(2,5,7,8-Tetramethyl-6-phenylmethoxy-3,4-dihydrochromen-2-yl)methyl trifluoromethanesulfonate | 161606-30-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (2,5,7,8-Tetramethyl-6-phenylmethoxy-3,4-dihydrochromen-2-yl)methyl trifluoromethanesulfonate
• CAS: 161606-30-0
• 化学式: C₂₂H₂₅F₃O₅S
• 分子量: 458.499
• InChiKey: DWUCNLZCHGTAID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2,5,7,8-Tetramethyl-6-phenylmethoxy-3,4-dihydrochromen-2-yl)methyl trifluoromethanesulfonate 在 哌啶 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 (Z)-5-{4-[(6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]-3-bromobenzylidene}thiazolidine-2,4-dione
  参考文献：
  名称：

  Development of Small-Molecule Cyclin D1-Ablative Agents

  摘要：

  Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPAR gamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta 2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPAR gamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta 2TG led to STG28 [(S)-5-(4-{[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)-thiazolidine-2,4- dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.

  DOI：

  10.1021/jm060057h
• 作为产物：
  描述：

  奎诺二甲基丙烯酸酯 在 吡啶 、 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 54.5h， 生成 (2,5,7,8-Tetramethyl-6-phenylmethoxy-3,4-dihydrochromen-2-yl)methyl trifluoromethanesulfonate
  参考文献：
  名称：

  Development of Small-Molecule Cyclin D1-Ablative Agents

  摘要：

  Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPAR gamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta 2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPAR gamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta 2TG led to STG28 [(S)-5-(4-{[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)-thiazolidine-2,4- dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.

  DOI：

  10.1021/jm060057h

文献信息

• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR THE PREVENTION AND/OR TREATMENT OF VARIOUS MITOCHONDRIAL DISEASES OR DISORDERS, INCLUDING FRIEDREICH'S ATAXIA<br/>[FR] COMPOSÉS, COMPOSITIONS ET PROCÉDÉS POUR LA PRÉVENTION ET/OU LE TRAITEMENT DE DIVERSES MALADIES OU TROUBLES MITOCHONDRIAUX, NOTAMMENT LA MALADIE DE FRIEDREICH
  申请人：STEALTH BIOTHERAPEUTICS INC

  公开号：WO2022261347A1

  公开（公告）日：2022-12-15

  The disclosure provides various new and existing compounds for use alone or as formulated in a composition (e.g., medicaments) and related methods and uses for treating, preventing, inhibiting, ameliorating or delaying the onset of a disease, disorder or condition associated with ferroptosis in a mammalian subject. Such ferroptosis related diseases, disorders or conditions can include: Friedreich's ataxia, Leigh syndrome, Leber's Hereditary Optic Neuropathy (LHON), (proliferative, non-proliferative, diabetic or hypertensive) retinopathy, refractory epilepsy, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), ischemic stroke, a cardiomyopathy (e.g. cardiac ischemia-reperfusion injury, myocardial infarction, Barth cardiomyopathy, hypertrophic cardiomyopathy or heart failure), renal injury, renal ischemia reperfusion injury or acute renal failure.

  该披露提供了各种新的和现有的化合物，可单独使用或作为组合物（例如药物）中的成分，并提供了用于治疗、预防、抑制、改善或延迟哺乳动物主体中与铁死亡相关的疾病、疾病或疾病的发作的相关方法和用途。这种与铁死亡相关的疾病、疾病或疾病可以包括：弗里德雷希共济失调、利氏综合征、勒伯遗传性视神经病变（LHON）、（增殖性、非增殖性、糖尿病或高血压）视网膜病变、难治性癫痫、帕金森病（PD）、阿尔茨海默病（AD）、亨廷顿病（HD）、肌萎缩性侧索硬化症（ALS）、缺血性中风、心肌病（例如心脏缺血再灌注损伤、心肌梗塞、巴斯心肌病、肥厚型心肌病或心力衰竭）、肾损伤、肾缺血再灌注损伤或急性肾衰竭。
• CHINONE-, HYDROCHINOME- AND NAPHTHOCHINONE-ANALOGUES OF VATIQUIONE FOR TREATMENT OF MITOCHONDRIAL DISORDER DISEASES
  申请人：Stealth BioTherapeutics Inc.

  公开号：EP4038076A1

  公开（公告）日：2022-08-10
• COMPOSITIONS AND METHODS FOR THE PREVENTION AND/OR TREATMENT OF MITOCHONDRIAL DISEASE, INCLUDING FRIEDREICH'S ATAXIA
  申请人：Keefe Dennis

  公开号：US20210206736A1

  公开（公告）日：2021-07-08

  The disclosure provides therapeutic compositions (i.e., therapeutic agents) and methods of preventing or treating Friedreich's ataxia in a mammalian subject, reducing risk factors, signs and/or symptoms associated with Friedreich's ataxia (e.g., Complex I deficiency), and/or reducing the likelihood or severity of Friedreich's ataxia. The disclosure further provides novel intermediates for the production of said therapeutic compositions and related reduced versions of said therapeutic compositions, which reduce forms may also be used as therapeutic agents (or prodrugs of the therapeutic agent(s)).
• [EN] CHINONE-, HYDROCHINOME- AND NAPHTHOCHINONE-ANALOGUES OF VATIQUIONE FOR TREATMENT OF MITOCHONDRIAL DISORDER DISEASES<br/>[FR] ANALOGUES CHINONE, HYDROCHINONE ET NAPHTOCHINONE DE VATIQUINONE POUR LE TRAITEMENT DE MALADIES À TROUBLES MITOCHONDRIAUX
  申请人：STEALTH BIOTHERAPEUTICS CORP

  公开号：WO2021067836A1

  公开（公告）日：2021-04-08

  The disclosure provides therapeutic compositions (i.e., therapeutic agents) and methods of preventing or treating Friedreich's ataxia in a mammalian subject, reducing risk factors, signs and/or symptoms associated with Friedreich's ataxia (e.g. Complex I deficiency), and/or reducing the likelihood or severity of Friedreich's ataxia. The disclosure further provides novel intermediates for the production of said therapeutic compositions and related reduced versions of said therapeutic compositions, which reduce forms may also be used as therapeutic agents (or prodrugs of the therapeutic agent(s)).
• Development of Small-Molecule Cyclin D1-Ablative Agents
  作者：Jui-Wen Huang、Chung-Wai Shiau、Jian Yang、Da-Sheng Wang、Hao-Chieh Chiu、Ching-Yu Chen、Ching-Shih Chen

  DOI：10.1021/jm060057h

  日期：2006.7.1

  Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPAR gamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta 2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPAR gamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta 2TG led to STG28 [(S)-5-(4-[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)-thiazolidine-2,4- dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.