N-(1,1,1-Trifluor-2-propyl)-4-methoxyanilin | 117730-46-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(1,1,1-Trifluor-2-propyl)-4-methoxyanilin
• 英文别名: 4-methoxy-N-(1,1,1-trifluoropropan-2-yl)aniline
• CAS: 117730-46-8
• 化学式: C₁₀H₁₂F₃NO
• 分子量: 219.207
• InChiKey: AQBRKHCIOOZFTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(1,1,1-Trifluor-2-propyl)-4-methoxyanilin 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 生成 N-(4-羟基苯基)-N-(1,1,1-三氟-2-丙基)-4-羟基苯甲酰胺
  参考文献：
  名称：

  N-（4-羟基苯基）-N-（1,1,1-三氟-2-丙基）-4-羟基苯甲酰胺：一种新型抗雌激素的合成和药理学评价

  摘要：

  描述了 N-(4-羟基苯基)-N-(1,1,1-三氟-2-丙基)-4-羟基苯甲酰胺 (1) 的合成。该化合物对雌激素受体 (ER) 的相对结合亲和力为 2.4。在对幼年 NMRI 小鼠进行的子宫重量测试中，1 证明是一种强抗雌激素。弱雌激素副作用仅在高剂量下才会出现。BD2F1 小鼠的激素依赖性、可移植 MXT 乳腺肿瘤和激素依赖性 9,10-二甲基-1,2-苯并蒽 (DMBA) 诱导的 SD 大鼠乳腺癌均未显示出显着的抗肿瘤作用。

  DOI：

  10.1002/ardp.19883210814
• 作为产物：
  描述：

  甲氧苯胺 在 lithium aluminium tetrahydride 、 硫酸 作用下， 以 乙醚 、 苯 为溶剂， 反应 16.0h， 生成 N-(1,1,1-Trifluor-2-propyl)-4-methoxyanilin
  参考文献：
  名称：

  Acyclic amides as estrogen receptor ligands: Synthesis, binding, activity and receptor interaction

  摘要：

  We have prepared a series of bisphenolic amides that mimic bibenzyl and homobibenzyl motifs commonly found as substructures in ligands for the estrogen receptor (ER). Representative members were prepared from three classes: N-phenyl benzamides, N-phenyl acetamides, and N-benzyl benzamides; in some cases the corresponding thiocarboxamides and sulfonamides were also prepared. Of these three classes, the N-phenyl benzamides had the highest affinity for ER, the N-phenyl acetamides had lower, and the N-benzyl benzamides were prone to fragmentation via a quinone methide intermediate. In the N-phenyl benzamide series, the highest affinity analogues had bulky N-substituents; a CF3 group, in particular, conferred high affinity. The thiocarboxamides bound better than the corresponding carboxamides and these bound better than the corresponding sulfonamides. Binding affinity comparisons suggest that the p-hydroxy group on the benzoate ring, which contributes most to the binding, is playing the role of the phenolic hydroxyl of estradiol. Computational studies and NMR and X-ray crystallographic analysis indicate that the two anilide systems studied have a strong preference for the s-cis or exo amide conformation, which places the two aromatic rings in a syn orientation. We used this structural template. together with the X-ray structure of the ER ligand binding domain, to elaborate an additional hydrogen bonding site on a benzamide system that elevated receptor binding further. When assayed on the individual ER subtypes, ER alpha and ER beta, these compounds show modest binding affinity preference for ER alpha. In a reporter gene transfection assay of transcriptional activity, the amides generally have full to nearly full agonist character on ERa, but have moderate to full antagonist character on ER beta. One high affinity carboxamide is 500-fold more potent as an agonist on ER alpha than on ER beta. This work illustrates that ER ligands having simple amide core structures can be readily prepared, but that high affinity binding requires an appropriate distribution of bulk, polarity, and functionality. The strong conformational preference of the core anilide function in all of these ligands defines a rather rigid geometry for further structural and functional expansion of these series. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00075-4

文献信息

• Antiestrogene N-(4-Hydroxyphenyl)-N-(1,1,1-trifluor-2-propyl)-4-hydroxybenzamide: Beeinflussung der Wirkung durch hydrophobe Reste in ortho-Position des Benzamidfragments
  作者：Rolf W. Hartmann、Hans-Dieter Vom Orde、Helmut Schönenberger

  DOI：10.1002/ardp.19903230204

  日期：——

  Einführung hydrophober Reste in 2‐bzw. 2,6‐Position des Benzamidfragments von N‐(4‐Hydroxyphenyl)‐N‐(1,1,1‐trifluor‐2‐propyl)‐4‐hydroxybenzamid zu Verbindungen mit antiestrogenen und mammatumorhemmenden Eigenschaften zu gelangen. Unter den neuen Verbindungen 2–7 (2; 2‐CH3, 3: 2‐F, 4: 2‐C1, 5: 2‐Br, 6: 2,6‐Cl2, 7:2‐CF3) erwiesen sich 2 und 3 als “echte” Antiestrogene. Verbindung 4 zeigte die stärkste Wirkung

  据报道，尝试在 2-resp 中引入疏水残基。N-(4-羟基苯基)-N-(1,1,1-三氟-2-丙基)-4-羟基苯甲酰胺的苯甲酰胺片段的2,6-位获得具有抗雌激素和乳腺肿瘤抑制特性的化合物。在新化合物 2-7 (2; 2 - CH3, 3: 2 - F, 4: 2 - C1, 5: 2 - Br, 6: 2,6 - Cl2, 7: 2 - CF3) 2 中被发现3 作为“真正的”抗雌激素。化合物 4 对 MXT-MC、ER + 的作用最强。
• Synthesis of functionalized α-trifluoroethyl amine scaffolds via Grignard addition to N-aryl hemiaminal ethers
  作者：Amrei Deutsch、Herbert Glas、Anja Hoffmann-Röder、Carl Deutsch

  DOI：10.1039/c3ra47708h

  日期：——

  The synthesis of a variety of α-branched trifluoroethyl amines was achieved by reaction of N-aryl hemiaminal ethers with organomagnesium reagents.

  通过将N-芳基半缩醛醚与有机镁试剂反应，成功合成了多种α-支链三氟乙基胺。
• HARTMANN, ROLF W.;ORDE, HANS-DIETER VOM;SCHONENBERGER, HELMUT, ARCH. PHARM., 323,(1990) N, C. 73-78
  作者：HARTMANN, ROLF W.、ORDE, HANS-DIETER VOM、SCHONENBERGER, HELMUT

  DOI：——

  日期：——
• HARTMANN, ROLF W.;ORDE, HANS-DIETER VOM;HEINDL, ALEXANDER;SCHONENBERGER, +, ARCH. PHARM., 321,(1988) N 8, C. 497-501
  作者：HARTMANN, ROLF W.、ORDE, HANS-DIETER VOM、HEINDL, ALEXANDER、SCHONENBERGER, +

  DOI：——

  日期：——