3,4-dichlorophenethyl methanesulfonate | 81156-65-2

• 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: 3,4-dichlorophenethyl methanesulfonate
• 英文别名: 2-(3,4-dichlorophenyl)ethyl methanesulfonate
• CAS: 81156-65-2
• 化学式: C₉H₁₀Cl₂O₃S
• 分子量: 269.149
• InChiKey: RPOJUXOCSVBANA-UHFFFAOYSA-N

物化性质

• 沸点：
  416.9±35.0 °C(Predicted)
• 密度：
  1.416±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-dichlorophenethyl methanesulfonate 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 溶剂黄146 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 98.0h， 生成 [(S)-1-{(R)-1-[({[2-(3,4-Dichloro-phenyl)-ethyl]-ethyl-carbamoyl}-methyl)-carbamoyl]-4-guanidino-butylcarbamoyl}-2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 2. Polar tri- and tetrapeptides

  摘要：

  The design, synthesis, and biological activity of a series of D-Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported. These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors. The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity. The peptides were all synthesized by classical solution methodology. The opioid activity of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents. That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests. As a class, the tetrapeptides were more potent than the tripeptides; N alpha-amidination generally increased activity. A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.

  DOI：

  10.1021/jm00125a028
• 作为产物：
  描述：

  3,4-二氯苯乙酸 在 硼烷四氢呋喃络合物 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 3,4-dichlorophenethyl methanesulfonate
  参考文献：
  名称：

  高亲和力西格玛受体配体的N-取代的顺式-N-甲基-2-（1-吡咯烷基）环己胺的合成与评价。鉴定出新型的高效和选择性sigma受体探针。

  摘要：

  最近报道某些苯乙酰胺[（-）-和（+）-顺-3,4-二氯-N-甲基-N- [2-（1-吡咯烷基）环己基]苯乙酰胺]是有效的σ受体配体。为了确定是否可以提高对sigma受体的功效，合成了一系列与苯乙酰胺有关的化合物N-取代的顺式-2-（1-吡咯烷基）-N-甲基环己胺，并确定了其结构活性的要求。通过从先前报道的（+/-）-，1S，2R-（+）-和1R，2S-（-）-顺-2-（1-吡咯烷基）-N-甲基环己胺开始合成化合物。σ（[3H]（+）-3-PPP），kappa（[3H] bremazocine和[3H] U69,593），多巴胺-d2（[3H]（-）-舒必利）和苯环利定（PCP）的分析（[3H] TCP）受体在豚鼠脑中的结合揭示了许多高效和选择性的sigma受体配体。值得注意的是，1S，2R-顺-（-）-N-甲基-N- [2-（1-吡咯烷基）环己基]-（2-萘基）乙酰胺[（-）-29]（Ki

  DOI：

  10.1021/jm00173a030

文献信息

• [EN] HETEROARYL RHEB INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE RHEB À BASE D'HÉTÉROARYLE ET LEURS UTILISATIONS
  申请人：NAVITOR PHARM INC

  公开号：WO2018191146A1

  公开（公告）日：2018-10-18

  The present invention provides compounds, compositions thereof, and methods of using the same. Compositions comprising a compound of this invention or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of the compound in compositions of this invention is such that it is effective to measurably inhibit Rheb, in a biological sample or in a patient.

  本发明提供了化合物、其组合物以及使用方法。包括本发明的化合物或其药学上可接受的衍生物与药学上可接受的载体、辅料或载体组成的组合物。本发明组合物中的化合物的量使其能够在生物样本或患者中明显抑制Rheb。
• [EN] TRICYCLIC NITROGEN CONTAINING COMPOUNDS AND THEIR USE AS ANTIBACTERIALS<br/>[FR] COMPOSÉS CONTENANT DE L'AZOTE TRICYCLIQUE ET UTILISATION DE CEUX-CI COMME ANTIBACTÉRIENS
  申请人：GLAXO GROUP LTD

  公开号：WO2009141399A1

  公开（公告）日：2009-11-26

  Compounds of Formula (I) or a pharmaceutically acceptable salt or N-oxide thereof; Formula (I) (relative stereochemistry shown) wherein: Z1, Z2 , L are as defined, U represents a cyclic group selected from: phenyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, furanyl, imidazolyl and thiophenyl; m is 0 or 1, n is independently 0 or 1; and substituent(s) R5 and R6 are independently selected from: halo, CF3, OCF3, C1_3 alkyl, C1_3 alkoxy, nitro and cyano. Compounds of Formula (I) have anti -tuberculosis and antibacterial activity.

  化合物的结构式（I）或其药学上可接受的盐或N-氧化物；结构式（I）（显示相对立体化学）其中：Z1、Z2、L如定义，U代表从中选择的环状基团：苯基、吡啶基、吡啶并嗪基、嘧啶基、吡嗪基、噻唑基、呋喃基、咪唑基和噻吩基；m为0或1，n独立为0或1；取代基R5和R6独立选择自：卤素、三氟甲基、三氟甲氧基、C1_3烷基、C1_3烷氧基、硝基和氰基。结构式（I）的化合物具有抗结核和抗菌活性。
• Design, Synthesis, and Biological Activity of Substrate Competitive SMYD2 Inhibitors
  作者：Scott D. Cowen、Daniel Russell、Leslie A. Dakin、Huawei Chen、Nicholas A. Larsen、Robert Godin、Scott Throner、Xiaolan Zheng、Audrey Molina、Jiaquan Wu、Tony Cheung、Tina Howard、Renee Garcia-Arenas、Nicholas Keen、Christopher S. Pendleton、Jennifer A. Pietenpol、Andrew D. Ferguson

  DOI：10.1021/acs.jmedchem.6b01303

  日期：2016.12.22

  methyltransferase that represses the functional activity of the tumor suppressor proteins p53 and RB. HTS screening led to identification of five distinct substrate-competitive chemical series. Determination of liganded crystal structures of SMYD2 contributed significantly to “hit-to-lead” design efforts, culminating in the creation of potent and selective inhibitors that were used to understand the functional

  蛋白质赖氨酸甲基转移酶（KMT）已成为表观遗传信号的重要调节剂。这些酶催化供体甲基从辅因子S-腺苷甲硫氨酸转移到组蛋白上的特定受体赖氨酸残基上，从而导致染色质结构和转录调控的改变。这些酶还使一系列非组蛋白蛋白甲基化，表明它们影响细胞生理的其他机制。据报道，SMYD2是一种致癌甲基转移酶，可抑制肿瘤抑制蛋白p53和RB的功能活性。HTS筛选导致鉴定出五个不同的底物竞争性化学系列。SMYD2配体晶体结构的确定显着有助于“铅中毒”设计工作，最终创造出了有效的和选择性的抑制剂，这些抑制剂用于了解SMYD2抑制的功能后果。综上所述，这些结果对于针对KMT的抑制剂设计具有广泛的意义，并清楚地证明了开发针对这些酶的新型疗法的潜力。
• [EN] BICYCLIC HETEROCYCLE DERIVATIVES AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS D'HÉTÉROCYCLES BICYCLIQUES COMME INHIBITEURS DE BROMODOMAINES
  申请人：ORION CORP

  公开号：WO2017001733A1

  公开（公告）日：2017-01-05

  The invention relates to novel bicyclic heterocycle derivatives of formula (I) wherein Cy1,Cy2, R1,R2 and L have the meaning given in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula (I) are usefulas bromodomain inhibitors in the treatment or prevention of diseases or disorders where bromodomain inhibition is desired.

  该发明涉及公式（I）的新型双环杂环衍生物，其中Cy1，Cy2，R1，R2和L的含义如规范中所述，并其药学上可接受的盐。公式（I）的化合物可用作溴结构域抑制剂，用于治疗或预防需要溴结构域抑制的疾病或紊乱。
• Synthesis and structure–activity relationship studies of LLY-507 analogues as SMYD2 inhibitors
  作者：Bin Zhang、Liping Liao、Fan Wu、Fengcai Zhang、Zhongya Sun、Haijun Chen、Cheng Luo

  DOI：10.1016/j.bmcl.2020.127598

  日期：2020.11

  potential target for cancer therapy, there are several SMYD2 inhibitors are reported, LLY-507 as a cell-active inhibitor exhibits submicromolar potency against SMYD2 in several cancer cell lines. To know which structural fragment of LLY-507 is suitable for chemical modification, three sites are chosen for structure–activity relationship studies (SARs). Among our focused library, compounds 43 and 44 with

  据报道，含有SET和MYND结构域的蛋白质2（SMYD2）是赖氨酸甲基转移酶，可催化组蛋白和非组蛋白蛋白质上赖氨酸残基的甲基化。作为癌症治疗的潜在靶标，有几种SMYD2抑制剂被报道，作为细胞活性抑制剂的LLY-507在几种癌细胞系中对SMYD2表现出亚微摩尔的效力。为了知道LLY-507的哪个结构片段适合化学修饰，选择了三个位点用于结构-活性关系研究（SAR）。在我们的重点文库中，化合物43和44 在位点C具有酰胺键的化合物显示了合理改善的效力，表明对该片段的修饰更加灵活，并且在该位置引入亲电子战斗部可能为SMYD2提供了靶向赖氨酸的共价抑制剂。