1,1-Diacetoxy-4-penten | 18360-64-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,1-Diacetoxy-4-penten
• 英文别名: 1-Acetyloxypent-4-enyl acetate
• CAS: 18360-64-0
• 化学式: C₉H₁₄O₄
• 分子量: 186.208
• InChiKey: NVKYIMNEHIHZML-UHFFFAOYSA-N

物化性质

• 沸点：
  63-64 °C(Press: 0.3 Torr)
• 密度：
  1.031 g/cm3

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-Diacetoxy-4-penten 在 四(三苯基膦)钯 sodium hydride 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 3.0h， 生成 Acetic acid (4aR,8aR)-1-acetoxy-4-methylene-1,2,3,4,4a,7,8,8a-octahydro-naphthalen-1-yl ester
  参考文献：
  名称：

  钯催化的分子内烯烃烯丙基化：双环系统的立体控制合成和烯丙基钯/烯烃顺式插入的证据

  摘要：

  的Pd（O）催化的的环化（1-乙酰氧基-3-烯基）-2-环烯烃，和提供在高diastereo-双环系统（，）和对映聚体（）纯度具有占优势的烯丙基钯/烯烃一致顺-插入。

  DOI：

  10.1016/s0040-4039(00)80586-9
• 作为产物：
  描述：

  4-戊烯醛 、 乙酸酐 在 indium(III) chloride 作用下， 以 二氯甲烷 为溶剂， 以15.3 g的产率得到1,1-Diacetoxy-4-penten
  参考文献：
  名称：

  NEOADJUVANT USE OF ANTIBODY-DRUG CONJUGATES

  摘要：

  本发明涉及改进的方法和组合物，用于抗体药物联合物（ADC）在癌症治疗中的新辅助使用，优选包含蒽环类或喜树碱的ADC，更优选是SN-38或pro-2-pyrrolinodoxorubicin（P2PDox）的ADC。ADC作为新辅助治疗在标准抗癌疗法（如手术、放疗、化疗或免疫疗法）之前给予。ADC的新辅助使用显著提高了标准抗癌疗法的疗效，并可减少原发肿瘤或消除微小转移。在最优选实施例中，新辅助ADC与标准抗癌疗法结合治疗对标准治疗有抵抗的癌症，如三阴性乳腺癌（TNBC）具有成功的疗效。

  公开号：

  US20160095939A1

文献信息

• [EN] PRO-DRUG FORM (P2PDOX) OF THE HIGHLY POTENT 2-PYRROLINODOXORUBICIN CONJUGATED TO ANTIBODIES FOR TARGETED THERAPY OF CANCER<br/>[FR] FORME DE PRO-MÉDICAMENT (P2PDOX) DE LA 2-PYRROLINODOXORUBICINE FORTEMENT PUISSANTE CONJUGUÉE À DES ANTICORPS POUR LA THÉRAPIE CIBLÉE DU CANCER
  申请人：IMMUNOMEDICS INC

  公开号：WO2014124227A1

  公开（公告）日：2014-08-14

  Disclosed are methods, compositions and uses of conjugates of prodrug forms of 2- pyrrolinodoxorubicin (P2PDox) with antibodies or antigen-binding fragments thereof (ADCs), with targetable construct peptides or with other targeting molecules that are capable of delivering the P2PDox to a targeted cell, tissue or pathogen. Once delivered to the target cell, the ADC or peptide conjugate is internalized, a highly toxic 2-pyrrolinodoxorubicin (2- PDox) is released intracellularly. The P2PDox-peptide or ADC conjugates are of use to treat a wide variety of diseases, such as cancer, autoimmune disease or infectious disease.

  本发明涉及2-吡咯烷基多柔比星（P2PDox）的前药形式与抗体或其抗原结合片段（ADC）、可靶向构建肽或其他靶向分子的结合物的共轭物的方法、组合物和用途，这些结合物能够将P2PDox递送到目标细胞、组织或病原体。一旦递送到目标细胞，ADC或肽共轭物被内吞，高毒性的2-吡咯烷基多柔比星（2-PDox）在细胞内释放。P2PDox-肽或ADC共轭物可用于治疗各种疾病，如癌症、自身免疫性疾病或传染病。
• HUMANIZED ANTI-CD22 ANTIBODY
  申请人：Immunomedics, Inc.

  公开号：US20150344573A1

  公开（公告）日：2015-12-03

  Disclosed are humanized RFB4 antibodies or antigen-binding fragments thereof. therapy of B-cell associated diseases, such as B-cell malignancies, autoimmune disease and immune dysfunction disease. Preferably, hRFB4 comprises the light and heavy chain RFB4 CDR sequences with human antibody FR and constant region sequences, along with heavy chain framework region (FR) amino acid residues Q1, F27, V48, A49, F68, R98, T117 and light chain residues L4, S22, K39, G100, V104, and K107. More preferably, the heavy and light chain variable region sequences of hRFB4 comprise SEQ ID NO:7 and SEQ ID NO:8, respectively. In certain embodiments, trogocytosis (antigen shaving) induced by hRFB4 plays a significant role in determining antibody efficacy and disease responsiveness for treatment of B-cell diseases, such as hematopoietic cancers, immune system dysfunction and/or autoimmune disease.

  本发明涉及人源化的RFB4抗体或其抗原结合片段，用于治疗B细胞相关疾病，如B细胞恶性肿瘤、自身免疫疾病和免疫功能障碍疾病。最好的情况是，hRFB4包括人源抗体FR和常数区序列的轻重链RFB4 CDR序列，以及重链框架区（FR）氨基酸残基Q1、F27、V48、A49、F68、R98、T117和轻链残基L4、S22、K39、G100、V104和K107。更好的是，hRFB4的重链和轻链可变区序列分别包括SEQ ID NO:7和SEQ ID NO:8。在某些实施例中，hRFB4诱导的胞间贡献（抗原剃须）在决定治疗B细胞疾病（如造血系统癌症、免疫系统功能障碍和/或自身免疫疾病）的抗体疗效和疾病响应性方面发挥重要作用。
• Intensely Potent Doxorubicin Analogues:  Structure−Activity Relationship
  作者：David Farquhar、Abdallah Cherif、Elena Bakina、J. Arly Nelson

  DOI：10.1021/jm9706980

  日期：1998.3.1

  N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin analogue that retains full potency against tumor cells that express elevated levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1-yl)doxorubicin, an aldehyde capable of existing in equilibrium with a cyclic carbinolamine. To investigate the structural determinants of potency for 1b, we have prepared a series of chemically related compounds in which various omega-[bis(acetoxy)]alkyl or omega-[bis(acetoxy)]alkoxyalkyl groups are substituted at the 3'-amino position of the daunosamine sugar. These groups were selected to assess the effect of chain length, oxygen substitution, and carbinolamine ring size on analogue potency. The compounds were evaluated for their ability to inhibit the in vitro growth of the following cell lines: (a) Chinese hamster ovary (CHO) cells, (b) a CHO cell mutant 100-fold resistant to doxorubicin that expresses elevated levels of P-glycoprotein, (c) a murine ductal cell pancreatic adenocarcinoma (Pane 02), and (d) a murine mammary carcinoma (CA 755). The most potent members of the series were those that could form a straight chain aldehyde intermediate after esterase-mediated hydrolysis of the omega-bis(acetoxy) groups and give rise to 5- or 6-membered ring carbinolamines. Analogues capable of forming 7-, 8-, or 9-membered carbinolamines were markedly less active. The N-methyl derivative of 1b, which cannot give rise to a cyclic carbinolamine, was 2 orders of magnitude less potent than 1b. A branched chain analogue, If, which contained a tertiary carbon atom adjacent to the omega-bis(acetoxy) groups, was also substantially less active than its nonbranched counterpart, 1a. These findings suggest that the chain length of the 3'-amino substituents and the ability of the derived aldehydes to form 5- or 6-membered carbinolamines are critical determinants of biologic potency.
• Scriabine,I., Bulletin de la Societe Chimique de France, 1961, p. 1194 - 1198
  作者：Scriabine,I.

  DOI：——

  日期：——
• PRO-DRUG FORM (P2PDOX) OF THE HIGHLY POTENT 2-PYRROLINODOXORUBICIN CONJUGATED TO ANTIBODIES FOR TARGETED THERAPY OF CANCER
  申请人：Immunomedics, Inc.

  公开号：US20140219956A1

  公开（公告）日：2014-08-07

  Disclosed are methods, compositions and uses of conjugates of prodrug forms of 2-pyrrolinodoxorubicin (P2PDox) with antibodies or antigen-binding fragments thereof (ADCs), with targetable construct peptides or with other targeting molecules that are capable of delivering the P2PDox to a targeted cell, tissue or pathogen. Once delivered to the target cell, the ADC or peptide conjugate is internalized, a highly toxic 2-pyrrolinodoxorubicin (2-PDox) is released intracellularly. The P2PDox-peptide or ADC conjugates are of use to treat a wide variety of diseases, such as cancer, autoimmune disease or infectious disease.