zinc,1,2-dichloro-4-methanidylbenzene,chloride | 737797-18-1

• 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: zinc,1,2-dichloro-4-methanidylbenzene,chloride
• 英文别名: 3,4-dichlorobenzylzinc chloride；3,4-dichlorobenzyl zincate
• CAS: 737797-18-1
• 化学式: C₇H₅Cl₃Zn
• 分子量: 260.866
• InChiKey: UILWBECCBXORDA-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.73
• 重原子数：
  11.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  0.0
• 氢给体数：
  0.0
• 氢受体数：
  0.0

反应信息

• 作为反应物：
  描述：

  zinc,1,2-dichloro-4-methanidylbenzene,chloride 在 碘 、 三乙胺 、 锌 作用下， 以 N,N-二甲基乙酰胺 、 丙酮 为溶剂， 生成 3-(3,4-dichlorophenyl)-2-oxopropyl acetate
  参考文献：
  名称：

  2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H]quinoline-4-carboxylic Acid (PSI-697):  Identification of a Clinical Candidate from the Quinoline Salicylic Acid Series of P-Selectin Antagonists

  摘要：

  P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.

  DOI：

  10.1021/jm060631p
• 作为产物：
  描述：

  3,4-二氯氯苄 、 锌 在 三甲基氯硅烷 、 1,2-二溴乙烷 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 zinc,1,2-dichloro-4-methanidylbenzene,chloride
  参考文献：
  名称：

  A Study of Negishi Cross-Coupling Reactions with Benzylzinc Halides­ To Prepare Original 3-Ethoxypyrazoles

  摘要：

  The Negishi palladium-catalyzed cross-coupling reaction between 3-ethoxy-4-iodo-1H-pyrazole and various benzylzinc halides was extensively studied. Using simplified, robust, and optimized reaction conditions, a series of electron-poor benzylzinc halides were prepared and used to synthesize 4-benzyl-3-ethoxy-1H-pyrazoles derivatives. From these, iodination on C5 of the pyrazole nucleus led to the corresponding 4-benzyl-3-ethoxy-5-iodo-1H-pyrazoles, these are original building blocks for the preparation of libraries of new chemical entities.

  DOI：

  10.1055/s-0034-1379458

文献信息

• Methods and compositions for selectin inhibition
  申请人：Kaila Neelu

  公开号：US20050101569A1

  公开（公告）日：2005-05-12

  The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selectins. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula I: wherein the constituent variables are defined herein.

  本发明涉及抗炎物质领域，更特别地涉及作为哺乳动物粘附蛋白拮抗剂的新化合物。在某些实施例中，提供了治疗选择素介导疾病的方法，包括给予式I的化合物： 其中组分变量在此定义。
• [EN] BIARYL ACYL-SULFONAMIDE COMPOUNDS AS SODIUM CHANNEL INHIBITORS<br/>[FR] COMPOSÉS D'ACYLSULFONAMIDE DE BIARYLE EN TANT QU'INHIBITEURS DES CANAUX SODIQUES
  申请人：AMGEN INC

  公开号：WO2015051043A1

  公开（公告）日：2015-04-09

  The present invention provides compounds of Formula (Ia), and pharmaceutically acceptable salts thereof. The compounds are useful as inhibitors of voltage-gated sodium channels, in particular Nav 1.7. (Ia); as described in the specification. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention, as well as intermediates and processes useful for making the compounds.

  本发明提供了化合物(Ia)及其药用可接受的盐。这些化合物可用作电压门控钠通道的抑制剂，特别是Nav 1.7。（Ia）；如规范中所述。这些化合物可用于治疗通过抑制钠通道可治疗的疾病，如疼痛性疾病。还提供了含有本发明化合物的药物组合物，以及用于制备这些化合物的中间体和工艺。
• Structural Determination of NSC 670224, Synthesis of Analogues and Biological Evaluation
  作者：Nathaniel B. Zuckerman、Andrew S. Myers、Tiffani K. Quan、Walter M. Bray、R. Scott Lokey、Grant A. Hartzog、Joseph P. Konopelski

  DOI：10.1002/cmdc.201200038

  日期：2012.5

  Follow my lead! NSC 670224, previously shown to be toxic to Saccharomyces cerevisiae at low micromolar concentrations, potentially acts via a mechanism of action related to that of tamoxifen (NSC 180973), breast cancer drug. The structure of NSC 670224, previously thought to be a 2,4-dichloro arene, was established as the 3,4-dichloro arene, and a focused library of analogues were synthesized and biologically

  跟着我！NSC 670224 以前显示在低微摩尔浓度下对酿酒酵母有毒，可能通过与他莫昔芬 (NSC 180973)（乳腺癌药物）相关的作用机制起作用。NSC 670224 的结构（以前被认为是 2,4-二氯芳烃）被确定为 3,4-二氯芳烃，并合成了一个集中的类似物库并进行了生物学评估。
• Methods for synthesis of diarylmethanes
  申请人：Dana-Farber Cancer Institute

  公开号：US20040267011A1

  公开（公告）日：2004-12-30

  The present invention relates to dihydrofolate reductase inhibitors having an aromatic group and a heteroaromatic group linked by a methylene group; methods of preparation of dihydrofolate reductase inhibitors that include metal mediated cross coupling of an aromatic halide or heteroaromatic halide with an organozinc reagent; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such dihydrofolate reductase inhibitors.

  本发明涉及具有芳香基和杂环芳基的二氢叶酸还原酶抑制剂，它们由一个亚甲基连接；制备二氢叶酸还原酶抑制剂的方法包括通过金属介导的芳基卤化物或杂环芳基卤化物与有机锌试剂的交叉偶联；以及利用或包含其中一种或多种二氢叶酸还原酶抑制剂的治疗方法和制药组合物。
• HETEROARYLS AND USES THEREOF
  申请人：Freeze Brian S.

  公开号：US20120172345A1

  公开（公告）日：2012-07-05

  This invention provides compounds of formula IA-i-a or IB-i-a and subsets thereof: wherein Z, HY, R 1 , R 2 , R 3 , G 1 , W, n, and A and subsets thereof are as described in the specification. The compounds are inhibitors of PI3K and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

  本发明提供了式IA-i-a或IB-i-a及其子集的化合物:其中Z、HY、R1、R2、R3、G1、W、n和A及其子集如说明书所述。这些化合物是PI3K的抑制剂，因此可用于治疗增殖、炎症或心血管疾病。