ethyl 3-benzoyl-5-chloro-1H-indole-2-carboxylate | 105399-06-2

• 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
• 英文名称: ethyl 3-benzoyl-5-chloro-1H-indole-2-carboxylate
• 英文别名: ethyl 3-benzoyl-5-chloroindole-2-carboxylate
• CAS: 105399-06-2
• 化学式: C₁₈H₁₄ClNO₃
• 分子量: 327.767
• InChiKey: LFCPJPZIBGJPQU-UHFFFAOYSA-N

物化性质

• 熔点：
  166-167.5 °C(Solv: benzene (71-43-2); hexane (110-54-3))
• 沸点：
  500.7±45.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-benzoyl-5-chloro-1H-indole-2-carboxylate 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  Novel indole sulfides as potent HIV-1 NNRTIs

  摘要：

  In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted S(N)1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.006
• 作为产物：
  描述：

  5-氯吲哚-2-羧酸乙酯 、 苯甲酰氯 在 氯化二乙基铝 作用下， 以 正庚烷 、 二氯甲烷 为溶剂， 反应 0.83h， 以31%的产率得到ethyl 3-benzoyl-5-chloro-1H-indole-2-carboxylate
  参考文献：
  名称：

  [EN] BETA-ARRESTIN-BIASED CANNABINOID CB1 RECEPTOR AGONISTS AND METHODS FOR MAKING AND USING THEM
  [FR] AGONISTES, BIAISÉS EN FAVEUR DE LA BÊTA-ARRESTINE, DES RÉCEPTEURS CB1 AUX CANNABINOÏDES ET LEURS PROCÉDÉS DE PRODUCTION ET D'UTILISATION

  摘要：

  本发明提供了具有CB1受体结合基团和导向基团的化合物。在相关方面，该发明提供了含有本发明化合物的药物组合物，用于抑制部分受CB1受体活性调节的途径的方法，以及用于治疗部分受CB1受体活性调节的疾病或疾病的方法。在某些实施例中，这些化合物是Formula（I）的化合物。还描述了制备Formula（I）化合物的方法。在另一个方面，该发明提供了识别β-阻滞蛋白途径选择性激动剂的方法，而不是G蛋白途径的方法。

  公开号：

  WO2015195486A1

文献信息

• Synthetic studies on indoles and related compounds. XII. A simple general method for the C-3 acylation of ethyl indole-2-carboxylates.
  作者：YASUOKI MURAKAMI、MASANOBU TANI、MICHIO SUZUKI、KEIZO SUDOH、MIDORI UESATO、KENJIRO TANAKA、YUUSAKU YOKOYAMA

  DOI：10.1248/cpb.33.4707

  日期：——

  Ethyl indole-2-carboxylate (1a) and its derivatives were reacted with various carboxylic acids by using trifluoroacetic anhydride and phosphoric acid (or polyphosphoric acid) to yield effectively the corresponding ethyl 3-acylindole-2-carboxylates (3). However, strongly acidic carboxylic acids and nitrogen-containing carboxylic acids were poor acylating agents. Ethyl 3-acylindole-2-carboxylate (3) could easily be converted to 3-acylindole (5)

  乙基吲哚-2-羧酸酯（1a）及其衍生物在三氟乙酸酐和磷酸（或聚磷酸）的作用下与多种羧酸反应，有效地合成了相应的乙基3-酰基吲哚-2-羧酸酯（3）。然而，强酸性羧酸和含氮羧酸的酰化效果较差。乙基3-酰基吲哚-2-羧酸酯（3）很容易转化为3-酰基吲哚（5）。
• [EN] SUBSTITUTED INDOLES AND THEIR USE AS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS<br/>[FR] INDOLES SUBSTITUÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS NON-NUCLÉOSIDIQUES DE LA TRANSCRIPTASE INVERSE
  申请人：UNIV STELLENBOSCH

  公开号：WO2015044928A1

  公开（公告）日：2015-04-02

  Compounds of Formula I or pharmaceutically acceptable salts thereof are claimed, wherein R1 is an ester, amide or a heterocycle; R2 is C or N; R3 is a methoxy or ethoxy group, an alkyl group or a heterocyclic group; R4 is a substituted or unsubstituted phenyl or heteroaromatic group; and R5 is a halide or a nitrile. The use of these compounds as non-nucleoside reverse transcriptase inhibitors (NNRTIs) for inhibiting or treating HIV infection or AIDS is also described.

  本发明涉及化合物I的配方或其药学上可接受的盐，其中R1是酯、酰胺或杂环；R2是C或N；R3是甲氧基或乙氧基基团、烷基或杂环基团；R4是取代或未取代的苯基或杂环芳基；R5是卤素或腈基。本发明还描述了这些化合物作为非核苷类逆转录酶抑制剂（NNRTIs）用于抑制或治疗HIV感染或艾滋病的用途。
• Beta-arrestin-biased cannabinoid CB1 receptor agonists and methods for making and using them
  申请人：The University of North Carolina at Greensboro

  公开号：US10118914B2

  公开（公告）日：2018-11-06

  The present invention provides compounds having a CB1 receptor-binding moiety and a directing moiety. In related aspects, the invention provides pharmaceutical compositions containing compounds of the invention, methods for inhibiting a pathway modulated in part by the CB1 receptor activity, and methods for treating a condition or disorder mediated in part by CB1 receptor activity. In certain embodiments, the compounds are compounds of Formula I. Methods of preparing compounds of Formula I are also described. In another aspect, the invention provides methods of identifying a selective agonist of the beta-arrestin pathway over the G-protein pathway.

  本发明提供了具有 CB1 受体结合分子和指导分子的化合物。在相关方面，本发明提供了含有本发明化合物的药物组合物、抑制部分由 CB1 受体活性调节的通路的方法，以及治疗部分由 CB1 受体活性介导的病症或紊乱的方法。在某些实施方案中，化合物是式 I 的化合物。本发明还描述了制备式 I 化合物的方法。在另一个方面，本发明提供了鉴定β-阿司匹林通路的选择性激动剂而不是G-蛋白通路的方法。
• Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Mohammad Hassam、Adriaan E. Basson、Dennis C. Liotta、Lynn Morris、Willem A. L. van Otterlo、Stephen C. Pelly

  DOI：10.1021/ml3000462

  日期：2012.6.14

  The HIV pandemic represents one of the most serious diseases to face mankind in both a social and economic context, with many developing nations being the worst afflicted. Due to ongoing resistance issues associated with the disease, the design and synthesis of anti-HIV agents presents a constant challenge for medicinal chemists. Utilizing molecular modeling, we have designed a series of novel cyclopropyl indole derivatives as HIV non-nucleoside reverse transcriptase inhibitors and carried out their preparation. These compounds facilitate a double hydrogen bonding interaction to Lys101 and efficiently occupy the hydrophobic pockets in the regions of Tyr181/188 and Val179. Several of these compounds inhibited HIV replication as effectively as nevirapine when tested in a phenotypic assay.
• Structure–Activity Relationship Study of Indole-2-carboxamides Identifies a Potent Allosteric Modulator for the Cannabinoid Receptor <b>1</b> (CB1)
  作者：Mariam M. Mahmoud、Hamed I. Ali、Kwang H. Ahn、Aparna Damaraju、Sushma Samala、Venkata K. Pulipati、Srikanth Kolluru、Debra A. Kendall、Dai Lu

  DOI：10.1021/jm4009828

  日期：2013.10.24

  The cannabinoid CB1 receptor is involved in complex physiological functions. The discovery of CB1 allosteric modulators generates new opportunities for drug discovery targeting the pharmacologically important CB1 receptor. 5-Chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (ORG27569; 1) represents a new class of indole-2-carboxamides that exhibit allostery of CBI. To better understand 0 the SAR, a group of indole-2-carboxamide analogues were synthesized and assessed for allostery of the CB1 receptor. We found that within the structure of indole-2-carboxamides, the presence of the indole ring is preferred for maintaining the modulator's high binding affinity for the allosteric site but not for generating allostery on the orthosteric site. However, the C3 substituents of the indole-2-carboxamides significantly impact the allostery of the ligand. A robust CBI allosteric modulator 5-chloro-N-(4-(dimethylamino)phenethyl)-3-pentyl-1H-indole-2-carboxamide (11j) was identified. It showed an equilibrium dissociation constant (K-B) of 167.3 nM with a markedly high binding cooperativity factor (alpha = 16.55) and potent antagonism of agonist-induced GTP gamma S binding.