4-(benzyloxy)phenyl chloroformate | 52177-75-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(benzyloxy)phenyl chloroformate
• 英文别名: Kohlensaeure-4-benzyloxyphenylester-chlorid；4-(Benzyloxy)phenyl Carbonochloridate；(4-phenylmethoxyphenyl) carbonochloridate
• CAS: 52177-75-0
• 化学式: C₁₄H₁₁ClO₃
• 分子量: 262.693
• InChiKey: AJGFKMWQFMDKTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(benzyloxy)phenyl chloroformate 、 5-羟基色胺盐酸盐 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以39%的产率得到4-(benzyloxy)phenyl N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]carbamate
  参考文献：
  名称：

  New N-Arachidonoylserotonin Analogues with Potential “Dual” Mechanism of Action against Pain

  摘要：

  N-Arachidonoylserotonin (AA-5-HT, 1a) is an inhibitor of fatty acid amide hydrolase (FAAH) that acts also as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels and is analgesic in rodents. We modified the chemical structure of 1a with the aim of developing "hybrid" FAAH/TRPV1 blockers more potent than the parent compound or obtaining analogues with single activity at either of the two targets to study the mechanism of the analgesic action of 1a. Thirty-eight AA-5-HT analogues, containing a serotonin "head" bound to a variety of lipophilic moieties via amide, urea, or carbamate functionalities, were synthesized. Unlike 1a, most of the new compounds possessed activity at only one of the two considered targets. The amides 1b and 1c of alpha- and gamma-linolenic acid, however, showed "hybrid" activity similar to 1a. The carbarnate 3f (OMDM 106), although unable to antagonize TRPV1 receptors, was the most potent FAAH inhibitor in this study (IC50 = 0.5 mu M). Compounds 3f and 1m (OMDM129), which exhibited activity at only FAAH or TRPV1, respectively, were 10-fold less potent than 1a at preventing formal in-induced hyperalgesia in mice.

  DOI：

  10.1021/jm070678q
• 作为产物：
  描述：

  光气 、 4-苄氧基苯酚 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 4-(benzyloxy)phenyl chloroformate
  参考文献：
  名称：

  New N-Arachidonoylserotonin Analogues with Potential “Dual” Mechanism of Action against Pain

  摘要：

  N-Arachidonoylserotonin (AA-5-HT, 1a) is an inhibitor of fatty acid amide hydrolase (FAAH) that acts also as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels and is analgesic in rodents. We modified the chemical structure of 1a with the aim of developing "hybrid" FAAH/TRPV1 blockers more potent than the parent compound or obtaining analogues with single activity at either of the two targets to study the mechanism of the analgesic action of 1a. Thirty-eight AA-5-HT analogues, containing a serotonin "head" bound to a variety of lipophilic moieties via amide, urea, or carbamate functionalities, were synthesized. Unlike 1a, most of the new compounds possessed activity at only one of the two considered targets. The amides 1b and 1c of alpha- and gamma-linolenic acid, however, showed "hybrid" activity similar to 1a. The carbarnate 3f (OMDM 106), although unable to antagonize TRPV1 receptors, was the most potent FAAH inhibitor in this study (IC50 = 0.5 mu M). Compounds 3f and 1m (OMDM129), which exhibited activity at only FAAH or TRPV1, respectively, were 10-fold less potent than 1a at preventing formal in-induced hyperalgesia in mice.

  DOI：

  10.1021/jm070678q

文献信息

• Synthesis, structure determination, and biological evaluation of phenylsulfonyl hydrazide derivatives as potential anti-inflammatory agents
  作者：Eun Beul Park、Kwang Jong Kim、Hui Rak Jeong、Jae Kyun Lee、Hyoung Ja Kim、Hwi Ho Lee、Ji Woong Lim、Ji-Sun Shin、Andreas Koeberle、Oliver Werz、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2016.09.070

  日期：2016.11

  conditions, which favor either of two regioisomers. One regioisomer corresponds to a kinetic product (7a–7c) and the other regioisomer corresponds to a thermodynamic product (8a–8c). Among them, the structure of kinetic product 7b was confirmed by measuring single X-ray crystallography. In vitro PGE2 assay studies showed that the kinetic product (7a and 7b; IC50 = 0.69 and 0.55 μM against PGE2) is generally

  在我们先前的研究中，发现了一系列新的苯磺酰肼衍生物，它们通过抑制mPGES-1酶来降低RAW 264.7巨噬细胞中LPS诱导的PGE 2水平。最近，发现根据反应条件形成苯基磺酰肼的区域异构体混合物，其有利于两种区域异构体中的任一种。一个区域异构体对应于动力学乘积（7a – 7c），另一个区域异构体对应于热力学乘积（8a – 8c）。其中，通过测量单X射线晶体学证实了动力学产物7b的结构。体外PGE 2分析研究表明，动力学产物（7a和7b ; 通常， 对PGE 2的IC 50 = 0.69和0.55μM ）比对热力学乘积（8a和8b； 对PGE 2的IC 50 => 10和0.79μM ）更有效。分子对接研究还显示，动力学产物（7a）的MolDock分数（−147.4）比8a（−142.4）高，这与PGE 2分析结果一致。一种新的强苯基磺酰肼（7d ; 针对PGE 2的IC 50 = 0.0
• Discovery of N-amido-phenylsulfonamide derivatives as novel microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors
  作者：Misong Kim、Geuntae Kim、Minji Kang、Dohyeong Ko、Yunchan Nam、Chang Sang Moon、Heung Mo Kang、Ji-Sun Shin、Oliver Werz、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2021.127992

  日期：2021.6

  PGE2 (IC50: 0.24 μM) in A549 cells via inhibition of mPGES-1 (IC50: 0.49 μM in a cell-free assay) and was found to be approximately 9- and 8-fold more potent than MK-886 as a reference inhibitor, respectively. A molecular docking study theoretically suggests that MPO-0186 could inhibit PGE2 production by blocking the PGH2 binding site of mPGES-1 enzyme. Furthermore, MPO-0186 demonstrated good liver

  我们之前的研究表明，N-羧基-苯磺酰肼（支架 A）可以通过抑制 mPGES-1 酶来降低RAW 264.7 巨噬细胞中LPS 刺激的 PGE 2水平。然而，许多支架A衍生物显示出诸如形成区域异构体和肝脏代谢稳定性差等缺点。因此，为了克服这些合成和代谢问题，我们决定用N-羧基-苯磺酰胺（支架 B）或N-酰胺基-苯磺酰胺骨架（支架 C）代替N-羧基-苯磺酰肼（支架 A ）作为生物等排结构。替代品。其中，MPO-0186（支架C）抑制PGE 2 的产生(IC 50 : 0.24 μM) 在 A549 细胞中通过抑制 mPGES-1（IC 50 : 0.49 μM 在无细胞试验中）并且被发现比作为参考的MK-886 的效力高约 9 倍和 8 倍抑制剂，分别。一项分子对接研究从理论上表明MPO-0186可以通过阻断mPGES-1 酶的 PGH 2结合位点来抑制 PGE 2 的产生。此外，MPO-01
• Substituted acid derivatives useful as antidiabetic and antiobesity agents and method
  申请人：Cheng T. Peter

  公开号：US20070015797A1

  公开（公告）日：2007-01-18

  Compounds are provided which have the structure wherein Q is C or N, A is O or S, Z is O or a bond, X is CH or N and R 1 , R 2 , R 2a , R 2b , R 2c , R 3 , Y, x, m, and n are as defined herein, which compounds are useful as antidiabetic, hypolipidemic, and antiobesity agents.

  提供了一些化合物，它们的结构如下：其中Q为C或N，A为O或S，Z为O或键，X为CH或N，R1、R2、R2a、R2b、R2c、R3、Y、x、m和n如此定义，这些化合物可用作抗糖尿病、降脂和抗肥胖药物。
• Oxa-and thiazole derivatives useful as antidiabetic and antiobesity agents
  申请人：Bristol-Myers Squibb Company

  公开号：EP1939188A1

  公开（公告）日：2008-07-02

  Compounds are provided which have structure (I), wherein Q is C or N; A is O or S; Z is O or a bond; X is CH or N and R1, R2, R2a, R2b, R2c, R3 Y, x, m, and n are as defined herein, which compounds are useful as antidiabetic, hypolipidemic, and antiobesity agents.

  提供了具有结构（I）的化合物，其中 Q 是 C 或 N；A 是 O 或 S；Z 是 O 或键；X 是 CH 或 N，R1、R2、R2a、R2b、R2c、R3 Y、x、m 和 n 如本文所定义，这些化合物可用作抗糖尿病、降血脂和抗肥胖药物。
• Hit-to-lead optimization of phenylsulfonyl hydrazides for a potent suppressor of PGE2 production: Synthesis, biological activity, and molecular docking study
  作者：Minju Kim、Sunhoe Lee、Eun Beul Park、Kwang Jong Kim、Hwi Ho Lee、Ji-Sun Shin、Katrin Fischer、Andreas Koeberle、Oliver Werz、Kyung-Tae Lee、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2015.11.024

  日期：2016.1

  Preliminary hit-to-lead optimization of a novel series of phenylsulfonyl hydrazide derivatives, which were derived from the high throughput screening hit compound 1 (IC50 = 5700 nM against PGE(2) production), for a potent suppressor of PGE(2) production is described. Subsequent optimization led to the identification of the potent lead compound 8n with IC50 values of 4.5 and 6.9 nM, respectively, against LPS-induced PGE(2) production and NO production in RAW 264.7 macrophage cells. In addition, 8n was about 30- and > 150-fold more potent against mPGES-1 enzyme in a cell-free assay (IC50 = 70 nM) than MK-886 and hit compound 1, respectively. Molecular docking suggests that compound 8n could inhibit PGE2 production by blocking the PGH(2) binding site of human mPGES-1 enzyme. (C) 2015 Elsevier Ltd. All rights reserved.