tert-butyl (4-{2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamido}butyl)carbamate | 960215-52-5

• 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: tert-butyl (4-{2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamido}butyl)carbamate
• 英文别名: tert-butyl N-[4-[[2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetyl]amino]butyl]carbamate
• CAS: 960215-52-5
• 化学式: C₂₈H₃₄ClN₃O₅
• 分子量: 528.048
• InChiKey: PIILKAZOCQCXFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-{2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamido}butyl)carbamate 在 盐酸 、 氨 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  CONJUGATES DERIVED FROM NON-STEROIDAL ANTI-INFLAMMATORY DRUGS AND METHODS OF USE THEREOF IN IMAGING

  摘要：

  披露了来自非甾体抗炎药（NSAIDs）的衍生物及其使用方法，这对于识别和定位患者疼痛感觉的病理和/或炎症部位；识别原发、继发、良性或恶性肿瘤的部位；以及诊断感染或确认或排除疑似感染非常有用。基于NSAID的偶联物含有成像基团。这些偶联物在环氧化酶表达增加的部位富集，从而揭示了前列腺素产生增加的部位，这与疼痛和炎症有关，并与肿瘤存在和/或位置有关。识别COX表达增加的区域也有助于筛查感染。

  公开号：

  US20150374858A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 tert-butyl (4-{2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamido}butyl)carbamate
  参考文献：
  名称：

  基于异恶唑的脚手架抑制剂靶向环氧化酶（COX）

  摘要：

  探索了一套具有附加功能的新的环氧合酶（COX）抑制剂。这些新化合物还包含若丹明6G或6,7-二甲氧基-1,2,3,4-四氢异喹啉，分别是外排泵底物和抑制剂的两个典型部分。在所有合成的化合物中，发现了两种具有相反选择性的新型COX抑制剂：化合物8 [ N-（9- {2-[（4-{2- [3-（5-氯呋喃-2-基）-4-苯基异恶唑-5-基]乙酰胺基}丁基]氨基甲酰基]苯基-6-（乙基氨基）-2,7-二甲基-3 H-黄嘌呤-3-亚基}乙氯化铵]被发现是一种选择性的COX-1抑制剂，而17（2- [3,4-双（4-甲氧基苯基）异恶唑-5-基] -1- [6,7-二甲氧基-3,4-二氢异喹啉-2-（1 H）-基]乙酮）被发现是亚微摩尔选择性COX-2抑制剂。但是，两者均显示与P-糖蛋白相互作用。对接实验有助于阐明观察到的COX选择性的分子方面。

  DOI：

  10.1002/cmdc.201500439

文献信息

• Methods and compositions for diagnostic and therapeutic targeting of COX-2
  申请人：Marnett J. Lawrence

  公开号：US20070292352A1

  公开（公告）日：2007-12-20

  The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

  目前公开的主题提供了选择性结合环氧合酶-2并包含治疗和/或诊断基团的组合物。还提供了使用公开的组合物进行诊断（即通过成像）目标细胞和/或治疗与环氧合酶-2生物活性相关的疾病的方法。
• 이종 종양을 표적화하기 위한 항암 약물전구체
  申请人：고려대학교 산학협력단

  公开号：KR20220034439A

  公开（公告）日：2022-03-18

  본 발명은 하기 [화학식 1]로 표시되는 화합물을 포함하는 항암 약물전구체에 관한 것이다: [화학식 1] .

  这项发明涉及包含以下化学式1所示的化合物的抗癌药物前体：[化学式1]。
• Podophyllotoxin analogues active versus Trypanosoma brucei
  作者：Md. Jashim Uddin、David C. Smithson、Kristin M. Brown、Brenda C. Crews、Michele Connelly、Fangyi Zhu、Lawrence J. Marnett、R. Kiplin Guy

  DOI：10.1016/j.bmcl.2010.01.009

  日期：2010.3

  In an effort to discover novel anti-trypanosomal compounds, a series of podophyllotoxin analogues coupled to non-steroidal anti-inflammatory drugs (NSAIDs) has been synthesized and evaluated for activity versus Trypanosoma brucei and a panel of human cell lines, revealing compounds with low nano-molar potencies. It was discovered that coupling of NSAIDs to podophyllotoxin increased the potencies of both compounds over 1300-fold. The compounds were shown to be cytostatic in nature and seem to act via de-polymerization of tubulin in a manner consistent with the known activities of podophyllotoxin. The potencies against T. brucei correlated directly with Log P values of the compounds, suggesting that the conjugates are acting as hydrophobic tags allowing podophyllotoxin to enter the cell. (C) 2010 Elsevier Ltd. All rights reserved.
• Targeting Heterogeneous Tumors Using a Multifunctional Molecular Prodrug
  作者：Amit Sharma、Min-Goo Lee、Miae Won、Seyoung Koo、Jonathan F. Arambula、Jonathan L. Sessler、Sung-Gil Chi、Jong Seung Kim

  DOI：10.1021/jacs.9b07171

  日期：2019.10.2

  Reported here is a molecular construct (K1) designed to overcome hurdles associated with delivering active drugs to heterogeneous tumor environments. Construct K1 relies on two cancer environment triggers (GSH and H2O2) to induce prodrug activation. It releases an active drug form (SN-38) under conditions of both oxidative and reductive stress in vitro. Specific uptake of K1 in COX-2 positive aggressive colon cancer cells (SW620 and LoVo) was seen, along with enhanced anticancer activity compared with the control agent SN-38. These findings are attributed to environmentally triggered drug release, as well as simultaneous scavenging of species giving rise to intracellular redox stress. K1 serves to downregulate various cancer survival signaling pathways (AKT, p38, IL-6, VEGF, and TNF-alpha) and upregulate an anti-inflammatory response (IL-10). Compared with SN-38 and DMSO as controls, K1 also displayed an improved in vivo therapeutic efficacy in a xenograft tumor regrowth model with no noticeable systematic toxicity at the administrated dose. We believe that the strategy described here presents an attractive approach to addressing solid tumors characterized by intratumoral heterogeneity.
• US9850183B2
  申请人：——

  公开号：US9850183B2

  公开（公告）日：2017-12-26