(R)-3-(4-aminophenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide | 476314-36-0

• 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: (R)-3-(4-aminophenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide
• 英文别名: (2R)-3-(4-aminophenyl)sulfanyl-2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
• CAS: 476314-36-0
• 化学式: C₁₇H₁₆F₃N₃O₄S
• 分子量: 415.393
• InChiKey: FWRSZVPNBCWJAI-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (R)-3-(4-aminophenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide 在 过氧乙酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.17h， 生成 (R)-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：

  (2R)-3-溴-2-羟基-2-甲基-N-[4-硝基-3-(三氟甲基)苯基]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 20.0h， 以85%的产率得到(R)-3-(4-aminophenylsulfanyl)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide
  参考文献：
  名称：

  前列腺癌的芳基异硫氰基选择性雄激素受体调节剂（SARM）。

  摘要：

  制备了一系列新的雄激素受体靶向剂（ARTA），并在雄激素依赖性和非依赖性前列腺癌细胞系中进行了测试。这些试剂是具有异硫氰酸根基取代的B环的比卡鲁胺类似物。同样，R-比卡鲁胺的连接基砜被保持或替换为几个可选的连接基，包括醚，胺，N-甲胺，硫醚和亚甲基（在这种情况下，该产品是外消旋混合物）在X位置的官能团。为了扩大这些芳基异硫氰酸根基AR配体的结构活性关系（SAR），还制备并测试了B环卤代芳基异硫氰酸根基配体。芳基异硫氰酸根基AR配体对AR的结合亲和力范围为0.6到54 nM。其中，硫醚和醚键表现出高结合亲和力（0.6和4.6 nM，与雄激素非依赖性前列腺癌细胞系（DU145，PC-3和PPC-1）相比，对LNCaP（一种雄激素依赖性前列腺癌细胞系）分别具有选择性和选择性的细胞生长抑制作用（约3至6倍），并且膀胱细胞系（TSU-Pr1）。但是，配体在正常猴肾细胞系（CV-1）中是无活性的（IC50>

  DOI：

  10.1016/j.bmc.2006.06.019

文献信息

• 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.
• Arylisothiocyanato selective androgen receptor modulators (SARMs) for prostate cancer
  作者：Dong Jin Hwang、Jun Yang、Huiping Xu、Igor M. Rakov、Michael L. Mohler、James T. Dalton、Duane D. Miller

  DOI：10.1016/j.bmc.2006.06.019

  日期：2006.10

  the linker sulfone of R-bicalutamide was maintained or replaced with several alternative linkages including ether, amine, N-methylamine, thioether, and methylene (in this case the product was a racemic mixture) functional groups at the X-position. To expand the structure-activity relationship (SAR) of these arylisothiocyanato AR ligands, B-ring halogenated arylisothiocyanato ligands were also prepared

  制备了一系列新的雄激素受体靶向剂（ARTA），并在雄激素依赖性和非依赖性前列腺癌细胞系中进行了测试。这些试剂是具有异硫氰酸根基取代的B环的比卡鲁胺类似物。同样，R-比卡鲁胺的连接基砜被保持或替换为几个可选的连接基，包括醚，胺，N-甲胺，硫醚和亚甲基（在这种情况下，该产品是外消旋混合物）在X位置的官能团。为了扩大这些芳基异硫氰酸根基AR配体的结构活性关系（SAR），还制备并测试了B环卤代芳基异硫氰酸根基配体。芳基异硫氰酸根基AR配体对AR的结合亲和力范围为0.6到54 nM。其中，硫醚和醚键表现出高结合亲和力（0.6和4.6 nM，与雄激素非依赖性前列腺癌细胞系（DU145，PC-3和PPC-1）相比，对LNCaP（一种雄激素依赖性前列腺癌细胞系）分别具有选择性和选择性的细胞生长抑制作用（约3至6倍），并且膀胱细胞系（TSU-Pr1）。但是，配体在正常猴肾细胞系（CV-1）中是无活性的（IC50>