2-(adamantan-1-yl)-5-methyl-4-bromophenol | 245434-50-8

• 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-(adamantan-1-yl)-5-methyl-4-bromophenol
• 英文别名: 2-(adamant-1-yl)-4-bromo-5-methylphenol；2-(1-adamantyl)-4-bromo-5-methylphenol；2-(Adamantan-1-YL)-4-bromo-5-methylphenol
• CAS: 245434-50-8
• 化学式: C₁₇H₂₁BrO
• 分子量: 321.257
• InChiKey: WAEAIUSJDSZUKD-UHFFFAOYSA-N

物化性质

• 熔点：
  155-156 °C
• 沸点：
  408.4±45.0 °C(Predicted)
• 密度：
  1.401±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(adamantan-1-yl)-5-methyl-4-bromophenol 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 28.0h， 生成
  参考文献：
  名称：

  钴催化吲哚的对映选择性 C-H 芳基化

  摘要：

  阻转异构（杂）联芳基是在制药和农业化学工业中越来越重要的支架。尽管构建此类化合物是最明显的分离，但通过同时诱导手性信息的直接对映选择性 C-H 芳基化仍然极具挑战性且不常见。在这里，报道了前所未有的地球丰富的 3d 金属催化的阻转选择性直接芳基化，提供了罕见的阻转异构 C2 芳基化吲哚。动力学研究和 DFT 计算揭示了这种不对称转变的不常见机制，氧化加成是决定速率和对映体的步骤。达到了出色的立体选择性（高达 96% ee），同时使用不寻常的N-杂环卡宾配体带有一个必要的远程取代基。有吸引力的色散相互作用以及配体施加的正 C-H---π 相互作用被确定为保证优异对映体选择的关键因素。

  DOI：

  10.1021/jacs.1c09889
• 作为产物：
  描述：

  4-溴-3-甲基苯酚 、 1-金刚烷醇 在 硫酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以98%的产率得到2-(adamantan-1-yl)-5-methyl-4-bromophenol
  参考文献：
  名称：

  钴催化吲哚的对映选择性 C-H 芳基化

  摘要：

  阻转异构（杂）联芳基是在制药和农业化学工业中越来越重要的支架。尽管构建此类化合物是最明显的分离，但通过同时诱导手性信息的直接对映选择性 C-H 芳基化仍然极具挑战性且不常见。在这里，报道了前所未有的地球丰富的 3d 金属催化的阻转选择性直接芳基化，提供了罕见的阻转异构 C2 芳基化吲哚。动力学研究和 DFT 计算揭示了这种不对称转变的不常见机制，氧化加成是决定速率和对映体的步骤。达到了出色的立体选择性（高达 96% ee），同时使用不寻常的N-杂环卡宾配体带有一个必要的远程取代基。有吸引力的色散相互作用以及配体施加的正 C-H---π 相互作用被确定为保证优异对映体选择的关键因素。

  DOI：

  10.1021/jacs.1c09889

文献信息

• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES
  申请人：UNIV WAYNE STATE

  公开号：WO2011079305A1

  公开（公告）日：2011-06-30

  The invention provides compounds of formula I or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for inducing apoptosis or treating cancer using compounds of formula I.

  该发明提供了如下所述的式I化合物或其盐。该发明还提供了包括式I化合物的药物组合物，制备式I化合物的方法，用于制备式I化合物的有用中间体以及利用式I化合物诱导凋亡或治疗癌症的治疗方法。
• THERAPEUTIC COMPOUNDS
  申请人：Fontana Joseph A.

  公开号：US20130137699A1

  公开（公告）日：2013-05-30

  The invention provides compounds of formula I or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for inducing apoptosis or treating cancer using compounds of formula I.

  本发明提供了式I或其盐的化合物，如本文所述。本发明还提供了包含式I化合物的制药组合物，制备式I化合物的方法，用于制备式I化合物的中间体以及使用式I化合物诱导凋亡或治疗癌症的治疗方法。
• Therapeutic compounds
  申请人：Fontana Joseph A.

  公开号：US09096544B2

  公开（公告）日：2015-08-04

  The invention provides compounds of formula I or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for inducing apoptosis or treating cancer using compounds of formula I.

  本发明提供了公式I的化合物或其盐，如本文所述。本发明还提供了包括公式I的化合物的药物组合物，制备公式I的化合物的方法，用于制备公式I的化合物的中间体以及使用公式I的化合物诱导细胞凋亡或治疗癌症的治疗方法。
• Synthesis and Structure−Activity Relationships of a New Series of Retinoid-Related Biphenyl-4-ylacrylic Acids Endowed with Antiproliferative and Proapoptotic Activity
  作者：Raffaella Cincinelli、Sabrina Dallavalle、Raffaella Nannei、Serena Carella、Daniele De Zani、Lucio Merlini、Sergio Penco、Enrico Garattini、Giuseppe Giannini、Claudio Pisano、Loredana Vesci、Paolo Carminati、Valentina Zuco、Chiara Zanchi、Franco Zunino

  DOI：10.1021/jm049440h

  日期：2005.7.1

  Atypical retinoids (AR) represent a class of proapoptotic agents with promising potential in the treatment of neoplastic diseases. In the present work 4'-hydroxybiphenyl-4-ylacrylic acids were studied as a novel series of AR. The synthesized compounds were evaluated for their antiproliferative activity in a human promyelocytic leukemia cell line (NB4) and in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild-type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of a bulky lipophilic group at position 3' (adamantan-1-yl being the best) and the E configuration of the acrylic moiety appear essential for activity below 1 mu M. No substitution on the rings or on the double bond improved the activity. A qualitative correlation between the log P and molecular volume of the 3'-substituent and the antiproliferative activity was found. From the study of a few selected compounds, it appears that the presence of the carboxylic group is an essential requirement for apoptogenic properties but not for antiproliferative activity, this being maintained in amide derivatives. On the other hand, compounds able to induce apoptosis produced a detectable level of genotoxic damage. This observation supports the hypothesis that the genotoxic stress is a critical event mediating apoptosis induction by compounds of this class. Among the compounds investigated, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (2) was chosen for further investigation.
• Highly twisted adamantyl arotinoids: Synthesis, antiproliferative effects and RXR transactivation profiles
  作者：Santiago Pérez-Rodríguez、Maria A. Ortiz、Raquel Pereira、Fátima Rodríguez-Barrios、Ángel R. de Lera、F. Javier Piedrafita

  DOI：10.1016/j.ejmech.2009.01.011

  日期：2009.6

  Retinoid-related molecules with an adamantyl group (adamantyl arotinoids) have been described with selective activities towards the retinoid receptors as agonists for NR1B2 and NR1B3 (RAR beta,gamma) (CD437, MX3350-1) or RAR antagonists (MX781) that induce growth arrest and apoptosis in cancer cells. Since these molecules induce apoptosis independently of RAR transactivation, we set up to synthesize novel analogs with impaired RAR binding. Here we describe adamantyl arotinoids with 2,2'-disubstituted biaryl rings prepared using the Suzuki coupling of the corresponding fragments. Those with cinnamic and naphthoic acid end groups showed significant antiproliferative activity in several cancer cell lines, and this effect correlated with the induction of apoptosis as measured by caspase activity. Strikingly, some of these compounds, whereas devoid of RAR binding capacity, were able to activate RXR. (C) 2009 Elsevier Masson SAS. All rights reserved.