methyl 3-<(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl>benzoate

• 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: methyl 3-<(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl>benzoate
• 英文别名: methyl 3-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl]benzoate；Methyl 3-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalene-2-carbonyl)benzoate
• 化学式: C₂₄H₂₈O₃
• 分子量: 364.485
• InChiKey: HCTGMOIZRDOKTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-<(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl>benzoate 在 正丁基锂 、 potassium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 3-(1-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)vinyl)benzoic acid
  参考文献：
  名称：

  [EN] NOVEL BEXAROTENE ANALOGS
  [FR] ANALOGUES INÉDITS DU BEXAROTÈNE

  摘要：

  本发明涉及贝沙罗汀的类似物及其使用方法。

  公开号：

  WO2011103321A1
• 作为产物：
  描述：

  2,5-二氯-2,5-二甲基己烷 在 aluminum (III) chloride aluminum (III) chloride 作用下， 生成 methyl 3-<(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl>benzoate
  参考文献：
  名称：

  [EN] NOVEL BEXAROTENE ANALOGS
  [FR] ANALOGUES INÉDITS DU BEXAROTÈNE

  摘要：

  本发明涉及贝沙罗汀的类似物及其使用方法。

  公开号：

  WO2011103321A1

文献信息

• Modeling, Synthesis and Biological Evaluation of Potential Retinoid X Receptor (RXR) Selective Agonists: Novel Analogues of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene)
  作者：Carl E. Wagner、Peter W. Jurutka、Pamela A. Marshall、Thomas L. Groy、Arjan van der Vaart、Joseph W. Ziller、Julie K. Furmick、Mark E. Graeber、Erik Matro、Belinda V. Miguel、Ivy T. Tran、Jungeun Kwon、Jamie N. Tedeschi、Shahram Moosavi、Amina Danishyar、Joshua S. Philp、Reina O. Khamees、Jevon N. Jackson、Darci K. Grupe、Syed L. Badshah、Justin W. Hart

  DOI：10.1021/jm900496b

  日期：2009.10.8

  This report describes the synthesis of analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), commonly known as bexarotene, and their analysis in acting as retinoid X receptor (RXR)-specific agonists. Compound 1 has FDA approval to treat cutaneous T-cell lymphoma (CTCL); however, its use can cause side effects such as hypothyroidism and increased triglyceride

  本报告描述了 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl] 苯甲酸 ( 1 )类似物的合成，众所周知作为贝沙罗汀，以及它们作为类视黄醇 X 受体 (RXR) 特异性激动剂的分析。化合物1已获得 FDA 批准用于治疗皮肤 T 细胞淋巴瘤 (CTCL)；然而，它的使用会引起副作用，例如甲状腺功能减退和甘油三酯浓度升高，这可能是由于 RXR 与其他核受体的异二聚化被破坏。本研究中的新型类似物已在 RXR 哺乳动物-2-杂交试验和 RXRE 介导的转录试验中评估了 RXR 激活，以及它们诱导细胞凋亡的能力以及它们的诱变性和细胞毒性。对 11 种新型化合物的分析表明，发现了三种最能诱导 RXR 介导的转录活性、刺激细胞凋亡、具有与1相当的K i和 EC 50值的类似物，并且是选择性 RXR 激动剂。我们的实验方法
• Design and Synthesis of Potent Retinoid X Receptor Selective Ligands That Induce Apoptosis in Leukemia Cells
  作者：Marcus F. Boehm、Lin Zhang、Lin Zhi、Michael R. McClurg、Elain Berger、Murriel Wagoner、Dale E. Mais、Carla M. Suto、Peter J. A. Davies、Richard A. Heyman、Alex M. Nadzan

  DOI：10.1021/jm00016a018

  日期：1995.8.1

  (RXR) selective compound 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid (LGD1069), which is currently in phase I/IIA clinical trials for cancer and dermatological indications, have resulted in the identification of increasingly potent retinoids with > 1000-fold selectivity for the RXRs. This paper describes the design and preparation of a series of RXR selective retinoids

  类维生素A X受体（RXR）选择性化合物4- [1-（3,5,5,8,8-五甲基-5,6,7,8-四氢-2-萘基）乙烯基]苯甲酸的结构修饰（LGD1069 ）（目前正处于癌症和皮肤病适应症的I / IIA期临床试验中）已导致鉴定出越来越强的类维生素A，对RXR的选择性> 1000倍。本文介绍了一系列RXR选择性类维生素A的设计和制备，以及从共转染和竞争性结合试验中获得的生物学数据，这些数据用于评估其效力和选择性。最有效和最具选择性的类似物是6- [1-（3,5,5,8,8-五甲基-5,6,7,8-四氢萘-2-基）环丙基]烟酸（12d; LG100268） 。已证明该化合物可用于研究RXR依赖性生物途径，包括诱导程序性细胞死亡（PCD）和转谷氨酰胺酶（TGase）活性。我们的研究表明，人白血病髓样细胞中PCD和TGase的诱导依赖于RXR介导的途径的激活。
• RETINOID RECEPTOR AGONISTS
  申请人：Institute of Medicinal Molecular Design, Inc.

  公开号：EP1048659A1

  公开（公告）日：2000-11-02

  The invention provides a substance acting on a retinoid receptor which has a retinoid-like activity or an action of controlling retinoid activities, for example, enhancement or suppression. Compounds represented by the following general formula (I) wherein R1, R2, R3, R4, and R5 independently represent hydrogen atom or a lower alkyl group, or two adjacent groups selected therefrom may combine together with carbon atoms of the phenyl ring to which they bind to form a 5- or 6-membered ring which may optionally be substituted with one or more alkyl groups; and X represents a group represented by -C(R6)=CH-, -CH=C(R7)-, -N(R8)-CO-, -CO-N(R9)-, -C(=CHR10), -CO-, or -NR11-wherein R6, R7, R8, R9, R10, and R11 independently represent hydrogen atom or a lower alkyl group.

  本发明提供了一种作用于视黄醇受体的物质，该物质具有视黄醇样活性或控制视黄醇活性的作用，例如增强或抑制视黄醇活性。 由以下通式(I)代表的化合物 其中 R1、R2、R3、R4 和 R5 独立地代表氢原子或低级烷基，或从中选出的两个相邻基团可与它们结合的苯基环的碳原子结合在一起，形成可任选被一个或多个烷基取代的 5 或 6 元环；X代表由-C(R6)=CH-、-CH=C(R7)-、-N(R8)-CO-、-CO-N(R9)-、-C(=CHR10)、-CO-或-NR11-代表的基团，其中 R6、R7、R8、R9、R10 和 R11 独立地代表氢原子或低级烷基。
• Treatment of disease states which result from neoplastic cell proliferation using PPAR-gamma activators and compositions useful therefor
  申请人：The Salk Institute for Biological Studies

  公开号：US20040162354A1

  公开（公告）日：2004-08-19

  In accordance with the present invention, it has been discovered that PPAR&ggr; is expressed consistently in tissues associated with each of a variety of disease states which result from neoplastic cell proliferation. It has further been discovered that maximal activation of PPAR&ggr; with exogenous ligand promotes terminal differentiation of primary cells which are otherwise subject to neoplastic cell proliferation. In accordance with another aspect of the invention, it has been discovered that RXR-specific ligands are also potent agents for induction of differentiation of cells expressing the PPAR&ggr;/RXR&agr; heterodimer, and that simultaneous treatment of cells subject to neoplastic cell proliferation with a PPAR&ggr;-selective ligand, in combination with an RXR-specific ligand, results in an additive stimulation of differentiation. Thus, the effect of neoplastic cell proliferation can be ameliorated by treatment of cells undergoing neoplastic cell proliferation with PPAR&ggr; agonists, optionally in the further presence of RXR agonists, thereby blocking further proliferation thereof. Accordingly, compounds and compositions which are useful for the treatment of a variety of disease states which result from neoplastic cell proliferation have been identified and are described herein.

  根据本发明，人们发现 PPAR&ggr; 在与肿瘤细胞增殖导致的各种疾病状态有关的组织中持续表达。本发明还进一步发现，PPAR&ggr; 在外源性配体的最大激活作用下，可促进原代细胞的终末分化，否则这些细胞就会受到肿瘤细胞增殖的影响。根据本发明的另一方面，发现 RXR 特异性配体也是诱导表达 PPAR&ggr;/RXR&agr; 异二聚体的细胞分化的有效药物，而且用 PPAR&ggr;- 选择性配体结合 RXR 特异性配体同时处理受肿瘤性细胞增殖影响的细胞，会对分化产生叠加刺激作用。因此，用 PPAR&ggr;激动剂（可选择在 RXR 激动剂进一步存在的情况下）处理发生肿瘤细胞增殖的细胞，可以改善肿瘤细胞增殖的影响，从而阻止其进一步增殖。因此，已经发现并在此描述了可用于治疗由肿瘤细胞增殖引起的各种疾病状态的化合物和组合物。
• NOVEL BEXAROTENE ANALOGS
  申请人：The Arizona Board Of Regents, A Body Corporate Of The State Of Arizona Acting For And On Behalf Of Arizona State University

  公开号：EP2536276B1

  公开（公告）日：2016-11-23