panicein A | 51847-80-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: panicein A
• 英文别名: 2-[(E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-methylpent-2-enyl]cyclohexa-2,5-diene-1,4-dione
• CAS: 51847-80-4
• 化学式: C₂₂H₂₆O₃
• 分子量: 338.447
• InChiKey: NXLCEZDPQUVCRS-MKMNVTDBSA-N

物化性质

• 沸点：
  488.9±34.0 °C(Predicted)
• 密度：
  1.075±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 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：

  panicein A 在 sodium metabisulfite 作用下， 以 水 、 丙酮 为溶剂， 反应 6.0h， 以86%的产率得到panicein A hydroquinone
  参考文献：
  名称：

  Inhibition of Patched Drug Efflux Increases Vemurafenib Effectiveness against Resistant BrafV600E Melanoma

  摘要：

  患有BRAFV600E突变的黑色素瘤患者接受vemurafenib治疗。几乎所有患者最终都会产生耐药性，导致疾病进展。在这里，我们发现来自海绵的一种小分子，panicein A hydroquinone（PAH），克服了BRAFV600E黑色素瘤细胞对vemurafenib的耐药性，在相应的小鼠人源异种移植模型中导致肿瘤消失。我们报道了PAH的合成，并证明该化合物抑制了Hedgehog受体Patched的药物外流活性。我们的SAR研究确定了一个关键的药效团负责这种活性。我们表明，在一组黑色素瘤患者的转移样本中，Patched强烈表达，并与总生存率降低相关。Patched是一种多药转运蛋白，使用质子动力驱动药物外流。这使其功能特异于癌细胞，从而避免了常见的ABC多药转运蛋白抑制剂的毒性问题。我们的数据提供了强有力的证据，表明PAH是治疗vemurafenib耐药性BRAFV600E黑色素瘤的极具前途的先导化合物。

  DOI：

  10.3390/cancers12061500
• 作为产物：
  描述：

  5-(4-methoxy-2,3,6-trimethylphenyl)-3-(4-methoxyphenoxy)-3-methylpentyne 在 喹啉 、 Lindlar's catalyst 、 ammonium cerium(IV) nitrate 、 氢气 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.33h， 生成 panicein A
  参考文献：
  名称：

  微波介导的克莱森重排，然后进行苯酚氧化：天然存在的1,4-苯醌的简单方法。Verapliquinones A和B和Panicein A的首次合成

  摘要：

  天然存在的1,4-苯醌2-甲氧基-6-丙基-1,4-苯醌（1），2-甲氧基-6-戊基-1,4-苯醌（primin 2），2-甲氧基-6-十五烷基-1,4-苯醌（3），2-甲氧基-6-十七烷基-1,4-苯醌（二氢铱，醌B; 4）是通过简单的方法合成的，该方法涉及微波加速烯丙基醚10的克莱森重排，然后氢化侧链烯烃，然后氧化成醌。基于克莱森（Claisen）的方法扩展到了海洋苯醌，verapliquinones A和B（5和6）和panicein A（7）的首次合成。异双呋喃酮（9）也是通过类似的策略合成的。

  DOI：

  10.1021/jo050336x

文献信息

• Paniceins, unusual aromatic sesquiterpenoids linked to a quinol or quinone system from the marine sponge Halichondria panicea
  作者：G. Cimino、S. De Stefano、L. Minale

  DOI：10.1016/0040-4020(73)80174-7

  日期：1973.1

  Five new substances, panicein-A, -B1, -B2, -B3 and C, containing an aromatic sesquiterpenoid moiety linked to a quinol or a quinone system, have been isolated from the sponge Halichondria panicea. The structures of these compounds were elucidated from their chemical and spectral properties.

  从海绵Halichondria panicea中分离出了五种新物质，panicein-A，-B 1，-B 2，-B 3和C，它们含有与喹诺醇或醌系统连接的芳族倍半萜部分。从它们的化学和光谱性质阐明了这些化合物的结构。
• Panicein compounds, compositions and uses thereof
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：US10376476B2

  公开（公告）日：2019-08-13

  The present invention relates to the fields of medicine and cancer treatment. The invention more specifically relates to the use of a panicein or a derivative thereof, to decrease or inhibit, in vitro or ex vivo, the Patched receptor drug efflux activity, in particular the chemotherapeutic drug efflux activity and chemotherapy resistance. The present disclosure further relates to uses of such compounds, in particular to prepare a pharmaceutical composition to allow or improve the efficiency of a therapy of cancer in a subject in need thereof. The compound of the invention can indeed be advantageously used, in combination with at least one chemotherapeutic drug, for treating cancer, for preventing cancer metastasis and/or for preventing cancer recurrence in a subject. The invention also discloses methods for preventing or treating cancer, cancer metastasis and/or cancer recurrence in a subject, as well as kits suitable for preparing a composition according to the present invention and/or for implementing the herein described methods.

  本发明涉及医药和癌症治疗领域。本发明更具体地涉及一种帕尼辛或其衍生物在体外或体内降低或抑制帕特受体药物外流活性，特别是化疗药物外流活性和化疗耐药性的用途。 本公开进一步涉及此类化合物的用途，特别是制备药物组合物，以允许或提高有需要的受试者治疗癌症的效率。本发明的化合物确实可以与至少一种化疗药物联合使用，有利地用于治疗癌症、防止癌症转移和/或防止受试者癌症复发。 本发明还公开了用于预防或治疗癌症、癌症转移和/或癌症复发的方法，以及适用于制备根据本发明的组合物和/或实施本文所述方法的试剂盒。
• PANICEIN COMPOUNDS, COMPOSITIONS AND THEIR USE IN THE TREATMENT OF CANCER
  申请人：Centre National de la Recherche Scientifique

  公开号：EP3212176B1

  公开（公告）日：2020-11-04
• PANICEIN COMPOUNDS, COMPOSITIONS AND USES THEREOF
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：US20170326076A1

  公开（公告）日：2017-11-16

  The present invention relates to the fields of medicine and cancer treatment. The invention more specifically relates to the use of a panicein or a derivative thereof, to decrease or inhibit, in vitro or ex vivo, the Patched receptor drug efflux activity, in particular the chemotherapeutic drug efflux activity and chemotherapy resistance. The present disclosure further relates to uses of such compounds, in particular to prepare a pharmaceutical composition to allow or improve the efficiency of a therapy of cancer in a subject in need thereof. The compound of the invention can indeed be advantageously used, in combination with at least one chemotherapeutic drug, for treating cancer, for preventing cancer metastasis and/or for preventing cancer recurrence in a subject. The invention also discloses methods for preventing or treating cancer, cancer metastasis and/or cancer recurrence in a subject, as well as kits suitable for preparing a composition according to the present invention and/or for implementing the herein described methods.
• [EN] PANICEIN COMPOUNDS, COMPOSITIONS AND USES THEREOF<br/>[FR] COMPOSÉS DE PANICÉINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2016066594A1

  公开（公告）日：2016-05-06

  The present invention relates to the fields of medicine and cancer treatment. The invention more specifically relates to the use of a panicein or a derivative thereof, to decrease or inhibit, in vitro or ex vivo, the Patched receptor drug efflux activity, in particular the chemotherapeutic drug efflux activity and chemotherapy resistance. The present disclosure further relates to uses of such compounds, in particular to prepare a pharmaceutical composition to allow or improve the efficiency of a therapy of cancer in a subject in need thereof. The compound of the invention can indeed be advantageously used, in combination with at least one chemotherapeutic drug, for treating cancer, for preventing cancer metastasis and/or for preventing cancer recurrence in a subject. The invention also discloses methods for preventing or treating cancer, cancer metastasis and/or cancer recurrence in a subject, as well as kits suitable for preparing a composition according to the present invention and/or for implementing the herein described methods.