Methyl 2-[3-[4-cyano-3-(trifluoromethyl)phenoxy]-4,4-dimethyl-2-oxopyrrolidin-1-yl]acetate | 1335100-01-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Methyl 2-[3-[4-cyano-3-(trifluoromethyl)phenoxy]-4,4-dimethyl-2-oxopyrrolidin-1-yl]acetate
• CAS: 1335100-01-0
• 化学式: C₁₇H₁₇F₃N₂O₄
• 分子量: 370.328
• InChiKey: KSRYRCDROGTYRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  79.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Methyl 2-[3-[4-cyano-3-(trifluoromethyl)phenoxy]-4,4-dimethyl-2-oxopyrrolidin-1-yl]acetate 在 锂硼氢 作用下， 以 四氢呋喃 为溶剂， 反应 26.0h， 生成 (R)-(+)-4-(1-(2-hydroxyethyl)-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Discovery of 3-aryloxy-lactam analogs as potent androgen receptor full antagonists for treating castration resistant prostate cancer

  摘要：

  High throughput cell-based screening led to the identification of 3-aryloxy lactams as potent androgen receptor (AR) antagonists. Refinement of these leads to improve the ADME profile and remove residual agonism led to the discovery of 12, a potent full antagonist with greater oral bioavailability. Improvements in the ADME profile were realized by designing more ligand-efficient molecules with reduced molecular weights and lower lipophilicities. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.068
• 作为产物：
  描述：

  (+/-)-4-(4,4-dimethyl-2-oxotetrahydrofuran-3-yloxy)-2-(trifluoromethyl)benzonitrile 在 吡啶 、 三乙基硅烷 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 生成 Methyl 2-[3-[4-cyano-3-(trifluoromethyl)phenoxy]-4,4-dimethyl-2-oxopyrrolidin-1-yl]acetate
  参考文献：
  名称：

  Pantolactams as androgen receptor antagonists for the topical suppression of sebum production

  摘要：

  A series of pantolactam based compounds were identified as potent antagonists for the androgen receptor (AR). Those that possessed properties suitable for topical delivery were evaluated in the validated Hamster Ear Model. Several compounds were found to be efficacious in reducing wax esters, a major component of sebum, initiating further preclinical work on these compounds. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.048

文献信息

• Discovery of 3-aryloxy-lactam analogs as potent androgen receptor full antagonists for treating castration resistant prostate cancer
  作者：Chuangxing Guo、Susan Kephart、Martha Ornelas、Javier Gonzalez、Angelica Linton、Mason Pairish、Asako Nagata、Samantha Greasley、Jeff Elleraas、Natilie Hosea、Jon Engebretsen、Andrea N. Fanjul

  DOI：10.1016/j.bmcl.2011.11.068

  日期：2012.1

  High throughput cell-based screening led to the identification of 3-aryloxy lactams as potent androgen receptor (AR) antagonists. Refinement of these leads to improve the ADME profile and remove residual agonism led to the discovery of 12, a potent full antagonist with greater oral bioavailability. Improvements in the ADME profile were realized by designing more ligand-efficient molecules with reduced molecular weights and lower lipophilicities. (C) 2011 Elsevier Ltd. All rights reserved.
• Pantolactams as androgen receptor antagonists for the topical suppression of sebum production
  作者：Karen E. Sexton、Stephen Barrett、Katy Bridgwood、Matthew Carroll、Danielle Dettling、Daniel Du、Stephen Fakhoury、Victor Fedij、Lain-Yen Hu、Catherine Kostlan、David Pocalyko、Neil Raheja、Yvonne Smith、Veerabahu Shanmugasundaram、Kimberly Wade

  DOI：10.1016/j.bmcl.2011.07.048

  日期：2011.9

  A series of pantolactam based compounds were identified as potent antagonists for the androgen receptor (AR). Those that possessed properties suitable for topical delivery were evaluated in the validated Hamster Ear Model. Several compounds were found to be efficacious in reducing wax esters, a major component of sebum, initiating further preclinical work on these compounds. (C) 2011 Elsevier Ltd. All rights reserved.