tert-butyl [(19S)-19-chlorocarbonyloxy-10,19-diethyl-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-7-yl]carbonate | 1036847-94-5

• 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: tert-butyl [(19S)-19-chlorocarbonyloxy-10,19-diethyl-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-7-yl]carbonate
• 英文别名: 10-O-tert-butoxycarbonyl-20-O-chloroformate-SN-38；BOC-SN38-20-O-chloroformate；tert-butyl [(19S)-19-carbonochloridoyloxy-10,19-diethyl-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-7-yl] carbonate
• CAS: 1036847-94-5
• 化学式: C₂₈H₂₇ClN₂O₈
• 分子量: 554.984
• InChiKey: QQBXLYMJAYSNMG-NDEPHWFRSA-N

物化性质

• 沸点：
  817.3±65.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl [(19S)-19-chlorocarbonyloxy-10,19-diethyl-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-7-yl]carbonate 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 14.67h， 生成
  参考文献：
  名称：

  Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates

  摘要：

  Antibody-drug conjugates (ADCs), combining monoclonal antibody with high cytotoxicity chemotherapeutic drug (warhead), have been successfully applied for clinical cancer therapy. Linker technology to select and design linker connecting warhead with antibody, is critical to the success of therapeutic ADCs. In this study, three kinds of linkers were designed to connect SN-38, the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100-1000 times more potent than CPT-11, with the anti-HER2 antibody trastuzumab to prepare three different ADC conjugates (T-SN38 A, B and C). Meanwhile, we compared the anti-ovarian cancer effect of these three T-SN38 conjugates with trastuzumab in vitro and in vivo. Our in vitro results showed that T-SN38 A, B and C (drug-to-antibody ratio, DAR = 3.7, 3.2, 3.4) were 2 to 3 times as cytotoxic as SN-38, and the IC50 for these three conjugates on SKOV-3 cell line at 72 h were 5.2 +/- 0.3, 4.4 +/- 0.7, and 5.1 +/- 0.4 nM respectively. In our in vivo studies, T-SN38 conjugates had well targeting ability for tumor tissue and all three of them had much higher anti-ovarian cancer potency than trastuzumab. Among of them, T-SN38 B, which coupled SN-38 with trastuzumab by a carbonate bond, has the best anti-ovarian cancer potency. In conclusion, the novel HER2-targeting ADCs T-SN38 have great potential for HER2-positive ovarian cancer. Moreover, the SN-38-Linkers designed in this study can also be used to connect with other antibodies for the therapy of other cancers. (C) 2015 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jconrel.2015.09.058
• 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 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 tert-butyl [(19S)-19-chlorocarbonyloxy-10,19-diethyl-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-7-yl]carbonate
  参考文献：
  名称：

  Rational design of multifunctional small-molecule prodrugs for simultaneous suppression of cancer cell growth and metastasis in vitro and in vivo

  摘要：

  新型“综合”前药平台被合理设计，能够同时诱导细胞凋亡并抑制癌细胞转移，无论是在体外还是体内。

  DOI：

  10.1039/c5cc10367c

文献信息

• [EN] PARA-AMINO-BENZYL LINKERS, PROCESS FOR THEIR PREPARATION AND THEIR USE IN CONJUGATES<br/>[FR] LIEURS PARA-AMINO-BENZYLE, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR UTILISATION DANS DES CONJUGUÉS
  申请人：SERVIER LAB

  公开号：WO2021233944A1

  公开（公告）日：2021-11-25

  The present invention relates to para-amino-benzyl linker compounds useful for linking drug moieties to antibodies, to linker-drug compounds in which said para-amino-benzyl linker compounds are covalently linked to drug moieties, and to antibody-drug conjugates in which said para-amino-benzyl linker compounds are covalently linked to drug wherein said drug is enzymatically cleaved from the conjugate at a particular cell or tissue type targeted by said antibody.

  本发明涉及对氨基苄基连接化合物，用于将药物部分与抗体连接，涉及将所述对氨基苄基连接化合物与药物部分共价连接的连接-药物化合物，以及涉及将所述对氨基苄基连接化合物与药物共价连接的抗体-药物偶联物，其中所述药物通过酶促裂解从偶联物中释放，在由所述抗体靶向的特定细胞或组织类型中。
• Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites
  申请人：Govindan Serengulam V.

  公开号：US20080171067A1

  公开（公告）日：2008-07-17

  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.

  本发明涉及将治疗剂递送到目标细胞、组织或生物体的方法和组合物。在优选的实施例中，治疗剂以负载治疗剂的聚合物形式递送，该聚合物可能包含一个或多个治疗剂的许多拷贝。在更优选的实施例中，聚合物可以与含有一种或多种半抗原的肽部分结合，例如HSG。例如，通过使用双特异性或多特异性抗体或片段的预定位技术，将治疗剂-聚合物-肽复合物递送到目标细胞，该抗体或片段至少有一个结合臂识别半抗原，并且至少有第二个结合臂特异性地结合到与疾病或病原体相关的抗原，例如肿瘤相关抗原。本发明提供了合成和使用此类负载治疗剂的聚合物及其缀合物的方法。
• iRGD-抗癌药物偶联物及其制备方法和应用
  申请人：浙江大学

  公开号：CN105396141B

  公开（公告）日：2018-08-24

  本发明公开了一种iRGD‑抗肿瘤药物偶联物及其制备方法和应用，该偶联物是由抗肿瘤药物通过化学键与iRGD连接而成，结构式如式(I)；其中，X1为喜树碱类和紫杉醇类抗肿瘤药物前体；L为连接桥。本发明的iRGD‑抗肿瘤药物偶联物在水中具有较好的溶解性，可直接静脉注射或加工成其它剂型；本发明的iRGD‑抗肿瘤药物偶联物具有抑制肿瘤细胞迁移和侵袭的能力，并能较好的抑制肿瘤细胞的生长，为肿瘤治疗研究提供了新的方案。
• [EN] CONJUGATES AND COMPOSITIONS FOR DRUG DELIVERY<br/>[FR] CONJUGUÉS ET COMPOSITIONS POUR UNE ADMINISTRATION MÉDICAMENTEUSE
  申请人：BRIGHTGENE BIO MEDICAL TECHNOLOGY CO LTD

  公开号：WO2015106599A1

  公开（公告）日：2015-07-23

  The present invention provides folate receptor binding ligand‐drug delivery conjugates having the formula (F) nL1L2D. The conjugates have high affinity to folate receptor‐positive tumor cells and low toxicity for normal cells. The present invention also relates to preparation methods for such conjugates, pharmaceutical compositions comprising such conjugates, and use of such conjugates for preparing anti‐tumor medicaments.

  本发明提供了具有公式（F）nL1L2D的叶酸受体结合配体-药物传递共轭物。这些共轭物对叶酸受体阳性肿瘤细胞具有高亲和力，对正常细胞毒性低。本发明还涉及这些共轭物的制备方法、包含这些共轭物的药物组合物，以及利用这些共轭物制备抗肿瘤药物的用途。
• [EN] CONJUGATE AND USE THEREOF<br/>[FR] CONJUGUÉ ET SON UTILISATION<br/>[ZH] 缀合物及其用途
  申请人：NANJING CHEMPION BIOTECHNOLOGY CO LTD

  公开号：WO2022161452A1

  公开（公告）日：2022-08-04

  式(I)化合物，或其互变异构体、立体异构体或药学上可接受的盐。式(I)所示化合物或其互变异构体、立体异构体或药学上可接受的盐作为一种新的连接子化合物，可用于制备高DAR值ADC药物。还涉及所述连接子制备的ADC药物。