1-(2-甲氧基苯基)-[1,4]二氮杂烷 | 152943-97-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 1-(2-甲氧基苯基)-[1,4]二氮杂烷
• 中文别名: [4-(2,2'：6'，2''-叔吡啶-4'-基)苯基]甲醇
• 英文名称: 1-(2-methoxyphenyl)-1,4-diazepane
• 英文别名: 4-(2-methoxy-phenyl)-[1,4]diazepane-1-carboxylic acid tret-butyl ester
• CAS: 152943-97-0
• 化学式: C₁₂H₁₈N₂O
• 分子量: 206.288
• InChiKey: AOVWBCZPFUFQJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-甲氧基苯基)-[1,4]二氮杂烷 在 potassium carbonate 、 1-羟基苯并三唑 、 一水合肼 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 17.0h， 生成 4-chloro-N-(4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butyl)benzamide
  参考文献：
  名称：

  Evaluation of N-phenyl homopiperazine analogs as potential dopamine D3 receptor selective ligands

  摘要：

  A series of N-(2-methoxyphenyl) homopiperazine analogs was prepared and their affinities for dopamine D-2, D-3, and D-4 receptors were measured using competitive radioligand binding assays. Several ligands exhibited high binding affinity and selectivity for the D-3 dopamine receptor compared to the D-2 receptor subtype. Compounds 11a, 11b, 11c, 11f, 11j and 11k had Ki values ranging from 0.7 to 3.9 nM for the D-3 receptor with 30- to 170-fold selectivity for the D-3 versus D-2 receptor. Calculated log P values (logP = 2.6-3.6) are within the desired range for passive transport across the blood-brain barrier. When the binding and the intrinsic efficacy of these phenylhomopiperazines was compared to those of previously published phenylpiperazine analogues, it was found that (a) affinity at D-2 and D-3 dopamine receptors generally decreased, (b) the D-3 receptor binding selectivity (D-2:D-3 K-i value ratio) decreased and, (c) the intrinsic efficacy, measured using a forskolin-dependent adenylyl cyclase inhibition assay, generally increased. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.074
• 作为产物：
  描述：

  高哌嗪 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 69.0h， 生成 1-(2-甲氧基苯基)-[1,4]二氮杂烷
  参考文献：
  名称：

  Evaluation of N-phenyl homopiperazine analogs as potential dopamine D3 receptor selective ligands

  摘要：

  A series of N-(2-methoxyphenyl) homopiperazine analogs was prepared and their affinities for dopamine D-2, D-3, and D-4 receptors were measured using competitive radioligand binding assays. Several ligands exhibited high binding affinity and selectivity for the D-3 dopamine receptor compared to the D-2 receptor subtype. Compounds 11a, 11b, 11c, 11f, 11j and 11k had Ki values ranging from 0.7 to 3.9 nM for the D-3 receptor with 30- to 170-fold selectivity for the D-3 versus D-2 receptor. Calculated log P values (logP = 2.6-3.6) are within the desired range for passive transport across the blood-brain barrier. When the binding and the intrinsic efficacy of these phenylhomopiperazines was compared to those of previously published phenylpiperazine analogues, it was found that (a) affinity at D-2 and D-3 dopamine receptors generally decreased, (b) the D-3 receptor binding selectivity (D-2:D-3 K-i value ratio) decreased and, (c) the intrinsic efficacy, measured using a forskolin-dependent adenylyl cyclase inhibition assay, generally increased. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.074

文献信息

• THERAPEUTIC COMPOUNDS AND COMPOSITIONS
  申请人：Salituro Francesco G.

  公开号：US20100331307A1

  公开（公告）日：2010-12-30

  Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.

  本文描述了调节丙酮酸激酶M2（PKM2）的化合物和含有这些化合物的组合物。本文还描述了利用调节PKM2的化合物治疗癌症的方法。
• THIENOPYRIDINE DERIVATIVES
  申请人：Sankyo Company, Limited

  公开号：EP1764367A1

  公开（公告）日：2007-03-21

  The present invention provides a compound promoting osteogenesis. The present invention provides a compound having the following general formula (I) wherein R1 is H or alkyl, R2 is RaS-, RaO-, RaNH-, Ra(Rb)N- or cyclic amino, and Ra and Rb are alkyl which may be substituted, cycloalkyl which may be substituted, or the like, or a pharmacologically acceptable salt thereof.

  本发明提供一种促进成骨的化合物。本发明提供具有以下一般式（I）的化合物 其中R1为H或烷基， R2为RaS-、RaO-、RaNH-、Ra(Rb)N-或环状氨基，且 Ra和Rb为可以被取代的烷基、可以被取代的环烷基等，或其药理学上可接受的盐。
• Identification of novel GLUT inhibitors
  作者：Holger Siebeneicher、Marcus Bauser、Bernd Buchmann、Iring Heisler、Thomas Müller、Roland Neuhaus、Hartmut Rehwinkel、Joachim Telser、Ludwig Zorn

  DOI：10.1016/j.bmcl.2016.02.050

  日期：2016.4

  The compound class of 1H-pyrazolo[3,4-d]pyrimidines was identified using HTS as very potent inhibitors of facilitated glucose transporter 1 (GLUT1). Extensive structure–activity relationship studies (SAR) of each ring system of the molecular framework was established revealing essential structural motives (i.e., ortho-methoxy substituted benzene, piperazine and pyrimidine). The selectivity against

  使用HTS将1 H-吡唑并[3,4- d ]嘧啶类化合物鉴定为促进葡萄糖转运蛋白1（GLUT1）的非常有效的抑制剂。建立了分子框架每个环系统的广泛结构-活性关系研究（SAR），揭示了必要的结构动机（即，邻甲氧基取代的苯，哌嗪和嘧啶）。对GLUT2的选择性非常好，并且最初的体外和体内药代动力学（PK）研究令人鼓舞。
• [EN] GLUCOSE TRANSPORT INHIBITORS<br/>[FR] INHIBITEURS DE TRANSPORT DE GLUCOSE
  申请人：BAYER PHARMA AG

  公开号：WO2015078799A1

  公开（公告）日：2015-06-04

  The present invention relates to chemical compounds of general formula (I), in which Z, Y1, Y2, Y3, R3, R4, R5, R6, m, and n are as given in the description and in the claims, and which effectively and selectively inhibit glucose transporter 1 (GLUT1), to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

  本发明涉及一般式（I）的化合物，其中Z、Y1、Y2、Y3、R3、R4、R5、R6、m和n如描述和索赔中所述，并且有效地和选择性地抑制葡萄糖转运蛋白1（GLUT1），以制备所述化合物的方法，包括包含所述化合物的药物组合物和药物组合物，用于制造用于治疗或预防疾病的药物组合物的用途，以及在制备所述化合物中有用的中间化合物。
• Discovery of Novel Spiroindoline Derivatives as Selective Tankyrase Inhibitors
  作者：Fumiyuki Shirai、Takeshi Tsumura、Yoko Yashiroda、Hitomi Yuki、Hideaki Niwa、Shin Sato、Tsubasa Chikada、Yasuko Koda、Kenichi Washizuka、Nobuko Yoshimoto、Masako Abe、Tetsuo Onuki、Yui Mazaki、Chizuko Hirama、Takehiro Fukami、Hirofumi Watanabe、Teruki Honma、Takashi Umehara、Mikako Shirouzu、Masayuki Okue、Yuko Kano、Takashi Watanabe、Kouichi Kitamura、Eiki Shitara、Yukiko Muramatsu、Haruka Yoshida、Anna Mizutani、Hiroyuki Seimiya、Minoru Yoshida、Hiroo Koyama

  DOI：10.1021/acs.jmedchem.8b01888

  日期：2019.4.11

  pathway inhibition on tumor growth, we set out to find small-molecule inhibitors of TNKS/TNKS2 with suitable drug-like properties. Starting from 1a, a high-throughput screening hit, the spiroindoline derivative 40c (RK-287107) was discovered as a potent TNKS/TNKS2 inhibitor with >7000-fold selectivity against the PARP1 enzyme, which inhibits WNT-responsive TCF reporter activity and proliferation of human

  经典的WNT途径在癌症发病机理中起重要作用。据报道，抑制端粒聚合酶（TNKS / TNKS2）的聚（ADP-核糖）聚合酶催化活性可通过防止AXIN（Wnt /β的负调节剂）的多聚ADP-核糖基化依赖性降解来降低Wnt /β-catenin信号。 -catenin信号传导。为了研究tankyrase和Wnt途径抑制对肿瘤生长的影响，我们着手寻找具有类似药物性质的TNKS / TNKS2小分子抑制剂。从1a开始，它是一种高通量筛选命中物，螺环丝氨酸衍生物40c（RK-287107）被发现是一种有效的TNKS / TNKS2抑制剂，对PARP1酶的选择性> 7000倍，从而抑制了WNT响应的TCF报道分子的活性和增殖。人结肠直肠癌细胞系COLO-320DM的制备。在小鼠异种移植模型中，RK-287107还显示出剂量依赖性的肿瘤生长抑制作用。这些观察结果表明，RK-287107是一种有前途的先导化