7-methoxy-3-methyl-9H-carbazol-2-yl 5-(dimethylamino)naphthalene-1-sulfonate | 1207532-13-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 7-methoxy-3-methyl-9H-carbazol-2-yl 5-(dimethylamino)naphthalene-1-sulfonate
• 英文别名: KED-4-67；(7-methoxy-3-methyl-9H-carbazol-2-yl) 5-(dimethylamino)naphthalene-1-sulfonate
• CAS: 1207532-13-5
• 化学式: C₂₆H₂₄N₂O₄S
• 分子量: 460.554
• InChiKey: CZTSUJBLLLDAQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  80
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-碘基-3-硝基苯甲醚 在 四(三苯基膦)钯 、 potassium carbonate 、 三乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 水 、 邻二氯苯 、 乙腈 为溶剂， 反应 15.0h， 生成 7-methoxy-3-methyl-9H-carbazol-2-yl 5-(dimethylamino)naphthalene-1-sulfonate
  参考文献：
  名称：

  Novel Carbazole Inhibits Phospho-STAT3 through Induction of Protein–Tyrosine Phosphatase PTPN6

  摘要：

  The aberrant activation of STAT3 occurs in many human cancers and promotes tumor progression. Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3. Synthesized carbazole derived with fluorophore compound 12 was discovered to target STAT3 phosphorylation. Compound 12 was found to inhibit STAT3-mediated transcription as well as to reduce IL-6 induced STAT3 phosphorylation in cancer cell lines expressing both elevated and low levels of phospho-STAT3 (Y705). Compound 12 potently induced apoptosis in a broad number of TNBC cancer cell lines in vitro and was effective at inhibiting the in vivo growth of human TNBC xenograft tumors (SUM149) without any observed toxicity. Compound 12 also effectively inhibited the growth of human lung tumor xenografts (A549) harboring aberrantly active STAT3. In vitro and in vivo studies showed that the inhibitory effects of 12 on phospho-STAT3 were through up-regulation of the protein-tyrosine phosphatase PTPN6. Our present studies strongly support the continued preclinical evaluation of compound 12 as a potential chemotherapeutic agent for TNBC and cancers with constitutive STAT3 signaling.

  DOI：

  10.1021/jm4018042

文献信息

• [EN] RADIOPROTECTOR COMPOUNDS<br/>[FR] COMPOSÉS RADIOPROTECTEURS
  申请人：ROSEN ELIOT M

  公开号：WO2013138600A1

  公开（公告）日：2013-09-19

  Radioprotector compounds including 3,3'-diindolylmethane (DIM) analogs, are provided. Further provided are methods for their use in reducing or preventing radiation damage, killing a tumor cell and protecting a non-tumor cell, and treating cancer.

  放射防护化合物包括3,3'-二吲哚甲烷（DIM）类似物。进一步提供了它们在减少或预防辐射损伤、杀死肿瘤细胞、保护非肿瘤细胞以及治疗癌症方面的使用方法。
• FLUORESCENT REGULATORS OF RASSF1A EXPRESSION AND HUMAN CANCER CELL PROLIFERATION
  申请人：Brown Milton L.

  公开号：US20110152339A1

  公开（公告）日：2011-06-23

  The invention provides methods for the treatment of cancer in a subject comprising administering a dansyl-carbazole compound.

  本发明提供了一种治疗癌症的方法，包括给予丹磺酰基-咔唑类化合物给受试者。
• Fluorescent regulators of RASSF1A expression and human cancer cell proliferation
  申请人：Georgetown University

  公开号：EP2484666A1

  公开（公告）日：2012-08-08

  The invention provides carbazole compounds, and prodrugs therefor, comprising a heterogroup coupled to an aryl group, wherein the heterogroup is selected from the group consisting of SO2, S=O, C=O, NH, and PO3. The aryl group may be substituted with one or more substituents selected from the group consisting of OH, NH2, NR1R2, NHR1, OCH3, OCHR1R2, OCH2R1, OCR1R2R3, C=O, or S=O, wherein R1, R2, and R3 are alkyl groups, optionally wherein the heterogroup coupled to the aryl group is a dansyl group, and optionally wherein the heterogroup coupled to the aryl group is a fluorescent group. The compounds are useful for the treatment of cancers, especially those with decreased Ras-association domain family 1A (RASSF1A) expression, including prostate cancer. The compounds may reduce DNA methyltransferase activity and/or increase RASSF1A expression. Retention of the compound in a cell is diagnostic for decreased RASSF1A expression, and hence potentially for a cancer cell.

  本发明提供了咔唑化合物及其原药，其包含与芳基偶联的杂基，其中杂基选自由SO2、S=O、C=O、NH和PO3组成的组。芳基可被一个或多个取代基取代，这些取代基选自由 OH、NH2、NR1R2、NHR1、OCH3、OCHR1R2、OCH2R1、OCR1R2R3、C=O 或 S=O 组成的组，其中 R1、R2 和 R3 为烷基，偶联至芳基的杂基可选为丹酰基，偶联至芳基的杂基可选为荧光基。 这些化合物可用于治疗癌症，尤其是 Ras-association domain family 1A (RASSF1A) 表达降低的癌症，包括前列腺癌。化合物可降低 DNA 甲基转移酶活性和/或增加 RASSF1A 的表达。 化合物在细胞中的滞留可诊断出 RASSF1A 表达的降低，从而可能诊断出癌细胞。
• Radioprotector compounds
  申请人：GEORGETOWN UNIVERSITY

  公开号：US10266490B2

  公开（公告）日：2019-04-23

  Radioprotector compounds including 3,3′-diindolylmethane (DIM) analogs, are provided. Further provided are methods for their use in reducing or preventing radiation damage, killing a tumor cell and protecting a non-tumor cell, and treating cancer.

  提供了包括 3,3′-二吲哚甲烷（DIM）类似物在内的辐射防护化合物。此外，还提供了将它们用于减少或防止辐射损伤、杀死肿瘤细胞和保护非肿瘤细胞以及治疗癌症的方法。
• Fluorescent Epigenetic Small Molecule Induces Expression of the Tumor Suppressor Ras-Association Domain Family 1A and Inhibits Human Prostate Xenograft
  作者：Kathryn D. Sheikh、Partha P. Banerjee、Shankar Jagadeesh、Scott C. Grindrod、Li Zhang、Mikell Paige、Milton L. Brown

  DOI：10.1021/jm9011615

  日期：2010.3.25

  Epigenetic silencing of Ras-association domain family 1A (RASSF1A) protein in cancer cells results in a disruption of cell cycle control, genetic instability, enhanced cell motility, and apoptotic resistance. Ectopic expression of RASSF1A reverses this tumorigenic phenotype. Thus, small molecules with the ability to restore RASSF1A expression may represent a new class of therapeutic agents. Recently, we designed and synthesized a fluorescent carbazole analogue of mahanine (alkaloid from Murraya koenigii) that restored RASSF1A mRNA expression. Our fluorescent lead compound up-regulated RASSF1A in vitro, potently inhibited human prostate cancer cell proliferation, and fluoresced at a visible wavelength, allowing for the observation of intracellular distribution. The small molecule lead was not acutely toxic up to 550 mg/kg, and dosing at 10 mg/kg reduced human xenograft tumor volume by about 40%.