N-benzyl-N-isopropylethylenediamine | 84478-09-1

• 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: N-benzyl-N-isopropylethylenediamine
• 英文别名: N-Benzyl-N-isopropylethane-1,2-diamine；N'-benzyl-N'-propan-2-ylethane-1,2-diamine
• CAS: 84478-09-1
• 化学式: C₁₂H₂₀N₂
• mdl: MFCD09723216
• 分子量: 192.304
• InChiKey: JHXBPQUKAFQZCE-UHFFFAOYSA-N

物化性质

• 沸点：
  258.8±15.0 °C(Predicted)
• 密度：
  0.963±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  N-benzyl-N-isopropylethylenediamine 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 16,17-Dimethoxy-21-[2-(propan-2-ylamino)ethyl]-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-苄基异丙胺 在 lithium aluminium tetrahydride 、 potassium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 N-benzyl-N-isopropylethylenediamine
  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

文献信息

• 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。
• Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)
  作者：Mavurapu Satyanarayana、Wei Feng、Liang Cheng、Angela A. Liu、Yuan-Chin Tsai、Leroy F. Liu、Edmond J. LaVoie

  DOI：10.1016/j.bmc.2008.06.046

  日期：2008.8

  Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting

  几个在乙基取代基上具有不同功能的11-乙基-2,3-二甲氧基-8,9-亚甲基二氧基-11H-异喹啉[4,3-c] cinnolin-12-具有强力的拓扑异构酶I（TOP1）靶向活性和抗肿瘤活性。评估了11-乙基取代基的2位上的各种极性取代基（包括N-甲基胺，N-异丙基胺，羟基和羟氨基）对TOP1靶向活性和细胞毒性的影响。在具有MDA-MB-435人肿瘤异种移植物的无胸腺裸鼠中，还评估了N-甲基胺和N-异丙基胺衍生物作为抗肿瘤剂。肠胃外或口服给药时，两种化合物均具有抗肿瘤活性。
• 2-aminocarbonyl-9H-purine derivatives
  申请人：——

  公开号：US20020058641A1

  公开（公告）日：2002-05-16

  The present invention relates to compounds of the formula. 1 and pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds.

  本发明涉及公式.1的化合物及其药学上可接受的盐和溶剂化物，以及制备这些化合物所使用的中间体、含有这些化合物的组合物的制备方法和用途。
• [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。
• 2-Aminocarbonyl-9H-purine derivatives
  申请人：Pfizer Inc

  公开号：US20040077584A1

  公开（公告）日：2004-04-22

  The present invention relates to compounds of the formula: 1 and pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds.

  本发明涉及公式1的化合物：1及其药学上可接受的盐和溶剂，以及制备这些化合物的中间体、含有这些化合物的组合物的制备过程和用途。