N1-[4-cyano-3-(trifluoromethyl)phenyl]-(2S)-3-[(4-aminophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide | 261904-44-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N1-[4-cyano-3-(trifluoromethyl)phenyl]-(2S)-3-[(4-aminophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide
• 英文别名: (2S)-3-[(4-aminophenyl)sulfanyl]-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide；(2S)-3-(4-aminophenyl)sulfanyl-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide
• CAS: 261904-44-3
• 化学式: C₁₈H₁₆F₃N₃O₂S
• 分子量: 395.405
• InChiKey: WKCXEVNNOLTSHZ-QGZVFWFLSA-N

物化性质

• 沸点：
  626.7±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  硫光气 、 N1-[4-cyano-3-(trifluoromethyl)phenyl]-(2S)-3-[(4-aminophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide 在 碳酸氢钠 作用下， 以 二氯甲烷 、 氯仿 、 乙酸乙酯 为溶剂， 反应 3.0h， 以87%的产率得到N₁-[4-cyano-3-(trifluoromethyl)phenyl]-(2S)-2-hydroxy-3-[(4-isothiocyanatophenyl)sulfanyl]-2-methylpropanamide
  参考文献：
  名称：

  雄激素受体的手性非甾体亲和配体。1.比卡鲁胺类似物在B芳环中带有亲电基团。

  摘要：

  合成了一系列在母体分子的芳香环B上带有亲电基团的比卡鲁胺手性类似物（异硫氰酸酯，N-氯乙酰基和N-溴乙酰基）。这些化合物被设计为雄激素受体（AR）的亲和配体。我们将这些化合物的（R）和（S）光学异构体制备为纯对映异构体。这些化合物的AR结合亲和力是用放射性标记的高亲和力AR配体[（3）H] mibolerone在竞争结合测定中测量的。根据我们先前关于比卡鲁胺的对映异构体的结果，我们发现，与它们相应的（S）异构体相比，所有（R）异构体均表现出对AR更高的结合亲和力。与相应的间位取代类似物相比，环B中的对位取代亲和配体以更高的亲和力结合AR。对于对位取代的化合物，硫酯亲和配体被氧化为它们的磺酰基类似物会降低AR结合亲和力，而类似的修饰会增加相应的对位类似物的结合亲和力。最无效的对位取代的磺酰基化合物比最有效的间位取代的磺酰基化合物具有更高的AR结合亲和力。总体而言，对位取代的未氧化分子表现出最

  DOI：

  10.1021/jm990027x
• 作为产物：
  描述：

  (2S)-3-溴-N-[4-氰基-3-(三氟甲基)苯基]-2-羟基-2-甲基-丙酰胺 、 4-氨基苯硫酚 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以71%的产率得到N1-[4-cyano-3-(trifluoromethyl)phenyl]-(2S)-3-[(4-aminophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide
  参考文献：
  名称：

  Novel nonsteroidal ligands with high binding affinity and potent functional activity for the androgen receptor

  摘要：

  While nonsteroidal androgen receptor (AR) antagonists have been known for many years, and used in the clinic for the treatment of hormone dependent prostate cancer, very little is known about nonsteroidal AR agonists. We designed and synthesized a series of chiral bicalutamide analogs, which bear electron-withdrawing groups (either a cyano or a nitro group at the 4-position and a trifluoromethyl group at the 3-position) in the aromatic A ring, and different substituents at the para position in the aromatic B ring of the parent molecule. We also synthesized a series of racemic bicalutamide analogs, which have a trifluoromethyl group instead of a methyl group at the R, position. We examined AR binding affinities of our compounds in a competitive binding assay with a radiolabeled high affinity AR ligand, H-3-mibolerone, and also measured their abilities to stimulate AR-mediated transcriptional activation in a cotransfection assay. These studies demonstrated that (1) nonsteroidal ligands can be structurally modified from known nonsteroidal antiandrogens to generate, ligands capable of activating AR-mediated transcriptional activation. (2) R-isomer analogs exhibit higher AR binding affinity and more potent functional activity than their corresponding S-isomers in all cases. (3) All sulphide analogs show higher AR binding affinity and more potent functional activity than their corresponding sulphone analogs, with the exception of ligand R-8. Those ligands which exhibit high AR binding affinity and potent functional activity for human AR may provide effective clinical uses for male fertility, male contraception, and hormone replacement therapy. (C) 2002 Editions scientifiques et medicales Elsevier SAS.-All rights reserved.

  DOI：

  10.1016/s0223-5234(02)01335-1

文献信息

• Bicalutamide Analogs Or (S)-Bicalutamide As Exocytosis Activating Compounds For Use In The Treatment Of A Lysosomal Storage Disorder Or Glycogenosis
  申请人：BCN PEPTIDES, S.A.

  公开号：US20160317489A1

  公开（公告）日：2016-11-03

  SUMMARY The invention provides a therapy for lysosomal storage diseases and glycogenosis by treatment with compounds that promote exocytosis, preferably lysosomal exocytosis. The treatment of cells from patients affected by different lysosomal storage disorders with exocytosis activating compounds leads to a decrease in the accumulation of toxic substrate in the lysosomes, thus allowing the treatment, prevention and relief of the symptoms of many lysosomal storage disorders.
• [EN] BICALUTAMIDE ANALOGS OR (S)-BI CALUTAM IDE AS EXOCYTOSIS ACTIVATING COMPOUNDS FOR USE IN THE TREATMENT OF A LYSOSOMAL STORAGE DISORDER OR GLYCOGENOSIS<br/>[FR] ANALOGUES DU BICALUTAMIDE OU (S)-BICALUTAMIDE EN TANT QUE COMPOSÉS ACTIVANT L'EXOCYTOSE POUR LEUR UTILISATION DANS LE TRAITEMENT D'UN TROUBLE DE SURCHARGE LYSOSOMALE OU DE LA GLYCOGENÈSE
  申请人：BCN PEPTIDES SA

  公开号：WO2015097088A1

  公开（公告）日：2015-07-02

  SUMMARY The invention provides a therapy for lysosomal storage diseases and glycogenosis by treatment with compounds thatpromote exocytosis, preferably lysosomal exocytosis. The treatment of cells frompatients affected by different lysosomal storage disorders with exocytosis activating compounds leads to a decreaseinthe accumulation of toxic substrate in the lysosomes, thus allowingthe treatment,prevention and relief of the symptoms of many lysosomal storage disorders.