(2,6-dichlorobenzyl)triphenylphosphonium bromide

• 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: (2,6-dichlorobenzyl)triphenylphosphonium bromide
• 英文别名: 1-(2',6'-bichlorobenzyl)triphenylphosphonium bromide；(2,6-dichlorobenzyl)(triphenyl)phosphonium bromide；(2,6-dichloro-benzyl)-triphenyl-phosphonium bromide；2,6-dichlorobenzyltriphenylphosphonium bromide；(2,6-dichlorophenyl)methyl-triphenylphosphanium;bromide
• 化学式: Br*C₂₅H₂₀Cl₂P
• 分子量: 502.218
• InChiKey: VYKODMIYQWCSBL-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.49
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2,6-dichlorobenzyl)triphenylphosphonium bromide 在 三乙胺 、 三氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以24%的产率得到[2,6-Dichlor-α-(dichlorphosphanyl)benzyliden]triphenylphosphoran
  参考文献：
  名称：

  Schmidpeter, Alfred; Noeth, Heinrich; Jochem, Georg, Chemische Berichte, 1995, vol. 128, # 4, p. 379 - 394

  摘要：

  DOI：
• 作为产物：
  描述：

  2,6-二氯甲苯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 苯 为溶剂， 反应 23.0h， 生成 (2,6-dichlorobenzyl)triphenylphosphonium bromide
  参考文献：
  名称：

  4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

  摘要：

  High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole- 1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.

  DOI：

  10.1021/jm0512591

文献信息

• [EN] (THIO)MORPHOLINE DERIVATIVES AS S1P MODULATORS<br/>[FR] DÉRIVÉS DE (THIO)MORPHOLINE MODULATEURS DE S1P
  申请人：ABBOTT HEALTHCARE PRODUCTS BV

  公开号：WO2011023795A1

  公开（公告）日：2011-03-03

  The present invention relates to (thio)morpholine derivatives of the formula (I), wherein R1 is selected from cyano, (2-4C)alkynyl, (1-4C)alkyl, (3-6C)cycloalkyl, (4-6C)cycloalkenyl, (6-8C)bicycloalkyl, (8-10C)bicyclic group, each optionally substituted with (1-4C)alkyl, phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, (1-4C)alkyloptionally substituted with one or more fluoro atoms, (2-4C)alkynyl, (1-4C)alkoxy optionally substituted with one or more fluoro atoms,amino, di(1-4C)alkylamino, -SO2-(1-4C)alkyl, -CO-(1-4C)alkyl, -CO-O-(1-4C)alkyl, -NH-CO-(1-4C)alkyl and (3-6C)cycloalkyl, phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl, monocyclic heterocycle optionally substituted with halogen, (1-4C)alkyl or with phenyl optionally substituted with (1-4C)alkyl, and bicyclic heterocycle optionally substituted with (1-4C)alkyl; A is selected from -CO-O-, -O-CO-, -NH-CO-, -CO-NH, -C=C-, -CCH3-O- and the linking group –Y-(CH2)n-X- wherein Y is attached to R1 and selected from a bond, -O-, -S-, -SO-, -SO2-, -CH2-O-, -CO-, -O-CO-, -CO-O-, -CO-NH-, -NH-CO-, -C=C-and -C≡C-; n is an integer from 1 to 10; and X is attached to the phenylene / pyridyl group and selected from a bond, -O-, -S-, -SO-, -SO2 -, -NH, -CO-, -C=C-and -C≡C-; ring structure B optionally contains one nitrogen atom; R2 is H, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, or halogen; and R3 is (1-4C)alkylene-R5 wherein the alkylene group may be substituted with (CH2)2 to form a cyclopropyl moiety or one or two halogen atoms, or R3 is is (3-6C)cycloalkylene-R5 or -CO-CH2-R5, wherein R5 is -OH, -PO3H2, -OPO3H2, -COOH, -COO(1-4C)alkyl or tetrazol-5-yl; R4 is H or (1-4C)alkyl; R6 is one or more substituents independently selected from H, (1-4C)alkyl or oxo; W is -O-, -S-, -SO- or -SO2-; or a pharmaceutically acceptable salt, a solvate or hydrate thereof; with the proviso that the derivative of formula (I) is not 2-(4-ethylphenyl)-4-morpholinoethanol or 4-[4-(2-hydroxyethyl)-2-morpholinyl]benzeneacetonitrile or a pharmaceutically acceptable salt, a solvate or hydrate thereof. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of S1P receptor mediated diseases and conditions.

  本发明涉及公式（I）的（硫）吗啉衍生物，其中R1从氰基，（2-4C）炔基，（1-4C）烷基，（3-6C）环烷基，（4-6C）环烯基，（6-8C）双环烷基，（8-10C）双环基团中选择，每个基团可选择地取代为（1-4C）烷基，苯基，联苯基，萘基，每个基团可选择地取代为一个或多个取代基，独立选择自卤素，（1-4C）烷基可选择地取代为一个或多个氟原子，（2-4C）炔基，（1-4C）氧烷基可选择地取代为一个或多个氟原子，氨基，二（1-4C）烷基氨基，-SO2-（1-4C）烷基，-CO-（1-4C）烷基，-CO-O-（1-4C）烷基，-NH-CO-（1-4C）烷基和（3-6C）环烷基，苯基取代为苯氧基，苄基，苄氧基，苯乙基或单环杂环烃，每个基团可选择地取代为（1-4C）烷基，单环杂环烃可选择地取代为卤素，（1-4C）烷基或取代为苯基的苯基，可选择地取代为（1-4C）烷基，和双环杂环烃可选择地取代为（1-4C）烷基；A从-CO-O-，-O-CO-，-NH-CO-，-CO-NH，-C=C-，-CCH3-O-和连接基-Y-（CH2）n-X-中选择，其中Y连接到R1并从键，-O-，-S-，-SO-，-SO2-，-CH2-O-，-CO-，-O-CO-，-CO-O-，-CO-NH-，-NH-CO-，-C=C-和-C≡C-中选择；n是1到10的整数；X连接到苯基/吡啶基团并从键，-O-，-S-，-SO-，-SO2-，-NH，-CO-，-C=C-和-C≡C-中选择；环结构B可选择地含有一个氮原子；R2是H，（1-4C）烷基可选择地取代为一个或多个氟原子，（1-4C）氧烷基可选择地取代为一个或多个氟原子，或卤素；R3是（1-4C）烷基-R5，其中烷基基团可取代为（CH2）2形成环丙基基团或一个或两个卤素原子，或R3是（3-6C）环烷基-R5或-CO-CH2-R5，其中R5是-OH，-PO3H2，-OPO3H2，-COOH，-COO（1-4C）烷基或四唑-5-基；R4是H或（1-4C）烷基；R6是一个或多个取代基，独立选择自H，（1-4C）烷基或氧代基；W是-O-，-S-，-SO-或-SO2-；或其药学上可接受的盐，溶剂或水合物；但是，公式（I）的衍生物不是2-（4-乙基苯基）-4-吗啉乙醇或4-[4-（2-羟乙基）-2-吗啉基]苯乙腈或其药学上可接受的盐，溶剂或水合物。本发明的化合物具有对S1P受体的亲和力，可用于治疗、缓解或预防S1P受体介导的疾病和症状。
• Compounds containing phenyl linked to aryl or heteroaryl by an
  申请人：Rhone-Poulenc Rorer Limited

  公开号：US05935978A1

  公开（公告）日：1999-08-10

  This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.

  这项发明涉及苯基化合物的药用，这些化合物通过各种连接与芳基团相连，用于抑制肿瘤坏死因子。该发明还涉及这些化合物、它们的制备以及含有这些化合物的药物组合物。此外，这项发明还涉及这些化合物的药用，用于抑制环磷酸腺苷磷酸二酯酶。
• A Novel Class of Orally Active Non-Peptide Bradykinin B₂ Receptor Antagonists. 1. Construction of the Basic Framework
  作者：Yoshito Abe、Hiroshi Kayakiri、Shigeki Satoh、Takayuki Inoue、Yuki Sawada、Keisuke Imai、Noriaki Inamura、Masayuki Asano、Chie Hatori、Akira Katayama、Teruo Oku、Hirokazu Tanaka

  DOI：10.1021/jm970591c

  日期：1998.2.1

  nanomolar IC50S and also displayed in vivo functional antagonistic activities against BK-induced bronchoconstriction in guinea pigs at an oral dose of 1 mg/kg. Pharmacokinetic studies of compounds 47c and 50b in rats highlighted their excellent oral bioavailabilities, indicating that they represent the first orally active non-peptide B2 antagonists reported to date.

  从8-苄氧基咪唑并[1,2-a]吡啶衍生物2开始，设计并合成了一类新型的有效，选择性和口服活性的非肽缓激肽（BK）B2受体拮抗剂。发现了独特的筛选前导物（2）。通过两步有意随机筛选过程，包括识别BK和血管紧张素II（Ang II）之间的关系以及常见的结构特征。2的系统化学修饰阐明了B2结合亲和力所必需的结构要求，从而导致鉴定了8-[[[3-（N-酰基甘氨酰基-N-甲基氨基）-2,6-二氯苄基]氧基] -3-卤代-2-甲基咪唑并[1,2-a]吡啶骨架作为该新系列B2拮抗剂的基本框架。分子建模研究表明，N-甲基苯胺部分在2的3位上起关键作用 6-二氯苯环允许这些化合物采用特征性的活性构象。代表性的先导化合物以纳摩尔IC50S抑制[3H] BK与表达B2受体的豚鼠回肠膜制剂的特异性结合，并且在口服剂量1 mg / ml时对豚鼠的BK诱导的支气管收缩表现出体内功能拮抗活性。公斤。化合物47c和50
• Solvolysis of 2-substituted-9-(<i>otrho</i>-substituted phenylmethyl)fluoren-9-yltrimethylammonium ions in various solvents. The effect of steric crowding on alkene formation
  作者：Peter James Smith、Jyotsna Pradhan

  DOI：10.1139/v86-178

  日期：1986.6.1

  The solvolytic reaction of several 9-(ortho-substituted phenylmethyl)fluoren-9-yltrimethylammonium salts has been investigated in several different solvents. Substitution and elimination products were found for the reactions in all the solvents studied, with the exceptions that reaction in both tert-butyl alcohol and chloroform led exclusively to the alkene product. The observed rate constants for alkene formation and the percent alkene were measured and it was found that the di-ortho compounds reacted at a faster rate but produced less alkene than the reaction of the corresponding mono-ortho salts. Hydrogen–deuterium isotope effects were also determined for the various reactions. The results are discussed in terms of the reaction proceeding by way of the E1 mechanism, where steric acceleration promotes the loss of the bulky ammonium leaving group to give the carbocation intermediate.

  本文研究了9-(邻取代苯甲基)芴-9-基三甲基铵盐在不同溶剂中的溶化解离反应。在所研究的所有溶剂中，除了在叔丁醇和氯仿中仅生成烯烃产物外，其他溶剂中均发现了取代和消除产物。测量了烯烃形成的观察速率常数和烯烃的百分比，发现二邻位化合物反应速率较快，但产生的烯烃比相应的单邻位盐少。还确定了各种反应的氢-氘同位素效应。结果讨论了反应通过E1机制进行，其中立体加速促进了庞大铵基团的丢失，从而形成碳正离子中间体。

• Compounds as PDE IV and TNF inhibitors
  申请人：Aventis Pharma Limited

  公开号：US06472412B1

  公开（公告）日：2002-10-29

  This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.

  该发明涉及一种用于抑制肿瘤坏死因子（TNF）的产生或生理效应的化合物，或其N-氧化物或药用可接受的盐，该化合物适用于治疗患有与生理上有害的肿瘤坏死因子（TNF）过剩相关的疾病状态的患者。本发明范围内的化合物还抑制环状AMP磷酸二酯酶，并且适用于治疗与通过抑制环状AMP磷酸二酯酶调节的病理条件相关的疾病状态，这些疾病状态包括炎症和自身免疫性疾病，特别是第四型环状AMP磷酸二酯酶。因此，本发明涉及它们在药理上用于抑制TNF和/或环状AMP磷酸二酯酶的用途，包括含有这些化合物的药理组合物和其制备方法。