1-(溴甲基)-2-乙基苯 | 57825-29-3

• 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-(溴甲基)-2-乙基苯
• 英文名称: 1-(bromomethyl)-2-ethylbenzene
• 英文别名: 2-ethylbenzyl bromide
• CAS: 57825-29-3
• 化学式: C₉H₁₁Br
• mdl: MFCD12024947
• 分子量: 199.09
• InChiKey: MLOYGHJCLXLZTL-UHFFFAOYSA-N

物化性质

• 沸点：
  120-121 °C(Press: 28 Torr)
• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  1-(溴甲基)-2-乙基苯 在 降冰片烯 、 双(乙腈)氯化钯(II) 、 sodium hydride 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 32.5h， 生成 2-(2-ethylbenzyl)-N-(4-(ethylsulfonyl)benzyl)-1-isopropyl-1H-indole-5-carboxamide
  参考文献：
  名称：

  发现 2-（邻位取代苄基）-吲哚衍生物作为具有抗肿瘤活性的强效口服生物可利用 RORγ 激动剂

  摘要：

  RORγ是一种双功能药物靶点，不仅涉及炎症的诱导，还涉及癌症免疫的促进。促进 Th17 细胞分化的 RORγ 激动剂的开发可以提供一种新的作用机制 (MOA) 作为一种免疫激活抗癌剂。在此，我们通过基于临床 RORγ 拮抗剂 VTP-43742 的支架跳跃描述了新的 2-（邻位取代苄基）-吲哚衍生物作为 RORγ 激动剂。有趣的是，这些化合物的细微结构差异导致了相反的生物 MOA。在对构效关系和药代动力学特征进行合理优化后，我们确定了一种有效的 RORγ 激动剂化合物17能够诱导肿瘤组织中 IL-17 和 IFNγ 的产生，并在 MC38 同源小鼠结肠直肠肿瘤模型中引发抗肿瘤功效。这是证明RORγ 激动剂的体内抗肿瘤功效的第一项综合工作。

  DOI：

  10.1021/acs.jmedchem.1c00828
• 作为产物：
  描述：

  2-乙基苯甲酸 在 三溴化磷 、 diborane(6) 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 1-(溴甲基)-2-乙基苯
  参考文献：
  名称：

  Discovery, synthesis and anti-atherosclerotic activities of a novel selective sphingomyelin synthase 2 inhibitor

  摘要：

  The sphingomyelin synthase 2 (SMS2) is a potential target for pharmacological intervention in atherosclerosis. However, so far, few selective SMS2 inhibitors and their pharmacological activities were reported. In this study, a class of 2-benzyloxybenzamides were discovered as novel SMS2 inhibitors through scaffold hopping and structural optimization. Among them, Ly93 as one of the most potent inhibitors exhibited IC50 values of 91 nM and 133.9 mu M against purified SMS2 and SMS1 respectively. The selectivity ratio of Ly93 was more than 1400-fold for purified SMS2 over SMS1. The in vitro studies indicated that Ly93 not only dose-dependently diminished apoB secretion from Huh7 cells, but also significantly reduced the SMS activity and increased cholesterol efflux from macrophages. Meanwhile, Ly93 inhibited the secretion of LPS-mediated pro-inflammatory cytokine and chemokine in macrophages. The pharmacokinetic profiles of Ly93 performed on C57BL/6J mice demonstrated that Ly93 was orally efficacious. As a potent selective SMS2 inhibitor, Ly93 significantly decreased the plasma SM levels of C57BL/6J mice. Furthermore, Ly93 was capable of dose-dependently attenuating the atherosclerotic lesions in the root and the entire aorta as well as macrophage content in lesions, in apolipoprotein E gene knockout mice treated with Ly93. In conclusion, we discovered a novel selective SMS2 inhibitor Ly93 and demonstrated its anti-atherosclerotic activities in vivo. The preliminary molecular mechanism-of-action studies revealed its function in lipid homeostasis and inflammation process, which indicated that the selective inhibition of SMS2 would be a promising treatment for atherosclerosis. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.028

文献信息

• Selective inhibition of aggrecanase in osteoarthritis treatment
  申请人：Noe C. Mark

  公开号：US20050227997A1

  公开（公告）日：2005-10-13

  This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC 50 s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, wherein X is carbon or nitrogen; R 1 and R 2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R 1 and R 2 is methyl; R 3 and R 4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R 3 and R 4 may be taken together to form a carbonyl group; and R 5 and R 6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl; with the provisos: when X is carbon, then R 7 and R 8 are both hydrogen and at least one of R 1 , R 2 , R 3 , and R 4 is hydroxy; when X is carbon and R 5 is para-halo, then at least one of R 6 , R 3 , and R 4 is not hydrogen; when X is nitrogen, then R 8 is not present and R 7 is hydrogen or a group of the formula: wherein, Y is —CH 2 —NH 2 or —NH—CH 3 ; and when X is nitrogen and R 7 is H, then R 3 and R 4 are taken together to form a carbonyl group.

  这项发明涉及一种治疗骨关节炎的方法，涉及抑制aggrecanase的抑制剂，其IC50小于20 nM，并且对基质金属蛋白酶（MMPs）和脱粒蛋白酶（ADAMs或reprolysins）表现出差异的效力。这项发明还涉及化合物、治疗方法和Formula I的组成： 或其治疗上可接受的盐，其中X为碳或氮； R1和R2分别选自氢、羟基和甲基组成的群，其中至少一个为甲基； R3和R4分别选自氢、羟基和甲基组成的群，或R3和R4可一起形成一个羰基；以及 R5和R6是正交位、间位或对位的独立取代基，分别选自氢、卤素、氰基、甲基和乙基；附加条件： 当X为碳时，R7和R8都是氢，且至少一个R1、R2、R3和R4为羟基； 当X为碳且R5为对位卤素时，至少一个R6、R3和R4不是氢； 当X为氮时，R8不存在且R7为氢或一个公式的基团： 其中，Y为—CH2—NH2或—NH—CH3；以及 当X为氮且R7为H时，R3和R4一起形成一个羰基。
• [EN] FUSED HETEROCYCLIC COMPOUNDS AS S1P MODULATORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES CONDENSÉS À TITRE DE MODULATEURS DE S1P
  申请人：ABBVIE INC

  公开号：WO2017036978A1

  公开（公告）日：2017-03-09

  The invention relates to heterocyclic compounds as S1P modulators, pharmaceutical compositions comprising such compounds, and uses thereof in the treatment, alleviation or prevention of diseases or disorders mediated by an S1P receptor.

  这项发明涉及杂环化合物作为S1P调节剂，包括这种化合物的药物组合物，以及在治疗、缓解或预防由S1P受体介导的疾病或紊乱中的用途。
• [EN] INDANONE AND INDANDIONE DERIVATIVES AND HETEROCYCLIC ANALOGS<br/>[FR] DÉRIVÉS D'INDANONE ET D'INDANEDIONE ET ANALOGUES HÉTÉROCYCLIQUES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2013068785A1

  公开（公告）日：2013-05-16

  The invention relates to indanone/indandione derivatives and heterocyclic analogs of Formula (I) wherein Ar1, A, B, L1, Y, Z, and (R1)n n are as described in the description; to pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments, especially as NPS receptor antagonists.

  这项发明涉及吲哚酮/吲哚二酮衍生物和式（I）中的杂环类似物，其中Ar1、A、B、L1、Y、Z和（R1）n n如描述中所述；其药学上可接受的盐，以及将这些化合物用作药物，特别是作为NPS受体拮抗剂。
• Selective inhibitors of aggrecanase in osteoarthritis treatment
  申请人：Pfizer Products Inc.

  公开号：EP1081137A1

  公开（公告）日：2001-03-07

  This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC50s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, wherein X is carbon or nitrogen; R1 and R2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R1 and R2 is methyl; R3 and R4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R3 and R4 may be taken together to form a carbonyl group; and R5 and R6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl; with the provisos: when X is carbon, then R7 and R8 are both hydrogen and at least one of R1, R2, R3, and R4 is hydroxy; when X is carbon and R5 is para-halo, then at least one of R6, R3, and R4 is not hydrogen; when X is nitrogen, then R8 is not present and R7 is hydrogen or a group of the formula: wherein, Y is -CH2-NH2 or -NH-CH3; and when X is nitrogen and R7 is H, then R3 and R4 are taken together to form a carbonyl group.

  这项发明涉及一种治疗骨关节炎的方法，涉及抑制aggrecanase的方法，其IC50小于20 nM，并且对基质金属蛋白酶（MMPs）和脱粒蛋白酶（ADAMs或reprolysins）表现出差异的效力。该发明还涉及化合物、治疗方法和Formula I的组成： 或其治疗上可接受的盐，其中 X为碳或氮； R1和R2分别选自氢、羟基和甲基组成的群，其中至少一个为甲基； R3和R4分别选自氢、羟基和甲基组成的群，或R3和R4可一起形成羰基；以及 R5和R6是正交位、间位或对位的独立取代基，分别选自氢、卤素、氰基、甲基和乙基组成的群； 附加条件： 当X为碳时，R7和R8均为氢，且R1、R2、R3和R4中至少一个为羟基； 当X为碳且R5为对位卤素时，至少一个R6、R3和R4不是氢； 当X为氮时，R8不存在，R7为氢或下式的基团： 其中，Y为-CH2-NH2或-NH-CH3；以及 当X为氮且R7为H时，R3和R4一起形成羰基。
• [EN] PYRIMIDINE CYCLOHEXYL GLUCOCORTICOID RECEPTOR MODULATORS<br/>[FR] MODULATEURS DE RÉCEPTEURS DE GLUCOCORTICOÏDES DE TYPE PYRIMIDINE CYCLOHEXYLE
  申请人：CORCEPT THERAPEUTICS INC

  公开号：WO2012129074A1

  公开（公告）日：2012-09-27

  The present invention provides a class of pyrimidinedione cyclohexyl compounds and methods of using these compounds as glucocorticoid receptor modulators.

  本发明提供了一类吡啶二酮环己基化合物以及将这些化合物用作糖皮质激素受体调节剂的方法。