2,2-dimethyl-3-(naphthalen-2-yl)propanenitrile | 1258315-84-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2,2-dimethyl-3-(naphthalen-2-yl)propanenitrile
• 英文别名: 2,2-dimethyl-3-naphthalen-2-ylpropanenitrile
• CAS: 1258315-84-2
• 化学式: C₁₅H₁₅N
• 分子量: 209.291
• InChiKey: NODQFMZLEKDPFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  2,2-dimethyl-3-(naphthalen-2-yl)propanenitrile 在 2-羟基吡啶 、 盐酸 、 氨 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙酸乙酯 为溶剂， 反应 50.0h， 生成 (2S,4S,5S,7S)-5-amino-N-(2,2-dimethyl-3-(naphthalen-2-yl)propyl)-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(3-methoxypropoxy)benzyl)-8-methylnonanamide hydrochloride
  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：

  2-萘甲醇 在 2-双环己基膦-2',6'-二甲氧基联苯 、 吡啶 、 bis(η3-allyl-μ-chloropalladium(II)) 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 15.0h， 生成 2,2-dimethyl-3-(naphthalen-2-yl)propanenitrile
  参考文献：
  名称：

  钯催化α-氰基脂肪族羧酸盐的脱羧苯甲酰化，构建β-芳基腈

  摘要：

  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。

  DOI：

  10.1002/adsc.201200383

文献信息

• Synthesis of Nitrile‐Bearing Quaternary Centers by an Equilibrium‐Driven Transnitrilation and Anion‐Relay Strategy
  作者：Sébastien Alazet、Michael S. West、Purvish Patel、Sophie A. L. Rousseaux

  DOI：10.1002/anie.201903215

  日期：2019.7.22

  preparation of nitrile‐containing building blocks is of interest due to their utility as synthetic intermediates and their prevalence in pharmaceuticals. As a result, significant efforts have been made to develop methods to access these motifs which rely on safer and non‐toxic sources of CN. Herein, we report that 2‐methyl‐2‐phenylpropanenitrile is an efficient, non‐toxic, electrophilic CN source for

  有趣的是，有效制备含腈基砌块的原因在于它们作为合成中间体的用途以及它们在药物中的普遍性。结果，已经做出了巨大的努力来开发依赖于更安全，无毒的CN来获取这些基序的方法。在此，我们报道2-甲基-2-苯基丙腈是一种有效的，无毒的，亲电子的CN来源，可通过热力学氮化和​​阴离子中继策略合成含腈的季铵盐中心。这种一锅法过程会导致烷基锂试剂的宝石双官能化，从而产生腈产品。
• Novel selective anti-androgens with a diphenylpentane skeleton
  作者：Keisuke Maruyama、Tomomi Noguchi-Yachide、Kazuyuki Sugita、Yuichi Hashimoto、Minoru Ishikawa

  DOI：10.1016/j.bmcl.2010.09.011

  日期：2010.11

  We have proposed a multi-template approach for drug development, focusing on similar fold structures of proteins, and have effectively generated lead compounds for several drug targets. Modification of these polypharmacological lead compounds is then needed to generate target-selective compounds. In the work presented here, we aimed at separation of the anti-androgen activity and vitamin D activity of previously identified diphenylpentane lead compounds. Based on the determined X-ray crystal structures of androgen receptor and vitamin D receptor, bulky substituents were introduced at the t-butyl group in the lead compounds 2 and 3. As a result of this structural development, we obtained 16c, which exhibits more potent anti-androgen activity (IC(50): 0.13 mu M) than clinically used anti-androgen bicalutamide (IC(50): 0.67 mu M) with 30-fold selectivity over vitamin D activity. This result indicates that lead compounds obtained via the multi-template approach can indeed be structurally modified to generate target-selective compounds. (C) 2010 Elsevier Ltd. All rights reserved.