(+)-(3R)-3-ethyl-3,4-dihydro-7-nitro-4-(2,2,2-trifluoroethyl)-2H-1,4-benzoxazine | 329229-78-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (+)-(3R)-3-ethyl-3,4-dihydro-7-nitro-4-(2,2,2-trifluoroethyl)-2H-1,4-benzoxazine
• 英文别名: (3R)-3-ethyl-3,4-dihydro-7-nitro-4-(2,2,2-trifluoroethyl)-2H-1,4-benzoxazine；(3R)-3-ethyl-7-nitro-4-(2,2,2-trifluoroethyl)-2,3-dihydro-1,4-benzoxazine
• CAS: 329229-78-9
• 化学式: C₁₂H₁₃F₃N₂O₃
• 分子量: 290.242
• InChiKey: ZIDJHUVRGVRHQZ-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+)-(3R)-3-ethyl-3,4-dihydro-7-nitro-4-(2,2,2-trifluoroethyl)-2H-1,4-benzoxazine 在 钯 作用下， 以 乙酸乙酯 为溶剂， 以to afford 4.8 g (95%) of (3R)-7-amino-3,4-dihydro-3-ethyl-4-trifluoroethyl-2H-1,4benzoxazine as a tan solid, which的产率得到(3R)-7-amino-3-ethyl-3,4-dihydro-4-(2,2,2-trifluoroethyl)-2H-1,4-benzoxazine
  参考文献：
  名称：

  Androgen receptor modulator compounds and methods

  摘要：

  化合物、药物组合物和调节类固醇受体介导过程的方法。具体而言，描述了非类固醇化合物和组合物的制备和使用方法，这些化合物和组合物是雄激素受体（AR）的激动剂、部分激动剂和拮抗剂。此外，还描述了制备和使用关键中间体的方法，包括用于AR调节剂的中间体的立体选择性合成路线。

  公开号：

  US20030186970A1
• 作为产物：
  描述：

  (2R)-(+)-2-(2-fluoro-4-nitrophenyl)amino-1-butanol 在 三乙基硅烷 、 三氟化硼乙醚 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 氯仿 、 苯 为溶剂， 反应 24.0h， 生成 (+)-(3R)-3-ethyl-3,4-dihydro-7-nitro-4-(2,2,2-trifluoroethyl)-2H-1,4-benzoxazine
  参考文献：
  名称：

  Novel Series of Potent, Nonsteroidal, Selective Androgen Receptor Modulators Based on 7H-[1,4]Oxazino[3,2-g]quinolin-7-ones

  摘要：

  Recent interest in orally available androgens has fueled the search for new androgens for use in hormone replacement therapy and as anabolic agents. In pursuit of this, we have discovered a series of novel androgen receptor modulators derived from 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. These compounds were synthesized and evaluated in competitive binding assays and an androgen receptor transcriptional activation assay. A number of compounds from the series demonstrated single-digit nanomolar agonist activity in vitro. In addition, lead compound (R)-16e was orally active in established rodent models that measure androgenic and anabolic properties of these agents. In this assay, (R)-16e demonstrated full efficacy in muscle and only partially stimulated the prostate at 100 mg/kg. These data suggest that these compounds may be utilized as selective androgen receptor modulators or SARMs. This series represents a novel class of compounds for use in androgen replacement therapy.

  DOI：

  10.1021/jm061329j

文献信息

• Tricyclic quinolinone and tricyclic quinoline androgen receptor modulator compounds and methods
  申请人：Ligand Pharmaceuticals Incorporated

  公开号：US20020183314A1

  公开（公告）日：2002-12-05

  Novel non-steroidal tricyclic quinolinone and tricyclic quinoline compounds and compositions that are agonists, partial agonists and/or antagonists for androgen receptors (AR), their preparation and their uses are described.

  描述了一种新型的非甾体三环喹诺酮和三环喹啉化合物以及对雄激素受体（AR）具有激动剂、部分激动剂和/或拮抗剂作用的组合物，以及它们的制备和用途。
• Efficient synthesis of an androgen receptor modulator
  作者：Neelakandha S. Mani、Jyun-Hung Chen、James P. Edwards、Min Wu、Penghui Chen、Robert I. Higuchi

  DOI：10.1016/j.tetlet.2008.01.114

  日期：2008.3

  An efficient synthesis of the androgen receptor modulator (R)-4a having an 8H-[1,4]oxazino[2,3-f]quinolin-8-one skeleton is described. Synthesis of this ring system, not readily accessible by classical Knorr cyclization methodology, was accomplished by an ortho-metallation strategy. Thus, lithiation of a pivaloyl-protected 7-amino-3,4-dihydro-1,4-benzoxazine using n-butyllithium allowed the introduction of a trifluoroacetyl group regioselectively at the 8-position. Subsequent Wittig reaction and acid catalyzed cyclization afforded the desired 8H-[1,4]oxazino[2,3-f]quinolin-8-one (R)-4a in very good overall yield from the corresponding benzoxazine. (c) 2008 Elsevier Ltd. All rights reserved.
• ANDROGEN RECEPTOR MODULATOR COMPOUNDS AND METHODS
  申请人：LIGAND PHARMACEUTICALS INCORPORATED

  公开号：EP1212330B1

  公开（公告）日：2006-04-19
• TRICYCLIC QUINOLINONE AND TRICYCLIC QUINOLINE AS ANDROGEN RECEPTOR MODULATOR COMPOUNDS
  申请人：LIGAND PHARMACEUTICALS INCORPORATED

  公开号：EP1368357A1

  公开（公告）日：2003-12-10
• US6462038B1
  申请人：——

  公开号：US6462038B1

  公开（公告）日：2002-10-08