α-(3-bromophenyl)-3-(tert-butyldimethylsilyloxy)-benzyl alcohol | 155767-23-0

• 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: α-(3-bromophenyl)-3-(tert-butyldimethylsilyloxy)-benzyl alcohol
• 英文别名: α-(3-bromophenyl)-3-(tert-butyldimethylsilyloxy)benzyl alcohol；[3-(t-butyldimethylsilyl)oxyphenyl]-(3-bromophenyl)methanol；3-(t-butyldimethylsilyloxy)(3-bromophenyl)methanol；(3-Bromophenyl)-[3-[tert-butyl(dimethyl)silyl]oxyphenyl]methanol
• CAS: 155767-23-0
• 化学式: C₁₉H₂₅BrO₂Si
• 分子量: 393.396
• InChiKey: ZTBJZCVKIFWPJU-UHFFFAOYSA-N

物化性质

• 沸点：
  428.8±40.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.91
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  α-(3-bromophenyl)-3-(tert-butyldimethylsilyloxy)-benzyl alcohol 在 咪唑 、 sodium hydroxide 、 氯化亚砜 、 草酰氯 、 四乙基氟化铵水合物 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium chloride 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 176.5h， 生成 DPI-3290
  参考文献：
  名称：

  3-(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)- N-alkyl-N-arylbenzamides:  Potent, Non-Peptidic Agonists of Both the μ and δ Opioid Receptors

  摘要：

  Opioid analgesics with both mu and delta opioid receptor activation represent a new approach to the treatment of severe pain with an improved safety profile. Compounds with this profile may exhibit strong analgesic properties due to mu agonism, with a reduced side effect profile resulting from delta agonism. Replacing the p-diethylamide of the known potent delta opioid receptor selective agonist BW373U86 with a m-diethylamide resulted in a compound with agonist activity at both the mu and delta opioid receptors. Modifying the amide to an N-methyl-N-phenylamide increased agonist potency at both receptors. A series of 3-(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides have been made to explore the structure-activity relationship (SAR) around the N-methyl-N-phenylamide. Several potent agonists of both the mu and delta opioid receptors have been identified, including (+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-l-piperazinyl)-3-hydroxybenzyl)-N-(4-fluorophenyl)-N-methylben-zamide (23), which has EC50 values of 0.67 and 1.1 nM at the mu (guinea pig ileum assay) and delta (mouse vas deferens assay) opioid receptors, respectively.

  DOI：

  10.1021/jm020395s
• 作为产物：
  描述：

  间溴苯酚 在 咪唑 、 正丁基锂 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 α-(3-bromophenyl)-3-(tert-butyldimethylsilyloxy)-benzyl alcohol
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR INHIBITION OF CATHEPSINS
  [FR] COMPOSITIONS ET PROCÉDÉS D'INHIBITION DE CATHEPSINES

  摘要：

  本公开涉及化合物I的公式以及在治疗需要调节蛋白酶的情况下使用这些化合物的方法，特别是蛋白酶L、蛋白酶K和/或蛋白酶B。公式I：或其溶剂或药用可接受盐。R1-R10中的每一个独立地选择自羟基、烷氧基、卤素、羟基、磷酸酯、磷酸盐、二钠磷酸盐、二磷酸二聚体、二磷酸二聚体盐和含有R1-R10中至少一个为磷酸酯或二磷酸二聚体基团的羟基。

  公开号：

  WO2017030983A1

文献信息

• Functionalized benzophenone, thiophene, pyridine, and fluorene thiosemicarbazone derivatives as inhibitors of cathepsin L
  作者：G.D. Kishore Kumar、Gustavo E. Chavarria、Amanda K. Charlton-Sevcik、Grace Kim Yoo、Jiangli Song、Tracy E. Strecker、Bronwyn G. Siim、David J. Chaplin、Mary Lynn Trawick、Kevin G. Pinney

  DOI：10.1016/j.bmcl.2010.09.026

  日期：2010.11

  of thiosemicarbazone analogs based on the benzophenone, thiophene, pyridine, and fluorene molecular frameworks has been prepared by chemical synthesis and evaluated as small-molecule inhibitors of the cysteine proteases cathepsin L and cathepsin B. The two most potent inhibitors of cathepsin L in this series (IC50 <135 nM) are brominated-benzophenone thiosemicarbazone analogs that are further functionalized

  已通过化学合成制备了一系列基于二苯甲酮，噻吩，吡啶和芴分子骨架的硫半碳zone类似物，并被评估为半胱氨酸蛋白酶组织蛋白酶L和组织蛋白酶B的小分子抑制剂。组织蛋白酶L的两种最有效抑制剂该系列（IC 50  <135 nM）是溴化二苯甲酮硫半碳酸盐类似物，可通过酚类部分（2和6）进一步官能化。此外，溴-二苯甲酮硫半脲酮乙酰衍生物（3）也强烈抑制组织蛋白酶L（IC 50 = 150.8 nM）。噻吩系列中的溴取代导致仅显示出对组织蛋白酶L的中等抑制作用的化合物。二苯甲酮硫代半碳环酮系列中两个活性最高的类似物对组织蛋白酶L的抑制比对组织蛋白酶B的选择性高。
• Initial evaluation of the antitumour activity of KGP94, a functionalized benzophenone thiosemicarbazone inhibitor of cathepsin L
  作者：Gustavo E. Chavarria、Michael R. Horsman、Wara M. Arispe、G.D. Kishore Kumar、Shen-En Chen、Tracy E. Strecker、Erica N. Parker、David J. Chaplin、Kevin G. Pinney、Mary Lynn Trawick

  DOI：10.1016/j.ejmech.2012.10.039

  日期：2012.12

  Kinetic analysis of the mode of inhibition of cathepsin L by KGP94, a lead compound from a privileged library of functionalized benzophenone thiosemicarbazone derivatives, demonstrated that it is a time-dependent, reversible, and competitive inhibitor of the enzyme. These results are consistent with the formation of a transient covalent bond, and are supported by molecular modeling that places the thiocarbonyl of the inhibitor in proximity to the thiolate moiety of the enzyme active site Cys25. KGP94 significantly decreased the activity of cathepsin L toward human type I collagen, and impeded both migration and invasion of MDA-MB-231 human breast cancer cells. Growth retardation was achieved in vivo against both recently implanted and established tumours using a C3H mouse mammary carcinoma model. (C) 2012 Elsevier Masson SAS. All rights reserved.
• 3-(α<i>R</i>)-α-((2<i>S</i>,5<i>R</i>)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-<i> N</i>-alkyl-<i>N</i>-arylbenzamides:  Potent, Non-Peptidic Agonists of Both the μ and δ Opioid Receptors
  作者：Michael J. Bishop、Dulce M. Garrido、G. Evan Boswell、Mark A. Collins、Philip A. Harris、Robert W. McNutt、Scott J. O'Neill、Ke Wei、Kwen-Jen Chang

  DOI：10.1021/jm020395s

  日期：2003.2.1

  Opioid analgesics with both mu and delta opioid receptor activation represent a new approach to the treatment of severe pain with an improved safety profile. Compounds with this profile may exhibit strong analgesic properties due to mu agonism, with a reduced side effect profile resulting from delta agonism. Replacing the p-diethylamide of the known potent delta opioid receptor selective agonist BW373U86 with a m-diethylamide resulted in a compound with agonist activity at both the mu and delta opioid receptors. Modifying the amide to an N-methyl-N-phenylamide increased agonist potency at both receptors. A series of 3-(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides have been made to explore the structure-activity relationship (SAR) around the N-methyl-N-phenylamide. Several potent agonists of both the mu and delta opioid receptors have been identified, including (+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-l-piperazinyl)-3-hydroxybenzyl)-N-(4-fluorophenyl)-N-methylben-zamide (23), which has EC50 values of 0.67 and 1.1 nM at the mu (guinea pig ileum assay) and delta (mouse vas deferens assay) opioid receptors, respectively.
• [EN] COMPOSITIONS AND METHODS FOR INHIBITION OF CATHEPSINS<br/>[FR] COMPOSITIONS ET PROCÉDÉS D'INHIBITION DE CATHEPSINES
  申请人：MATEON THERAPEUTICS INC

  公开号：WO2017030983A1

  公开（公告）日：2017-02-23

  This present disclosure is directed to compound of Formula I and methods of using these compounds in the treatment of conditions in which modulation of a cathepsin, particularly cathepsin L, cathepsin K, and/or cathepsin B, will be therapeutically useful. Formula I: or a solvate or pharmaceutically acceptable salt thereof. Each of Rl -Rl 0 are independently selected from the group consisting of: hydrogen, alkoxy, halo, hydroxy, phosphate, phosphate salts, disodium phosphate, diphosphate dimer, diphosphate dimer salt, and sodium diphosphate dimer with at least one of R1 -R10 is a phosphate or diphosphate dimer group.

  本公开涉及化合物I的公式以及在治疗需要调节蛋白酶的情况下使用这些化合物的方法，特别是蛋白酶L、蛋白酶K和/或蛋白酶B。公式I：或其溶剂或药用可接受盐。R1-R10中的每一个独立地选择自羟基、烷氧基、卤素、羟基、磷酸酯、磷酸盐、二钠磷酸盐、二磷酸二聚体、二磷酸二聚体盐和含有R1-R10中至少一个为磷酸酯或二磷酸二聚体基团的羟基。