N-[3-(4-amino-3-methylphenoxy)propyl]urea | 329946-00-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-[3-(4-amino-3-methylphenoxy)propyl]urea
• 英文别名: 3-(4-amino-3-methylphenoxy)propylurea
• CAS: 329946-00-1
• 化学式: C₁₁H₁₇N₃O₂
• 分子量: 223.275
• InChiKey: ONNCEXKANCWEAK-UHFFFAOYSA-N

物化性质

• 沸点：
  432.4±45.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  90.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[3-(4-amino-3-methylphenoxy)propyl]urea 、 [4-chloro-2-(3-fluoro-5-trifluoromethylbenzoyl)phenoxy]acetic acid 在 碳酸氢钠 作用下， 以 丙酮 为溶剂， 反应 2.5h， 以44%的产率得到N-[4-[3-(carbamoylamino)propoxy]-2-methylphenyl]-2-[4-chloro-2-[3-fluoro-5-(trifluoromethyl)benzoyl]phenoxy]acetamide
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Benzophenones Leading to the Discovery of a Potent, Next Generation HIV Nonnucleoside Reverse Transcriptase Inhibitor

  摘要：

  Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC50 values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies.

  DOI：

  10.1021/jm050670l
• 作为产物：
  描述：

  4-硝基间甲苯酚 在 palladium on activated charcoal 氢气 、 caesium carbonate 、 一水合肼 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~55.0 ℃ 、358.53 kPa 条件下， 反应 10.0h， 生成 N-[3-(4-amino-3-methylphenoxy)propyl]urea
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Benzophenones Leading to the Discovery of a Potent, Next Generation HIV Nonnucleoside Reverse Transcriptase Inhibitor

  摘要：

  Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC50 values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies.

  DOI：

  10.1021/jm050670l