N-[3-(naphthalene-2-carbonyl)-4,5-diphenylthiophen-2-yl]-2,2,2-trifluoroacetamide | 538326-97-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[3-(naphthalene-2-carbonyl)-4,5-diphenylthiophen-2-yl]-2,2,2-trifluoroacetamide
• 英文别名: 2,2,2-trifluoro-N-[3-(naphthalene-2-carbonyl)-4,5-diphenylthiophen-2-yl]acetamide
• CAS: 538326-97-5
• 化学式: C₂₉H₁₈F₃NO₂S
• 分子量: 501.529
• InChiKey: LOOOJUKLTCKEIG-UHFFFAOYSA-N

物化性质

• 沸点：
  650.8±55.0 °C(Predicted)
• 密度：
  1.351±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  74.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[3-(naphthalene-2-carbonyl)-4,5-diphenylthiophen-2-yl]-2,2,2-trifluoroacetamide 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 以30%的产率得到(2-Amino-4,5-diphenylthiophen-3-yl)-naphthalen-2-ylmethanone
  参考文献：
  名称：

  2-Amino-3-benzoylthiophene Allosteric Enhancers of A₁ Adenosine Agonist Binding:  New 3, 4-, and 5-Modifications

  摘要：

  2-Amino-3-aroylthiophenes are agonist allosteric enhancers (AE) at the A, adenosine receptor (A(1)AR). Here we report the syntheses of three kinds of novel 2-aminothiophenes and assays of their AE activity at the human A(1)AR (hA(1)AR), namely, (1) 2-amino-4,5-diphenylthiophene-3-carboxylates, 3a-h, (2) 2-amino-3-benzoyl-4,5-diphenylthiophenes, 7a-p, and (3) 2-amino-5-bromo-3-benzoyl-4-phenylthiophenes, 10a-h. An in vitro assay employing the A(1)AR agonist [I-125]ABA and membranes from CHO-K1 cells stably expressing the hA(1)AR measured an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex, scored as the percentage of ternary complex remaining after 10 min of dissociation initiated by CPX and GTPgammaS. The AE activity score of 2-amino-4,5-dimethyl-3-(3-trifluoromethylbenzoyl)thiophene (PD 81,723), which was 19%, served as a standard for comparison. Two 3-carboxythiophene 3-trifluoromethylbenzyl esters, 3d (49%) and 3f (63%), had substantial AE activity. The 3-(1-naphthoyl) substituent of 7e (52%) also supported AE activity. Compounds in series 3 tended to be more potent, 10a and 10c having scores of 91 and 80%, respectively. The activity of 2-amino-5-bromo-3-ethoxycarbonyl-4-(3-nitrophenyl)thiophene, 10h (26%), is an exception to the rule that a 3-ethoxycarbonyl substituent cannot support AE activity.

  DOI：

  10.1021/jm020295m
• 作为产物：
  描述：

  2-cyano-3,4-diphenyl-crotonic acid ethyl ester 在 sodium hydroxide 、 四氯化锡 、 sulfur 、 二乙胺 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 1,2-二氯乙烷 为溶剂， 反应 49.0h， 生成 N-[3-(naphthalene-2-carbonyl)-4,5-diphenylthiophen-2-yl]-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  2-Amino-3-benzoylthiophene Allosteric Enhancers of A₁ Adenosine Agonist Binding:  New 3, 4-, and 5-Modifications

  摘要：

  2-Amino-3-aroylthiophenes are agonist allosteric enhancers (AE) at the A, adenosine receptor (A(1)AR). Here we report the syntheses of three kinds of novel 2-aminothiophenes and assays of their AE activity at the human A(1)AR (hA(1)AR), namely, (1) 2-amino-4,5-diphenylthiophene-3-carboxylates, 3a-h, (2) 2-amino-3-benzoyl-4,5-diphenylthiophenes, 7a-p, and (3) 2-amino-5-bromo-3-benzoyl-4-phenylthiophenes, 10a-h. An in vitro assay employing the A(1)AR agonist [I-125]ABA and membranes from CHO-K1 cells stably expressing the hA(1)AR measured an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex, scored as the percentage of ternary complex remaining after 10 min of dissociation initiated by CPX and GTPgammaS. The AE activity score of 2-amino-4,5-dimethyl-3-(3-trifluoromethylbenzoyl)thiophene (PD 81,723), which was 19%, served as a standard for comparison. Two 3-carboxythiophene 3-trifluoromethylbenzyl esters, 3d (49%) and 3f (63%), had substantial AE activity. The 3-(1-naphthoyl) substituent of 7e (52%) also supported AE activity. Compounds in series 3 tended to be more potent, 10a and 10c having scores of 91 and 80%, respectively. The activity of 2-amino-5-bromo-3-ethoxycarbonyl-4-(3-nitrophenyl)thiophene, 10h (26%), is an exception to the rule that a 3-ethoxycarbonyl substituent cannot support AE activity.

  DOI：

  10.1021/jm020295m

文献信息

• 2-Amino-3-benzoylthiophene Allosteric Enhancers of A₁ Adenosine Agonist Binding:  New 3, 4-, and 5-Modifications
  作者：Henning Lütjens、Andrea Zickgraf、Heidi Figler、Joel Linden、Ray A. Olsson、Peter J. Scammells

  DOI：10.1021/jm020295m

  日期：2003.5.1

  2-Amino-3-aroylthiophenes are agonist allosteric enhancers (AE) at the A, adenosine receptor (A(1)AR). Here we report the syntheses of three kinds of novel 2-aminothiophenes and assays of their AE activity at the human A(1)AR (hA(1)AR), namely, (1) 2-amino-4,5-diphenylthiophene-3-carboxylates, 3a-h, (2) 2-amino-3-benzoyl-4,5-diphenylthiophenes, 7a-p, and (3) 2-amino-5-bromo-3-benzoyl-4-phenylthiophenes, 10a-h. An in vitro assay employing the A(1)AR agonist [I-125]ABA and membranes from CHO-K1 cells stably expressing the hA(1)AR measured an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex, scored as the percentage of ternary complex remaining after 10 min of dissociation initiated by CPX and GTPgammaS. The AE activity score of 2-amino-4,5-dimethyl-3-(3-trifluoromethylbenzoyl)thiophene (PD 81,723), which was 19%, served as a standard for comparison. Two 3-carboxythiophene 3-trifluoromethylbenzyl esters, 3d (49%) and 3f (63%), had substantial AE activity. The 3-(1-naphthoyl) substituent of 7e (52%) also supported AE activity. Compounds in series 3 tended to be more potent, 10a and 10c having scores of 91 and 80%, respectively. The activity of 2-amino-5-bromo-3-ethoxycarbonyl-4-(3-nitrophenyl)thiophene, 10h (26%), is an exception to the rule that a 3-ethoxycarbonyl substituent cannot support AE activity.