7-amino-1,2,3-trimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]-heptalen-9-one | 2731-16-0

• 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: 7-amino-1,2,3-trimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]-heptalen-9-one
• 英文别名: N-deacetylthiocolchicine；Thiocolciran；7-amino-1,2,3-trimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]heptalen-9-one
• CAS: 2731-16-0
• 化学式: C₂₀H₂₃NO₄S
• 分子量: 373.473
• InChiKey: NUNCOHUMTCDISK-UHFFFAOYSA-N

物化性质

• 熔点：
  198 °C
• 沸点：
  631.6±55.0 °C(Predicted)
• 密度：
  1.1860 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  96.1
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  7-amino-1,2,3-trimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]-heptalen-9-one 在 吡啶 、 盐酸 作用下， 反应 72.0h， 生成 (7S)-7-氨基-1,2,3-三甲氧基-10-甲硫基-6,7-二氢-5H-苯并[g]庚搭烯-9-酮
  参考文献：
  名称：

  Antitumor agents—CLXXV. Anti-tubulin action of (+)-thiocolchicine prepared by partial synthesis

  摘要：

  (+)-硫秋水仙素(2b)由(+/-)-秋水仙素(1)经过五步反应制得，其中包括对合适樟脑化衍生物的色谱分离。对(+)-立体异构体进行酸水解，随后乙酰化，得到目标产物2b。与(-)-硫秋水仙素相比，(+)-硫秋水仙素对微管聚合的抑制活性低15倍，且对人骨髓瘤细胞生长的抑制效力低29倍。由(-)-樟脑化立体异构体制备的对映体2a，在所有测定中的活性均与采用其他方法制备的(-)-硫秋水仙素相当。这些结果支持以下假设：秋水仙素相关化合物的正确构型是其抗微管作用的重要要求。 (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00171-5
• 作为产物：
  描述：

  N-(1,2,3,10-四甲氧基-9-氧代-5,6,7,9-四氢苯并[a]庚搭烯-7-基)乙酰胺 在 盐酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 7-amino-1,2,3-trimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]-heptalen-9-one
  参考文献：
  名称：

  Antitumor agents—CLXXV. Anti-tubulin action of (+)-thiocolchicine prepared by partial synthesis

  摘要：

  (+)-硫秋水仙素(2b)由(+/-)-秋水仙素(1)经过五步反应制得，其中包括对合适樟脑化衍生物的色谱分离。对(+)-立体异构体进行酸水解，随后乙酰化，得到目标产物2b。与(-)-硫秋水仙素相比，(+)-硫秋水仙素对微管聚合的抑制活性低15倍，且对人骨髓瘤细胞生长的抑制效力低29倍。由(-)-樟脑化立体异构体制备的对映体2a，在所有测定中的活性均与采用其他方法制备的(-)-硫秋水仙素相当。这些结果支持以下假设：秋水仙素相关化合物的正确构型是其抗微管作用的重要要求。 (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00171-5

文献信息

• COLCHICINE DERIVATIVES
  申请人：——

  公开号：US20040204370A1

  公开（公告）日：2004-10-14

  Certain N-deacetylcolchicine and N-deacetylthiocolchine derivatives are described wherein the 7-N position on the B ring is substituted with the group —C(O)—(CHR 4 ) m -AR, wherein m is an integer of 0-10, A is S, O, N or a covalent bond; R 1 is substituted phenyl or substituted benzoyl; optionally substituted cycloalkyl of 3-7 carbons; optionally substituted naphtyl; an optionally substituted imide ring; an optionally substituted 5 or 6 member heterocycle with at least one N, S, or O in the ring; or an optionally substituted fused heterocyclic or fused carboxyclic ring system; R 2 (at the 2 -position of the A ring) is methoxy, hydroxy, or methylenedioxy when taken together with R 3 ; R 3 (at the 3 -position of the A ring) is methoxy, hydroxy, a monosaccharide radical, or is methylenedioxy when taken together with R 2 ; and R 4 is H or is H or methyl when m is 1. Also dimers of such compounds are disclosed. When combined with suitable pharmaceutical excipients, these compounds are useful for treating various types of cancer.

  描述了某些N-去乙酰基秋水仙碱和N-去乙酰基硫秋水仙碱衍生物，其中B环上的7-N位置被取代为基团—C(O)—(CHR4)m-AR，其中m为0-10的整数，A为S、O、N或共价键；R1为取代苯基或取代苯甲酰基；可选择取代的含有3-7个碳原子的环烷基；可选择取代的萘基；可选择取代的亚胺环；可选择取代的含有至少一个N、S或O的5或6元杂环；或可选择取代的融合杂环或融合环戊二酸环系统；R2（在A环的2位）为甲氧基、羟基或与R3一起时为亚甲二氧基；R3（在A环的3位）为甲氧基、羟基、单糖基团，或与R2一起时为亚甲二氧基；R4为H或在m为1时为H或甲基。此外，还公开了这些化合物的二聚体。与适当的药用辅料结合时，这些化合物可用于治疗各种类型的癌症。
• Tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them
  申请人：Kim Myung-Hwa

  公开号：US20070179143A1

  公开（公告）日：2007-08-02

  The present invention relates to tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. More precisely, the present invention relates to tricyclic derivatives as colchicine derivatives, pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. Tricyclic derivatives of the present invention show very powerful cytotoxicity to cancer cell lines but were much less toxic than colchicine or taxol, confirmed through animal toxicity test. Tricyclic derivatives of the invention also decrease the volume and weight of a tumor and have a strong angiogenesis inhibiting activity in HUVEC cells. Thus, tricyclic derivatives of the present invention can effectively be used as an anticancer agent, anti-proliferation agent and an angiogenesis inhibitor.

  本发明涉及三环衍生物或其药学上可接受的盐、它们的制备方法以及含有它们的制药组合物。更具体地说，本发明涉及三环衍生物作为秋水仙素衍生物，药学上可接受的盐、它们的制备方法以及含有它们的制药组合物。本发明的三环衍生物对癌细胞株表现出非常强大的细胞毒性，但毒性比秋水仙素或紫杉醇要小得多，经动物毒性测试证实。本发明的三环衍生物还可以减少肿瘤的体积和重量，并在HUVEC细胞中表现出强大的抑制血管生成的活性。因此，本发明的三环衍生物可以有效地用作抗癌剂、抗增殖剂和抑制血管生成剂。
• Synthesis and biological activities of chloroethylurea, methylurea, and nitrosourea analogs of N-deacetylmethylthiocolchicine
  作者：Tai-Shun Lin、George T. Shiau、William H. Prusoff、Robert E. Harmon

  DOI：10.1021/jm00186a028

  日期：1980.12

  A series of urea and nitrosourea analogues of N-deacetylmethylthiocolchicine (1) has been synthesized, and their antineoplastic and antiviral activities were evaluated. The objective for combination of two active moieties, such as thiocolchicine and nitrosourea, into one molecule was the generation of compounds with potential improved biological and pharmacological properties. The ED50 for 2, 3, 4, and 5 was 1.6, 1.2, 3.3, and 1.8 X 10(-8) M for L1210 cells and 3.0, 2.7, 2.9, and 2.6 X 10(-8) M for S-180 cells, respectively. The synthesis and cytotoxic and antiviral properties of these compounds are discussed.
• LIN T.; SHIAU G. T.; PRUSOFF W. H.; HARMON R. E., J. MED. CHEM., 1980, 23, NO 12, 1440-1442
  作者：LIN T.、 SHIAU G. T.、 PRUSOFF W. H.、 HARMON R. E.

  DOI：——

  日期：——
• TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：JE IL Pharmaceutical Co., Ltd.

  公开号：EP1646608B1

  公开（公告）日：2011-03-02