1-(4-溴丁氧基)-4-苯氧基苯 | 119454-89-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(4-溴丁氧基)-4-苯氧基苯
• 英文名称: 1-bromo-4-(4-phenoxyphenoxy)butane
• 英文别名: 4-(4-bromobutoxy)-1-phenoxybenzene；1-(4-Bromobutoxy)-4-phenoxybenzene
• CAS: 119454-89-6
• 化学式: C₁₆H₁₇BrO₂
• mdl: MFCD12542320
• 分子量: 321.214
• InChiKey: TZWHGMOBHDECOQ-UHFFFAOYSA-N

物化性质

• 沸点：
  410.2±30.0 °C(Predicted)
• 密度：
  1.301±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-溴丁氧基)-4-苯氧基苯 在 sodium hydroxide 、 四丁基溴化铵 、 硫酸羟胺 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成
  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：
• 作为产物：
  描述：

  1,4-二溴丁烷 、 4-苯氧基苯酚 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 1-(4-溴丁氧基)-4-苯氧基苯
  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

• Design of PAP-1, a Selective Small Molecule Kv1.3 Blocker, for the Suppression of Effector Memory T Cells in Autoimmune Diseases
  作者：Alexander Schmitz、Ananthakrishnan Sankaranarayanan、Philippe Azam、Kristina Schmidt-Lassen、Daniel Homerick、Wolfram Hänsel、Heike Wulff

  DOI：10.1124/mol.105.015669

  日期：2005.11

  The lymphocyte K+ channel Kv1.3 constitutes an attractive pharmacological target for the selective suppression of terminally differentiated effector memory T (TEM) cells in T cell-mediated autoimmune diseases, such as multiple sclerosis and type 1 diabetes. Unfortunately, none of the existing small-molecule Kv1.3 blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3-(methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4 inhibit the cardiac K+ channel Kv1.5. By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern. The most potent and “drug-like” compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel. PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels. PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations. PAP-1 potently inhibits the proliferation of human TEM cells and suppresses delayed type hypersensitivity, a TEM cell-mediated reaction, in rats. PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators.

  淋巴细胞K+通道Kv1.3是选择性抑制T细胞介导的自身免疫性疾病（如多发性硬化症和1型糖尿病）中终末分化效应记忆T（TEM）细胞的有吸引力的药理学靶点。不幸的是，目前存在的所有小分子Kv1.3阻断剂均不具备选择性，其中许多如柯里奥利德、4-苯基-4-[3-(甲氧苯基)-3-酮-2-氮杂丙基]环己酮以及我们自己的化合物Psora-4均可抑制心脏K+通道Kv1.5。通过结合传统药物化学和全细胞膜片钳技术进一步探索Psora-4的构效关系，我们鉴定了一系列新的苯氧烷氧基补骨脂素，它们对Kv1.3的选择性比Kv1.5高2至50倍，具体取决于其取代模式。这一系列化合物中，最具有强效和“类药物”性质的化合物为5-(4-苯氧基丁氧基)补骨脂素（PAP-1），它以使用依赖性方式阻断Kv1.3，Hill系数为2，EC50为2 nM，通过优先结合通道的C型失活态。PAP-1对Kv1.5的选择性为23倍，对其他Kv1家族通道的选择性为33至125倍，对Kv2.1、Kv3.1、Kv3.2、Kv4.2、HERG、钙激活K+通道、Na+、Ca2+及Cl-通道的选择性为500至7000倍。PAP-1无细胞毒性或光毒性，Ames试验呈阴性，对细胞色素P450依赖性酶的影响仅在微摩尔浓度下显现。PAP-1能强效抑制人TEM细胞的增殖并抑制大鼠中的迟发型超敏反应（一种TEM细胞介导的反应）。因此，PAP-1及其若干衍生物构成了探索Kv1.3作为免疫抑制靶点的新工具，并有可能开发成口服可用的免疫调节剂。
• [EN] HETEROCYCLIC COMPOUNDS AS MODULATORS OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS, USEFUL FOR THE TREATMENT AND/OR PREVENTION OF DISORDERS MODULATED BY A PPAR<br/>[FR] COMPOSES HETEROCYCLIQUES UTILISES COMME MODULATEURS DES RECEPTEURS ACTIVES PROLIFERATEURS DU PEROXYSOME (PPAR), UTILES DANS LE TRAITEMENT ET/OU LA PREVENTION DE TROUBLES MODULES PAR UN PPAR
  申请人：LILLY CO ELI

  公开号：WO2005051945A1

  公开（公告）日：2005-06-09

  The present invention is directed to a compound of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate or stereoisomer thereof, which is useful in treating or preventing disorders mediated by a peroxisome proliferator activated receptor (PPAR) such as syndrome X, type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to syndrome X and cardiovascular diseases.

  本发明涉及一种式(I)的化合物，或其药学上可接受的盐、溶剂合物、水合物或立体异构体，该化合物在治疗或预防由过氧化物酶体增殖激活受体（PPAR）介导的疾病中具有用途，如X综合征、2型糖尿病、高血糖、高脂血症、肥胖、凝血障碍、高血压、动脉硬化以及与X综合征和心血管疾病相关的其他疾病。
• Modulators of peroxisome proliferator activated receptors (ppar)
  申请人：Gossett Stacy Lynn

  公开号：US20050075378A1

  公开（公告）日：2005-04-07

  The present invention is directed to a compound of formula I, and pharmaceutically acceptable salts, solvates, hydrates or stereoisomer thereof, which are useful in treating Syndrome X, Type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to Syndrome X as well as cardiovascular diseases.

  本发明涉及一种I式化合物，以及其药学上可接受的盐、溶剂、水合物或立体异构体，该化合物在治疗X综合征、2型糖尿病、高血糖、高脂血症、肥胖症、凝血障碍、高血压、动脉硬化以及与X综合征相关的其他疾病以及心血管疾病方面有用。
• Heterocyclic Compounds As Modulators Of Peroxisome Proliferator Activated Receptors, Useful For The Treatment And/Or Prevention Of Disorders Modulated By A Ppar
  申请人：Henry James Robert

  公开号：US20080207685A1

  公开（公告）日：2008-08-28

  The present invention is directed to a compound of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate or stereoisomer thereof, which is useful in treating or preventing disorders mediated by a peroxisome proliferator activated receptor (PPAR) such as syndrome X, type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to syndrome X and cardiovascular diseases.

  本发明涉及一种式为(I)的化合物，或其药学上可接受的盐、溶剂合物、水合物或立体异构体，该化合物用于治疗或预防由过氧化物酶体增殖激活受体（PPAR）介导的疾病，如X综合征、2型糖尿病、高血糖、高脂血症、肥胖症、凝血障碍、高血压、动脉硬化以及其他与X综合征和心血管疾病相关的疾病。
• MODULATORS OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS (PPAR)
  申请人：Gossett Lynn Stacy

  公开号：US20080167310A1

  公开（公告）日：2008-07-10

  The present invention is directed to a compound of formula I, and pharmaceutically acceptable salts, solvates, hydrates or stereoisomer thereof, which are useful in treating Syndrome X, Type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to Syndrome X as well as cardiovascular diseases.

  本发明涉及公式I的化合物及其药学上可接受的盐、溶剂化合物、水合物或立体异构体，其可用于治疗X综合症、II型糖尿病、高血糖、高血脂、肥胖症、凝血异常、高血压、动脉硬化以及与X综合症和心血管疾病有关的其他疾病。