3-(3-chlorophenyl)-2,2-dimethylpropanenitrile | 1268077-32-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(3-chlorophenyl)-2,2-dimethylpropanenitrile
• CAS: 1268077-32-2
• 化学式: C₁₁H₁₂ClN
• 分子量: 193.676
• InChiKey: IGJKIQKJURWHKW-UHFFFAOYSA-N

物化性质

• 沸点：
  309.5±17.0 °C(Predicted)
• 密度：
  1.093±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-(3-chlorophenyl)-2,2-dimethylpropanenitrile 在 2-羟基吡啶 、 氨 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 48.0h， 生成 tert-butyl (3S,5S,6S,8S)-8-(3-(3-chlorophenyl)-2,2-dimethylpropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate
  参考文献：
  名称：

  Discovery of highly potent renin inhibitors potentially interacting with the S3′ subsite of renin

  摘要：

  To exploit the S3' subsite of renin active site for renin inhibitor design, 42 aliskiren derivatives with modified P2' portion were designed, synthesized and biologically evaluated. Some highly potent renin inhibitors (IC50 < 3 nM) were identified, among which compounds 38 (IC50 = 0.9 nM) and 39 (IC50 = 0.7 nM) were over 2.5-fold more potent than aliskiren (IC50 = 2.3 nM). SAR analysis indicated that incorporation of polar hydrophilic moieties into the P2' portion of renin inhibitors generally enhanced the potency. Consistently with this, molecular modeling study revealed that the triazole part of 39 could provide additional interactions to the S3' subsite of renin active site. Moreover, in vivo evaluation in the double transgenic mouse hypertension model demonstrated that 39 produced greater reduction of the mean arterial blood pressure than ariskiren at the doses of 17.0 and 34.0 mu mol/kg, respectively. Taken together, the S3' subsite of renin active site merits further consideration for renin inhibitor design. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.060
• 作为产物：
  描述：

  异丁腈 、 3-氯苄溴 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 4.5h， 以50%的产率得到3-(3-chlorophenyl)-2,2-dimethylpropanenitrile
  参考文献：
  名称：

  Discovery of highly potent renin inhibitors potentially interacting with the S3′ subsite of renin

  摘要：

  To exploit the S3' subsite of renin active site for renin inhibitor design, 42 aliskiren derivatives with modified P2' portion were designed, synthesized and biologically evaluated. Some highly potent renin inhibitors (IC50 < 3 nM) were identified, among which compounds 38 (IC50 = 0.9 nM) and 39 (IC50 = 0.7 nM) were over 2.5-fold more potent than aliskiren (IC50 = 2.3 nM). SAR analysis indicated that incorporation of polar hydrophilic moieties into the P2' portion of renin inhibitors generally enhanced the potency. Consistently with this, molecular modeling study revealed that the triazole part of 39 could provide additional interactions to the S3' subsite of renin active site. Moreover, in vivo evaluation in the double transgenic mouse hypertension model demonstrated that 39 produced greater reduction of the mean arterial blood pressure than ariskiren at the doses of 17.0 and 34.0 mu mol/kg, respectively. Taken together, the S3' subsite of renin active site merits further consideration for renin inhibitor design. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.060

文献信息

• β‐Aryl Nitrile Construction<i>via</i>Palladium‐Catalyzed Decarboxylative Benzylation of α‐Cyano Aliphatic Carboxylate Salts
  作者：Rui Shang、Zheng Huang、Xiao Xiao、Xi Lu、Yao Fu、Lei Liu

  DOI：10.1002/adsc.201200383

  日期：2012.9.17

  The palladium‐catalyzed decarboxylative benzylation of α‐cyano aliphatic carboxylate salts with benzyl electrophiles was discovered. This reaction exhibits good functional group compatibility and proceeds under relatively mild conditions. A diverse range of quaternary, tertiary and secondary β‐aryl nitriles can be conveniently prepared by this method.

  发现了α-氰基脂肪族羧酸盐与苄基亲电试剂的钯催化脱羧苄基化反应。该反应表现出良好的官能团相容性，并且在相对温和的条件下进行。通过这种方法可以方便地制备各种范围的季，叔和仲β-芳基腈。
• Discovery of highly potent renin inhibitors potentially interacting with the S3′ subsite of renin
  作者：Xiaowei Sun、Xiaoan Wen、Yan-yan Chen、Chen Shi、Chengzhe Gao、Yong Wu、Li-jun Wang、Xiu-hong Yang、Hongbin Sun

  DOI：10.1016/j.ejmech.2015.08.060

  日期：2015.10

  To exploit the S3' subsite of renin active site for renin inhibitor design, 42 aliskiren derivatives with modified P2' portion were designed, synthesized and biologically evaluated. Some highly potent renin inhibitors (IC50 < 3 nM) were identified, among which compounds 38 (IC50 = 0.9 nM) and 39 (IC50 = 0.7 nM) were over 2.5-fold more potent than aliskiren (IC50 = 2.3 nM). SAR analysis indicated that incorporation of polar hydrophilic moieties into the P2' portion of renin inhibitors generally enhanced the potency. Consistently with this, molecular modeling study revealed that the triazole part of 39 could provide additional interactions to the S3' subsite of renin active site. Moreover, in vivo evaluation in the double transgenic mouse hypertension model demonstrated that 39 produced greater reduction of the mean arterial blood pressure than ariskiren at the doses of 17.0 and 34.0 mu mol/kg, respectively. Taken together, the S3' subsite of renin active site merits further consideration for renin inhibitor design. (C) 2015 Elsevier Masson SAS. All rights reserved.