1-bromo-4-(3-methoxyphenoxy)butane | 6487-92-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-bromo-4-(3-methoxyphenoxy)butane
• 英文别名: 1-Brom-4-(3-methoxy-phenyloxy)-butan；4-(3-Methoxyphenoxy)butyl bromide；1-(4-bromobutoxy)-3-methoxybenzene
• CAS: 6487-92-9
• 化学式: C₁₁H₁₅BrO₂
• 分子量: 259.143
• InChiKey: HMIRHFRURCHFGW-UHFFFAOYSA-N

物化性质

• 沸点：
  334.1±22.0 °C(Predicted)
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 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-bromo-4-(3-methoxyphenoxy)butane 在 氢氧化钾 作用下， 以 二甲基亚砜 为溶剂， 反应 32.0h， 生成 5-(m-methoxyphenoxy)pentanoic acid
  参考文献：
  名称：

  Ghosh, Arindam; Bhattacharya, Sudin; Raychaudhuri, S. R., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1992, vol. 31, # 6, p. 299 - 309

  摘要：

  DOI：
• 作为产物：
  描述：

  4-(3-methoxy-phenoxy)-butyric acid 在 lithium aluminium tetrahydride 、 三溴化磷 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 反应 4.33h， 生成 1-bromo-4-(3-methoxyphenoxy)butane
  参考文献：
  名称：

  Ghosh, Arindam; Bhattacharya, Sudin; Raychaudhuri, S. R., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1992, vol. 31, # 6, p. 299 - 309

  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。
• Studies on Solubilization. (Part I). Note on the synthesis of some quaternary N-(?-aryloxyalkyl) piperidinium, pyridinium, benzyl-dimethyl-ammonium, and trimethyl-ammonium bromides
  作者：R. K. Joshi、L. Krasnec、I. Lacko

  DOI：10.1002/hlca.19710540111

  日期：——

  A series of new N-(ω-aryloxyalkyl) piperidinium, pyridinium, benzyl dimethyl ammonium, and trimethyl ammonium bromides is described.

  描述了一系列新的N-（ω-芳氧基烷基）哌啶，吡啶鎓，苄基二甲基铵和三甲基溴化铵。
• Synthesis of N-aryloxyalkylanabasine derivatives
  作者：N. M. Slyn’ko、L. E. Tatarova、M. M. Shakirov、E. E. Shul’ts

  DOI：10.1007/s10600-013-0585-1

  日期：2013.5

  N-Aryloxyalkylanabasine derivatives were prepared via the reaction of anabasine hydrochloride with various aryloxyhaloalkanes in the presence of potash in DMF. The reaction occurred with retention of the chiral center C-(2) of the piperidine group. Side products of bis(aryloxy)ethanes were characterized.

  N-芳氧烷基烟碱衍生物是通过在DMF中存在氢氧化钾的条件下，将烟碱盐酸盐与各种芳氧卤烷反应而制备的。反应中保留了哌啶基团的手性中心C-(2)。双(芳氧)乙烷的副产物得到了表征。
• Benzoic acid compounds and use thereof as medicaments
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：US05864039A1

  公开（公告）日：1999-01-26

  Benzoic acid compounds of the formula ##STR1## wherein each symbol is as defined in the specification, optical isomers thereof and pharmaceutically acceptable salts thereof; pharmaceutical composition comprising this compound and pharmaceutically acceptable additive; and serotonin 4 receptor agonists, gastrointestinal prokinetic agents and therapeutic agents for various gastrointestinal diseases, which comprise this compound as active ingredient. The compounds of the present invention have high and selective affinity for serotonin 4 receptor, and show agonistic effects thereon. Accordingly, they are useful medications for the prophylaxis and treatment of various gastrointestinal diseases, central nervous disorders, cardiac function disorders, urinary diseases, and the like, as well as useful anti-nociceptors for analgesic use which increase threshold of pain.

  本发明涉及苯甲酸化合物的配方##STR1##其中每个符号如规范中所定义，其光学异构体和药学上可接受的盐；包含该化合物和药学上可接受的添加剂的制药组合物；以及将该化合物作为活性成分的5-羟色胺4受体激动剂、胃肠动力药和用于各种胃肠疾病的治疗剂。本发明的化合物具有对5-羟色胺4受体的高选择性亲和力，并显示出激动作用。因此，它们是用于预防和治疗各种胃肠疾病、中枢神经紊乱、心脏功能紊乱、泌尿系统疾病等的有用药物，以及用于增加疼痛阈值的有用抗痛药。
• BENZOIC ACID COMPOUNDS AND MEDICINAL USE THEREOF
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0873990A1

  公开（公告）日：1998-10-28

  A benzoic acid compound of the formula wherein each symbol is as defined in the specification, an optical isomer thereof and a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising this compound and a pharmaceutically acceptable additive, a serotonin 4 receptor agonist comprising this compound as an active ingredient, a gastrointestinal prokinetic agent and a therapeutic agent for gastrointestinal diseases. The compound of the present invention shows selective and high affinity for serotonin 4 receptors, activates same, is useful as a pharmaceutical agent for the prophylaxis and treatment of gastrointestinal diseases (e.g., reflux esophagitis; gastroesophageal reflux such as that accompanying cystic fibrosis; Barrett syndrome; intestinal pseudoileus; acute or chronic gastritis; gastric or duodenal ulcer; Crohn's disease; non-ulcer dyspepsia; ulcerative colitis; postgastrectomy syndrome; postoperative digestive function failure; delayed gastric emptying caused by gastric neurosis, gastroptosis, diabetes, and the like; gastrointestinal disorders such as indigestion, meteorism, abdominal indefinite complaint, and the like; constipation such as atonic constipation, chronic constipation, and that caused by spinal cord injury, pelvic diaphragm failure and the like; and irritable bowel syndrome), central nervous disorders (e.g., schizophrenia, depression, anxiety, disturbance of memory and dementia), cardiac function disorders (e.g., cardiac failure and myocardial ischemia), urinary diseases (e.g., dysuria caused by urinary obstruction, ureterolith, prostatomegaly, spinal cord injury, pelvic diaphragm failure, etc.), and shows superior absorption.

  式中的苯甲酸化合物 其中各符号如说明书中所定义，其光学异构体及其药学上可接受的盐。由该化合物和药学上可接受的添加剂组成的药物组合物、以该化合物为活性成分的血清素 4 受体激动剂、胃肠促动力药和胃肠疾病治疗剂。 本发明的化合物对 5-羟色胺 4 受体具有选择性和高亲和力，能激活 5-羟色胺 4 受体，可用作预防和治疗胃肠道疾病（如反流性食管炎；反流性食管炎；反流性食管炎；反流性食管炎；反流性食管炎；反流性食管炎；反流性食管炎）的药物、反流性食管炎；胃食管反流，如伴随囊性纤维化的胃食管反流；巴雷特综合征；肠道假膜；急性或慢性胃炎；胃或十二指肠溃疡；克罗恩病；非溃疡性消化不良；溃疡性结肠炎；胃切除术后综合征；术后消化功能衰竭；胃神经官能症、胃下垂、糖尿病等引起的胃排空延迟；消化不良、陨石症、腹部不适等胃肠道疾病；失张性便秘、慢性便秘、脊髓损伤引起的便秘、骨盆膈肌功能衰竭等便秘；肠易激综合征）、中枢神经紊乱（如溃疡性结肠炎g.,精神分裂症、抑郁症、焦虑症、记忆障碍和痴呆症）、心脏功能紊乱（如心力衰竭和心肌缺血）、泌尿系统疾病（如尿路梗阻、输尿管结石、前列腺肥大、脊髓损伤、盆腔膈肌衰竭等引起的排尿困难），并显示出良好的吸收性。