4-iodo-2-(3-methyl-2-butenyl)phenyl acetate | 151071-04-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 4-iodo-2-(3-methyl-2-butenyl)phenyl acetate
• 英文别名: 4-iodo-2-(3-methylbut-2-en-1-yl)phenyl acetate；Phenol, 4-iodo-2-(3-methyl-2-buten-1-yl)-, 1-acetate；[4-iodo-2-(3-methylbut-2-enyl)phenyl] acetate
• CAS: 151071-04-4
• 化学式: C₁₃H₁₅IO₂
• 分子量: 330.165
• InChiKey: FNOBCDSEJFZFPA-UHFFFAOYSA-N

物化性质

• 沸点：
  358.3±42.0 °C(Predicted)
• 密度：
  1.468±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-iodo-2-(3-methyl-2-butenyl)phenyl acetate 在 palladium diacetate 氢氧化钾 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 23.0h， 生成 drupanin
  参考文献：
  名称：

  Artepillin C isoprenomics: Design and synthesis of artepillin C isoprene analogues as lipid peroxidation inhibitor having low mitochondrial toxicity

  摘要：

  We designed and synthesized isoprene analogues of artepillin C, a major component of Brazilian propolis, and investigated the inhibitory activity on lipid peroxidation of rat liver mitochondria (RLM) and RLM toxicity based on isoprenomics. We succeeded in the synthesis of artepillin C isoprene analogues using regioselective prenylation within the range from 22% to 53% total yield. Reactivity of artepillin C and its isoprene analogues with ABTS (2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonate)) radical cations showed only a slight difference among the molecules. The isoprene side-chain elongation analogues of artepillin C showed almost the same inhibitory activity against RLM lipid peroxidation as artepillin C. Artepillin C and its isoprene analogues had very weak RLM uncoupling activity. Moreover, artepillin C and its isoprene analogues exhibited a lower inhibitory activity against adenosine 5'-triphosphate (ATP) synthesis by about two orders of magnitude than the effective inhibitory activity against RLM lipid peroxidation. From these results we conclude that artepillin C isoprene analogues could be potent lipid peroxidation inhibitors having low mitochondrial toxicity. We also conclude that elongation of the isoprene side chain of artepillin C to increase lipophilicity had little influence on the inhibitory activity toward RLM lipid peroxidation. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.04.015
• 作为产物：
  描述：

  4-碘苯酚 在 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 、 mineral oil 为溶剂， 生成 4-iodo-2-(3-methyl-2-butenyl)phenyl acetate
  参考文献：
  名称：

  Potent and Highly Selective Aldo–Keto Reductase 1C3 (AKR1C3) Inhibitors Act as Chemotherapeutic Potentiators in Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia

  摘要：

  Aldo-keto reductase 1C3 (AKR1C3) catalyzes the synthesis of 9 alpha,11 beta-prostaglandin (PG) F-2 alpha and PGF(2 alpha) prostanoids that sustain the growth of myeloid precursors in the bone marrow. The enzyme is overexpressed in acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). Moreover, AKR1C3 confers chemotherapeutic resistance to the anthracyclines: first-line agents for the treatment of leukemias. The highly homologous isoforms AKR1C1 and AKR1C2 inactivate 5 alpha-dihydrotestosterone, and their inhibition would be undesirable. We report herein the identification of AKR1C3 inhibitors that demonstrate exquisite isoform selectivity for AKR1C3 over the other closely related isoforms to the order of >2800-fold. Biological evaluation of our isoform-selective inhibitors revealed a high degree of synergistic drug action in combination with the clinical leukemia therapeutics daunorubicin and cytarabine in in vitro cellular models of AML and primary patient-derived T-ALL cells. Our developed compounds exhibited >100-fold dose reduction index that results in complete resensitization of a daunorubicin-resistant AML cell line to the chemotherapeutic and >100-fold dose reduction of cytarabine in both AML cell lines and primary T-ALL cells.

  DOI：

  10.1021/acs.jmedchem.9b00090

文献信息

• [EN] HIGHLY SELECTIVE AKR1C3 INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS D'AKR1C3 HAUTEMENT SÉLECTIFS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV TEXAS TECH SYSTEM

  公开号：WO2018148721A1

  公开（公告）日：2018-08-16

  The present invention includes methods and compositions that inhibit AKR1C3 enzymatic activity and consequently reduces androgen receptor (AR) transactivation, AR and prostate specific antigen (PSA) expression levels in, for example, prostate cancer, castration-resistant prostate cancer, breast cancer, acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (T-ALL), or a leukemia.

  本发明涵盖了抑制AKR1C3酶活性的方法和组合物，从而降低雄激素受体（AR）的转录活性，AR和前列腺特异性抗原（PSA）在例如前列腺癌、去势抵抗性前列腺癌、乳腺癌、急性髓性白血病（AML）、T细胞急性淋巴细胞白血病（T-ALL）或白血病中的表达水平。
• Synthesis of phenolic natural products using palladium catalyzed coupling reactions
  作者：Roderick W. Bates、Christine J. Gabel、Jianhua Ji、Thota Rama-Devi

  DOI：10.1016/0040-4020(95)00441-a

  日期：1995.7

  Derivatives of 2,4-diiodophenol are shown to undergo palladium catalyzed carbonylation and alkyne coupling reactions in excellent to moderate yield and high regioselectivity. The scope of these reactions is explored. Palladium catalyzed reactions are employed as the key steps in the synthesis of three phenolic natural products: Plicatin B, Drupanin and Eutypine.
• The synthesis of Plicatin B via the Heck reaction
  作者：Roderick W Bates、Christine J Gabel

  DOI：10.1016/s0040-4039(00)73632-x

  日期：1993.5

  The anti-microbial natural product Plicatin B has been synthesized in 53% overall yield using a Heck reaction as the key step. The optimum conditions for this reaction have been determined. Halophenols proved much less reactive than their corresponding acetates.