colchinolmethyl ether | 84092-82-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: colchinolmethyl ether
• 英文别名: N-deacetylcolchinyl methyl ether；Colchinol-methylaether；(S)-3,9,10,11-tetramethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-ylamine；(S)-7-Amino-1.2.3.9-tetramethoxy-6.7-dihydro-5H-dibenzo[a.c]cyclohepten；(S)-3,9,10,11-Tetramethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-ylamin; Colchinol-methylaether；(5S)-3,9,10,11-tetramethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-ylamine；O-Methyl-colchinol；(8S)-5,13,14,15-tetramethoxytricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,11,13-hexaen-8-amine
• CAS: 84092-82-0
• 化学式: C₁₉H₂₃NO₄
• 分子量: 329.396
• InChiKey: MAHWPDWNBBRICZ-HNNXBMFYSA-N

物化性质

• 沸点：
  498.8±45.0 °C(Predicted)
• 密度：
  1.146±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  62.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  colchinolmethyl ether 在 敌草腈 、 草酸 、 N-甲基吡啶-4-羰甲醛苯磺酸盐 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以67%的产率得到7-Deamino-7-oxocolchinol methyl ether
  参考文献：
  名称：

  NCME系列的新型B环修饰的allocolchicinoids：设计，合成，抗微管活性和细胞毒性。

  摘要：

  合成了两个新的模拟（-）-N-乙酰胆碱O-甲基醚（2，NCME）结构的新的allocolchicinoids系列，并评估了它们抑制微管蛋白装配的能力。在人MCF-7乳腺癌细胞系上体外评估了由此产生的可能的抗肿瘤特性。第一组NCME衍生物是通过将七元B环延伸至新颖的半合成变异，并使用含氮的八元B环，例如类似于人工有效的替加那星氮杂类似物3而形成的。第二个系列是通过用杂环系统进行环修饰对NCME（2）的七元B环进行修饰。外消旋酮7a是参与所有目标NCME变体9-13和15合成的关键前体 通过相应的E-肟8的贝克曼重排，将16容易地转变成八元B-环内酰胺9和10。通过叠氮三甲基硅烷介导的施密特重排制备四唑环化的同源物11。用Bredereck试剂处理离析物7a会产生烯胺酮14，该烯胺酮很容易转化为吡唑或嘧啶环化的拟鬼臼类固醇15和16。值得注意的是，所有带有偶氮霉素B环的拟鬼臼类固醇9-13都会

  DOI：

  10.1016/s0968-0896(02)00639-9
• 作为产物：
  描述：

  3,9,10,11-tetramethoxy-6,7-dihydro-dibenzo[a,c]cyclohepten-5-one oxime 在 甲醇 、 镍 、 6,6′-dinitro[1,1′-biphenyl]-2,2′-dicarboxylic acid 作用下， 80.0~90.0 ℃ 、7.35 MPa 条件下， 生成 colchinolmethyl ether
  参考文献：
  名称：

  Cook et al., Journal of the Chemical Society, 1951, p. 1397,1401

  摘要：

  DOI：

文献信息

• Antitumor Agents. 192. Antitubulin Effect and Cytotoxicity of C(7)-Oxygenated Allocolchicinoids
  作者：Jian Guan、Xiao-Kang Zhu、Arnold Brossi、Yoko Tachibana、Kenneth F. Bastow、Pascal Verdier-Pinard、Ernest Hamel、Andrew T. McPhail、Kuo-Hsiung Lee

  DOI：10.1135/cccc19990217

  日期：——

  Two allocolchicinoids 6 and 8, prepared from colchicine, together with allo compounds 9-11, made from 6 by reduction and regiodemethylation, were evaluated for antitubulin and antitumor activities. Structures of 6, 8, and 10 were confirmed by X-ray crystallographic analysis. Compounds 6, 8, and 9 have high tubulin binding affinity and display potent inhibitory activities against tubulin polymerization and solid human tumor cell lines. Particularly, drug-resistant KB cell lines, including KB-7d, KB-VCR, and KB-CPT, do not show marked resistance to these compounds.

  两种源自秋水仙碱的异秋水仙素衍生物 6 和 8，以及通过还原和区域去甲基化从 6 制得的异化合物 9-11，被评估了它们的抗微管和抗肿瘤活性。6、8 和 10 的结构通过 X 射线晶体学分析得到了确认。化合物 6、8 和 9 对微管结合有高亲和力，并且对微管聚合和实体人类肿瘤细胞系显示出强大的抑制活性。特别是，包括 KB-7d、KB-VCR 和 KB-CPT 在内的耐药 KB 细胞系对这些化合物并未表现出显著的耐药性。
• Colchinol derivatives as angiogenesis inhibitors
  申请人：——

  公开号：US20030195173A1

  公开（公告）日：2003-10-16

  The invention related to colchinol derivatives of the formula (I): Wherein: R 1 , R 2 and R 3 are each independently hydroxy, phosphoryloxy (—OPO 3 H 2 ), C 1-4 alkoxy or an in vivo hydrolysable ester of hydroxy, with the proviso that at least 2 of R 1 , R 2 and R 3 are C 1-4 alkoxy; A is —CO—, —C(O)O—, —CON(R 8 )— (wherein R 8 is hydrogen, C 1-4 alkyl, C 1-3 alkoxyC 1-3 alkyl, aminoC 1-3 alkyl or hydroxyC 1-3 alkyl); a is an integer from 1 to 4 inclusive; R a and R b are independently selected from hydrogen, hydroxy and amino; B is —O—, —CO—, N(R 9 )CO—, —CON(R 9 )—, —N(R 9 )C(O)O—, —N(R 9 )CON(R 10 )—, —N(R 9 )SO 2 —, —SO 2 N(R 9 )— or a direct single blond (wherein R 9 and R 10 are independently selected from hydrogen, C 1-4 alkyl, C 1-3 alkoxyC 1-3 alkyl,aminoC 1-3 alkyl and hydroxyC 1-3 alkyl); b is O or an integer from 1 to 4 inclusive, (provided that when bis O, B is a single direct bond); D is carboxy, sulpho, tetrazolyl, imidazolyl, phosphoryloxy, hydroxy, amino, N-(C 1-4 alkyl)amino, N,N-di(C 1-3 alkyl)amino, or of the formula-Y 1 (CH 2 ) 0 R 11 or —NHCH(R 12 )COOH;[wherein Y 1 is a direct single bond, —O—, —C(O)—, —N(R 13 )C(O)— or —C(O)N(R 13 )— (wherein R 13 is hydrogen, C 1-4 alkyl,C 1-3 alkoxyC 2-3 alkyl, aminoC 2-3 alkyl or hydroxyC 2-3 alkyl); e is O or an integer from 1 to 4 inclusive.

  与化学相关的发明，涉及公式(I)的秋水仙碱衍生物：其中：R1、R2和R3分别独立地为羟基、磷酸酯基（—OPO3H2）、C1-4烷氧基或羟基的体内可水解酯，但至少其中2个为C1-4烷氧基；A为—CO—、—C(O)O—、—CON(R8)—（其中R8为氢、C1-4烷基、C1-3烷氧基烷基、氨基烷基或羟基烷基）；a为1到4的整数；Ra和Rb分别独立地选自氢、羟基和氨基；B为—O—、—CO—、N(R9)CO—、—CON(R9)—、—N(R9)C(O)O—、—N(R9)CON(R10)—、—N(R9)SO2—、—SO2N(R9)—或直接单键（其中R9和R10分别独立地选自氢、C1-4烷基、C1-3烷氧基烷基、氨基烷基和羟基烷基）；b为O或1到4的整数，（当b为O时，B为单一直接键）；D为羧基、磺酸基、四唑基、咪唑基、磷酸酯基、羟基、氨基、N-(C1-4烷基)氨基、N,N-二(C1-3烷基)氨基，或公式-Y1(CH2)0R11或—NHCH(R12)COOH；[其中Y1为直接单键、—O—、—C(O)—、—N(R13)C(O)—或—C(O)N(R13)—（其中R13为氢、C1-4烷基、C1-3烷氧基烷基、氨基烷基或羟基烷基）；e为O或1到4的整数。
• 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。
• Antitumor Agents 238. Anti-tubulin and in vitro Cytotoxic Effects of N-Substituted Allocolchicinoids
  作者：Kuo-Hsiung Lee、Kyoko Nakagawa-Goto、M. Katherine Jung、Ernest Hamel、Chin-Chung Wu、Kenneth F. Bastow、Arnold Brossi、Shunsaku Ohta

  DOI：10.3987/com-04-10244

  日期：——
• Oxidation of Gas Mixtures Containing Dimethyl Sulfide, Hydrogen Sulfide, and Methanethiol Using a Two-Stage Biotrickling Filter
  作者：Arja Ruokojärvi、Juhani Ruuskanen、Pertti J. Martikainen、Minna Olkkonen

  DOI：10.1080/10473289.2001.10464260

  日期：2001.1

  A biofiltration technique was developed for removing a mixture of hydrogen sulfide (H2S), methanethiol (MeSH), and dimethyl sulfide (Me2S) from waste gases. Since H2S, especially at high concentrations, disturbs the removal of Me2S, two biotrickling filters with different microbes and operating pH levels were connected in series to create a two-stage system. Different loads of these gases were studied in order to determine their impact on the removal capacity of the system. The microbial consortia for these filters were enriched from the sludge of a Finnish refinery with bubbling H2S or Me2S. Acclimation for Me2S took 2 weeks, though no acclimation time was needed for the other gases. The first filter, at a pH of 2, removed most of the H2S and some of the MeSH and Me2S. The second filter, at a pH of similar to6.5, removed the rest of the MeSH and most of the Me2S. The total maximum loads of the whole two-stage biotrickling filter were 1150 g/m(3)/day for H2S-S (suffix S indicates the results are counted as sulfur amounts), 879 g/m(3)/day for Me2S-S, and 66 g/m(3)/day for MeSH-S treated in a gas mixture. The average removal efficiencies for all gases tested were 99% or higher.