2-(benzyl(tert-butyl)amino)acetonitrile | 50587-77-4

• 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: 2-(benzyl(tert-butyl)amino)acetonitrile
• 英文别名: Acetonitrile, [(1,1-dimethylethyl)(phenylmethyl)amino]-；2-[benzyl(tert-butyl)amino]acetonitrile
• CAS: 50587-77-4
• 化学式: C₁₃H₁₈N₂
• 分子量: 202.299
• InChiKey: UETGTCWIRYHYPU-UHFFFAOYSA-N

物化性质

• 沸点：
  305.5±17.0 °C(Predicted)
• 密度：
  0.984±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(benzyl(tert-butyl)amino)acetonitrile 在 palladium diacetate 、 lithium aluminium tetrahydride 、 三乙胺 、 三(邻甲基苯基)磷 、 silver carbonate 、 苯酚 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 21-[2-[Benzyl(tert-butyl)amino]ethyl]-16,17-dimethoxy-5,7-dioxa-11,21-diazapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(13),2,4(8),9,11,14,16,18-octaen-20-one
  参考文献：
  名称：

  5-(2-Aminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones:  Variation of N-Alkyl Substituents Modulates Sensitivity to Efflux Transporters Associated with Multidrug Resistance

  摘要：

  5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo [c, h]-[1,6]naphthyridin-6-one (ARC-111) has potent TOP1-targeting activity and pronounced antitumor activity. Several analogues of ARC-111 were synthesized with NH2, N-alkyl, N,N-dialkyl, pyrrolidinyl, piperidinyl, and piperazinyl substituents at the 2-position of the 5-ethyl group. The relative TOP1-targeting activity and cytotoxicity of these structural analogues were assessed in RPMI8402 and P388 tumor cells and their camptothecin-resistant variants CPT-K5 and P388/CPT45, respectively. Potent TOP1-targeting activity was retained within a series of mono N-alkyl analogues that included NHCH2CH3, NHCH(CH3)(2), and NHC(CH3)(3). TOP1-targeting activity was diminished by the presence of a N-benzyl moiety. In a comparison of a series of N-alkyl-N-isopropyl analogues, activity decreased in the order CH3 > CH2CH3 > CH(CH3)(2). Cytotoxicity in RPMI8402 and P388 did correlate with TOP1-targeting activity. Cytotoxic activity was also determined in KB3-1 cells and its variants KB/V-1 and KBH5.0. As KB/V-1 cells overexpress MDR1 and KBH5.0 cells overexpress BCRP, decreased cytotoxicity in these cell lines relative to the parent cell line is indicative of compounds that are substrates for these efflux transporters. In view of their diminished cytotoxicity in KB/V-1 cells, it appears that the likely demethylated metabolites of ARC-111, i.e., where NH2 or NHCH3 replaces the N(CH3)(2) at the 2-position of the 5-ethyl substituent, are substrates for MDR1. In contrast, no significant difference in cytotoxicity among these three cell lines was observed with other N-alkyl analogues, including NHC2H5, NHCH(CH3)(2), NHC(CH3)(3), N(CH3)(2), N(CH2CH3)(2), NCH3(CH(CH)(3))(2)), and either the pyrrolidinyl or the piperidinyl analogues. The 2-(piperazinyl) analogues were associated with diminished cytotoxicity in KB/V-1 cells, suggesting that the second basic amino substituent is associated with their recognition as substrates by MDR1. Comparative studies on the antitumor activity of ARC-111 and its N-demethylated derivatives (the NHCH3 and NH2 analogues) against SJ-BT45 medulloblastoma xenografts in scid mice revealed that the secondary amine metabolite is at least as active as ARC-111 in vivo, although the primary amine derivative was significantly less potent.

  DOI：

  10.1021/jm049447z
• 作为产物：
  描述：

  N-叔丁基苄胺 、 溴乙腈 在 potassium carbonate 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以79%的产率得到2-(benzyl(tert-butyl)amino)acetonitrile
  参考文献：
  名称：

  α-氨基腈的非对映选择性醛醇缩合。β-氨基醇和β，γ-二氨基醇的非对映选择性合成。

  摘要：

  通过将锂化的N-苄基-N-叔丁基氨基乙腈加到醛中进行的醛醇缩合提供了非对映体纯的抗β-羟基-α-氨基腈。通过两步法将它们转化为顺式，抗保护的β，γ-二氨基醇，包括添加格氏试剂并还原。N-叔丁基的裂解是通过简单的酸性处理实现的。研究了该方法在手性，非外消旋醛上的应用。从D-异亚丙基甘油醛开始，以可接受的收率和良好的非对映选择性制备抗，抗，顺，抗-（2R，3S，4S，5R，6R）-二氨基三醇。

  DOI：

  10.1021/jo025872t

文献信息

• THERAPEUTIC AGENT FOR CEREBRAL INFARCTION
  申请人：Nakao Akira

  公开号：US20120196824A1

  公开（公告）日：2012-08-02

  The invention provides a therapeutic drug for ischemic stroke. The therapeutic drug has the formula (I) wherein each symbol is as defined herein, or a pharmacologically acceptable salt thereof, or a solvate thereof, as an active ingredient.

  这项发明提供了一种用于缺血性中风的治疗药物。该治疗药物具有如下式（I）的化学式，其中每个符号如本文所定义，或其药理学上可接受的盐，或其溶剂化物，作为活性成分。
• Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif
  作者：Kevin J. Frankowski、Stephen R. Slauson、Kimberly M. Lovell、Angela M. Phillips、John M. Streicher、Lei Zhou、David A. Whipple、Frank J. Schoenen、Thomas E. Prisinzano、Laura M. Bohn、Jeffrey Aubé

  DOI：10.1016/j.bmc.2014.12.033

  日期：2015.7

  sulfonamide nitrogen within a tetrahydroisoquinoline moiety afforded a marked increase in potency. This strategy, when combined with additional structure–activity relationship exploration, has led to a compound only six-fold less potent than norBNI, a widely utilized KOR antagonist tool compound, but significantly more synthetically accessible. The new optimized probe is suitably potent for use as an in vivo

  通过限制四氢异喹啉部分中磺酰胺氮的优化，使基于磺酰胺的κ阿片受体（KOR）拮抗剂探针分子ML140的效力显着提高。当与其他结构-活性关系探索相结合时，该策略已使该化合物的效力仅比norBNI（一种被广泛使用的KOR拮抗剂工具化合物）低六倍，但合成途径明显更容易。新的优化探针适合用作研究KOR拮抗剂治疗潜力的体内工具。
• [EN] ANTAGONISTS OF THE KAPPA OPIOID RECEPTOR<br/>[FR] ANTAGONISTES DU RÉCEPTEUR OPIOÏDE KAPPA
  申请人：UNIV KANSAS

  公开号：WO2016086149A1

  公开（公告）日：2016-06-02

  The present technology is directed to compounds, compositions, and methods related to non-morphinan-like kappa opioid receptor (KOR) antagonists. The technology is suited to treat addiction, diuresis, depression, post traumatic stress disorder, an eating disorder, panic disorder, social anxiety disorder, general anxiety disorder, obsessive compulsive disorders, excessive or unreasonable specific phobias, and/or other conditions related to anxiety or aversion-reward responses.

  本技术涉及非吗啡样的kappa阿片受体（KOR）拮抗剂相关的化合物、组合物和方法。该技术适用于治疗成瘾、利尿、抑郁症、创伤后应激障碍、进食障碍、惊恐障碍、社交焦虑障碍、广泛性焦虑障碍、强迫症、过度或不合理的特定恐惧症，以及/或其他与焦虑或厌恶-奖赏反应有关的疾病。
• Homocysteine synthase inhibitor
  申请人：Nakao Akira

  公开号：US08513235B2

  公开（公告）日：2013-08-20

  The invention provides a homocysteine synthase inhibitor useful for the prophylaxis or treatment of diseases involving homocysteine synthase. The homocysteine synthase inhibitor is a compound of the formula (I) wherein each symbol is as defined herein, or a pharmacologically acceptable salt thereof, or a solvate thereof.

  本发明提供了一种对于预防或治疗涉及到同型半胱氨酸合酶的疾病有用的同型半胱氨酸合酶抑制剂。该同型半胱氨酸合酶抑制剂是式(I)的化合物，其中每个符号如本文所定义，或其药理学可接受的盐，或其溶剂化物。
• HOMOCYSTEINE SYNTHASE INHIBITOR
  申请人：Nakao Akira

  公开号：US20110034440A1

  公开（公告）日：2011-02-10

  The invention provides a homocysteine synthase inhibitor useful for the prophylaxis or treatment of diseases involving homocysteine synthase. The homocysteine synthase inhibitor is a compound of the formula (I) wherein each symbol is as defined herein, or a pharmacologically acceptable salt thereof, or a solvate thereof.

  本发明提供了一种同型半胱氨酸合酶抑制剂，可用于预防或治疗涉及同型半胱氨酸合酶的疾病。该同型半胱氨酸合酶抑制剂是公式(I)的化合物，其中每个符号如本文所定义，或其药理学上可接受的盐，或其溶剂化物。