3-(cycloheptyloxy)benzenamine | 76252-90-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(cycloheptyloxy)benzenamine
• 英文别名: 3-Cycloheptyloxyaniline
• CAS: 76252-90-9
• 化学式: C₁₃H₁₉NO
• 分子量: 205.3
• InChiKey: UXBLBAXQMJEFKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  氯乙基异氰酸酯 、 3-(cycloheptyloxy)benzenamine 以 二氯甲烷 为溶剂， 以81%的产率得到1-(2-chloroethyl)-3-(3-(cycloheptyloxy)phenyl)urea
  参考文献：
  名称：

  Cycloalkyl-substituted aryl chloroethylureas inhibiting cell cycle progression in G0/G1 phase and thioredoxin-1 nuclear translocation

  摘要：

  1-(2-Chloroethyl)-3-(4-cyclohexylphenyl) urea (cHCEU) has been shown to abrogate the presence of thioredoxin-1 into the nucleus through its selective covalent alkylation. In the present letter we have evaluated the structure-activity relationships of the substituents at positions 3 and 4 of the phenyl ring of cHCEU derivatives on cell cycle progression and thioredoxin-1 nuclear translocation. Active CEU derivatives exhibited GI(50) ranging from 1.9 to 49 mu M on breast carcinoma MCF-7, skin melanoma M21, and colon carcinoma HT-29 cells. On one hand, compounds 1, 2, 9c, 10c, 13, and 14 arrested the cell cycle in G(2)/M phase while CEUs 3, 4, 5c, 6c, 11c, and 12c blocked the cell division in G(0)/G(1) phase. On the other hand, CEUs 2-4, 5c, 7c, 8c, 11c, and 12c abrogated the translocation of thioredoxin-1 while the other CEU derivatives were inactive in that respect. Our results suggest that CEU substituted on the phenyl ring at position 3 or 4 by lower cycloalkyl or cycloalkoxy groups arrest cell progression in G(0)/G(1) phase through mechanism of action different from their antimicrotubule counterparts, presumably via thioredoxin-1 alkylation and modulation of its activity. The mechanism of action of these new molecules is still undetermined. However, the significant accumulation of cells in G(0)/G(1) phase suggests that these molecules may act similarly to known chemopreventive agents against cancers. In addition, the inhibition of Trx-1 nuclear localization also suggests the abrogation of an important chemoresistance mechanism towards a variety of chemotherapeutic agents. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.028
• 作为产物：
  描述：

  环庚醇 在 偶氮二甲酸二异丙酯 、 铁粉 、 氯化铵 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 24.0h， 生成 3-(cycloheptyloxy)benzenamine
  参考文献：
  名称：

  使用 DNA 编码的小分子文库筛选发现铜绿假单胞菌的 PqsE 硫酯酶抑制剂。

  摘要：

  铜绿假单胞菌是美国医院获得性感染的主要原因。PqsE 是一种硫酯酶，对铜绿假单胞菌的毒力至关重要，这使得 PqsE 成为一个有吸引力的抑制目标。PqsE 催化的底物和产物均未鉴定。筛选了一个包含 5.5 亿个 DNA 编码的药物样小分子的文库，以寻找那些与纯化的 PqsE 蛋白结合的小分子。通过连接的 DNA 条形码的高通量测序鉴定结合分子的结构。在体外检测了具有最强亲和力特征的假定 PqsE 结合剂对 PqsE 硫酯酶活性的抑制作用. 最有效的抑制剂从 DNA 中重新合成，并检查了改变 PqsE 热熔解和 PqsE 硫酯酶抑制的能力。在这里，我们报告了一系列非竞争性抑制 PqsE 的 2-(苯基氨基甲酰基)苯甲酸的合成、生物活性、作用机制和早期构效关系。设计用于探测初始结构-活性关系的一小组类似物显示出相对于原始命中物的效力增加，其中最好的具有 IC 50 = 5 μM。由于目前的化合物

  DOI：

  10.1021/acschembio.9b00905

文献信息

• Aromatic 2-chloroethyl urea derivatives and bioisosteres. Part 2: Cytocidal activity and effects on the nuclear translocation of thioredoxin-1, and the cell cycle progression
  作者：Jessica S. Fortin、Marie-France Côté、Jacques Lacroix、Éric Petitclerc、René C.-Gaudreault

  DOI：10.1016/j.bmc.2008.06.006

  日期：2008.8

  Recently, a subset of N-phenyl-N'-(2-chloroethyl) ureas (CEU) was found abrogating the nuclear translocation of thioredoxin-1 and arresting the cell cycle in G(0)/G(1) phase. Several derivatives were prepared to assess their effect on cell cycle progression and on the intracellular location of Trx-1. Compounds 1-20, 21-40, and 41-60 exhibited GI(50) between 1 and 80 mu M. Immunocytochemistry analysis showed compounds 4, 6, 8, 10, 11, 23, 24, 26-31, 34, 37, 41, 44, 46-51, 53, 56, and 57 inhibiting the nuclear translocation of Trx-1. Our results suggest that increasing the electrophilic character of these molecules might enhance the antiproliferative activity at the expense of the selectivity toward thioredoxin-1 and the G(0)/G(1) phase arrest. (C) 2008 Elsevier Ltd. All rights reserved.
• Cycloalkyl-substituted aryl chloroethylureas inhibiting cell cycle progression in G0/G1 phase and thioredoxin-1 nuclear translocation
  作者：Jessica S. Fortin、Marie-France Côté、Jacques Lacroix、Alexandre Patenaude、Éric Petitclerc、René C.-Gaudreault

  DOI：10.1016/j.bmcl.2008.05.028

  日期：2008.6

  1-(2-Chloroethyl)-3-(4-cyclohexylphenyl) urea (cHCEU) has been shown to abrogate the presence of thioredoxin-1 into the nucleus through its selective covalent alkylation. In the present letter we have evaluated the structure-activity relationships of the substituents at positions 3 and 4 of the phenyl ring of cHCEU derivatives on cell cycle progression and thioredoxin-1 nuclear translocation. Active CEU derivatives exhibited GI(50) ranging from 1.9 to 49 mu M on breast carcinoma MCF-7, skin melanoma M21, and colon carcinoma HT-29 cells. On one hand, compounds 1, 2, 9c, 10c, 13, and 14 arrested the cell cycle in G(2)/M phase while CEUs 3, 4, 5c, 6c, 11c, and 12c blocked the cell division in G(0)/G(1) phase. On the other hand, CEUs 2-4, 5c, 7c, 8c, 11c, and 12c abrogated the translocation of thioredoxin-1 while the other CEU derivatives were inactive in that respect. Our results suggest that CEU substituted on the phenyl ring at position 3 or 4 by lower cycloalkyl or cycloalkoxy groups arrest cell progression in G(0)/G(1) phase through mechanism of action different from their antimicrotubule counterparts, presumably via thioredoxin-1 alkylation and modulation of its activity. The mechanism of action of these new molecules is still undetermined. However, the significant accumulation of cells in G(0)/G(1) phase suggests that these molecules may act similarly to known chemopreventive agents against cancers. In addition, the inhibition of Trx-1 nuclear localization also suggests the abrogation of an important chemoresistance mechanism towards a variety of chemotherapeutic agents. (C) 2008 Elsevier Ltd. All rights reserved.
• Discovery of PqsE Thioesterase Inhibitors for <i>Pseudomonas aeruginosa</i> Using DNA-Encoded Small Molecule Library Screening
  作者：Julie S. Valastyan、Michael R. Tota、Isabelle R. Taylor、Vasiliki Stergioula、Graham A. B. Hone、Chari D. Smith、Brad R. Henke、Kenneth G. Carson、Bonnie L. Bassler

  DOI：10.1021/acschembio.9b00905

  日期：2020.2.21

  making PqsE an attractive target for inhibition. Neither the substrate nor the product of PqsE catalysis has been identified. A library of 550 million DNA-encoded drug-like small molecules was screened for those that bind to the purified PqsE protein. The structures of the bound molecules were identified by high throughput sequencing of the attached DNA barcodes. Putative PqsE binders with the strongest

  铜绿假单胞菌是美国医院获得性感染的主要原因。PqsE 是一种硫酯酶，对铜绿假单胞菌的毒力至关重要，这使得 PqsE 成为一个有吸引力的抑制目标。PqsE 催化的底物和产物均未鉴定。筛选了一个包含 5.5 亿个 DNA 编码的药物样小分子的文库，以寻找那些与纯化的 PqsE 蛋白结合的小分子。通过连接的 DNA 条形码的高通量测序鉴定结合分子的结构。在体外检测了具有最强亲和力特征的假定 PqsE 结合剂对 PqsE 硫酯酶活性的抑制作用. 最有效的抑制剂从 DNA 中重新合成，并检查了改变 PqsE 热熔解和 PqsE 硫酯酶抑制的能力。在这里，我们报告了一系列非竞争性抑制 PqsE 的 2-(苯基氨基甲酰基)苯甲酸的合成、生物活性、作用机制和早期构效关系。设计用于探测初始结构-活性关系的一小组类似物显示出相对于原始命中物的效力增加，其中最好的具有 IC 50 = 5 μM。由于目前的化合物