1-[(2S,3'R)-3'-(2-aminoethyl)-5-(2,5-difluorophenyl)-6'-fluorospiro[1,3,4-thiadiazole-2,4'-2,3-dihydrochromene]-3-yl]ethanone | 1146209-44-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1-[(2S,3'R)-3'-(2-aminoethyl)-5-(2,5-difluorophenyl)-6'-fluorospiro[1,3,4-thiadiazole-2,4'-2,3-dihydrochromene]-3-yl]ethanone
• CAS: 1146209-44-0
• 化学式: C₂₀H₁₈F₃N₃O₂S
• 分子量: 421.443
• InChiKey: KFXNELORCIYYJO-ODXCJYRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  93.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-[(2S,3'R)-5-(2,5-difluorophenyl)-6'-fluoro-3'-(2-nitroethyl)spiro[1,3,4-thiadiazole-2,4'-2,3-dihydrochromene]-3-yl]ethanone 在 铁粉 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 1.5h， 以77%的产率得到1-[(2S,3'R)-3'-(2-aminoethyl)-5-(2,5-difluorophenyl)-6'-fluorospiro[1,3,4-thiadiazole-2,4'-2,3-dihydrochromene]-3-yl]ethanone
  参考文献：
  名称：

  Synthesis, determination of absolute configuration, and biological evaluation of spiro-fused thiadiazoline inhibitors of kinesin spindle protein (KSP)

  摘要：

  A facile and highly convergent synthesis of biologically active spiro-fused thiadiazoline KSP inhibitors is reported. The highlights of the synthesis include the Michael reaction and cyclization of thiosemicarbazone to 1,3,4-thiadiazoline. This chemistry lends itself to the preparation of (+)-2, a potent and orally bioavailable anti-cancer agent, and to the development of a structure-activity relationship program. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.09.066

文献信息

• [EN] SPIRO-CONDENSED 1, 3, 4-THIADIAZOLE DERIVATIVES FOR INHIBITING KSP KINESIN ACTIVITY<br/>[FR] DÉRIVÉS DE 1,3,4-THIADIAZOLE SPIRO-CONDENSÉS POUR INHIBER L'ACTIVITÉ DE LA KINÉSINE KSP
  申请人：SCHERING CORP

  公开号：WO2009052288A1

  公开（公告）日：2009-04-23

  The present invention relates to compounds of Formula (I), below, (wherein X, R1, R2, R3, p, E, ring A, and ring B are as defined herein). The present invention also relates to compositions (including pharmaceutically acceptable compositions) comprising these compounds, alone and in combination with one or more additional therapeutic agents, and to methods for their use in inhibiting KSP kinesin activity, and for treating cellular proliferative diseases or disorders associated with KSP kinesin activity. Formula I [Chemical formula should be inserted here as it appears on abstract in paper form.]

  本发明涉及以下式（I）的化合物（其中X、R1、R2、R3、p、E、环A和环B的定义如本文所述）。本发明还涉及包括这些化合物的组合物（包括药学上可接受的组合物），单独或与一个或多个额外治疗剂的组合物，并且涉及它们在抑制KSP动力蛋白活性以及治疗与KSP动力蛋白活性相关的细胞增殖性疾病或紊乱的用途的方法。Formula I [化学式应按照纸质形式中的摘要插入在此处。]
• COMPOUNDS FOR INHIBITING KSP KINESIN ACTIVITY
  申请人：Siddiqui M. Arshad

  公开号：US20110123435A1

  公开（公告）日：2011-05-26

  The present invention relates to compounds of Formula (I), below, (wherein X, R1, R2, R3, p, E, ring A, and ring B are as defined herein). The present invention also relates to compositions (including pharmaceutically acceptable compositions) comprising these compounds, alone and in combination with one or more additional therapeutic agents, and to methods for their use in inhibiting KSP kinesin activity, and for treating cellular proliferative diseases or disorders associated with KSP kinesin activity. Formula I
• METHODS OF TREATING LUNG DISEASE
  申请人：Morgans, JR. David J.

  公开号：US20130210733A1

  公开（公告）日：2013-08-15

  Provided herein are methods of treating lung disease in a subject by administering to the subject a therapeutically effective amount of a mitotic kinesin inhibitor, optionally in combination with another therapy.
• US8796460B2
  申请人：——

  公开号：US8796460B2

  公开（公告）日：2014-08-05
• [EN] SEQUENTIAL ADMINISTRATION OF CHEMOTHERAPEUTIC AGENTS FOR TREATMENT OF CANCER<br/>[FR] ADMINISTRATION SÉQUENTIELLE D'AGENTS DE CHIMIOTHÉRAPIE POUR LE TRAITEMENT DU CANCER
  申请人：SCHERING CORP

  公开号：WO2009137378A2

  公开（公告）日：2009-11-12

  The present invention relates to the sequential administration of a cytotoxic agent followed by an IGF1R antagonist (e.g., an antibody) for the treatment of hyperproliferative disorders including cancer.