Indolocarbazole deriv. 4(g)

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Indolocarbazole deriv. 4(g)
• 英文别名: 6-fluoro-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17,19,21-nonaene-12,14-dione
• 化学式: C₂₀H₁₀FN₃O₂
• 分子量: 343.317
• InChiKey: CHOKPCNUYFDUDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(6-fluoro-1H-indol-3-yl)-3-(1H-indol-3-yl)-maleinimide 在 对甲苯磺酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 苯 为溶剂， 生成 Indolocarbazole deriv. 4(g)
  参考文献：
  名称：

  设计和合成氟吲哚并咔唑系列作为选择性拓扑异构酶I活性剂。发现水溶性3,9-二氟-12,13-二氢-13- [6-氨基-β-D-吡喃葡萄糖基] -5H，13H-苯并[b]-噻吩基[2,3-a]吡咯[ 3,4-c]咔唑-5,7（6H）-二酮（BMS-251873）具有针对前列腺癌异种移植肿瘤模型的治愈性抗肿瘤活性。

  摘要：

  研究了一系列氟吲哚并咔唑的拓扑异构酶I活性，细胞毒性，选择性和体内抗肿瘤活性。从该系列中诞生的是BMS-251873，这是一种潜在的临床候选药物，具有强大的药理特性，包括对前列腺癌的治愈性抗肿瘤活性。

  DOI：

  10.1021/jm034197s

文献信息

• Synthesis, Structure−Activity Relationship, and Biological Studies of Indolocarbazoles as Potent Cyclin D1-CDK4 Inhibitors
  作者：Guoxin Zhu、Scott E. Conner、Xun Zhou、Chuan Shih、Tiechao Li、Bryan D. Anderson、Harold B. Brooks、Robert Morris Campbell、Eileen Considine、Jack A. Dempsey、Margaret M. Faul、Cathy Ogg、Bharvin Patel、Richard M. Schultz、Charles D. Spencer、Beverly Teicher、Scott A. Watkins

  DOI：10.1021/jm0256169

  日期：2003.5.1

  Novel substituted indolocarbazoles were synthesized, and their kinase inhibitory capability was evaluated in vitro. 6-Substituted indolocarbazoles 4 were found to be potent and selective D1/CDK4 inhibitors. 4d and 4h exhibited potent and ATP-competitive D1/CDK4 activities with IC50 values of 76 and 42 nM, respectively. Both compounds had high selectivity against the other kinases. These D1/CDK4 inhibitors inhibited tumor cell growth, arrested tumor cells at the G1 phase, and inhibited pRb phosphorylation.
• Design and Synthesis of a Fluoroindolocarbazole Series as Selective Topoisomerase I Active Agents. Discovery of Water-Soluble 3,9-Difluoro-12,13-dihydro-13-[6-amino-β- <scp>d</scp>-glucopyranosyl]-5<i>H</i>,13<i>H</i>-benzo[<i>b</i>]- thienyl[2,3-<i>a</i>]pyrrolo[3,4-<i>c</i>]carbazole- 5,7(6<i>H</i>)-dione (BMS-251873) with Curative Antitumor Activity against Prostate Carcinoma Xenograft Tumor Model
  作者：Balu N. Balasubramanian、Denis R. St. Laurent、Mark G. Saulnier、Byron H. Long、Carol Bachand、Francis Beaulieu、Wendy Clarke、Milind Deshpande、Jeffrey Eummer、Craig R. Fairchild、David B. Frennesson、Robert Kramer、Frank Y. Lee、Mikael Mahler、Alain Martel、B. Narasimhulu Naidu、William C. Rose、John Russell、Edward Ruediger、Carola Solomon、Karen M. Stoffan、Henry Wong、Kurt Zimmermann、Dolatrai M. Vyas

  DOI：10.1021/jm034197s

  日期：2004.3.1

  A series of fluoroindolocarbazoles were studied with respect to their topoisomerase I activity, cytotoxicity, selectivity, and in vivo antitumor activity. Emerging from this series was BMS-251873, a potential clinical candidate possessing a robust pharmacological profile including curative antitumor activity against prostate carcinoma.

  研究了一系列氟吲哚并咔唑的拓扑异构酶I活性，细胞毒性，选择性和体内抗肿瘤活性。从该系列中诞生的是BMS-251873，这是一种潜在的临床候选药物，具有强大的药理特性，包括对前列腺癌的治愈性抗肿瘤活性。