3'-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]-3'-[4-hydroxy-3-methylphenyl]pentane | 259733-96-5

• 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-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]-3'-[4-hydroxy-3-methylphenyl]pentane
• 英文别名: 3-[4-hydroxy-3-methylphenyl)-3-[3-methyl-4-(2-hydroxy-3,3-dimethylbutoxy)phenyl]pentane；4-[3-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]pentan-3-yl]-2-methylphenol
• CAS: 259733-96-5
• 化学式: C₂₅H₃₆O₃
• 分子量: 384.559
• InChiKey: NFLHFGGDWSQURL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3'-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]-3'-[4-hydroxy-3-methylphenyl]pentane 在 羟胺 、 potassium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 反应 60.0h， 生成 N-hydroxy-4-(4-(3-(4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl)pentan-3-yl)-2-methylphenoxy)butanamide
  参考文献：
  名称：

  Optimization of histone deacetylase inhibitor activity in non-secosteroidal vitamin D-receptor agonist hybrids

  摘要：

  The combination of (1 alpha,25)-dihydroxyvitamin D-3 (1,25D) and histone deacetylase inhibitor (HDACi) trichostatin A is highly antiproliferative in numerous cancer cell lines. We have previously prepared novel non-secosteroidal hybrid molecules which simultaneously act as both vitamin D receptor (VDR) agonists and HDACi. These molecules function as cytostatic and cytotoxic agents in 1,25D-resistant SCC4 squamous carcinoma cells. Here we have extended the scope of the hybrids by making several modifications to the diarylpentane core and to the aliphatic spacer unit to develop molecules with increased potency towards HDACs while maintaining VDR agonist activity. Notably, hybrid DK-366 (33a), a direct analog of first-generation hybrids but lacking a methyl group on one aryl ring possesses low micromolar potency for HDAC3 and HDAC6 and is a highly effective antiproliferative agent in SCC4 cells. Chain extended hybrids such as DK-367 (33c) possess even greater HDAC potency and are also highly antiproliferative. These results show that we can optimize HDACi potency in hybrid molecules without sacrificing VDR agonism. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.011
• 作为产物：
  描述：

  1-(4-(3-(4-hydroxy-3-methylphenyl)pentan-3-yl)-2-methylphenoxy)-3,3-dimethylbutan-2-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以98%的产率得到3'-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]-3'-[4-hydroxy-3-methylphenyl]pentane
  参考文献：
  名称：

  [EN] VITAMIN D RECEPTOR MODULATORS
  [FR] MODULATEURS DU RECEPTEUR DE LA VITAMINE D

  摘要：

  公开号：

  WO2005051898A3

文献信息

• [EN] BIS-(ARYL/HETEROARYL)-METHYLENE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND THEIR USE FOR TREATING CANCER<br/>[FR] COMPOSÉS DE BIS(ARYL/HÉTÉROARYL)MÉTHYLÈNE, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT ET LEUR UTILISATION POUR LE TRAITEMENT DU CANCER
  申请人：UNIV MCGILL

  公开号：WO2013091082A1

  公开（公告）日：2013-06-27

  The present disclosure relates to novel bis-(aryl/heteroaryl)-methylene compounds of formula (I) having vitamin D receptor agonist and histone deacetylase (HDAC) inhibitory efficacy as well as to methods for reducing or inhibiting the proliferation of cancer cells or for treating cancer cells.

  本公开涉及具有维生素D受体激动剂和组蛋白去乙酰化酶（HDAC）抑制活性的新型双（芳基/杂芳基）亚甲基化合物（I）的公式，以及用于减少或抑制癌细胞增殖或治疗癌细胞的方法。
• Vitamin D3 mimics
  申请人：Ligand Pharmaceuticals Incorporated

  公开号：US06218430B1

  公开（公告）日：2001-04-17

  The present invention relates to non-secosteroidal compounds which activate and modulate the vitamin D receptor (VDR). Because compounds of the present invention display many of the beneficial properties of 1,25(OH)2D3, but with reduced calcium mobilization effects, they may be used advantageously to treat and prevent conditions that show vitamin D sensitivity. Such disease states typically show abnormal calcium regulatory, abnormal immune responsive, hyperproliferative, and/or neurodegenerative characteristics.

  本发明涉及激活和调节维生素D受体（VDR）的非类固醇化合物。由于本发明的化合物显示出许多1,25(OH)2D3的有益特性，但具有减少的钙动员效应，因此它们可以有利地用于治疗和预防显示维生素D敏感性的疾病。这种疾病状态通常显示异常的钙调节、异常的免疫响应、过度增殖和/或神经退行性特征。
• [EN] VITAMIN D3 MIMICS<br/>[FR] SUBSTANCES MIMETIQUES DE VITAMINE D3
  申请人：LIGAND PHARM INC

  公开号：WO2000010958A1

  公开（公告）日：2000-03-02

  The present invention relates to non-secosteroidal compounds which activate and modulate the vitamin D receptor (VDR). Because the compounds of the present invention display many of the beneficial properties of 1,25(OH)2D3, but with reduced calcium mobilization effects, they may be used advantageously to treat and prevent conditions that show vitamin D sensitivity. Such disease states typically show abnormal calcium regulatory, abnormal immune responsive, hyperproliferative, and/or neurodegenerative characteristics.

  本发明涉及非类固醇化合物，其能够激活和调节维生素D受体（VDR）。由于本发明的化合物表现出许多1,25（OH）2D3的有益特性，但具有减少钙动员效应，因此它们可以有利地用于治疗和预防显示维生素D敏感性的疾病状态。这些疾病状态通常表现出异常的钙调节、异常的免疫响应、过度增殖和/或神经退行性特征。
• Vitamin d receptor modulators
  申请人：Gajewski Peter Robert

  公开号：US20060293385A1

  公开（公告）日：2006-12-28

  The present invention relates to novel, non-secosteroidal, sulfonate and sulfonamide functional diaryl compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1α,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

  本发明涉及一种新型的非内酯类、磺酸盐和磺酰胺类二芳基化合物，具有维生素D受体（VDR）调节活性，比1α，25-二羟基维生素D3更少引起高钙血症。这些化合物可用于治疗骨病和牛皮癣。
• BIS-(ARYL/HETEROARYL)-METHYLENE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND THEIR USE FOR TREATING CANCER
  申请人：The Royal Institution For The Advancement of Learning/McGill University

  公开号：US20140315965A1

  公开（公告）日：2014-10-23

  The present disclosure relates to novel compounds having vitamin D receptor agonist and histone deacetylase inhibitory efficacy as well as methods for reducing or inhibiting the proliferation of cancer cells or for treating cancer.

  本公开涉及具有维生素D受体激动剂和组蛋白去乙酰化酶抑制剂功效的新化合物，以及用于减少或抑制癌细胞增殖或治疗癌症的方法。