3-(4-cyclohexylphenyl)-3-oxopropanenitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(4-cyclohexylphenyl)-3-oxopropanenitrile
• 化学式: C₁₅H₁₇NO
• 分子量: 227.306
• InChiKey: REQZDGMWROEVRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(4-cyclohexylphenyl)-3-oxopropanenitrile 、 环庚酮 在 sulfur 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以31%的产率得到(2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)-(4-cyclohexylphenyl)methanone
  参考文献：
  名称：

  2-Amino-3-aroyl-4,5-alkylthiophenes:  Agonist Allosteric Enhancers at Human A₁ Adenosine Receptors

  摘要：

  2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A(1) adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A(1)AR (hA(1)AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). 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, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH2)(n)- bridge, n = 3 < n = 4 < n = 5. The 3-carbethoxy substituents of 17a, 18a, and 19a did not support AE activity, but a 3-aroyl group did. Bulky (or hydrophobic) substituents at the meta and para positions of the 3-benzoyl group and also 3-naphthoyl groups greatly enhanced activity. Thus, the hA(1)AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.

  DOI：

  10.1021/jm010081p
• 作为产物：
  描述：

  ethyl 4-cyclohexylbenzoate 、 乙腈 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以72%的产率得到3-(4-cyclohexylphenyl)-3-oxopropanenitrile
  参考文献：
  名称：

  铱催化串联苯甲酰乙腈与重氮化合物的连续串联环化反应，通过连续CH官能团官能化取代萘并[1,8-bc]吡喃

  摘要：

  benzoylacetonitriles与重氮化合物级联环反应在铱催化剂的存在下有效地进行，得到取代的萘并[1,8- BC ]通过C（的顺序裂解吡喃SP 2）-H / C（SP 3）-H和C（sp 2）-H / OH键。有趣的是，涉及环状重氮化合物和开链重氮化合物的反应会导致不同类型的萘并[1,8- bc ]吡喃。大多数产品都是以中等到良好的收率获得的，并具有广泛的底物。

  DOI：

  10.1002/adsc.201800149

文献信息

• Structure-activity relationships of 2-substituted phenyl- N -phenyl-2-oxoacetohydrazonoyl cyanides as novel antagonists of exchange proteins directly activated by cAMP (EPACs)
  作者：Zhiqing Liu、Yingmin Zhu、Haiying Chen、Pingyuan Wang、Fang C. Mei、Na Ye、Xiaodong Cheng、Jia Zhou

  DOI：10.1016/j.bmcl.2017.10.056

  日期：2017.12

  Exchange proteins directly activated by cAMP (EPACs) are critical cAMP-dependent signaling pathway mediators that play important roles in cancer, diabetes, heart failure, inflammations, infections, neurological disorders and other human diseases. EPAC specific modulators are urgently needed to explore EPAC's physiological function, mechanism of action and therapeutic applications. On the basis of a previously identified EPAC specific inhibitor hit ESI-09, herein we have designed and synthesized a novel series of 2-substituted phenyl-N-phenyl-2-oxoacetohydrazonoyl cyanides as potent EPAC inhibitors. Compound 31 (ZL0524) has been discovered as the most potent EPAC inhibitor with IC50 values of 3.6 mu M and 1.2 mu M against EPAC1 and EPAC2, respectively. Molecular docking of 31 onto an active EPAC2 structure predicts that 31 occupies the hydrophobic pocket in cAMP binding domain (CBD) and also opens up new space leading to the solvent region. These findings provide inspirations for discovering next generation of EPAC inhibitors. (C) 2017 Elsevier Ltd. All rights reserved.
• 2-Amino-3-aroyl-4,5-alkylthiophenes:  Agonist Allosteric Enhancers at Human A₁ Adenosine Receptors
  作者：C. Elisabet Tranberg、Andrea Zickgraf、Brian N. Giunta、Henning Luetjens、Heidi Figler、Lauren J. Murphree、Ruediger Falke、Holger Fleischer、Joel Linden、Peter J. Scammells、Ray. A. Olsson

  DOI：10.1021/jm010081p

  日期：2002.1.1

  2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A(1) adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A(1)AR (hA(1)AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). 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, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH2)(n)- bridge, n = 3 < n = 4 < n = 5. The 3-carbethoxy substituents of 17a, 18a, and 19a did not support AE activity, but a 3-aroyl group did. Bulky (or hydrophobic) substituents at the meta and para positions of the 3-benzoyl group and also 3-naphthoyl groups greatly enhanced activity. Thus, the hA(1)AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.
• Iridium-Catalyzed Tandem Cyclization of Benzoylacetonitriles with Diazo Compounds Leading to Substituted Naphtho[1,8-<i>bc</i> ]pyrans by Sequential C−H Functionalization
  作者：Kelu Yan、Bin Li、Baiquan Wang

  DOI：10.1002/adsc.201800149

  日期：2018.6.15

  annulation reactions of benzoylacetonitriles with diazo compounds proceed efficiently in the presence of an iridium catalyst to give substituted naphtho[1,8‐bc]pyrans by sequential cleavage of C(sp2)−H/C(sp3)−H and C(sp2)−H/O−H bonds. Interestingly, the reactions involving cyclic diazo compounds and open‐chain diazo compounds lead to different types of naphtho[1,8‐bc]pyrans. Most products are obtained

  benzoylacetonitriles与重氮化合物级联环反应在铱催化剂的存在下有效地进行，得到取代的萘并[1,8- BC ]通过C（的顺序裂解吡喃SP 2）-H / C（SP 3）-H和C（sp 2）-H / OH键。有趣的是，涉及环状重氮化合物和开链重氮化合物的反应会导致不同类型的萘并[1,8- bc ]吡喃。大多数产品都是以中等到良好的收率获得的，并具有广泛的底物。