SN38-propionate-C20

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: SN38-propionate-C20
• 英文别名: [(19S)-10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl] propanoate
• 化学式: C₂₅H₂₄N₂O₆
• 分子量: 448.475
• InChiKey: YYUJETXHZGWYLR-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  7-乙基-10-羟基喜树碱 在 吡啶 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 SN38-propionate-C20
  参考文献：
  名称：

  SN38的亲脂性前药：口服化学疗法的合成和体外表征。

  摘要：

  SN38（7-乙基-10-羟基喜树碱）是一种有效的抗癌药物，属于喜树碱家族；然而，其口服递送受到在药学上可接受的赋形剂中不良的溶解性和低的透粘膜渗透性的广泛限制。基于脂质的载体因其改善脂质可溶和高渗透性化合物的口服吸收和生物利用度的能力而闻名。因此，该研究集中于通过特定的化学修饰来提高在脂质赋形剂中的溶解度，控制稳定性和增强SN38的透粘膜通透性。为了实现这些目的，设计了一系列亲脂性前药，并通过在SN38的C10和/或C20正子上用各种烃链长度的饮食脂肪酸进行酯化来合成。与SN38相比，这些新型前药在长链甘油三酸酯中的溶解度提高了444倍，并且细胞毒性显着降低。前药在模拟胃液中稳定，但在模拟肠液中（在存在酶的情况下）表现出不同的水解速率（t1 / 2 <5分钟至t1 / 2> 2小时），具体取决于烷基链长和修饰的位置。还证实了血浆中前药可预测地转化为SN38。在这些研究的基础上，SN38-

  DOI：

  10.1021/acs.molpharmaceut.5b00785

文献信息

• Multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamptothecin for treatment of breast, colorectal, pancreatic, ovarian and lung cancers
  申请人：Zhao Hong

  公开号：US20070197575A1

  公开（公告）日：2007-08-23

  A four arm-polyethylene glycol-7-ethyl-10-hydroxycamptothecin conjugate, such as, is disclosed. Methods of making the conjugates and methods of treating mammals using the same are also disclosed.

  披露了一种四臂聚乙二醇-7-乙基-10-羟基喜树碱共轭物，以及制备这些共轭物的方法和利用它们治疗哺乳动物的方法。
• Multi-arm polymeric targeting anti-cancer conjugate
  申请人：BrightGene Bio-Medical Technology Co., Ltd.

  公开号：US10869863B2

  公开（公告）日：2020-12-22

  Disclosed is a multi-arm targeting drug conjugate modified by a water-soluble polymer; the drug conjugate has the structural formula of (III). In formula (III), R is an organic core, POLY is a polymer, L is a multivalent linker, T is a targeting molecule, D is a camptothecin-based drug, and q is any integer between 3 and 8. The drug conjugate may improve the poor water solubility, high toxicity and low bioavailability of camptothecin-based drugs.

  本发明公开了一种由水溶性聚合物修饰的多臂靶向药物共轭物；该药物共轭物的结构式为(III)。 式（III）中，R 是有机核，POLY 是聚合物，L 是多价连接体，T 是靶向分子，D 是喜树碱类药物，q 是 3 到 8 之间的任意整数。 该药物共轭物可改善喜树碱类药物水溶性差、毒性大和生物利用率低的问题。
• TREATMENT OF RESISTANT OR REFRACTORY CANCERS WITH MULTI-ARM POLYMERIC CONJUGATES OF 7-ETHYL-10-HYDROXYCAMPTOTHECIN
  申请人：ZHAO Hong

  公开号：US20080193408A1

  公开（公告）日：2008-08-14

  A method of treating a resistant or refractory cancer in a mammal includes administering an effective amount of a compound of to the mammal. In preferred aspects, the cancer is resistant or refractory to CPT-11 or CPT therapy.
• MULTI-ARM POLYMERIC CONJUGATES OF 7-ETHYL-10-HYDROXYCAMPTOTHECIN FOR TREATMENT OF BREAST, COLORECTAL, PANCREATIC, OVARIAN AND LUNG CANCERS
  申请人：ZHAO Hong

  公开号：US20090074706A1

  公开（公告）日：2009-03-19

  A four arm-polyethylene glycol-7-ethyl-10-hydroxycamptothecin conjugate, such as, is disclosed. Methods of making the conjugates and methods of treating mammals using the same are also disclosed.
• Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites
  申请人：Govindan Serengulam V.

  公开号：US20120040431A1

  公开（公告）日：2012-02-16

  The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.