(1H-indol-3-yl)-(1,3-thiazol-2-yl)methanone | 1588782-83-5

• 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: (1H-indol-3-yl)-(1,3-thiazol-2-yl)methanone
• 英文别名: 1H-indol-3-yl(1,3-thiazol-2-yl)methanone；(1H-indol-3-yl)(thiazol-2-yl)methanone；2-(1'H-indole-3'-carbonyl)thiazole；indothiazinone；indolyl thiazolyl ketone
• CAS: 1588782-83-5
• 化学式: C₁₂H₈N₂OS
• 分子量: 228.274
• InChiKey: DFYPIVYFSGGXGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1H-indol-3-yl)-(1,3-thiazol-2-yl)methanone 、 4-甲氧基氯苄 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到(1-(4-methoxybenzyl)-1H-indol-3-yl)(thiazol-2-yl)methanone
  参考文献：
  名称：

  Studies on the Synthesis of Indothiazinone and Its Derivatives via Direct 3-Acylation of Indole

  摘要：

  Indothiazinone is a natural 3-acylindole alkaloid, isolated from a culture of myxobacterial strain. It was found to possess antibacterial activity against yeast and filamentous fungi. Indothiazinone is also structurally related with a mammalian endogenous aryl hydrocarbon receptor ligand, (2-(1H-indole-3-carbonyl)thiazol-4-carboxylic acid methyl ester (ITE). In this article, the synthesis of indothiazinone has been disclosed for the first time. Key feature includes direct and selective 3-acylation of indole in the presence of Lewis acid. In addition, an efficient preparation of N-substituted indothiazinone derivatives has been demonstrated.

  DOI：

  10.1080/00397911.2015.1040513
• 作为产物：
  描述：

  吲哚 以 四氢呋喃 、 正己烷 为溶剂， 反应 25.0h， 生成 (1H-indol-3-yl)-(1,3-thiazol-2-yl)methanone
  参考文献：
  名称：

  通过常见的N-吲哚基三乙基硼酸酯从游离（NH）吲哚中集体合成3-乙酰基吲哚，吲哚-3-羧酸酯，吲哚-3-亚磺酸和3-（甲基磺酰基）吲哚

  摘要：

  据报道，通过常见的N-吲哚基三乙基硼酸酯中间体，可以利用容易获得的亲电子试剂（如酰氯，氯甲酸酯，亚硫酰氯和甲基磺酰氯）对游离（NH）吲哚进行一般和直接的C3功能化。反应在温和条件下平稳进行，收率高达93％。在C2，C4，C5，C6和C7位置带有取代基的吲哚具有良好的耐受性。各种重要的3-acylindoles，吲哚-3-羧酸酯，吲哚-3-亚磺酸和3-（甲基磺酰基）吲哚的易于获得证明了该方法的高度相容性和实用性。

  DOI：

  10.1021/acs.orglett.6b01970

文献信息

• [EN] 2-(1H-INDOLE-3-CARBONYL)-THIAZOLE-4-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS FOR THE TREATMENT OF E.G. ANGIOGENESIS IMPLICATED OR INFLAMMATORY DISORDERS<br/>[FR] DÉRIVÉS DE 2-(1H-INDOLE-3-CARBONYL)-THIAZOLE-4-CARBOXAMIDE ET COMPOSÉS CORRESPONDANTS UTILISÉS EN TANQUE QUE AGONISTES DU RÉCEPTEUR D'HYDROCARBURE ARYLE (AHR) UTILISÉS POUR LE TRAITEMENT DE, P.EX., DE L'ANGIOGENÈSE IMPLIQUÉE OU DE TROUBLES INFLAMMATOIRES
  申请人：IKENA ONCOLOGY INC

  公开号：WO2021127302A1

  公开（公告）日：2021-06-24

  2-(1H-lndole-3-carbonyl)-thiazole-4-carboxamide derivatives and the corresponding imidazole, oxazole and thiophene derivatives and related compounds as aryl hydrocarbon receptor (AHR) agonists for the treatment of angiogenesis implicated disorders, such as e.g. retinopathy, psoriasis, rheumatoid arthritis, obesity and cancer, or inflammatory disorders. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 27 to 32 and 59 to 219; examples 1 to 8; compounds 1-1 to 1-97; tables 1-a, 2 and 3).

  2-(1H-吲哚-3-甲酰基)-噻唑-4-羧酰胺衍生物及相应的咪唑、噁唑和噻吩衍生物以及相关化合物作为芳香烃受体（AHR）激动剂，用于治疗涉及血管生成的疾病，例如视网膜病变、银屑病、类风湿性关节炎、肥胖和癌症，或炎症性疾病。本说明书揭示了示例化合物的合成和表征以及其药理数据（例如第27至32页和59至219页；示例1至8；化合物1-1至1-97；表1-a、2和3）。
• [EN] EFFICIENT AND SCALABLE SYSTHESIS OF 2-(1'H-INDOLE-3'-CARBONYL)-THIAZOLE-4-CARBOXYLIC ACID METHYL ESTER AND ITS STRUCTURAL ANALOGS<br/>[FR] PROCÉDÉS DE SYNTHÈSE EFFICACES ET ADAPTABLES DE L'ESTER DE MÉTHYLE D'ACIDE 2-(1'H-INDOLE-3'-CARBONYL)-THIAZOLE-4-CARBOXYLIQUE ET DE SES ANALOGUES STRUCTURAUX
  申请人：AHR PHARMACEUTICALS INC

  公开号：WO2016040553A1

  公开（公告）日：2016-03-17

  Methods of synthesizing 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and structural analogs thereof. The methods include condensation reactions or condensation and oxidation reactions to form the thiazoline or thiazole moiety of ITE or its structural analogs.

  合成2-(1'H-吲哚-3'-甲酰基)-噻唑-4-羧酸甲酯（ITE）及其结构类似物的方法。这些方法包括缩合反应或缩合和氧化反应，以形成ITE或其结构类似物的噻唑啉或噻唑基团。
• Efficient and scalable synthesis of 2-(1′h-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester and its structural analogs
  申请人：ARIAGEN, INC.

  公开号：US10081610B2

  公开（公告）日：2018-09-25

  Methods of synthesizing 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) and structural analogs thereof. The methods include condensation reactions or condensation and oxidation reactions to form the thiazoline or thiazole moiety of ITE or its structural analogs.

  合成2-(1′H-吲哚-3′-羰基)-噻唑-4-羧酸甲酯(ITE)及其结构类似物的方法。这些方法包括缩合反应或缩合和氧化反应，以形成 ITE 或其结构类似物的噻唑啉或噻唑分子。
• Synthesis of indole thiazole compounds as ligands for the Ah receptor
  申请人：——

  公开号：US20040204588A1

  公开（公告）日：2004-10-14

  A method of synthesizing aromatic ketone compositions of formula I comprising the step of introducing a double bond into the 5 membered ring of the 4,5-dihydro-1,3-azoles moiety of formula II is disclosed. A method of synthesizing aromatic ketone compositions of formula I comprising the step of ring synthesis of the tetrahydro-1,3-azoles of formula XI is also disclosed.

  本发明公开了一种合成式 I 的芳香酮组合物的方法，该方法包括将双键引入式 II 的 4,5-二氢-1,3-唑分子的 5 位环的步骤。还公开了一种合成式 I 的芳香酮组合物的方法，包括式 XI 的四氢-1,3-唑的环合成步骤。
• Identification of indothiazinone as a natural antiplatelet agent
  作者：Chansik Yang、Sugyeong Kwon、Se-Jong Kim、Minseon Jeong、Ji-Young Park、Dongeun Park、Soon Jun Hong、Jong-Wha Jung、Chungho Kim

  DOI：10.1111/cbdd.13008

  日期：2017.11

  Cardiovascular disease, which is caused by unregulated platelet aggregation, is one of the main causes of deaths worldwide. Many studies have focused on natural products with antiplatelet effects as a safe alternative therapy to prevent the disease. In this context, an in‐house chemical library was screened to find natural products capable of inhibiting the interaction between platelet integrin αIIbβ3 and fibrinogen, which is an essential step in platelet aggregation. On the basis of the screening results, indothiazinone, an alkaloid found in microbial cultures, was identified as a potential antiplatelet agent. Specifically, indothiazinone treatment significantly inhibited the binding of fibrinogen to Chinese hamster ovary cells expressing integrin αIIbβ3. It also restricted thrombin‐ and adenosine diphosphate‐dependent spreading of human platelets on a fibrinogen matrix. More importantly, surface plasmon resonance and molecular dynamics studies suggested that indothiazinone suppressed talin‐induced activation of integrin αIIbβ3 presumably by inhibiting talin–integrin interaction. In conclusion, these results suggest that indothiazinone can be used as a lead compound for the development of antiplatelet drugs with a novel mode of action.