(2S,6'R)-(7-chloro-4,6-dimethoxy-benzofuran-3-one)-2-spiro-1'-(2'-(4-biphenylmethoxy)-6'-methyl-cyclohex-2'-en-4'-one) | 1158186-24-3

• 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: (2S,6'R)-(7-chloro-4,6-dimethoxy-benzofuran-3-one)-2-spiro-1'-(2'-(4-biphenylmethoxy)-6'-methyl-cyclohex-2'-en-4'-one)
• 英文别名: (2S,6'R)-(7-chloro-4,6-dimethoxybenzofuran-3-one)-2-spiro-1'-(2'-(4-biphenylmethoxy)-6'-methylcyclohex-2'-ene-4'-one)；(2S,5'R)-7-chloro-4,6-dimethoxy-5'-methyl-3'-[(4-phenylphenyl)methoxy]spiro[1-benzofuran-2,4'-cyclohex-2-ene]-1',3-dione
• CAS: 1158186-24-3
• 化学式: C₂₉H₂₅ClO₆
• 分子量: 504.967
• InChiKey: MFPJCDKJLCZACG-JWRCQZCYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  灰黄霉素 在 硫酸 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium chloride 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 (2S,6'R)-(7-chloro-4,6-dimethoxy-benzofuran-3-one)-2-spiro-1'-(2'-(4-biphenylmethoxy)-6'-methyl-cyclohex-2'-en-4'-one)
  参考文献：
  名称：

  Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells

  摘要：

  Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions. The SAR of the griseofulvin analogues toward the two fungi followed the same trend with the majority being less active than griseofulvin and none had more than twice the potency of the parent compound. A comparison of the antifungal the anticancer SAR revealed distinct differences, as the majority of analogues showed increased activity against the cancer cell line MDA-MB-231, highlighted by 2'-benzyloxy-2'-demethoxy-griseofulvin, which showed low activity against both fungi but was among the most potent compounds against MDA-MB-231 cancer cells. Tubulin has been proposed as the target of griseofulvin in both fungal and mammalian cells, but the differences revealed by this SAR study strongly suggest that the mode-of-action of the compound class toward fungi and mammalian cancer cells is different.

  DOI：

  10.1021/jm200835c

文献信息

• Synthesis and Structure−Activity Relationship of Griseofulvin Analogues as Inhibitors of Centrosomal Clustering in Cancer Cells
  作者：Mads H. Rønnest、Blanka Rebacz、Lene Markworth、Anette H. Terp、Thomas O. Larsen、Alwin Krämer、Mads H. Clausen

  DOI：10.1021/jm801517j

  日期：2009.5.28

  Griseofulvin was identified as an inhibitor of centrosomal clustering in a recently developed assay. Centrosomal clustering is an important cellular event that enables bipolar mitosis for cancer cell lines harboring supernumerary centrosomes. We report herein the synthesis and SAR of 34 griseofulvin analogues as inhibitors of centrosomal clustering. The variations in the griseofulvin structure cover

  在最近开发的测定中，灰黄霉素被鉴定为中心体簇的抑制剂。中心体簇是重要的细胞事件，其使具有过多数量中心体的癌细胞系实现双极有丝分裂。我们在此报道了34个灰黄霉素的类似物的合成和SAR，其为中心体簇的抑制剂。灰黄霉素结构的变化覆盖五个位置，即4、5、2'，3'和4'位置。4和5位的修饰提供了非活性分子。烯醇醚必须位于2'位置，并且4'位置必须为sp 2杂交的。与灰黄霉素相比，活性最高的类似物是2'-苄氧基和2'-（4-甲基苄氧基）类似物，以及前者的肟，其活性增加了25倍。在这项工作中获得的结果与先前报道的皮肤真菌的生长抑制数据的比较显示了相同点和不同点。
• GRISEOFULVIN ANALOGUES FOR THE TREATMENT OF CANCER BY INHIBITION OF CENTROSOMAL CLUSTERING
  申请人：Kraemer Alwin

  公开号：US20120035200A1

  公开（公告）日：2012-02-09

  The invention relates to compounds of the formula (I), where the symbols have the meaning given in the specification, for use in a method for treating cancer, to use of these compounds for the manufacture of a pharmaceutical composition for the treatment of cancer, and to methods of treatment for said diseases employing a compound of formula (I).
• US9108941B2
  申请人：——

  公开号：US9108941B2

  公开（公告）日：2015-08-18
• Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells
  作者：Mads H. Rønnest、Marc S. Raab、Simon Anderhub、Sven Boesen、Alwin Krämer、Thomas O. Larsen、Mads H. Clausen

  DOI：10.1021/jm200835c

  日期：2012.1.26

  Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions. The SAR of the griseofulvin analogues toward the two fungi followed the same trend with the majority being less active than griseofulvin and none had more than twice the potency of the parent compound. A comparison of the antifungal the anticancer SAR revealed distinct differences, as the majority of analogues showed increased activity against the cancer cell line MDA-MB-231, highlighted by 2'-benzyloxy-2'-demethoxy-griseofulvin, which showed low activity against both fungi but was among the most potent compounds against MDA-MB-231 cancer cells. Tubulin has been proposed as the target of griseofulvin in both fungal and mammalian cells, but the differences revealed by this SAR study strongly suggest that the mode-of-action of the compound class toward fungi and mammalian cancer cells is different.