(2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-(2-hydrazinyl-2-oxoethyl)-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate | 1609106-03-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-(2-hydrazinyl-2-oxoethyl)-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate
• 英文别名: [(Z,2S)-5-[[(2R,3R,5S,6S)-6-[(2E,4E)-5-[(3R,4R,5R,7S)-7-(2-hydrazinyl-2-oxoethyl)-4-hydroxy-1,6-dioxaspiro[2.5]octan-5-yl]-3-methylpenta-2,4-dienyl]-2,5-dimethyloxan-3-yl]amino]-5-oxopent-3-en-2-yl] acetate
• CAS: 1609106-03-7
• 化学式: C₂₈H₄₃N₃O₈
• 分子量: 549.665
• InChiKey: NVPLIMAEJQXUSM-FUDLAKRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  162
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-(2-hydrazinyl-2-oxoethyl)-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate 、 N-(6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}hexanoyl)-L-valyl-L-alanine 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.58h， 以77%的产率得到(2S,3Z)-5-({(2R,3R,5S,6S)-6-[(2E,4E)-5-{(3R,4R,5R,7S)-7-[(12S,15S)-1-(9H-fluoren-9-yl)-15-methyl-3,10,13,16,19-pentaoxo-12-(propan-2-yl)-2-oxa-4,11,14,17,18-pentaazaicosan-20-yl]-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl}-3-methylpenta-2,4-dien-1-yl]-2,5-dimethyltetrahydro-2H-pyran-3-yl}amino)-5-oxopent-3-en-2-yl acetate
  参考文献：
  名称：

  [EN] SPLICEOSTATIN ANALOGS
  [FR] ANALOGUES DE SPLICÉOSTATINE

  摘要：

  本发明涉及新型细胞毒性剪接抑制素类似物（I）及其衍生物，涉及其抗体药物结合物，以及使用它们治疗包括癌症在内的医疗状况的方法。

  公开号：

  WO2014068443A1
• 作为产物：
  描述：

  (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-{2-[(2,5-dioxopyrrolidin-1-yl)oxy]-2-oxoethyl}-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate 在 肼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 以58%的产率得到(2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-(2-hydrazinyl-2-oxoethyl)-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate
  参考文献：
  名称：

  [EN] SPLICEOSTATIN ANALOGS
  [FR] ANALOGUES DE SPLICÉOSTATINE

  摘要：

  本发明涉及新型细胞毒性剪接抑制素类似物（I）及其衍生物，涉及其抗体药物结合物，以及使用它们治疗包括癌症在内的医疗状况的方法。

  公开号：

  WO2014068443A1

文献信息

• SPLICEOSTATIN ANALOGS AND METHODS FOR THEIR PREPARATION
  申请人：PFIZER INC.

  公开号：US20140134193A1

  公开（公告）日：2014-05-15

  The present invention is directed to novel cytotoxic spliceostatin analogs and derivatives, to antibody drug conjugates thereof, and to methods for using the same to treat medical conditions including cancer.

  本发明涉及新型细胞毒性剪接素类似物和衍生物，其抗体药物偶联物，以及使用它们治疗包括癌症在内的医学状况的方法。
• Therapeutic antibodies and their uses
  申请人：PFIZER INC.

  公开号：US10040860B2

  公开（公告）日：2018-08-07

  The present invention relates to antibodies, e.g., full length antibodies or antigen binding fragments thereof, that specifically bind to BCMA (B-Cell Maturation Antigen) and/or CD3 (Cluster of Differentiation 3). The invention also relates to antibody conjugates (e.g., antibody-drug-conjugates) comprising the BCMA antibodies, compositions comprising the BCMA antibodies, and methods of using the BCMA antibodies and their conjugates for treating conditions associated with cells expressing BCMA (e.g., cancer or autoimmune disease). The invention further relates to heteromultimeric antibodies that specifically bind to CD3 and a tumor cell antigen, (e.g., bispecific antibodies that specifically bind to CD3 and BCMA). Compositions comprising such heteromultimeric antibodies, methods for producing and purifying such heterodimeric antibodies, and their use in diagnostics and therapeutics are also provided.

  本发明涉及特异性结合BCMA（B细胞成熟抗原）和/或CD3（Cluster of Differentiation 3）的抗体，如全长抗体或其抗原结合片段。本发明还涉及包含BCMA抗体的抗体共轭物（如抗体-药物-共轭物）、包含BCMA抗体的组合物，以及使用BCMA抗体及其共轭物治疗与表达BCMA的细胞有关的疾病（如癌症或自身免疫性疾病）的方法。本发明进一步涉及特异性结合 CD3 和肿瘤细胞抗原的异源多聚物抗体（例如，特异性结合 CD3 和 BCMA 的双特异性抗体）。本发明还提供了包含这种异源二聚体抗体的组合物、生产和纯化这种异源二聚体抗体的方法及其在诊断和治疗中的用途。
• Antibodies specific for epidermal growth factor receptor variant III and their uses
  申请人：PFIZER INC.

  公开号：US10221242B2

  公开（公告）日：2019-03-05

  The present invention provides antibodies that specifically bind to EGFRvIII (Epidermal Growth Factor Receptor Variant III). The invention further provides bispecific antibodies that bind to EGFRvIII and another antigen (e.g., CD3) as well as antibody conjugates (e.g., antibody-drug-conjugates). The invention further relates to antibody encoding nucleic acids, and methods of obtaining such antibodies (monospecific and bispecific) and antibody conjugates. The invention further relates to therapeutic methods for use of these antibodies and antibody conjugates for the treatment of EGFRvIII-mediated pathologies, including cancer such as glioblastoma.

  本发明提供特异性结合表皮生长因子受体变体 III（EGFRvIII）的抗体。本发明进一步提供了与表皮生长因子受体变异体 III 和另一种抗原（如 CD3）结合的双特异性抗体以及抗体共轭物（如抗体-药物-共轭物）。本发明进一步涉及抗体编码核酸，以及获得这种抗体（单特异性和双特异性）和抗体共轭物的方法。本发明进一步涉及使用这些抗体和抗体共轭物治疗表皮生长因子受体vIII介导的病症（包括癌症，如胶质母细胞瘤）的治疗方法。
• SPLICEOSTATIN ANALOGS
  申请人：Pfizer Inc.

  公开号：EP2917195B9

  公开（公告）日：2018-05-30
• ANTIBODY-DRUG CONJUGATES WITH HIGH DRUG LOADING
  申请人：Rinat Neuroscience Corp.

  公开号：EP3134127B1

  公开（公告）日：2020-02-26