ethyl 2-iodo-4,5,6,7-tetrahydrobenzothiophene-3-carboxylate | 1309873-11-7

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: ethyl 2-iodo-4,5,6,7-tetrahydrobenzothiophene-3-carboxylate
• 英文别名: ethyl 2-iodo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate；Ethyl 2-iodo-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
• CAS: 1309873-11-7
• 化学式: C₁₁H₁₃IO₂S
• 分子量: 336.194
• InChiKey: QQPUEMIXOMBDEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-iodo-4,5,6,7-tetrahydrobenzothiophene-3-carboxylate 在 copper(l) iodide 、 palladium 10% on activated carbon 、 碘 、 palladium diacetate 、 potassium carbonate 、 三乙胺 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 1-(4-hydroxyphenyl)-2-phenyl-4H-5,6,7,8-tetrahydrobenzo[b]thieno[3,2-c]pyran-4-one
  参考文献：
  名称：

  Thieno[3,2-c]pyran-4-one based novel small molecules: Their synthesis, crystal structure analysis and in vitro evaluation as potential anticancer agents

  摘要：

  Novel thieno[3,2-c]pyran-4-one based small molecules were designed as potential anticancer agents. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of few steps such as Gewald reaction, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of thiophene ring followed by the fused pyranone moiety and then functionalization at C-7 position of the resultant thieno[3,2-c]pyran-4-one framework. Some of the compounds synthesized showed selective growth inhibition of cancer cells in vitro among which two compounds for example, 5d and 6c showed IC50 values in the range of 2.0-2.5 mu M. The crystal structure analysis of an active compound along with hydrogen bonding patterns and molecular arrangement present within the molecule is described. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.109
• 作为产物：
  描述：

  氰乙酸乙酯 在 吗啉 、 盐酸 、 sulfur 作用下， 以 乙醇 、 水 为溶剂， 反应 3.58h， 生成 ethyl 2-iodo-4,5,6,7-tetrahydrobenzothiophene-3-carboxylate
  参考文献：
  名称：

  支架跳跃策略识别前列腺素 EP4 受体拮抗剂用于癌症免疫治疗

  摘要：

  癌细胞可以有效抑制人体的自然免疫反应，而前列腺素E 2 (PGE 2 )是肿瘤细胞对免疫治疗产生耐药性的关键介质。作为 PGE 2引发的免疫抑制活性的主要贡献者，EP4 受体在肿瘤微环境中促进肿瘤的发展和进展，开发选择性和有效的 EP4 受体拮抗剂应该具有肿瘤免疫治疗的广阔潜力。为提高类药性能，通过支架跳跃策略设计合成了一系列4,7-二氢-5 H-噻吩并[2,3 - c ]吡喃衍生物。最有前途的化合物47表现出良好的EP4拮抗活性和优异的亚型选择性，以及良好的药物样特性。它有效地抑制了巨噬细胞中多种免疫抑制相关基因的表达。同时，在小鼠 CT26 结肠癌模型中，单独或与抗 PD-1 抗体联合口服化合物47可显着增强抗肿瘤免疫反应并抑制肿瘤生长。

  DOI：

  10.1021/acs.jmedchem.2c00448

文献信息

• Sequential coupling/desilylation–coupling/cyclization in a single pot under Pd/C–Cu catalysis: Synthesis of 2-(hetero)aryl indoles
  作者：R. Mohan Rao、Upendar Reddy CH、Alinakhi、Naveen Mulakayala、Mallika Alvala、M. K. Arunasree、Rajamohan R. Poondra、Javed Iqbal、Manojit Pal

  DOI：10.1039/c0ob01161d

  日期：——

  A new one-pot synthesis of 2-(hetero)aryl indolesvia sequential C–C coupling followed by C–Si bond cleavage and a subsequent tandem C–C/C–N bond forming reaction is described. A variety of functionalized indole derivatives were prepared by conducting this four step reaction under Pd/C–Cu catalysis. The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10%

  描述了通过一连串的C-C偶联，随后的C-Si键断裂和随后的串联C-C / C-N键形成反应的新的一锅法合成2-（杂）芳基吲哚的方法。通过在Pd / C-Cu催化下进行此四步反应，可以制备各种功能化的吲哚衍生物。该方法涉及耦合（三甲基甲硅烷基）乙炔与在10％的存在的Pd / C-的CuI-PPH iodoarenes 3和三乙胺 在 甲醇，然后在水溶液中用K 2 CO 3处理反应混合物甲醇，最后与邻碘碘化物偶联。给出了合成的吲哚衍生物的单晶X射线数据。描述了该方法的应用，合成化合物的体外药理特性以及对接研究。
• SUSTAINED HIV PROTEASE INHIBITOR
  申请人：Shionogi & Co., Ltd.

  公开号：EP3192794A1

  公开（公告）日：2017-07-19

  The present invention provides useful compounds for HIV protease inhibitor. A compound represented by formula or its pharmaceutically acceptable salt Formula: wherein ring A is R4 is -Y-Z, hydrogen atom, halogen, hydroxy and the like, R5 is hydrogen atom, halogen, hydroxy and the like, R6 is each independently halogen, hydroxy, carboxy and the like, ring A may be substituted with said R6 at any substitutable position(s), a is an integer of 0 to 7, ring B is substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic heterocyclyl, ring C is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, R1 is -Y-Z, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl and the like, R2 and R3 are each independently -Y-Z or hydrogen atom, provided that at least one of R1, R2, R3 and R4 is a group represented by formula: -Y-Z, Y is a bond, or a spacer of any combination selected from the group consisting of -O-, -S-, -NR7-, -C(=O)-, -SO-, -SO2-, -NR7-C(=O)-, -C(=O)-NR7-, -NR7-C(=O)-NR7-, -NR7-C(=O)-O-, -SO2-NR7-, -NR7-SO2-, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene, substituted or unsubstituted aromatic carbocyclediyl, substituted or unsubstituted non-aromatic carbocyclediyl, substituted or unsubstituted aromatic heterocyclediyl and substituted or unsubstituted non-aromatic heterocyclediyl, R7 are each independently hydrogen atom, hydroxy, carboxy and the like, and Z is substituted aromatic carbocyclyl, substituted non-aromatic carbocyclyl, substituted aromatic heterocyclyl or substituted non-aromatic heterocyclyl.

  本发明提供了用于 HIV 蛋白酶抑制剂的有用化合物。由式或其药学上可接受的盐代表的化合物 式： 其中环 A 是 R4为-Y-Z、氢原子、卤素、羟基等、 R5 是氢原子、卤素、羟基等、 R6 各自独立地为卤素、羟基、羧基等、 环 A 可在任何可取代的位置被所述 R6 取代、 a 是 0 至 7 的整数、 环 B 是取代或未取代的芳香族碳环，或取代或未取代的芳香族杂环、 环 C 是取代或未取代的芳香族碳环，取代或未取代的非芳香族碳环，取代或未取代的芳香族杂环，或取代或未取代的非芳香族杂环、 R1 是-Y-Z、取代或未取代的烷基、取代或未取代的烯基、取代或未取代的炔基等、 R2 和 R3 各自独立地为-Y-Z 或氢原子、 条件是 R1、R2、R3 和 R4 中至少有一个是由式表示的基团：-Y-Z、 Y 是键，或选自以下组别的任意组合的间隔物：-O-、-S-、-NR7-、-C(=O)-、-SO-、-SO2-、-NR7-C(=O)-、-C(=O)-NR7-、-NR7-C(=O)-NR7-、-NR7-C(=O)-O-、-SO2-、-NR7-SO2-、取代或未取代的亚烷基、取代或未取代的烯基、取代或未取代的炔基、取代或未取代的芳香族碳环基、取代或未取代的非芳香族碳环基、取代或未取代的芳香族杂环基和取代或未取代的非芳香族杂环基、 R7 各自独立地为氢原子、羟基、羧基等，以及 Z 是取代的芳香族碳环基、取代的非芳香族碳环基、取代的芳香族杂环基或取代的非芳香族杂环基。
• Synthesis and in vitro anti-proliferative effects of 3-(hetero)aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives on various cancer cell lines
  作者：Upendar Reddy Chamakura、E. Sailaja、Balakrishna Dulla、Arunasree M. Kalle、S. Bhavani、D. Rambabu、Ravikumar Kapavarapu、M.V. Basaveswara Rao、Manojit Pal

  DOI：10.1016/j.bmcl.2014.01.044

  日期：2014.3

  A series of 3-(hetero) aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives were designed as potential anticancer agents. These compounds were conveniently prepared by using Pd/C-Cu mediated Sonogashira type coupling as a key step. Many of these compounds were found to be promising when tested for their in vitro anti-proliferative properties against six cancer cell lines. All these compounds were found to be selective towards the growth inhibition of cancer cells with IC50 values in the range of 0.9-1.7 mu M (against MDA-MB 231 and MCF7 cells), comparable to the known anticancer drug doxorubicin. (C) 2014 Elsevier Ltd. All rights reserved.
• LONG-ACTING HIV PROTEASE INHIBITOR
  申请人：Shionogi & Co., Ltd.

  公开号：US20170253607A1

  公开（公告）日：2017-09-07

  The present invention provides useful compounds for HIV protease inhibitor. A compound represented by the following formula or its pharmaceutically acceptable salt: wherein ring A is R 4 is —Y—Z, hydrogen atom, halogen, hydroxy and the like, R 5 is hydrogen atom, halogen, hydroxy and the like, R 6 is each independently halogen, hydroxy, carboxy and the like, ring A may be substituted with said R 6 at any substitutable position(s), a is an integer of 0 to 7, ring B is substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic heterocyclyl, ring C is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, R 1 is —Y—Z, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl and the like, R 2 and R 3 are each independently —Y—Z or hydrogen atom, provided that at least one of R 1 , R 2 , R 3 and R 4 is a group represented by formula: —Y—Z, Y is a bond, or a spacer of any combination selected from the group consisting of —O—, —S—, —NR 7 —, —C(═O)—, —SO—, —SO 2 —, —NR 7 —C(═O)—, —C(═O)—NR 7 —, —NR 7 —C(═O)—NR 7 —, —O—C(═O)—NR 7 —, —NR 7 —C(═O)—O—, —SO 2 —NR 7 —, —NR 7 —SO 2 —, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene, substituted or unsubstituted aromatic carbocyclediyl, substituted or unsubstituted non-aromatic carbocyclediyl, substituted or unsubstituted aromatic heterocyclediyl and substituted or unsubstituted non-aromatic heterocyclediyl, R 7 are each independently hydrogen atom, hydroxy, carboxy and the like, and Z is substituted aromatic carbocyclyl, substituted non-aromatic carbocyclyl, substituted aromatic heterocyclyl or substituted non-aromatic heterocyclyl.