benzyl 1H-indole-5-carboxylate | 136564-69-7

• 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: benzyl 1H-indole-5-carboxylate
• 英文别名: benzyl indole-5-carboxylate
• CAS: 136564-69-7
• 化学式: C₁₆H₁₃NO₂
• mdl: MFCD13176765
• 分子量: 251.285
• InChiKey: TYHQDGAMZGNGCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.062
• 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：

  benzyl 1H-indole-5-carboxylate 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 methyl 4-<<5-carboxy-1-methylindol-3-yl>methyl>-3-methoxybenzoate
  参考文献：
  名称：

  Substituted 3-(phenylmethyl)-1H-indole-5-carboxamides and 1-(phenylmethyl)indole-6-carboxamides as potent, selective, orally active antagonists of the peptidoleukotrienes

  摘要：

  Substituted indole-5-carboxamides and indole-6-carboxamides have been found to be potent and selective antagonists of the peptidoleukotrienes. Initial derivatives of these series (4-[[5-[(cyclopentylmethyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl] benzamide (5a) and 4-[[6-[(cyclopentylmethyl)carbamoyl]-3-methylindol-1-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (6a), respectively), when compared to the corresponding indole amides (e.g. 28 and 29), were found to be approximately 10-fold less potent in vitro and substantially less active when administered orally to guinea pigs. Efforts to improve the potency of the title series by variation of the amide, indole, or sulfonamide substituents led to compounds of comparable in vitro potency to ICI 204,219, but of somewhat lower oral activity. A trend which suggested that more lipophilic transposed amides were needed to increase oral activity was exploited with some success and has led to the discovery of 5q (4-[[5-[(2-ethylbutyl)-carbamoyl]-1-ethylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide), a trans-posed amide with subnanomolar affinity for the leukotriene receptor and an oral ED50 of 5 mg/kg in a model of asthma in guinea pigs. In this model, ICI 204,219 was active at 0.4 mg/kg. The absolute bioavailability of 5q has been found to be 28% in the rat, as compared to 68% for ICI 204,219, with significant levels of 5q observed in the blood of rats up to 24 h postdose.

  DOI：

  10.1021/jm00055a011
• 作为产物：
  描述：

  吲哚-5-羧酸 、 氯化苄 在 calcium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 39.0h， 以85%的产率得到benzyl 1H-indole-5-carboxylate
  参考文献：
  名称：

  Cyanopyrrolidines useful for the treatment of inter alia metabolic syndrome

  摘要：

  公开号：

  EP1595866B1

文献信息

• 1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A₂α with Reduced Lipophilicity: Synthesis, Biological Activity, Metabolic Stability, Solubility, Bioavailability, And Topical in Vivo Activity
  作者：Andreas Drews、Stefanie Bovens、Kirsten Roebrock、Cord Sunderkötter、Dirk Reinhardt、Michael Schäfers、Andrea van der Velde、Alwine Schulze Elfringhoff、Jörg Fabian、Matthias Lehr

  DOI：10.1021/jm1001088

  日期：2010.7.22

  acids with 3-aryloxy-2-oxopropyl residues in position 1 were previously reported to be potent inhibitors of human cytosolic phospholipase A2α (cPLA2α). In continuation of our attempts to develop clinical active cPLA2α inhibitors, a series of structurally related indole-5-carboxylic acids with reduced lipophilicity was synthesized and tested for cPLA2α-inhibitory potency. Furthermore, the thermodynamic solubility

  在位置1 3-芳氧基-2-氧代丙基残基吲哚-5-羧酸先前报道为人类的有效抑制剂胞浆型磷脂酶甲2 α（与cPLA 2 α）。在我们试图开发临床活性与cPLA延续2 α抑制剂，具有降低的亲油性合成并用于与cPLA测试一系列结构上相关的吲哚-5-羧酸的2 α-抑制效力。此外，评估了这些化合物在大鼠肝微粒体中的热力学溶解度及其代谢稳定性。化合物36对分离的酶的IC 50为0.012μM ，是最有效的cPLA 2之一在结构活性关系研究期间出现的α抑制剂。同时，在所有新的目标化合物中，36的水溶性最高（在pH 7.4时为212μg/ mL）。尽管具有这些有利的特性，但在小鼠中口服施用36（100 mg / kg）仅会导致血浆中该物质的浓度降低。静脉注射36（10 mg / kg）后观察到非常高的血浆清除率。然而，在接触性皮炎的局部鼠模型中，36显示出明显的抗炎体内活性。
• Carbamoyl derivatives
  申请人：Imperial Chemical Industries PLC

  公开号：US05286740A1

  公开（公告）日：1994-02-15

  The present invention concerns novel carbamoyl derivatives of formula I, set out herein, which antagonize the pharmacological actions of one or more of the arachidonic acid metabolites known as leukotrienes, making them useful whenever such antagonism is desired, such as in the treatment of those diseases in which leukotrienes are implicated, for example, in the treatment of allergic or inflammatory diseases, or of endotoxic or traumatic shock conditions. The invention also provides pharmaceutical compositions containing the novel derivatives for use in such treatments, methods for their use and processes and intermediates for the manufacture of the novel derivatives.

  本发明涉及一种新的氨基甲酰衍生物，其化学式为I，该衍生物在此处列出，能拮抗被称为白三烯的花生四烯酸代谢产物的药理作用，使其在需要拮抗这种作用的情况下非常有用，例如在白三烯参与的疾病治疗中，例如在过敏性或炎症性疾病的治疗中，或在内毒素性或创伤性休克症状的治疗中。该发明还提供了含有这些新衍生物的药物组合物，用于进行这种治疗的方法，以及用于制造这些新衍生物的方法和中间体。
• Structure-Based Design of Dual Partial Peroxisome Proliferator-Activated Receptor γ Agonists/Soluble Epoxide Hydrolase Inhibitors
  作者：Felix F. Lillich、Sabine Willems、Xiaomin Ni、Whitney Kilu、Carmen Borkowsky、Mirko Brodsky、Jan S. Kramer、Steffen Brunst、Victor Hernandez-Olmos、Jan Heering、Simone Schierle、Roxane-I. Kestner、Franziska M. Mayser、Moritz Helmstädter、Tamara Göbel、Lilia Weizel、Dmitry Namgaladze、Astrid Kaiser、Dieter Steinhilber、Waltraud Pfeilschifter、Astrid S. Kahnt、Anna Proschak、Apirat Chaikuad、Stefan Knapp、Daniel Merk、Ewgenij Proschak

  DOI：10.1021/acs.jmedchem.1c01331

  日期：2021.12.9

  hydrolase (sEH) and peroxisome proliferator-activated receptor γ (PPARγ) synergistically counteracted MetS in various in vivo models, and dual sEH inhibitors/PPARγ agonists hold great potential to reduce the problems associated with polypharmacy in the context of MetS. However, full activation of PPARγ leads to fluid retention associated with edema and weight gain, while partial PPARγ agonists do not have

  多种药物方案通常会损害代谢综合征 (MetS) 患者的治疗，这是一种复杂的疾病集群，包括肥胖、高血压、心脏病和 II 型糖尿病。同时靶向可溶性环氧化物水解酶 (sEH) 和过氧化物酶体增殖物激活受体 γ (PPARγ) 在各种体内协同抵消 MetS模型和双重 sEH 抑制剂/PPARγ 激动剂在减少与多药治疗相关的问题方面具有巨大潜力。然而，完全激活 PPARγ 会导致与水肿和体重增加相关的液体潴留，而部分 PPARγ 激动剂则没有这些缺点。在这项研究中，我们使用结构引导的方法设计了一种双重部分 PPARγ 激动剂/sEH 抑制剂。详尽的结构-活性关系研究导致设计的引线成功优化。一种具有两个目标的代表性化合物的晶体结构揭示了潜在的优化点。优化后的化合物在脂肪细胞和巨噬细胞中表现出良好的代谢稳定性、毒性、选择性和理想的活性。
• [EN] INDOLYL- PYRIDONE DERIVATIVES HAVING CHECKPOINT KINASE 1 INHIBITORY ACTIVITY<br/>[FR] DÉRIVÉS D'INDOLYL-PYRIDONE
  申请人：VERNALIS R & D LTD

  公开号：WO2009093012A1

  公开（公告）日：2009-07-30

  Compounds of formula (I) have checkpoint kinase 1 (CHK1 ) inhibitory activity: wherein R1, R2, R5 and R6 are independently selected from hydrogen, hydroxy, methyl, trifluoromethyl, hydroxymethyl, methoxy, trifluoromethoxy, methylamino and dimethylamino; R3, and R4 are independently selected from hydrogen, hydroxy, C1-C3 alkyl, fluoro-(C1-C3)-alkyl, hydroxy-(C1C3)-alkyl, C1-C3 alkoxy, fluoro-(C1-C3)-alkoxy, hydroxy-(C1-C3)-alkoxy, -N(R11)-R12, -AIk-N(R11)-R12, -0-AIk-N(R11)-R12, -C(=O)OH, carboxy-(C1-C3)-alkyl, or -C(=O)-NH-R13; AIk is a straight or branched chain divalent C1-C6 alkylene radical; R7 and R8 are independently selected from hydrogen, hydroxy, or C1-C3 alkoxy; X is a straight chain divalent C1-C3 alkylene radical, optionally substituted on one or more carbons by R9 and/or R10; W is selected from -C(=O)-N(-R16)- or -N(-R17)-C(=O)-; Y is hydrogen, C1-C3 alkyl, C1-C3 alkoxy, or halo; and Q is selected from optionally substituted phenyl, optionally substituted cyclohexyl, or an optionally substituted 6-membered monocyclic heteroaryl ring.

  化合物的结构式（I）具有检查点激酶1（CHK1）抑制活性：其中R1、R2、R5和R6分别选自氢、羟基、甲基、三氟甲基、羟甲基、甲氧基、三氟甲氧基、甲基氨基和二甲基氨基；R3和R4分别选自氢、羟基、C1-C3烷基、氟代（C1-C3）-烷基、羟基（C1-C3）-烷基、C1-C3烷氧基、氟代（C1-C3）-烷氧基、羟基（C1-C3）-烷氧基、-N（R11）-R12、-AIk-N（R11）-R12、-O-AIk-N（R11）-R12、-C（=O）OH、羧基（C1-C3）-烷基或-C（=O）-NH-R13；AIk是直链或支链二价的C1-C6烷基基团；R7和R8分别选自氢、羟基或C1-C3烷氧基；X是直链二价的C1-C3烷基基团，可选地在一个或多个碳上由R9和/或R10取代；W选自-C（=O）-N（-R16）-或-N（-R17）-C（=O）-；Y为氢、C1-C3烷基、C1-C3烷氧基或卤素；Q选自可选取代的苯基、可选取代的环己基或可选取代的6-成员单环杂环芳基。
• Nickel-catalyzed alkoxycarbonylation of aryl iodides with 1 atm CO
  作者：Ning Liu、Xianqing Wu、Chenglong Wang、Jingping Qu、Yifeng Chen

  DOI：10.1039/d2cc00876a

  日期：——

  nickel-catalyzed alkoxycarbonylation of aromatic iodides with alcohols under atmospheric pressure of carbon monoxide is presented here. This operationally simple protocol allows the facile synthesis of (hetero)aromatic esters, exhibiting broad substrate scope with excellent functional group tolerance. Various primary and secondary aliphatic alcohols as well as phenols are suitable for this transformation

  本文介绍了在大气压的一氧化碳条件下，镍催化的芳香碘化物与醇的烷氧基羰基化反应。这种操作简单的协议允许轻松合成（杂）芳族酯，表现出广泛的底物范围和出色的官能团耐受性。各种伯和仲脂肪醇以及酚类都适用于这种转化。