3-(4-fluoro-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide | 401900-41-2

• 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: 3-(4-fluoro-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide
• 英文别名: (S)-3-(4-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide；S-3-(4-Fluorophenoxy)-2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide；(2S)-3-(4-fluorophenoxy)-2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
• CAS: 401900-41-2
• 化学式: C₁₇H₁₄F₄N₂O₅
• 分子量: 402.302
• InChiKey: KJMFOTCDISOHDX-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 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：
  104
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 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 在 potassium carbonate 作用下， 以 异丙醇 、 丙酮 为溶剂， 生成 3-(4-fluoro-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Characterization of Metabolically Stable Selective Androgen Receptor Modulators

  摘要：

  A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K-i values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

  DOI：

  10.1021/jm030336u

文献信息

• Selective androgen receptor modulators and method of use thereof
  申请人：Dalton T. James

  公开号：US20070123563A1

  公开（公告）日：2007-05-31

  This invention provides SARM compounds and uses thereof in treating a variety of diseases or conditions in a subject, including, inter-alia, a muscle wasting disease and/or disorder or a bone-related disease and/or disorder.

  这项发明提供了SARM化合物及其在治疗受试者中的各种疾病或情况中的用途，包括但不限于肌肉消耗性疾病和/或紊乱或骨相关疾病和/或紊乱。
• Selective androgen receptor modulators for treating muscle wasting
  申请人：Dalton T. James

  公开号：US20070161608A1

  公开（公告）日：2007-07-12

  This invention provides SARM compounds and uses thereof in treating a variety of diseases or conditions in a subject, including, inter-alia, a muscle wasting disease and/or disorder or a bone-related disease and/or disorder.

  该发明提供了选择性雄激素受体调节剂(SARM)化合物及其在治疗受试者中的各种疾病和病症中的应用，包括但不限于肌肉消耗性疾病和/或紊乱或骨相关疾病和/或紊乱。
• Selective androgen receptor modulators and methods of use thereof
  申请人：University of Tennessee Research Foundation

  公开号：EP2284149A1

  公开（公告）日：2011-02-16

  This invention provides a novel class of androgen receptor targeting agents (ARTA). The agents define a new subclass of compounds which are tissue-selective androgen receptor modulators (SARM), which are useful for in treating, preventing, suppressing, inhibiting or reducing the incidence of osteoporosis. These agents have an unexpected in-vivo activity for an androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. These agents may be active alone or in combination with progestins or estrogens.

  本发明提供了一类新型雄激素受体靶向制剂（ARTA）。这些制剂定义了一种新的亚类化合物，它们是组织选择性雄激素受体调节剂（SARM），可用于治疗、预防、抑制、抑制或降低骨质疏松症的发病率。这些制剂对雄激素受体的非甾体配体具有意想不到的体内雄激素活性和同化活性。这些制剂可单独使用，也可与孕激素或雌激素合用。
• TREATING MUSCLE WASTING WITH SELECTIVE ANDROGEN RECEPTOR MODULATORS
  申请人：GTX, Inc.

  公开号：EP1463497B1

  公开（公告）日：2011-10-05
• THERAPEUTIC MODULATION OF OCULAR SURFACE LUBRICATION
  申请人：The Regents of the University of California

  公开号：EP2276496B1

  公开（公告）日：2019-07-10