(S)-3-(4-Acetylamino-phenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide | 476314-54-2

• 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: (S)-3-(4-Acetylamino-phenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide
• 英文别名: (2S)-3-(4-acetamidophenyl)sulfanyl-2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
• CAS: 476314-54-2
• 化学式: C₁₉H₁₈F₃N₃O₅S
• 分子量: 457.43
• InChiKey: NDPHFBYLOVVWLR-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  150
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-3-(4-Acetylamino-phenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide 在 过氧乙酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以99%的产率得到(S)-3-(4-Acetylamino-benzenesulfonyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide
  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
• 作为产物：
  描述：

  (S)-(-)-3-bromo-2-hydroxy-2-methyl-N-[(4-nitro-3-trifluoromethyl)phenyl]propanamide 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.17h， 生成 (S)-3-(4-Acetylamino-phenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide
  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.
• Novel nonsteroidal ligands with high binding affinity and potent functional activity for the androgen receptor
  作者：Yali He、Donghua Yin、Minoli Perera、Leonid Kirkovsky、Nina Stourman、Wei Li、James T Dalton、Duane D Miller

  DOI：10.1016/s0223-5234(02)01335-1

  日期：2002.8

  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.