ethyl 2-(5-nitro-1H-indol-1-yl)acetate | 226901-49-1

• 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: ethyl 2-(5-nitro-1H-indol-1-yl)acetate
• 英文别名: (5-Nitro-1H-indol-1-YL)-acetic acid ethyl ester；ethyl 2-(5-nitroindol-1-yl)acetate
• CAS: 226901-49-1
• 化学式: C₁₂H₁₂N₂O₄
• mdl: MFCD11543812
• 分子量: 248.238
• InChiKey: WZZYPIGFBQMUAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-(5-nitro-1H-indol-1-yl)acetate 在 calcium sulfate 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 50.0~60.0 ℃ 、101.33 kPa 条件下， 生成 (E,Z)-ethyl 3-(1-((ethoxycarbonyl)methyl)-1H-indol-5-ylamino)-3-phenylacrylate
  参考文献：
  名称：

  Novel 3-Substituted 7-Phenylpyrrolo[3,2-f]quinolin-9(6H)-ones as Single Entities with Multitarget Antiproliferative Activity

  摘要：

  A series of chemically modified 7-phenylpyrrolo[3,2-f]quinolinones was synthesized and evaluated as anticancer agents. Among them, the most cytotoxic (subnanomolar GI(50) values) amidic derivative 5f was shown to act as an inhibitor of tubulin polymerization (IC50, 0.99 mu M) by binding to the colchicine site with high affinity. Moreover, 5f induced cell cycle arrest in the G2/M phase of the cell cycle in a concentration dependent manner, followed by caspase-dependent apoptotic cell death. Compound 5f also showed lower toxicity in nontumoral cells, suggesting selectivity toward cancer cells. Additional experiments revealed that 5f inhibited the enzymatic activity of multiple kinases, including AURKA, FLT3, GSK3A, MAP3K, MEK, RSK2, RSK4, PLK4, ULK1, and JAK1. Computational studies showed that 5f can be properly accommodated in the colchicine binding site of tubulin as well as in the ATP binding clefts of all examined kinases. Our data indicate that the excellent antiproliferative profile of 5f may be derived from its interactions with multiple cellular targets.

  DOI：

  10.1021/acs.jmedchem.5b00805
• 作为产物：
  描述：

  5-硝基吲哚 、 溴乙酸乙酯 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以100 %的产率得到ethyl 2-(5-nitro-1H-indol-1-yl)acetate
  参考文献：
  名称：

  [EN] ANTAGONISTS OF 5-HYDROXYTRYPTAMINE RECEPTOR SUBTYPE 2B
  [FR] ANTAGONISTES DE RÉCEPTEURS 5-HYDROXYTRYPTAMINE DE SOUS-TYPE 2B

  摘要：

  Heteroaryl-substituted thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones are 5-HT2B receptor antagonists and the compounds and their pharmaceutical compositions are useful in the treatment of disorders such as pulmonary arterial hypertension, aortic valve disease, and myocardial infarction.

  公开号：

  WO2024036183A1

文献信息

• Substituted indoles and methods of their use
  申请人：Hu Baihua

  公开号：US20070043101A1

  公开（公告）日：2007-02-22

  The present invention relates generally to substituted indoles and methods of using them.

  本发明一般涉及替代吲哚化合物及其使用方法。
• Substituted Indoles And Methods Of Their Use
  申请人：HU Baihua

  公开号：US20100137363A1

  公开（公告）日：2010-06-03

  The present invention relates generally to substituted indoles and methods of using them.

  本发明涉及替代吲哚及其使用方法。
• [DE] SUBSTITUIERTE INDOLE MIT THROMBIN-HEMMENDER WIRKUNG<br/>[EN] SUBSTITUTED INDOLES, HAVING A THROMBIN INHIBITING EFFECT<br/>[FR] INDOLES SUBSTITUES AYANT UN EFFET INHIBITEUR DE LA THROMBINE
  申请人：BOEHRINGER INGELHEIM PHARMA KG

  公开号：WO1999028297A1

  公开（公告）日：1999-06-10

  (DE) Die vorliegende Erfindung betrifft neue substituierte Indole der allgemeinen Formel (I), in der Ra bis Rd wie im Anspruch 1 definiert sind, deren Tautomere, deren Stereoisomere, deren Gemische und deren Salze, welche wertvolle Eigenschaften aufweisen. So stellen die Verbindungen der obigen allgemeinen Formel (I), in denen Rb oder Rd eine Cyanophenylgruppe enthält, stellen wertvolle Zwischenprodukte zur Herstellung der übrigen Verbindungen der allgemeinen Formel (I) dar, und die Verbindungen der obigen allgemeinen Formel (I), in denen Rb oder Rd eine R1NH-C(=NH)-phenylgruppe enthält, sowie deren Tautomere und deren Stereoisomere weisen wertvolle pharmakologische Eigenschaften auf, insbesondere eine antitrombotische Wirkung, eine die Thrombinzeit verlängernde Wirkung und eine fibrinogenrezeptorantagonistische Wirkung.(EN) The invention relates to novel substituted indoles of general formula (I) in which Ra to Rd are defined as in claim 1. The tautomers, stereoisomers, mixtures and salts of Ra to Rd have valuable properties. The compounds of general formula (I) in which Rb or Rd contains a cyanophenyl group form valuable intermediate products in order to produce the remaining compounds of general formula (I), and the compounds of general formula (I) in which Rb or Rd contain a R1NH-C(=NH)-phenyl group in addition to the tautomers and stereoisomers thereof have valuable pharmacological properties, especially a thrombin inhibiting effect which extends the thrombin time and a fibrinogen receptor antagonistic effect.(FR) La présente invention concerne de nouveaux indoles substitués correspondant à la formule générale (I), dans laquelle les symboles Ra à Rd correspondent à la définition donnée dans la revendication 1, leurs tautomères, leurs stéréo-isomères, leurs mélanges et leurs sels, qui présentent des caractéristiques précieuses. Les composés correspondants à la formule générale (I) susmentionnée, dans laquelle Rb ou Rd contient un groupe cyanophényle, constituent des produits intermédiaires précieux pour la production des autres composés correspondants à ladite formule générale (I), et les composés correspondants à la formule générale (I) susmentionnée, dans laquelle Rb ou bien Rd comportent un groupe R1NH-C(=NH)-phényle ainsi que leurs tautomères et stéréo-isomères, présentent des caractéristiques pharmacologiques précieuses, en particulier un effet inhibiteur de la thrombine, un effet prolongeant le temps de thrombine et un effet antagoniste vis-à-vis des récepteurs du fibrinogène.

  本发明涉及一类新型的取代的茚类化合物，其一般式为(I)，其中Ra到Rd的定义为在权利要求1中所定义的。该类化合物的本体异构体、立体异构体、混合物及盐均具有优良特性。一般式(I)中若Rb或Rd含有苯环上的氰基基团的化合物，它们为合成式(I)中其他化合物的优良中间体;而对于一般式(I)中的Rb或Rd含有苯环上的-R1NH-C(=NH)-基团，或其本体异构体、立体异构体的化合物则具有优良药理特性，尤其是抗凝血效力，延迟血小板凝固时间，以及对抗 fibrinogen 受体的药理作用。
• Optimization of 1,3,4-Benzotriazepine-Based CCK₂ Antagonists to Obtain Potent, Orally Active Inhibitors of Gastrin-Mediated Gastric Acid Secretion
  作者：Iain M. McDonald、James W. Black、Ildiko M. Buck、David J. Dunstone、Eric P. Griffin、Elaine A. Harper、Robert A. D. Hull、S. Barret Kalindjian、Elliot J. Lilley、Ian D. Linney、Michael J. Pether、Sonia P. Roberts、Mark E. Shaxted、John Spencer、Katherine I. M. Steel、David A. Sykes、Martin K. Walker、Gillian F. Watt、Laurence Wright、Paul T. Wright、Wei Xun

  DOI：10.1021/jm070139l

  日期：2007.6.1

  Starting from a novel, achiral 1,3,4-benzotriazepine-based CCK2 receptor antagonist, a process of optimization has afforded further compounds of this type that maintain the nanomolar affinity for recombinant, human CCK2 receptors and high selectivity over CCK1 receptors observed in the initial lead but display more potent inhibition of pentagastrin-stimulated gastric acid secretion in vivo. Moreover, this has largely been achieved without altering their potency at wild-type canine and rat receptors, as judged by their displacement of [I-125]-BH-CCK-8S in a radioligand binding assay and by their activity in an isolated, perfused rat stomach bioassay, respectively. 2-(5-Cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-N-(3-(5-oxo-2,5-dihydro- [1,2,4]oxadiazol-3-yl)-phenyl)-acetamide (47) was identified as the most effective compound stemming from this approach, proving to be a potent inhibitor of pentagastrin-stimulated gastric acid secretion in rats and dogs by intravenous bolus as well as by enteral administration.
• US7683091B2
  申请人：——

  公开号：US7683091B2

  公开（公告）日：2010-03-23