CH5137291 | 1043446-39-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: CH5137291
• 英文别名: 6-[3-(4-cyano-3-trifluoromethylphenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]pyridine-2-sulfonic acid amide；Unii-A5ZX7J376H；6-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]pyridine-2-sulfonamide
• CAS: 1043446-39-4
• 化学式: C₁₈H₁₄F₃N₅O₃S₂
• 分子量: 469.468
• InChiKey: JIIHFLNYGVNTFP-UHFFFAOYSA-N

物化性质

• 沸点：
  654.4±65.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  161
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  6-溴吡啶-2-磺酰氯 在 4-二甲氨基吡啶 、 硫酸 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 1,3-二甲基-2-咪唑啉酮 、 甲醇 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 31.42h， 生成 CH5137291
  参考文献：
  名称：

  Design and synthesis of an androgen receptor pure antagonist (CH5137291) for the treatment of castration-resistant prostate cancer

  摘要：

  A series of 5,5-dimethylthiohydantoin derivatives were synthesized and evaluated for androgen receptor pure antagonistic activities for the treatment of castration-resistant prostate cancer. Since CH4933468, which we reported previously, had a problem with agonist metabolites, novel thiohydantoin derivatives were identified by applying two strategies. One was the replacement of the alkylsulfonamide moiety by a phenylsulfonamide to avoid the production of agonist metabolites. The other was the replacement of the phenyl ring with a pyridine ring to improve in vivo potency and reduce hERG affinity. Pharmacological assays indicated that CH5137291 (17b) was a potent AR pure antagonist which did not produce the agonist metabolite. Moreover, CH5137291 completely inhibited in vivo tumor growth of LNCaP-BC2, a castration-resistant prostate cancer model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.10.023

文献信息

• Method for Treatment of Castration-Resistant Prostate Cancer
  申请人：The University of British Columbia

  公开号：US20150157656A1

  公开（公告）日：2015-06-11

  Castrate resistant prostate cancer cell lines exhibiting resistance to the androgen-receptor antagonist enzaluatamide overexpress one or both of IGFBP-2 or IGFBP-5 when compared to non-resistant cell lines. Oligonucleotides that target IGFBP-2 and IGFBP-5 can be used to overcome this resistance or as part of a treatment program when administered concurrently with the administration of androgen-receptor antagonist treatments.
• US9205102B2
  申请人：——

  公开号：US9205102B2

  公开（公告）日：2015-12-08
• Design and synthesis of an androgen receptor pure antagonist (CH5137291) for the treatment of castration-resistant prostate cancer
  作者：Hitoshi Yoshino、Haruhiko Sato、Takuya Shiraishi、Kazutaka Tachibana、Takashi Emura、Akie Honma、Nobuyuki Ishikura、Toshiaki Tsunenari、Miho Watanabe、Ayako Nishimoto、Ryo Nakamura、Toshito Nakagawa、Masateru Ohta、Noriyuki Takata、Kentaro Furumoto、Kazuya Kimura、Hiromitsu Kawata

  DOI：10.1016/j.bmc.2010.10.023

  日期：2010.12

  A series of 5,5-dimethylthiohydantoin derivatives were synthesized and evaluated for androgen receptor pure antagonistic activities for the treatment of castration-resistant prostate cancer. Since CH4933468, which we reported previously, had a problem with agonist metabolites, novel thiohydantoin derivatives were identified by applying two strategies. One was the replacement of the alkylsulfonamide moiety by a phenylsulfonamide to avoid the production of agonist metabolites. The other was the replacement of the phenyl ring with a pyridine ring to improve in vivo potency and reduce hERG affinity. Pharmacological assays indicated that CH5137291 (17b) was a potent AR pure antagonist which did not produce the agonist metabolite. Moreover, CH5137291 completely inhibited in vivo tumor growth of LNCaP-BC2, a castration-resistant prostate cancer model. (C) 2010 Elsevier Ltd. All rights reserved.