2-methyl-N-[(7R)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]cyclopropane-1-carboxamide | 920759-80-4

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 英文名称: 2-methyl-N-[(7R)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]cyclopropane-1-carboxamide
• CAS: 920759-80-4
• 化学式: C₂₅H₂₉NO₆
• 分子量: 439.508
• InChiKey: CLVDOAYACKFXOJ-PVCYVWKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methyl-N-[(7R)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]cyclopropane-1-carboxamide 、 sodium thiomethoxide 以 四氢呋喃 、 水 为溶剂， 以59%的产率得到2-methyl-N-[(7R)-1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]cyclopropane-1-carboxamide
  参考文献：
  名称：

  Part II. Development of novel colchicine-derived immunosuppressants with improved pharmacokinetic properties

  摘要：

  We have developed a new series of immunosuppressant with improved pharmacokinetic properties as the second-generation of colchicine analogs, which were designed based on the privileged structure derived from our previous work. In particular, we identified an analog (14), which exhibited a potent in vitro activity (IC50: 5 nM) in MLR and excellent in vivo efficacy in the Zymosan A-induced arthritis model, in the Carrageenan-induced edema model and in the local lymph node assay (LLNA). Analog 14 also revealed a good oral bioavailability (F: 67.3%) in BALB/c mice. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.068
• 作为产物：
  描述：

  2-甲基环丙羧酸 、 (+)-N-去乙酰基秋水仙碱 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以86%的产率得到2-methyl-N-[(7R)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]cyclopropane-1-carboxamide
  参考文献：
  名称：

  Part II. Development of novel colchicine-derived immunosuppressants with improved pharmacokinetic properties

  摘要：

  We have developed a new series of immunosuppressant with improved pharmacokinetic properties as the second-generation of colchicine analogs, which were designed based on the privileged structure derived from our previous work. In particular, we identified an analog (14), which exhibited a potent in vitro activity (IC50: 5 nM) in MLR and excellent in vivo efficacy in the Zymosan A-induced arthritis model, in the Carrageenan-induced edema model and in the local lymph node assay (LLNA). Analog 14 also revealed a good oral bioavailability (F: 67.3%) in BALB/c mice. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.068

文献信息

• Novel tricyclic derivatives and their use
  申请人：Chang Dong Jo

  公开号：US20070021427A1

  公开（公告）日：2007-01-25

  The present invention relates to tricyclic colchicine derivatives represented by the formulas (I) or (II), pharmaceutically acceptable salts thereof, and a method for providing an immuno-suppressive or immuno-modulating effect, an anti-proliferative effect, an anti-inflammatory effect or a method for treating cancer comprising administering to a patient an effective amount of one or more colchicine derivatives:

  本发明涉及三环秋水仙素衍生物，其公式表示为(I)或(II)，以及其药学上可接受的盐，以及提供免疫抑制或免疫调节作用、抗增殖作用、抗炎作用或治疗癌症的方法，包括向患者施用一种或多种秋水仙素衍生物的有效量。
• US7622612B2
  申请人：——

  公开号：US7622612B2

  公开（公告）日：2009-11-24
• Part II. Development of novel colchicine-derived immunosuppressants with improved pharmacokinetic properties
  作者：Dong-Jo Chang、Sujin Lee、Jaebong Jang、Soon-Ok Kim、Wan-Joo Kim、Young-Ger Suh

  DOI：10.1016/j.bmcl.2012.08.068

  日期：2012.11

  We have developed a new series of immunosuppressant with improved pharmacokinetic properties as the second-generation of colchicine analogs, which were designed based on the privileged structure derived from our previous work. In particular, we identified an analog (14), which exhibited a potent in vitro activity (IC50: 5 nM) in MLR and excellent in vivo efficacy in the Zymosan A-induced arthritis model, in the Carrageenan-induced edema model and in the local lymph node assay (LLNA). Analog 14 also revealed a good oral bioavailability (F: 67.3%) in BALB/c mice. (C) 2012 Elsevier Ltd. All rights reserved.