methyl 2-fluoro-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate | 1190848-45-3

• 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 2-fluoro-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate
• 英文别名: Methyl 2-fluoro-4-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalene-2-carbonyl)benzoate
• CAS: 1190848-45-3
• 化学式: C₂₄H₂₇FO₃
• 分子量: 382.475
• InChiKey: WIMMJZVJAVMPDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  28
• 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：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-fluoro-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate 在 正丁基锂 、 水 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 2.0h， 生成 2-氟-4-[1-(5-,6,7,8-四氢-3,5,5,8,8-五甲基-2-萘基)乙烯基]苯甲酸
  参考文献：
  名称：

  Synthesis of a new fluorine-18-labeled bexarotene analogue for PET imaging of retinoid X receptor

  摘要：

  The reference standard 2-fluoro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from 2,5-dimethyl-2,5-hexanediol and 2-fluoro-4-methylbenzoic acid in 10 steps with 3% overall chemical yield. The precursor 2-nitro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from 2,5-dimethyl-2,5-hexanediol and dimethyl-2-nitroterephthalate in seven steps with 2% overall chemical yield. The target tracer 2-[F-18]fluoro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from its nitro-precursor by the nucleophilic substitution with K[F-18]F/Kryptofix 2.2.2 and isolated by HPLC combined with solid-phase extraction (SPE) purification in 20-30% radiochemical yield with 37-370 GBq/mu mol specific activity at end of bombardment (EOB). (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.037
• 作为产物：
  描述：

  2-氟-4-甲基苯甲酸甲酯 在 aluminum (III) chloride 、 sodium chlorite 、 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 氨基磺酸 、 水 、 silver nitrate 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 43.58h， 生成 methyl 2-fluoro-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate
  参考文献：
  名称：

  Synthesis of a new fluorine-18-labeled bexarotene analogue for PET imaging of retinoid X receptor

  摘要：

  The reference standard 2-fluoro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from 2,5-dimethyl-2,5-hexanediol and 2-fluoro-4-methylbenzoic acid in 10 steps with 3% overall chemical yield. The precursor 2-nitro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from 2,5-dimethyl-2,5-hexanediol and dimethyl-2-nitroterephthalate in seven steps with 2% overall chemical yield. The target tracer 2-[F-18]fluoro-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid was synthesized from its nitro-precursor by the nucleophilic substitution with K[F-18]F/Kryptofix 2.2.2 and isolated by HPLC combined with solid-phase extraction (SPE) purification in 20-30% radiochemical yield with 37-370 GBq/mu mol specific activity at end of bombardment (EOB). (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.037

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