N¹-benzyl-N¹-(tert-butyl)ethane-1,2-diamine | 61694-83-5

• 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: N¹-benzyl-N¹-(tert-butyl)ethane-1,2-diamine
• 英文别名: N-benzyl-N-(tert-butyl)ethane-1,2-diamine；N-benzyl-N-tert-butylethylene-diamine；N-benzyl-N-tert-butylethylenediamine；N~1~-Benzyl-N~1~-tert-butylethane-1,2-diamine；N'-benzyl-N'-tert-butylethane-1,2-diamine
• CAS: 61694-83-5
• 化学式: C₁₃H₂₂N₂
• 分子量: 206.331
• InChiKey: QLLOSKPKUMWQLP-UHFFFAOYSA-N

物化性质

• 沸点：
  272.0±15.0 °C(Predicted)
• 密度：
  0.956±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N¹-benzyl-N¹-(tert-butyl)ethane-1,2-diamine 在 钯 palladium diacetate 、 甲酸 、 溶剂黄146 、 三乙胺 、 三(邻甲基苯基)磷 、 silver carbonate 、 苯酚 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.5h， 生成 21-[2-(Tert-butylamino)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：

  2-(benzyl(tert-butyl)amino)acetonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以25%的产率得到N¹-benzyl-N¹-(tert-butyl)ethane-1,2-diamine
  参考文献：
  名称：

  通过利用四氢异喹啉基序的磺酰胺约束增强κ阿片受体拮抗剂探针ML140的效力

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2014.12.033

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。
• SOMATOSTATIN MODULATORS AND USES THEREOF
  申请人：Crinetics Pharmaceuticals, Inc.

  公开号：US20170002001A1

  公开（公告）日：2017-01-05

  Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.

  本文描述了一些肽类抑制素调节剂化合物，制备这些化合物的方法，包含这些化合物的药物组合物和药物以及使用这些化合物治疗需要调节肽类抑制素活性的疾病、病症或疾病的方法。
• N-1-Benzyl-3-pyrrolidinyl-4-dimethylamino benzamide derivatives
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US04197243A1

  公开（公告）日：1980-04-08

  ##STR1## wherein R represents a hydrogen atom or a lower alkyl group; X represents a lower alkoxy group; Y represents a hydrogen atom, an amino group, or mono- or di-lower alkylamino group; Z represents a halogen atom, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a sulfamoyl group, or a lower alkylsulfamoyl group; said Y and Z may combine to form --N.dbd.N--NH--; W represents a group shown by the formula ##STR2## (wherein A represents a phenyl group, a cyclohexyl group, a furyl group, or a pyridyl group; R.sub.1, R.sub.2, and R.sub.4, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, or a phenyl group; R.sub.3 represents a lower alkyl group, a phenyl lower alkyl group, or a di-lower alkylamino lower alkyl group; R.sub.5, R.sub.6, and R.sub.7, which may be the same or different, each represents a hydrogen atom, a halogen atom, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, or a trifluoromethyl group; R.sub.8 represents a lower alkyl group; and n represents 1 or 2), a 1-ethyl-5-phenyl-2-pyrrolidinylmethyl group, a 1-ethyl-2-isoindolinylmethyl group, a 2-ethyl-1,2,3,4-tetrahydro-4-isoquinolyl group, a 2-(2-phenylpyrrolidino)ethyl group, a 2-(2-isoindolinyl)ethyl group, or a 2-(1,2,3,4-tetrahydro-2-isoquinolyl)ethyl group and the pharmaceutically acceptable nontoxic salts thereof. The compounds of this invention are strong central nervous system depressants, in particular strong antipsychotics.

  其中，R代表氢原子或较低的烷基基团；X代表较低的烷氧基团；Y代表氢原子、氨基团或单或双较低的烷基氨基团；Z代表卤原子、较低的烷氧基团、较低的烷基硫基团、较低的烷基亚硫氧基团、较低的烷基砜基团、磺胺基团或较低的烷基磺胺基团；所述的Y和Z可以结合形成--N.dbd.N--NH--；W代表由以下公式所示的基团（其中A代表苯基团、环己基团、呋喃基团或吡啶基团；R.sub.1、R.sub.2和R.sub.4，可以相同也可以不同，每个代表氢原子、较低的烷基基团或苯基团；R.sub.3代表较低的烷基基团、苯基较低的烷基基团或双较低的烷基氨基较低的烷基基团；R.sub.5、R.sub.6和R.sub.7，可以相同也可以不同，每个代表氢原子、卤原子、较低的烷氧基团、较低的烷基硫基团、较低的烷基亚硫氧基团、较低的烷基砜基团、三氟甲基基团；R.sub.8代表较低的烷基基团；n代表1或2），1-乙基-5-苯基-2-吡咯啉基基团，1-乙基-2-异吲哚基基团，2-乙基-1,2,3,4-四氢-4-异喹啉基团，2-(2-苯基吡咯啉基)乙基基团，2-(2-异吲哚基)乙基基团，或2-(1,2,3,4-四氢-2-异喹啉基)乙基基团及其在药学上可接受的无毒盐。本发明的化合物是强大的中枢神经系统抑制剂，特别是强效抗精神病药物。
• Pyrrolidinyl and piperidinyl benzamide derivatives
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US04097487A1

  公开（公告）日：1978-06-27

  ##STR1## wherein R represents a hydrogen atom or a lower alkyl group; X represents a lower alkoxy group; Y represents a hydrogen atom, an amino group, or a mono- or di-lower alkylamino group; Z represents a halogen atom, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a sulfamoyl group, or a lower alkylsulfamoyl group; said Y and Z may combine to form --N.dbd.N--NH--; W represents a group shown by the formula ##STR2## (wherein A represents a phenyl group, a cyclohexyl group, a furyl group, or a pyridyl group; R.sub.1, R.sub.2, and R.sub.4, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, or a phenyl group; R.sub.3 represents a lower alkyl group, a phenyl lower alkyl group, or a di-lower alkylamino lower alkyl group; R.sub.5, R.sub.6, and R.sub.7, which may be the same or different, each represents a hydrogen atom, a halogen atom, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, or a trifluoromethyl group; R.sub.8 represents a lower alkyl group; and n represents 1 or 2), a 1-ethyl-5-phenyl-2-pyrrolidinylmethyl group, a 1-ethyl-2-isoindolinylmethyl group, a 2-ethyl-1,2,3,4-tetrahydro-4-isoquinolyl group, a 2-(2-phenylpyrrolidino)ethyl group, a 2-(2-isoindolinyl)ethyl group, or a 2-(1,2,3,4-tetrahydro-2-isoquinolyl)-ethyl group and the pharmaceutically acceptable nontoxic salts thereof. The compounds of this invention are strong central nervous system depressants, in particular strong antipsychotics.

  其中，R代表氢原子或较低的烷基基团；X代表较低的烷氧基团；Y代表氢原子、氨基团或一种或二种较低烷基氨基团；Z代表卤素原子、较低的烷氧基团、较低的烷基硫基团、较低的烷基亚砜基团、较低的烷基砜基团、磺酰胺基团或较低的烷基磺酰胺基团；所述的Y和Z可以组合形成--N.dbd.N--NH--；W代表由以下公式所示的基团（其中A代表苯基、环己基、呋喃基或吡啶基；R.sub.1、R.sub.2和R.sub.4，可以相同也可以不同，每个代表氢原子、较低的烷基基团或苯基；R.sub.3代表较低的烷基基团、苯基较低的烷基基团或二烷基氨基较低的烷基基团；R.sub.5、R.sub.6和R.sub.7，可以相同也可以不同，每个代表氢原子、卤素原子、较低的烷氧基团、较低的烷基硫基团、较低的烷基亚砜基团、较低的烷基砜基团或三氟甲基基团；R.sub.8代表较低的烷基基团；n代表1或2），1-乙基-5-苯基-2-吡咯啉甲基基团，1-乙基-2-异吲哚甲基基团，2-乙基-1,2,3,4-四氢-4-异喹啉基团，2-(2-苯基吡咯啉基团)，2-(2-异吲哚基团)，或2-(1,2,3,4-四氢-2-异喹啉)-乙基基团及其药学上可接受的无毒盐。本发明的化合物是强中枢神经系统抑制剂，特别是强抗精神病药物。
• 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。