<2-²H₂>-p-nitrophenylacetic acid | 113715-46-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: <2-²H₂>-p-nitrophenylacetic acid
• 英文别名: p-nitrophenylacetic acid-α,α-d2；2,2-dideuterio-2-(4-nitro-phenyl)-acetic acid；2,2-dideuterio-2-(4-nitrophenyl)acetic acid
• CAS: 113715-46-1
• 化学式: C₈H₇NO₄
• 分子量: 183.132
• InChiKey: YBADLXQNJCMBKR-BFWBPSQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.22
• 重原子数：
  13.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  80.44
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  <2-²H₂>-p-nitrophenylacetic acid 在 palladium on barium sulfate 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 二甲基亚砜 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 17.0h， 生成 N-acetylcysteamine thioester of <2-²H₂>-p-aminophenylacetic acid
  参考文献：
  名称：

  Herbert, Richard B.; Knaggs, Andrew R., Journal of the Chemical Society. Perkin transactions I, 1992, # 1, p. 103 - 108

  摘要：

  DOI：
• 作为产物：
  描述：

  苯乙酸-Alpha,Alpha-d2 在 硫酸 、 硝酸 作用下， 反应 1.0h， 以33%的产率得到<2-²H₂>-p-nitrophenylacetic acid
  参考文献：
  名称：

  Secondary α-Deuterium Kinetic Isotope Effects Signifying a Polar Transition State in the Thermolysis of Ring-Substituted tert-Butyl Phenylperacetates

  摘要：

  Several ring-substituted tert-butyl phenylperacetates (YC6H4CH2CO3But) and their deuterated versions (YC6H4CD2CO3But) were prepared (Y: p-OCH3, P-CH3, p-H; and p-NO2). Thermolyses at 80 degrees C in CDCl3 showed excellent first-order kinetics. The rates have been measured as k(YH) x 10(4) and k(YD) x 10(4) s(-1): 11.9 and 9.20 (p-OCH3), 2.64 and 2.22 (p-CH3), 1.06 and 0.93 (p-H), 0.164 and 0.156 (p-NO2). Hammett correlations were derived to yield rho(YH)(+) = -1.17 and rho(YD)(+) = -1.12. However, better Hammett plots were obtained with three points (p-OCH3, p-CH3, and p-H) showing rho(YH)(+) = -1.35 and rho(YD)(+) = -1.28. SDKIE was calculated as 1.293 (p-OCH3), 1.189 (p-CH3), 1.140 (p-H), and 1.051 (p-NO2), showing substantial substituent effects. Values of k(YH)/k(YD) for p-NO2 showed little temperature dependence. Hammett correlations and SDKIE were derived from the same kinetic entity that is the band cleavage.

  DOI：

  10.1021/jo9814492

文献信息

• [EN] DEUTERATED ANALOGS OF ELACRIDAR<br/>[FR] ANALOGUES DEUTÉRÉS D'ÉLACRIDAR
  申请人：IZUMI TECH LLC

  公开号：WO2019183403A1

  公开（公告）日：2019-09-26

  The present invention relates to efflux inhibitor compounds, compositions, and methods of using the same. More specifically, the instant invention comprises deuterated analogs of elacridar with superior pharmacokinetic properties such that it is now possible to facilitate accumulation and distribution of therapeutic agents to effective levels in cells or compartments protected by efflux transporter proteins such as Breast Cancer Resistance Protein (BCRP) and P-Glycoprotein (P-GP). Such transporter protected compartments include brain, spinal cord, nerves, cerebrospinal fluid, testis, eyeballs, retina, inner ear, placenta, mammary gland, liver, biliary tract, kidney, intestines, lung, adrenal cortex, endometrium, hematopoietic cells, stem cells, and solid tumors. In other embodiments, the present invention comprises methods of using the instant deuterated analogs.

  本发明涉及外流抑制剂化合物、组合物以及使用这些化合物的方法。更具体地，本发明涵盖了具有优越药代动力学性质的氘代谱拉达的类似物，使得现在可以促进治疗剂在由外流转运蛋白（如乳腺癌耐药蛋白（BCRP）和P-糖蛋白（P-GP）保护的细胞或隔室中的有效水平的积累和分布。这样的转运蛋白保护的隔室包括大脑、脊髓、神经、脑脊液、睾丸、眼球、视网膜、内耳、胎盘、乳腺、肝脏、胆道、肾脏、肠道、肺、肾上腺皮质、子宫内膜、造血细胞、干细胞和实体肿瘤。在其他实施方案中，本发明涵盖了使用这些氘代谱拉达的类似物的方法。