N1-[4-cyano-3-(trifluoromethyl)phenyl]-(2R)-3-({4-[(2-chloroacetyl)amino]phenyl}sulfonyl)-2-hydroxy-2-methylpropanamide

• 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]-(2R)-3-({4-[(2-chloroacetyl)amino]phenyl}sulfonyl)-2-hydroxy-2-methylpropanamide
• 英文别名: (2R)-3-{[4-(2-chloroacetamido)benzene]sulfonyl}-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide；(2R)-3-[4-[(2-chloroacetyl)amino]phenyl]sulfonyl-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide
• 化学式: C₂₀H₁₇ClF₃N₃O₅S
• 分子量: 503.886
• InChiKey: NUUCDWKSNMKUDQ-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide 在 过氧乙酸 、 sodium hydride 、 calcium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 49.0h， 生成 N1-[4-cyano-3-(trifluoromethyl)phenyl]-(2R)-3-({4-[(2-chloroacetyl)amino]phenyl}sulfonyl)-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

• Chiral Nonsteroidal Affinity Ligands for the Androgen Receptor. 1. Bicalutamide Analogues Bearing Electrophilic Groups in the B Aromatic Ring
  作者：Leonid Kirkovsky、Arnab Mukherjee、Donghua Yin、James T. Dalton、Duane D. Miller

  DOI：10.1021/jm990027x

  日期：2000.2.1

  parent molecule were synthesized. These compounds were designed as affinity ligands for the androgen receptor (AR). We prepared the (R)- and (S)-optical isomers of these compounds as pure enantiomers. The AR binding affinities of these compounds were measured in a competitive binding assay with the radiolabeled high-affinity AR ligand, [(3)H]mibolerone. In accordance with our previous results for the enantiomers

  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
• 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.