2-[4-(phenylmethyl)phenoxy]ethyl 4-methylbenzenesulfonate | 60225-65-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[4-(phenylmethyl)phenoxy]ethyl 4-methylbenzenesulfonate
• 英文别名: 2-(4-Benzylphenoxy)ethyl 4-methylbenzenesulfonate
• CAS: 60225-65-2
• 化学式: C₂₂H₂₂O₄S
• 分子量: 382.48
• InChiKey: AEJXDXPVSRAXJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-(phenylmethyl)phenoxy]ethyl 4-methylbenzenesulfonate 在 20percent Pd(OH)2/C 氢气 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0~80.0 ℃ 、413.7 kPa 条件下， 反应 40.0h， 生成 2-[2-(4-Benzyl-phenoxy)-ethyl]-2,5-diaza-bicyclo[2.2.1]heptane
  参考文献：
  名称：

  结构-活性关系研究1- [2-（4-苯基苯氧基）乙基]吡咯烷（SC-22716），白三烯A（4）（LTA（4））水解酶的有效抑制剂。

  摘要：

  白三烯B（4）（LTB（4））是促炎性介质，已与包括炎症性肠病（IBD）和牛皮癣在内的多种疾病的发病机制有关。由于LTA（4）水解酶的作用是LTB（4）生产的限速步骤，因此该酶代表了抑制LTB（4）生产的诱人药理学目标。通过内部筛选程序，SC-22716（1，1- [2-（4-苯基苯氧基）乙基]吡咯烷）被确定为LTA（4）水解酶的有效抑制剂。围绕此结构类别的结构活性关系（SAR）研究导致鉴定了许多新型的，有效的LTA（4）水解酶抑制剂，其中几种在小鼠离体全血试验中表现出良好的口服活性。

  DOI：

  10.1021/jm990496z
• 作为产物：
  描述：

  2-(4-苄基苯氧基)乙酸乙酯 在 lithium aluminium tetrahydride 作用下， 以 吡啶 、 乙醚 为溶剂， 生成 2-[4-(phenylmethyl)phenoxy]ethyl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Ohsumi, Tadashi; Hatakoshi, Makoto; Kisida, Hirosi, Agricultural and Biological Chemistry, 1985, vol. 49, # 11, p. 3197 - 3202

  摘要：

  DOI：

文献信息

• LTA4 Hydrolase inhibitors
  申请人：G.D. SEARLE & CO.

  公开号：EP1221441A2

  公开（公告）日：2002-07-10

  The present invention provides compounds of the formula Ar1-Q-Ar2-Y-R-Z and pharmaceutically acceptable salts thereof wherein Ar1 and Ar2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB4 production, such as proriasis, ulcerative colitis, IBD and asthma.

  本发明提供了具有公式Ar1-Q-Ar2-Y-R-Z的化合物及其药用可接受的盐，其中Ar1和Ar2是可选地取代的芳基部分，Z是可选地取代的含氮部分，可以是环状、环状或双环状的胺，或可选地取代的单环或双环的含氮杂芳基部分；Q是能够连接两个芳基团的连接基团；R是烷基亚基；Y是能够连接芳基团和烷基亚基的连接基团，并且其中Z通过氮原子与R键合。本发明的化合物和药物组合物在治疗由LTB4产生介导的炎症性疾病中是有用的，例如银屑病、溃疡性结肠炎、炎症性肠病和哮喘。
• Synthesis of Potent Leukotriene A₄ Hydrolase Inhibitors. Identification of 3-[Methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]propanoic Acid
  作者：Thomas D. Penning、Mark A. Russell、Barbara B. Chen、Helen Y. Chen、Chi-Dean Liang、Matthew W. Mahoney、James W. Malecha、Julie M. Miyashiro、Stella S. Yu、Leslie J. Askonas、James K. Gierse、Elizabeth I. Harding、Maureen K. Highkin、James F. Kachur、Suzanne H. Kim、Doreen Villani-Price、E. Yvonne Pyla、Nayereh S. Ghoreishi-Haack、Walter G. Smith

  DOI：10.1021/jm0200916

  日期：2002.8.1

  related to screening hit SC-22716 (1, 1-[2-(4-phenylphenoxy)ethyl]pyrrolidine) and resulted in the identification of potent, orally active inhibitors such as 2. Additional structure-activity relationship studies around this structural class resulted in the identification of a series of alpha-, beta-, and gamma-amino acid analogues that are potent inhibitors of the LTA(4) hydrolase enzyme and demonstrated

  白三烯B（4）（LTB（4））是一种强效的促炎介质，参与多种疾病的发病机理，包括炎症性肠病，牛皮癣，类风湿性关节炎和哮喘。LTA（4）水解酶代表了在这些疾病状态下进行药物干预的诱人靶标，因为该酶的作用是LTB（4）生产中的限速步骤。我们先前的工作重点是探索与筛选热门SC-22716（1，1- [2-（4-苯基苯氧基）乙基]吡咯烷）有关的一系列类似物，并确定了有效的口服活性抑制剂，例如2 。围绕该结构类别进行的其他结构-活性关系研究导致鉴定出一系列α-，β-，和γ-氨基酸类似物，它们是LTA（4）水解酶的有效抑制剂，在小鼠离体全血LTB（4）生产测定中显示出良好的口服活性。描述了导致鉴定临床候选SC-57461A（8d，3- [甲基[3- [4-（苯基甲基）苯氧基]丙基]氨基]丙酸的努力）。
• Pyrrolidine and piperidine analogues of SC-57461A as potent, orally active inhibitors of leukotriene A4 hydrolase
  作者：Thomas D Penning、Nizal S Chandrakumar、Bipin N Desai、Stevan W Djuric、Alan F Gasiecki、Chi-Dean Liang、Julie M Miyashiro、Mark A Russell、Leslie J Askonas、James K Gierse、Elizabeth I Harding、Maureen K Highkin、James F Kachur、Suzanne H Kim、Doreen Villani-Price、E.Yvonne Pyla、Nayereh S Ghoreishi-Haack、Walter G Smith

  DOI：10.1016/s0960-894x(02)00760-6

  日期：2002.12

  The synthesis and biological evaluation of a series of functionalized pyrrolidine- and piperidine-containing analogues of our lead LTA(4) hydrolase inhibitor, SC-57461A. is described. A number of compounds showed excellent potency in our in vitro screens and several demonstrated good oral activity in a mouse ex vivo assay. These efforts led to the identification of SC-56938 (14) as a potent. orally active inhibitor of LTA(4) hydrolase. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Structure−Activity Relationship of New Growth Inhibitors of <i>Trypanosoma</i> <i>cruzi</i>
  作者：Güendalina M. Cinque、Sergio H. Szajnman、Li Zhong、Roberto Docampo、Andrea J. Schvartzapel、Juan B. Rodriguez、Eduardo G. Gros

  DOI：10.1021/jm970860z

  日期：1998.4.1

  Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety replacing selected aromatic protons by different groups via electrophilic aromatic substitution reactions as well as introducing a sulfur atom at the polar extreme. Of the designed compounds, sulfur-containing derivatives were shown to be potent antireplicative agents against T. cruzi. Among these drugs, 4-phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC50 of 2.2 mu M. Under the same assay conditions, this drug was much more active than Nifurtimox, one of the drugs currently in clinical use to control this disease. This thiocyanate derivative was also a very active inhibitor against the intracellular form of the parasite at the nanomolar level. Other sulfur derivatives prepared also exhibited very potent antiproliferative action against T. cruzi. The presence of a sulfur atom at the polar extreme for this family of compounds seems to be very important for biological action because this atom was always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate presents very good prospective not only as a lead drug but also as a potential chemotherapeutic agent.
• Synthesis of Imidazopyridines and Purines as Potent Inhibitors of Leukotriene A4 Hydrolase
  作者：Thomas D Penning、Nizal S Chandrakumar、Bipin N Desai、Stevan W Djuric、Alan F Gasiecki、James W Malecha、Julie M Miyashiro、Mark A Russell、Leslie J Askonas、James K Gierse、Elizabeth I Harding、Maureen K Highkin、James F Kachur、Suzanne H Kim、Doreen Villani-Price、E.Yvonne Pyla、Nayereh S Ghoreishi-Haack、Walter G Smith

  DOI：10.1016/s0960-894x(03)00039-8

  日期：2003.3

  The synthesis and biological evaluation of a series of heterocyclic analogues of the previously reported LTA(4) hydrolase inhibitor 1b are described. Imidazopyridine and purine analogues are specifically highlighted with several demonstrating excellent potency in our in vitro assays, as well as good oral activity in a mouse ex vivo assay. (C) 2003 Elsevier Science Ltd. All rights reserved.