2-(pyrrolidin-1-yl)ethoxyamine hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2-(pyrrolidin-1-yl)ethoxyamine hydrochloride
• 英文别名: 2-(pyrrolidino)ethoxyamine hydrochloride；2-(pyrrolidin-1-yl)ethoxyamine*HCl；O-(2-pyrrolidin-1-ylethyl)hydroxylamine;hydrochloride
• 化学式: C₆H₁₄N₂O*ClH
• 分子量: 166.651
• InChiKey: YYDLUHJSVFWLCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.39
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  氟哌啶醇 、 2-(pyrrolidin-1-yl)ethoxyamine hydrochloride 在 吡啶 作用下， 以 乙醇 为溶剂， 反应 32.0h， 以67.7%的产率得到4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-(2-pyrrolidin-1-ylethoxyimino)butyl]piperidin-4-ol
  参考文献：
  名称：

  Synthesis of some novel oxime ether derivatives and their activity in the ‘behavioral despair test’

  摘要：

  In this study, a new series of 2-aminoethyloxime ether derivatives of some aralkylketones was synthesized. Their structures have been elucidated by UV, IR, H-1-NMR, C-13-NMR, mass spectra and elementary analysis. These compounds were then screened for their inhibition of immobility as an indicator of possible antidepressant activities by using the 'behavioral despair test'. Results showed that all the new compounds decreased the immobility time, however, the inhibition observed with A03, A04 and H01 was significantly higher compared to fluvoxamine (p < 0.01). (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80038-x

文献信息

• Design, synthesis and biological evaluation of 4-aminopyrimidine-5-cabaldehyde oximes as dual inhibitors of c-Met and VEGFR-2
  作者：Hao Qiang、Weijie Gu、DanDan Huang、Wei Shi、Qianqian Qiu、Yuxuan Dai、Wenlong Huang、Hai Qian

  DOI：10.1016/j.bmc.2016.03.061

  日期：2016.8

  various human cancers. Therefore, inhibiting both HGF/c-Met and VEGF/VEGFR signaling may provide a novel and effective therapeutic approach for treating patients with abroad spectrum of tumors. Toward this goal, we designed and synthesized a series of derivatives bearing 4-aminopyrimidine-5-cabaldehyde oxime scaffold as potent dual inhibitors of c-Met and VEGFR-2. The cell proliferation assay in vitro

  c-Met / HGF和VEGFR-2 / VEGF的协同作用导致肿瘤血管生成的发展和各种人类癌症的进展。因此，同时抑制HGF / c-Met和VEGF / VEGFR信号传导可能为治疗国外肿瘤患者提供一种新颖有效的治疗方法。为了实现这个目标，我们设计并合成了一系列带有4-氨基嘧啶-5-多聚甲醛肟支架的衍生物，它们是c-Met和VEGFR-2的有效双重抑制剂。体外细胞增殖试验表明，大多数目标化合物对c-Met和VEGFR-2均具有抑制作用，IC 50值在纳摩尔范围内，尤其是化合物14i，18a和18b。根据进一步的体外酶分析，化合物18a被认为是最有效的化合物，其c-Met和VEGFR-2的IC 50分别为210 nM和170 nM。之后，我们将化合物10和18a与c-Met和VEGFR-2蛋白对接，并解释了这些类似物的SAR。所有结果表明，18a是c-Met和VEGFR-2的双重抑制剂，具有广阔的发展前景。
• Synthesis and Antiproliferative Evaluation of Certain Indeno[1,2-<i>c</i>]quinoline Derivatives. Part 2
  作者：Chih-Hua Tseng、Cherng-Chyi Tzeng、Chiao-Li Yang、Pei-Jung Lu、Hui-Ling Chen、Hao-Yi Li、You-Chung Chuang、Chia-Ning Yang、Yeh-Long Chen

  DOI：10.1021/jm1005447

  日期：2010.8.26

  activities has been observed for indeno[1,2-c]quinoline derivatives; (5) compound 8c induced DNA fragmentation may through caspase-3 activation, phosphorylation of the histone protein H2AX at Ser139 (γ-H2AX), and PARP cleavage; (6) compound 8c demonstrated significant tumor regression in the human breast xenograft model; (7) indeno[1,2-c]quinoline derivatives are a new class of molecules that have the

  合成了某些茚并[1,2- c ]喹啉衍生物，并对其抗增殖，DNA结合亲和力和拓扑异构酶（拓扑I和拓扑II）抑制活性进行了评估。初步结果如下：（1）在C 11的氨基烷氧基亚氨基侧链的取代基对于其中端胺优选为叔或环状五元吡咯烷基环的抗增殖活性是重要的；（2）在所评估的茚并[1,2- c ]喹啉衍生物中，（E）-6-羟基-9-甲氧基-11 H-茚并[1,2 - c ]喹啉-11-one O -2-（吡咯烷-1-基）乙基肟（8c）被发现是最具细胞毒性的药物之一，对SAS，A549和BT483的GI 50值分别为0.84、0.89和0.79μM，比喜树碱更具活性; （3）C 6上的取代基对于选择性细胞毒性至关重要，其中最优选OH基，而氢或哌嗪对癌细胞和底特律551均具有细胞毒性。（4）已观察到茚并[1,2- c ]喹啉衍生物的抗增殖活性，DNA结合亲和力和topo I和topo II抑制活性呈正相关
• 4-ANILINOFURO[2,3-B]QUINOLINE DERIVATIVES, THEIR PREPARATION PROCESSES, AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
  申请人：Tzeng Cherng-Chyi

  公开号：US20130172336A1

  公开（公告）日：2013-07-04

  Disclosed herein are novel 4-anilinofuro[2,3-b]quinoline derivatives of formula (I): or a pharmaceutically acceptable salt thereof, wherein each of the substituents is given the definition as set forth in the Specification and Claims. Also disclosed are the preparation processes of these derivatives and their uses in the manufacture of pharmaceutical compositions and in the treatment of cancers.

  本文披露了新型的4-苯胺基呋喃[2,3-b]喹啉衍生物，其化学式为(I):或其药学上可接受的盐，其中每个取代基的定义如规范和权利要求中所述。还披露了这些衍生物的制备过程以及它们在制造药物组合物和治疗癌症方面的用途。
• Synthesis and biological study of 4-aminopyrimidine-5-carboxaldehyde oximes as antiproliferative VEGFR-2 inhibitors
  作者：Shenlin Huang、Ronghua Li、Peter J. Connolly、Guozhang Xu、Michael D. Gaul、Stuart L. Emanuel、Kenneth R. LaMontagne、Lee M. Greenberger

  DOI：10.1016/j.bmcl.2006.08.107

  日期：2006.12

  A novel 4-aminopyrimidine-5-carboxaldehyde oxime scaffold with inhibitory activity against VEGFR-2 kinase has been identified. With a 4-fluoro-2-methylindol-5-yloxy group at the 6-position and alkyl groups as the oxime side chains, many analogues showed good potency for VEGFR-2. This series also exhibited antiproliferative activity against cancer cells, causing cell accumulation at the G2/M phase of the cell cycle and preventing cells from entering mitosis. Described here are the chemistry, structure-activity relationships (SAR), and biological testing for this series.
• Discovery of indeno[1,2- b ]quinoxaline derivatives as potential anticancer agents
  作者：Chih-Hua Tseng、You-Ren Chen、Cherng-Chyi Tzeng、Wangta Liu、Chon-Kit Chou、Chien-Chih Chiu、Yeh-Long Chen

  DOI：10.1016/j.ejmech.2015.11.031

  日期：2016.1

  We have synthesized certain indeno[1,2-b]quinoxaline derivatives for antiproliferative evaluation. Among them, 11-[3-(dimethylamino)propoxy]imino}-N-[3-(dimethylamino) propyl]-11H-indeno(1,2-b] quinoxaline-6-carboxamide (10a) was active against the growth of MDA-MB231, PC-3, and Huh-7 with IC50 values of 0.87 (selectivity index, SI = 36.22), 0.82 (SI = 38.43), and 0.64 mu M (SI = 49.23) respectively. Compound 10a was inactive against the growth of normal human fetal lung fibroblast cell line (MRC-5) with an IC50 value of 31.51 mu M. Its analogs, 10b and 10c, were also active against the growth of MB231, PC-3, and Huh-7 with IC50 values of <1.0.mu M in each case. Our results have also indicated compounds 10a-10c exhibited comparable inhibitory activities against topo I and topo II with the positive compound 2 at a concentration of 10 mu M. Mechanism studies indicated that compound 10a induced cell cycle arrest at S phase via activation of caspase-3, -7 and an increase in the protein expression of Bad and Bax but a decrease in expression of Bcl-2 and PARP, which consequently cause cell death. In addition, compound 10a attenuated the levels of phosphorylated Src, Akt-1, and Akt-2 protein levels but did not affect the total protein expression of Akt. We have also implanted human hepatocellular carcinoma cells into the yolk sac of zebrafish larvae and incubated larvae with various concentrations of 10a. Our results of the zebrafish xenograft assay confirmed the anti-tumor effect of 10a in vivo. (C) 2015 Elsevier Masson SAS. All rights reserved.