5-叔丁基-1H-吲哚-2-甲酸乙酯 | 194490-18-1

• 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: 5-叔丁基-1H-吲哚-2-甲酸乙酯
• 中文别名: 5-叔丁基吲哚-2-羧酸乙酯；2-甲酸乙酯-5-叔丁基吲哚
• 英文名称: 5-tert-butyl-1H-indole-2-carboxylic acid ethyl ester
• 英文别名: ethyl 5-(tert-butyl)-1H-indole-2-carboxylate；ethyl 5-tert-butyl-1H-indole-2-carboxylate；ethyl 5-t-butyl-1H-indole-2-carboxylate；ethyl 5-tert-butylindole-2-carboxylate；Ethyl 5-t-butylindole-2-carboxylate
• CAS: 194490-18-1
• 化学式: C₁₅H₁₉NO₂
• 分子量: 245.321
• InChiKey: ULMVLLISCAWCMZ-UHFFFAOYSA-N

物化性质

• 熔点：
  137 °C
• 沸点：
  379.8±22.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-叔丁基-1H-吲哚-2-甲酸乙酯 在 N-碘代丁二酰亚胺 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以100%的产率得到ethyl 5-(tert-butyl)-3-iodo-1H-indole-2-carboxylate
  参考文献：
  名称：

  Structure–Activity Relationship (SAR) Development and Discovery of Potent Indole-Based Inhibitors of the Hepatitis C Virus (HCV) NS5B Polymerase

  摘要：

  Starting with the indole-based C-3 pyridone lead HCV polymerase inhibitor 2, extensive SAR studies were performed at different positions of the indole core. The best C-5 groups were found to be compact and nonpolar moieties and that the C-6 attachments were not affecting potency. Limited N-1 benzyl-type substituent studies indicated that the best substitutions were fluoro or methyl groups at 2' or 5' positions of the benzyl group. To improve pharmacokinetic (PK) properties, acylsulfonamides were incorporated as acid isosteres at the C-2 position. Further optimization of the combination at N-1, C-2, C-5, and C-6 resulted in the identification of compound 56, which had an excellent potency in both NS5B enzyme (IC50 = 0.008 mu M) and cell-based replicon (EC50 = 0.02 mu M) assays and a good oral PK profile with area-under-the curve (AUC) of 14 and 8 mu M.h in rats and dogs, respectively. X-ray structure of inhibitor 56 bound to the enzyme was also reported.

  DOI：

  10.1021/jm201258k
• 作为产物：
  描述：

  2-(4-tert-Butyl-phenylazo)-2-methyl-3-oxo-butyric acid ethyl ester 在 对甲苯磺酸 、 溶剂黄146 作用下， 以40%的产率得到5-叔丁基-1H-吲哚-2-甲酸乙酯
  参考文献：
  名称：

  Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches

  摘要：

  A data set consisting of twenty-two sertindole analogues and ten structurally diverse inhibitors, spanning a wide range in potency, was analyzed using CoMSiA. A homology model of HERG was constructed from the crystal structure of the open MthK potassium channel. A complementary relationship between our CoMSiA and homology models is apparent when the long inhibitor axis is oriented parallel to the longitudinal axis of the pore, with the tail region pointed toward the selectivity filter. The key elements of the pharmacophore, the CoMSiA and the homology model are: (1) The hydrophobic feature optimally consists of an aromatic group that is capable of engaging in pi-stacking with a Phe656 side chain. Optionally, a second aromatic or hydrophobic group present in some inhibitors may contact an additional Phe656 side chain. (2) The basic nitrogen appears to undergo a pi-cation interaction with Tyr652. (3) The pore diameter (12Angstrom +), and depth of the selectivity loop relative to the intracellular opening, act as constraints on the conformation-dependent inhibitor dimensions. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00196-3

文献信息

• Thiazolylbenzofuran derivatives and pharmaceutical compositions
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05994378A1

  公开（公告）日：1999-11-30

  This invention relates to novel thiazolylbenzofuran derivatives of formula (I) wherein R.sup.1 is lower alkyl, L is single bond or lower alkylene optionally substituted with aryl, oxo or hydroxy, and Q is a heterocyclic group optionally substituted with one or more suitable substituent(s); or lower alkoxy substituted with aryl which is substituted with one or more suitable substituent(s) and at least one of which is lower alkoxy optionally substituted with cyano, protected carboxy, carboxy, lower alkylene, a heterocyclic group optionally substituted with oxo, or amidino optionally substituted with hydroxy or lower alkoxy, or its salt, which possess activities as leukotriene and SRS-A antagonists or inhibitors.

  本发明涉及新颖的噻唑基苯并呋喃衍生物，其具有公式（I），其中R1是低级烷基，L是单键或可被芳基、氧基或羟基取代的低级亚烷基，Q是可被一个或多个适当取代基取代的杂环基；或者是被芳基取代的低级烷氧基，该芳基被一个或多个适当取代基取代，并且至少一个是可被氰基、受保护的羧基、羧基、低级亚烷基、可被氧基取代的杂环基或可被羟基或低级烷氧基取代的胍基取代的低级烷氧基，或其盐，其具有作为白三烯和SRS-A拮抗剂或抑制剂的作用。
• Variations of acidic functions at position 2 and substituents at positions 4, 5 and 6 of the indole moiety and their effect on NMDA-glycine site affinity
  作者：M Jansen

  DOI：10.1016/j.ejmech.2003.07.001

  日期：2003.10

  The synthetic procedures to obtain indole derivatives with different acidic functions at position 2 of the indole are reported. The synthesised and tested derivatives comprise 5-tetrazolyl, 1,3,4-oxadiazol-5-yl-2-one, and indole-2-carboxylic acid amides with 5-aminotetrazole, methanesulphonamide and trifluoromethanesulphonamide moieties. The binding affinity was evaluated using [3H]MDL 105,519 and

  报道了在吲哚的2位得到具有不同酸性功能的吲哚衍生物的合成方法。合成和测试的衍生物包含具有5-氨基四唑，甲磺酰胺和三氟甲磺酰胺部分的5-四唑基，1,3,4-恶二唑-5-基-2-酮和吲哚-2-羧酸酰胺。使用[3H] MDL 105,519和猪皮质脑膜评估结合亲和力。通常，具有不同于羧酸部分的酸性功能的化合物的效力低于吲哚-2-羧酸衍生物。同样，将4,6-二氯取代模式与5-叔丁基衍生物和吲哚的苯部分中未取代的化合物进行了比较，表明亲和力从5-叔丁基超过未取代的到4,6-二氯取代的衍生物。
• Carboxylic Acid-Promoted Single-Step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling
  作者：Long Ren、Guanglei Nan、Yongcheng Wang、Zhiyan Xiao

  DOI：10.1021/acs.joc.8b02180

  日期：2018.12.7

  cross-dehydrogenative coupling (CDC) reaction is an efficient strategy for indole synthesis. However, most CDC methods require special substrates, and the presence of inherent groups limits the versatility for further transformation. A carboxylic acid-promoted aerobic catalytic system is developed herein for a single-step synthesis of indoles from simple anilines and ketones. This versatile system is featured

  交叉脱氢偶联（CDC）反应是吲哚合成的有效策略。但是，大多数CDC方法需要特殊的底物，并且固有基团的存在限制了进一步转化的通用性。本文开发了一种羧酸促进的需氧催化系统，用于由简单的苯胺和酮一步合成吲哚。这种多功能的系统具有广泛的底物范围和使用环境氧气作为氧化剂的特点，对于实验室和工业应用均既方便又经济。C-3上不稳定的氢和C-2上高度可转化的羰基的存在，使吲哚在各种情况下成为有机合成的通用结构单元。基于密度泛函理论（DFT）的计算研究表明，决定速率的步骤是底物的羧酸辅助缩合，而不是芳基CH的官能化。因此，经由亚胺中间体的途径被认为是优选的机制。与一般的推论相反，据信原位形成的亚胺代替其烯胺异构体参与了α-Me的首次配体交换和随后的碳pal化，这为这种吲哚化机理提供了新的思路。
• 一种2-取代吲哚衍生物的合成方法
  申请人：中国医学科学院药物研究所

  公开号：CN109748840B

  公开（公告）日：2021-12-07

  本发明涉及一种制备2‑取代吲哚衍生物的合成方法，将芳香胺类化合物(I)，酮类化合物(II)和干燥剂在有机溶剂中混合，加入钯类催化剂后在有氧的弱酸性环境下反应制得所述吲哚类化合物(III)，(I)为(II)为(III)为其中R1选自氢、C1‑C6烷基、C1‑C6烷氧基、C1‑C6烷酰基、C2‑C6烯基、C2‑C6炔基、卤素、羟基、取代或未取代的氨基、取代或未取代的苯基及吡啶基及杂环芳基；(I)也可以取代或未取代的吡啶胺、嘧啶胺、哒嗪胺或吡嗪胺；取代基选自一个或多个C1‑C6烷基、C1‑C6烷氧基、C1‑C6烷酰基、C2‑C6烯基、C2‑C6炔基、卤素、羟基、氨基；R2选自C1‑C6烷基、甲酸酯基或C1‑C6烷酰胺基。
• N-(Heteroaryl)-1-heteroarylalkyl-1H-indole-2-carboxamide derivatives, preparation and therapeutic use thereof
  申请人：DUBOIS Laurent

  公开号：US20080146646A1

  公开（公告）日：2008-06-19

  The invention concerns compounds of general formula (I), wherein n, X 1 , X 2 , X 3 , X 4 , Y and W are as defined herein. The invention also concerns a method for preparing said compounds and their therapeutic use.

  这项发明涉及通式（I）的化合物，其中n、X1、X2、X3、X4、Y和W的定义如本文所述。该发明还涉及一种制备所述化合物及其治疗用途的方法。