去乙酰氨基秋水仙碱 | 1420-08-2

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 中文名称: 去乙酰氨基秋水仙碱
• 英文名称: deacetamidocolchicine
• 英文别名: 1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one；1,2,3,10-Tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-on；Desacetamidocolchicine；1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one
• CAS: 1420-08-2
• 化学式: C₂₀H₂₂O₅
• 分子量: 342.392
• InChiKey: IPDJRYUVROTJTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 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：
  54
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2914509090

反应信息

• 作为反应物：
  描述：

  去乙酰氨基秋水仙碱 、 sodium thiomethoxide 以 四氢呋喃 、 水 为溶剂， 生成 1,2,3-Trimethoxy-10-methylmercapto-6,7-dihydro-5H-benzoheptalen-9-on
  参考文献：
  名称：

  Discovery of structurally simplified analogs of colchicine as an immunosuppressant

  摘要：

  We have discovered a new class of colchicine-derived therapeutic agents for immune diseases including rejection of organ-transplantation and autoimmune disease. Compound 2, which had been developed to overcome poor pharmacokinetic properties of compound 1, a first-generation colchicine analog, turned out to show toxicity such as intestinal toxicity and loss of weight during in vivo tests. The deletion of 7-carboxamide group and middle ring-truncation in colchicine allowed us to have structurally simplified analogs with strong immunosuppressive activity. Herein, we report non-alkaloid tricyclic compound 7 and 12 as immunosuppressants which exhibited a strong immunosuppressive in vivo efficacy on the T-dependent antibody response, the Zymosan A-induced arthritis model and the Carrageenan-induced edema model. Compound 7 and 12 revealed less toxicity than the previous lead compound 2, and their minimum lethal doses (MLD) were proved to exceed 100 mg/kg. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.007
• 作为产物：
  描述：

  Eschenmoser's α-pyrone 在 氢氧化钾 、 溶剂黄146 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 甲苯 、 苯 为溶剂， 反应 32.0h， 生成 去乙酰氨基秋水仙碱
  参考文献：
  名称：

  Thermal, four-carbon + three-carbon cycloaddition reaction of cyclopropenone ketals. Total synthesis of deacetamidocolchiceine: formal total synthesis of colchicine

  摘要：

  DOI：

  10.1021/jo00218a042

文献信息

• [EN] POLYOXAZOLINE ANTIBODY DRUG CONJUGATES<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENT DE POLYOXAZOLINE
  申请人：SERINA THERAPEUTICS INC

  公开号：WO2016019340A1

  公开（公告）日：2016-02-04

  In the present disclosure, polymer conjugates, including polymer-antibody-drug conjugates (polymer ADCs) are described, as well as the use of such conjugates to treat human disease. The polymer conjugates can contain a large number of polymer-bound agents, thus effectively increasing the drug antibody ration (DAR) of the antibody significantly beyond the currently available technology. This may be of particular importance when antibodies to low density antigens are used as target antibodies. The described polymer-ADCs have improved pharmacokinetics and solubility relative to traditional ADCs. The linker between agent and the polymer can be tailored to provide release of toxin at the desired site and under the desired conditions within the tumor. An additional feature of the polymer-ADCs of the current disclosure is that a purification moiety can be attached to the polymer backbone to provide ease of purification of the polymer-ADCs.

  本公开描述了聚合物偶联物，包括聚合物-抗体-药物偶联物（聚合物ADCs），以及使用这些偶联物治疗人类疾病。该聚合物偶联物可以含有大量的聚合物结合剂，从而有效提高抗体的药物抗体比率（DAR），显著超过目前现有技术。当使用针对低密度抗原的抗体作为靶点抗体时，这一点可能尤为重要。与传统的ADC相比，所述聚合物ADC具有改善的药代动力学和溶解性。毒素与聚合物之间的连接器可以根据需要在肿瘤内特定部位和特定条件下释放毒素进行定制。当前公开的聚合物ADC的另一个特点是，可以在聚合物主链上附着一个纯化部分，以提供聚合物ADC的纯化便利。
• Conformationally Restricted 4-Substituted-2,6-dimethylfuro[2,3-d]pyrimidines as Multi-targeted Receptor Tyrosine Kinase Inhibitors and Microtubule Targeting Antitumor Agents
  申请人：Duquesne University of the Holy Spirit

  公开号：US20160176891A1

  公开（公告）日：2016-06-23

  Compounds of Formula I: and compounds of Formula II: are provided. Pharmaceutical compositions comprising either the compound of Formula I or Formula II are disclosed. Methods of treating patients having cancer are provided by administering to the patient a therapeutically effective amount of one or more compounds having Formula I or Formula II to treat the patient. The compounds of Formula I or II are preferably conformationally restricted furo[2,3-d]pyrimidines having dual inhibition of microtubule assembly and receptor tyrosine kinases.

  提供了化学式I和化学式II的化合物。揭示了包含化学式I或化学式II化合物的制药组合物。通过向患有癌症的患者投与具有化学式I或化学式II的一个或多个化合物的治疗有效量来治疗患者的方法。化学式I或II的化合物通常是具有微管组装和受体酪氨酸激酶双重抑制作用的构象限制的呋喃[2,3-d]嘧啶类化合物。
• CLEAVABLE DRUG CONJUGATES, COMPOSITIONS THEREOF AND METHODS OF USE
  申请人：Nguyen Mark Quang

  公开号：US20160129027A1

  公开（公告）日：2016-05-12

  Base-labile crosslinkers, base-labile conjugates comprising such crosslinkers, methods of their synthesis and use are disclosed.

  本发明揭示了一种碱敏感的交联剂，包括这种交联剂的碱敏感的共轭物，以及它们的合成方法和使用方法。
• Sustained-release formulations of colchicine and methods of using same
  申请人：Murray and Poole Enterprises, LTD.

  公开号：US10610488B2

  公开（公告）日：2020-04-07

  Pharmaceutical compositions of colchicine for once-a-day oral administration are provided. The formulations comprise a sustained-release component and an optional immediate-release component, the compositions of which can be selectively adjusted, respectively, to release the active ingredient along a pre-determined or desired release profile. Methods of treating or preventing cardiovascular disease and/or inflammatory disease in mammalian subjects comprising the administration of the novel formulations disclosed herein are also provided.

  本研究提供了每日口服一次的秋水仙碱药物组合物。这些制剂包括一种缓释成分和一种可选的速释成分，其组合物可分别进行选择性调整，以按照预先确定或所需的释放曲线释放活性成分。此外，还提供了治疗或预防哺乳动物心血管疾病和/或炎症性疾病的方法，包括施用本文公开的新型制剂。
• Method of treating cardiovascular events using colchicine concurrently with an antiplatelet agent
  申请人：Murray and Poole Enterprises, LTD.

  公开号：US10842762B2

  公开（公告）日：2020-11-24

  Methods of treating and/or preventing a cardiovascular event in a patient, the method comprising orally administering a colchicine to a patient who is receiving concurrent treatment with at least one antiplatelet agent, thereby treating and/or preventing the cardiovascular event in the patient are provided.

  提供了治疗和/或预防患者心血管事件的方法，该方法包括向同时接受至少一种抗血小板药物治疗的患者口服秋水仙碱，从而治疗和/或预防患者的心血管事件。