2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-[(2-hydroxyethanesulfonyl)amino]benzamide hydrochloride | 2727070-60-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-[(2-hydroxyethanesulfonyl)amino]benzamide hydrochloride
• 英文别名: N-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-4-((2-hydroxyethyl)sulfonamido)-2-(6-azaspiro[2.5]octan-6-yl)benzamide hydrochloride；Sovilnesib hydrochloride；2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-(2-hydroxyethylsulfonylamino)benzamide;hydrochloride
• CAS: 2727070-60-0
• 化学式: C₂₆H₃₄F₂N₆O₄S*ClH
• 分子量: 601.118
• InChiKey: WHRCMXZMJQISBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  sodium dodecyl-sulfate 、 2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-[(2-hydroxyethanesulfonyl)amino]benzamide hydrochloride 生成
  参考文献：
  名称：

  WO2023/4075

  摘要：

  公开号：
• 作为产物：
  描述：

  (l)-4-((2-(benzyloxy)ethyl)sulfonamido)-N-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-2-(6-azaspiro[2.5]octan-6-yl)benzamide 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 水 、 丙酮 为溶剂， 20.0~47.0 ℃ 、310.27 kPa 条件下， 反应 25.5h， 生成 2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-[(2-hydroxyethanesulfonyl)amino]benzamide hydrochloride
  参考文献：
  名称：

  [EN] SYNTHESIS OF A KIF18A INHIBITOR
  [FR] SYNTHÈSE D'UN INHIBITEUR DE KIF18A

  摘要：

  The present invention relates to improved preparation of a KIF18A inhibitor having the chemical structure Compound (1), or a salt thereof Compound (1a);wherein HA is as defined herein; and key intermediates thereof, i.e.,Compound (2a),Compound (3a),Compound (5)or a salt thereof, andCompound (6a) or a hydrate thereof, of the formulae: Compound (2a); Compound (3a); Compound (5) or a salt thereof; and Compound (6a) or a hydrate thereof, preferably Compound (6a-1). The present invention further relates to solid form of Compound (6a), preferably the crystalline hydrate form of Compound (6a-1).

  公开号：

  WO2023146973A1

文献信息

• [EN] KIF18A INHIBITORS FOR TREATMENT OF NEOPLASTIC DISEASES<br/>[FR] INHIBITEURS DE KIF18A POUR LE TRAITEMENT DES MALADIES NÉOPLASIQUES
  申请人：AMGEN INC

  公开号：WO2021211549A1

  公开（公告）日：2021-10-21

  Provided herein are methods of treating a subject having a neoplastic disease, comprising administering to the subject a KIF18A inhibitor in an amount effective to treat the neoplastic disease a neoplastic disease in a subject. Also provided are methods of inducing or increasing tumor regression in a subject with a tumor and methods of reducing tumor or cancer growth in a subject. In exemplary aspects, the method comprises administering to the subject a KIF18A inhibitor. Methods of inducing or increasing death of tumor or cancer cells in a subject comprising administering to the subject a KIF18A inhibitor are also provided herein. Advantageously, the KIF18A inhibitors selectively treat the neoplastic disease, induce or increase tumor regression, and/or induce or increase death of tumor or cancer cells without overt toxicity to normal somatic cells.

  本文提供了治疗患有肿瘤性疾病的受试者的方法，包括向受试者施用有效治疗肿瘤性疾病的KIF18A抑制剂。还提供了诱导或增加受试者肿瘤退缩的方法以及减少受试者肿瘤或癌症生长的方法。在示范性方面，该方法包括向受试者施用KIF18A抑制剂。本文还提供了诱导或增加受试者肿瘤或癌细胞死亡的方法，包括向受试者施用KIF18A抑制剂。有益的是，KIF18A抑制剂能选择性地治疗肿瘤性疾病，诱导或增加肿瘤退缩，以及/或诱导或增加肿瘤或癌细胞死亡，而不对正常体细胞产生明显毒性。