N-(2-((S)-4-isopropyl-4,5-dihydrooxazol-2-yl)-6-(((1S,2R,5S)-2-isopropyl-5-methylcyclohexyl)oxy)phenyl)benzenesulfonamide | 1192815-31-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-(2-((S)-4-isopropyl-4,5-dihydrooxazol-2-yl)-6-(((1S,2R,5S)-2-isopropyl-5-methylcyclohexyl)oxy)phenyl)benzenesulfonamide
• 英文别名: N-[2-[(1S,2R,5S)-5-methyl-2-propan-2-ylcyclohexyl]oxy-6-[(4S)-4-propan-2-yl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]benzenesulfonamide
• CAS: 1192815-31-8
• 化学式: C₂₈H₃₈N₂O₄S
• 分子量: 498.687
• InChiKey: RIBMEIXKQHDUCD-RXDHMRHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  85.4
• 氢给体数：
  1
• 氢受体数：
  6

文献信息

• PROCESS FOR THE PREPARATION OF MACROCYCLIC KETONE ANALOGS OF HALICHONDRIN B OR PHARMACEUTICALLY ACCEPTABLE SALTS AND INTERMEDIATES THEREOF
  申请人：CIPLA LIMITED

  公开号：US20170240561A1

  公开（公告）日：2017-08-24

  The present invention discloses a novel process for the preparation of macrocyclic ketone analogs of halichondrin B or pharmaceutically acceptable salts thereof and to novel intermediates which are produced during the course of carrying out the novel process.

  本发明揭示了一种制备halichondrin B的大环酮类似物或其药学上可接受的盐的新工艺，并揭示了在执行新工艺的过程中产生的新中间体。
• Chromium-mediated coupling and application to the synthesis of halichondrins
  申请人：President and Fellows of Harvard College

  公开号：US10344038B2

  公开（公告）日：2019-07-09

  The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.

  本发明提供了在铬介导的偶联反应中利用多卤代亲核物的选择性偶联来统一合成卤代姜黄素及其类似物的 CI-CI 9 结构单元。本发明还提供了一种实用高效的卤代龙毒素及其类似物的 C20-C38 结构单元的合成方法。本发明还提供了选择性活化多卤代类似物并将其与醛偶联的一般方法。所提供的偶联反应对卤代烯酮和卤代乙炔缩酮具有选择性，而对乙烯基卤化物和连接到 sp 水化物碳上的卤化物则没有选择性。所提供的高效选择性偶联反应可以方便地获得卤代烯酮及其类似物的 CI-CI 9 结构单元和 C20-C38 结构单元，中间产物的纯化或分离程度有限或根本不需要。
• Synthesis of halichondrin analogs and uses thereof
  申请人：President and Fellows of Harvard College

  公开号：US10556910B2

  公开（公告）日：2020-02-11

  The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.

  本发明提供了卤虫菊酯类似物，如式（I）化合物。这些化合物可与微管位点结合，从而抑制微管动力学。本发明还提供了化合物的合成方法、药物组合物、试剂盒、治疗方法以及用于治疗增殖性疾病（如癌症）的用途。本发明的化合物尤其适用于治疗转移性乳腺癌、非小细胞肺癌、前列腺癌和肉瘤。本发明所包含的合成方法可用于制备式（I）-（III）化合物以及天然卤化膦（例如，卤化膦 B 和 C，去卤化膦 A、B 和 C，同卤化膦 A、B 和 C）。此外，还包括通过使用酸介导的平衡，在 C38 酮立体中心实现卤化琼脂、去卤化琼脂和高卤化琼脂及其非天然表聚物之间相互转化的方法。
• SYNTHESIS OF HALICHONDRINS
  申请人：President and Fellows of Harvard College

  公开号：EP3649135B1

  公开（公告）日：2022-12-28
• SYNTHESIS OF HALICHONDRIN ANALOGS AND USES THEREOF
  申请人：President and Fellows of Harvard College

  公开号：US20170137437A1

  公开（公告）日：2017-05-18

  The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.