitumor agents. Compound 2 had inhibitory potency against human DHFR similar to N-[4-[2-(amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,

  两种新颖的类似物，N- [2-氨基-4-乙基[（吡咯并[2,3-d]嘧啶-5-基）乙基]苯甲酰基] -1-谷氨酸（2）和N- [2-氨基-设计并合成了4-乙基-6-甲基[（吡咯并[2,3-d]嘧啶-5-基）乙基]苯甲酰基] -1-谷氨酸（4），作为有效的胸苷酸合酶双重抑制剂（TS ）和二氢叶酸还原酶（DHFR）并用作抗肿瘤药。化合物2具有类似于N- [4- [2-（氨基-3,4-二氢-4-氧代-7H-吡咯并[2,3-d]嘧啶-5-基）乙基]苯甲酰基的对人DHFR的抑制能力。 ] -L-谷氨酸（LY231514）和1，而4对人DHFR没有活性。2和4都比LY231514更能抵抗大肠杆菌。抗人TS的功效比LY231514低7倍，而4表现出与LY231514相似的抑制活性。与2相比，它是人类草氨酸谷氨酸合成酶（FPGS）的有效底物，4是FPGS的不良底物。在标准的NCI临床前体外筛选中，化合物2
• Process for the preparation of fused pyridine compounds
  申请人：The Trustees of Princeton University

  公开号：US04818819A1

  公开（公告）日：1989-04-04

  2-Amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-en-1-yl]pyrido[2,3,-d]pyrimid ines and 2-amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-yn-1-yl]pyrido[2,3-d]pyrimid ines are prepared through the reaction of a haloaromatic compound and an unsaturated compound in the presence of a palladium catalyst. The products are chemical intermediates for the preparation of antineoplastic agents. A typical embodiment is the reaction of a protected 2-amino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine and an ester of 4-iodobenzoic acid.

  2-氨基-4-羟基-6-[2-(4-羧基苯基)烯基]吡啶[2,3-d]嘧啶和2-氨基-4-羟基-6-[2-(4-羧基苯基)炔基]吡啶[2,3-d]嘧啶是在钯催化剂存在下，卤代芳香化合物和不饱和化合物反应制备而成。该产品是抗肿瘤药物制备的化学中间体。典型实施方式是保护的2-氨基-4-羟基-6-乙炔基吡啶[2,3-d]嘧啶和4-碘苯甲酸酯反应。
• 6-alkenyl and ethynyl derivatives of
  申请人：The Trustees of Princeton University

  公开号：US04902796A1

  公开（公告）日：1990-02-20

  2-Amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-en-1-yl]pyrido[2,3,-d]pyrimid ines and 2-amino-4-hydroxy-6-[2-(4-carboxyphenyl)alk-1-yn-1-yl]pyrido[2,3-d]pyrimid ines are prepared through the reaction of a halo-aromatic compound and an unsaturated compound in the prosence of a palladium catalyst. The products are chemical intermediates for the preparation of antineo-plastic agents. A typical embodiment is the reaction of a protected 2-amino-4-hydroxy-6-ethynylpyrido[2,3-d]pyrimidine and an ester of 4-iodobenzoic acid.

  2-氨基-4-羟基-6-[2-(4-羧基苯基)烯基]吡啶[2,3-d]嘧啶和2-氨基-4-羟基-6-[2-(4-羧基苯基)炔基]吡啶[2,3-d]嘧啶是通过在钯催化剂的存在下，卤素芳香化合物和不饱和化合物的反应制备而成。这些产物是制备抗肿瘤药物的化学中间体。一个典型的实施例是保护的2-氨基-4-羟基-6-乙炔基吡啶[2,3-d]嘧啶和4-碘苯甲酸酯的反应。
• Glutamic acid derivatives as antineoplastic agents
  申请人：ELI LILLY AND COMPANY

  公开号：EP0567223A1

  公开（公告）日：1993-10-27

  This invention relates to N-[2-amino-4-substituted-[[(pyrrolo or pyrido)[2,3-d]pyrimidinyl]-alkyl]benzoyl]-L-glutamic acid compounds of formula wherein Ar is dihydropyrrolo, pyrrolo, pyrido or tetrahydropyrido ; R1 is hydrogen, chloro, alkylthio, alkoxy, alkylamino, or dialkylamino ; and R2 is C2-C3 alkyl intermediates for their synthesis, pharmaceutical formulations containing those compounds, and their use as antineoplastic agents.

  本发明涉及 N-[2-氨基-4-取代-[[(吡咯或吡啶)[2,3-d]嘧啶基]-烷基]苯甲酰基]-L-谷氨酸化合物，其式为 其中 Ar 是二氢吡咯、吡咯、吡啶或四氢吡啶； R1 是氢、氯、烷硫基、烷氧基、烷基氨基或二烷基氨基；以及 R2 是 C2-C3 烷基中间体，用于合成、配制含有这些化合物的药物以及用作抗肿瘤剂。
• The Synthesis of N-{2-Amino-4-substituted [(Pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic Acids as Antineoplastic Agents
  作者：Chuan Shih、L. S. Gossett

  DOI：10.3987/com-92-s(t)65

  日期：——

  A series of N-2-amino-4-substituted[(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acids were synthesized. In this current synthesis, compound 2-amino-4-chloro-pyrrolo[2,3-d]pyrimidine (4) was selected as an important precursor for the preparation of key intermediates such as 5b, 10b, 15a and 15b. These highly functionalized pyrrolo[2,3-d]pyrimidines were then later coupled with either 4-ethynylbenzoylglutamate or 4-iodobenzoylglutamate in a palladium catalyzed Heck reaction and thus provided the basic skeleton of the targeted molecules. The availability of the chlorine atom at the 4-position of the pyrrolopyrimidine nucleus has allowed us to introduce different substituents at this position efficiently. By this approach, we were able to prepare a variety of 4-substituted pyrrolo[2,3d]pyrimidine based folate antagonists (2a-2g) which are closely related to the novel thymidylate synthase inhibitor LY231514. In vitro analysis has demonstrated that some of these agents are highly cytotoxic against human leukemic cells (CCRF-CEM) in culture.