[10-(3-hydroxy-4-methoxybenzylidene)]-9(10H)-anthracenone

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: [10-(3-hydroxy-4-methoxybenzylidene)]-9(10H)-anthracenone
• 英文别名: 10-[(3-Hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one
• 化学式: C₂₂H₁₆O₃
• 分子量: 328.367
• InChiKey: MQLACMBJVPINKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  异香兰素 、 蒽酮 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以55%的产率得到[10-(3-hydroxy-4-methoxybenzylidene)]-9(10H)-anthracenone
  参考文献：
  名称：

  新型亚苄基-9（10H）-蒽酮作为高活性抗微管剂。合成，抗增殖活性和抑制微管蛋白聚合。

  摘要：

  合成了一系列新的10-亚苄基-9（10H）-蒽酮和10-（苯甲基）-9（10H）-蒽酮，并在基于K562白血病细胞的试验中评估了其抗增殖活性。发现3-羟基-4-甲氧基亚苄基类似物9h是活性最高的化合物（IC（50）K562：20 nM）。还考虑了构效关系。使用XTT测定法，包括五种抗药性表型，针对五种肿瘤细胞系测试了高活性化合物9h和2,4-二甲氧基-3-羟基亚苄基类似物9l。使用碘化丙啶在单层测定中确定了多种肿瘤细胞系中细胞死亡的诱导。值得注意的是，与长春碱处理过的细胞相似，该系列中的所有化合物均可在K562细胞中诱导伸长。铅化合物9h对K562细胞生长的影响与G2 / M中的细胞周期停滞有关。测定在用9h和9l处理后停在G2 / M中的50％KB / HeLa细胞的浓度，发现其在0.2μM的范围内。此外，我们监测了9h处理的K562细胞和MCF-7 / Casp-3细胞中剂量依赖性ca

  DOI：

  10.1021/jm0307685

文献信息

• Novel Benzylidene-9(10<i>H</i>)-anthracenones as Highly Active Antimicrotubule Agents. Synthesis, Antiproliferative Activity, and Inhibition of Tubulin Polymerization
  作者：Helge Prinz、Yukihito Ishii、Takeo Hirano、Thomas Stoiber、Juan A. Camacho Gomez、Peter Schmidt、Heiko Düssmann、Angelika M. Burger、Jochen H. M. Prehn、Eckhard G. Günther、Eberhard Unger、Kazuo Umezawa

  DOI：10.1021/jm0307685

  日期：2003.7.1

  compounds such as colchicine, podophyllotoxin, and nocodazole. In general, the antiproliferative activity correlated with inhibition of tubulin polymerization. The most active compounds strongly displaced [(3)H]colchicine from its binding site in the tubulin, yielding IC(50) values 3- to 4-fold lower than that of colchicine. The novel benzylidene-9(10H)-anthracenones described in the present study constitute

  合成了一系列新的10-亚苄基-9（10H）-蒽酮和10-（苯甲基）-9（10H）-蒽酮，并在基于K562白血病细胞的试验中评估了其抗增殖活性。发现3-羟基-4-甲氧基亚苄基类似物9h是活性最高的化合物（IC（50）K562：20 nM）。还考虑了构效关系。使用XTT测定法，包括五种抗药性表型，针对五种肿瘤细胞系测试了高活性化合物9h和2,4-二甲氧基-3-羟基亚苄基类似物9l。使用碘化丙啶在单层测定中确定了多种肿瘤细胞系中细胞死亡的诱导。值得注意的是，与长春碱处理过的细胞相似，该系列中的所有化合物均可在K562细胞中诱导伸长。铅化合物9h对K562细胞生长的影响与G2 / M中的细胞周期停滞有关。测定在用9h和9l处理后停在G2 / M中的50％KB / HeLa细胞的浓度，发现其在0.2μM的范围内。此外，我们监测了9h处理的K562细胞和MCF-7 / Casp-3细胞中剂量依赖性ca
• Nitrosated and nitrosylated compounds, compositions and methods use
  申请人：Earl A. Richard

  公开号：US20060009431A1

  公开（公告）日：2006-01-12

  The invention describes novel nitrosated and/or nitrosylated compounds of the invention, and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated compound of the invention, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one compound of the invention, that is optionally nitrosated and/or nitrosylated, and at least one nitric oxide donor compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating cardiovascular diseases, for inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering at least one compound of the invention that is optionally nitrosated and/or nitrosylated, in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The compounds of the invention are preferably estradiol compounds, troglitazone compounds, tranilast compounds, retinoic acid compounds, resveratol compounds, myophenolic acid compounds, acid compounds, anthracenone compounds and trapidil compounds.

  该发明描述了该发明的新型亚硝酰化和/或亚硝基化化合物及其药学上可接受的盐，并且描述了包含至少一种该发明的亚硝酰化和/或亚硝基化化合物的新型组合物，以及可选地包含至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型组合物。该发明还提供了包含至少一种该发明化合物的新型组合物，该化合物可选地亚硝酰化和/或亚硝基化，以及至少一种一氧化氮供体化合物和/或至少一种治疗剂。该发明的化合物和组合物也可以与基质结合。该发明还提供了治疗心血管疾病、抑制血液暴露于医疗设备导致的血小板聚集和粘附、治疗由异常细胞增殖引起的病理性状况；移植排斥、自身免疫、炎症、增殖、过度增殖或血管疾病；减少瘢痕组织或抑制伤口收缩，特别是通过在生理条件下给予至少一种可选地亚硝酰化和/或亚硝基化的该发明化合物与能够释放一氧化氮或在生理条件下间接传递或传递一氧化氮到靶位点的一氧化氮供体的组合物来预防和/或治疗再狭窄的预防性和/或治疗性治疗的方法。该发明的化合物首选为雌二醇化合物、曲格列酮化合物、曲安奈德化合物、视黄酸化合物、白藜芦醇化合物、肌酚酸化合物、酸化合物、蒽酮化合物和曲唑酮化合物。
• NITROSATED AND NITROSYLATED COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Nitromed, Inc.

  公开号：EP1603933A2

  公开（公告）日：2005-12-14
• [EN] NITROSATED AND NITROSYLATED COMPOUNDS, COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSES ET COMPOSITIONS NITROSES ET NITROSYLES, ET LEURS METHODES D'UTILISATION
  申请人：NITROMED INC

  公开号：WO2004098538A2

  公开（公告）日：2004-11-18

  The invention describes novel nitrosated and/or nitrosylated compounds of the invention, and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated compound of the invention, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one compound of the invention, that is optionally nitrosated and/or nitrosylated, and at least one nitric oxide donor compound and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating cardiovascular diseases, for inhibiting platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering at least one compound of the invention that is optionally nitrosated and/or nitrosylated, in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The compounds of the invention are preferably estradiol compounds, troglitazone compounds, tranilast compounds, retinoic acid compounds, resveratol compounds, myophenolic acid compounds, acid compounds, anthracenone compounds and trapidil compounds.
• 177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy
  作者：Josefine Reber、Stephanie Haller、Christopher P. Leamon、Cristina Müller

  DOI：10.1158/1535-7163.mct-13-0422-t

  日期：2013.11.1

  Targeted radionuclide therapy has shown impressive results for the palliative treatment of several types of cancer diseases. The folate receptor has been identified as specifically associated with a variety of frequent tumor types. Therefore, it is an attractive target for the development of new radionuclide therapies using folate-based radioconjugates. Previously, we found that pemetrexed (PMX) has a favorable effect in reducing undesired renal uptake of radiofolates. Moreover, PMX also acts as a chemotherapeutic and radiosensitizing agent on tumors. Thus, the aim of our study was to investigate the combined application of PMX and the therapeutic radiofolate 177Lu-EC0800. Determination of the combination index (CI) revealed a synergistic inhibitory effect of 177Lu-EC0800 and PMX on the viability of folate receptor–positive cervical (KB) and ovarian (IGROV-1) cancer cells in vitro (CI &lt; 0.8). In an in vivo study, tumor-bearing mice were treated with 177Lu-EC0800 (20 MBq) and a subtherapeutic (0.4 mg) or therapeutic amount (1.6 mg) of PMX. Application of 177Lu-EC0800 with PMXther resulted in a two- to four-fold enhanced tumor growth delay and a prolonged survival of KB and IGROV-1 tumor-bearing mice, as compared to the combination with PMXsubther or untreated control mice. PMXsubther protected the kidneys from undesired side effects of 177Lu-EC0800 (20 MBq) by reducing the absorbed radiation dose. Intact kidney function was shown by determination of plasma parameters and quantitative single-photon emission computed tomography using 99mTc-DMSA. Our results confirmed the anticipated dual role of PMX. Its unique features resulted in an improved antitumor effect of folate-based radionuclide therapy and prevented undesired radio-nephrotoxicity. Mol Cancer Ther; 12(11); 2436–45. ©2013 AACR.

  摘要 靶向放射性核素疗法在几种癌症的姑息治疗方面取得了令人瞩目的成果。叶酸受体已被确认与多种常见肿瘤类型特别相关。因此，它是利用基于叶酸的放射性缀合物开发新型放射性核素疗法的一个有吸引力的靶点。此前，我们发现培美曲塞（PMX）在减少肾脏对放射性叶酸的摄取方面具有良好的效果。此外，培美曲塞（PMX）还是一种肿瘤化疗和放射增敏剂。因此，我们的研究旨在探讨 PMX 和治疗性放射性酚 177Lu-EC0800 的联合应用。组合指数（CI）的测定显示，177Lu-EC0800 和 PMX 对叶酸受体阳性的宫颈癌（KB）和卵巢癌（IGROV-1）细胞在体外的活力有协同抑制作用（CI &lt; 0.8）。在一项体内研究中，用 177Lu-EC0800（20 MBq）和亚治疗量（0.4 毫克）或治疗量（1.6 毫克）的 PMX 对携带肿瘤的小鼠进行治疗。与联合使用 PMXsubther 或未经处理的对照组小鼠相比，使用 177Lu-EC0800 和 PMXther 可使 KB 和 IGROV-1 肿瘤小鼠的肿瘤生长延缓率提高 2 至 4 倍，存活时间延长。PMXsubther 通过减少吸收的辐射剂量，保护肾脏免受 177Lu-EC0800（20 MBq）不良副作用的影响。通过测定血浆参数和使用 99mTc-DMSA 进行定量单光子发射计算机断层扫描显示了肾脏功能完好。我们的研究结果证实了 PMX 预期的双重作用。它的独特功能提高了以叶酸为基础的放射性核素疗法的抗肿瘤效果，并防止了不必要的放射性肾毒性。Mol Cancer Ther; 12(11); 2436-45。©2013 AACR。