tert-Butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: tert-Butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylate
• 英文别名: 4-(2-methoxy-phenyl)-[1,4]diazepane-1-carboxylic acid tret-butyl ester
• 化学式: C₁₇H₂₆N₂O₃
• 分子量: 306.405
• InChiKey: LYCDXZQZEMBMLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-Butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylate 在 potassium carbonate 、 1-羟基苯并三唑 、 一水合肼 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 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 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 69.0h， 生成 tert-Butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylate
  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
• 作为试剂：
  描述：

  2-溴苯甲醚 、 高哌嗪 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium t-butanolate 、 二碳酸二叔丁酯 在 (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one;palladium 甲苯 、 氮气 、 乙酸乙酯 、 Brine 、 Sodium sulfate-III 、 silica gel 、 tert-Butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.17h， 以to give tert-butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylate (intermediate 28) (396 mg, 10%) as a yellow oil的产率得到tert-Butyl 4-(2-methoxyphenyl)-1,4-diazepane-1-carboxylate
  参考文献：
  名称：

  Novel Functionally Selective Ligands of Dopamine D2 Receptors

  摘要：

  本发明涉及多巴胺D2受体的新型功能选择性配体，包括激动剂、拮抗剂和反向激动剂，其中图1为配体结构。本发明还涉及使用这些化合物治疗与D2受体相关的中枢神经系统疾病。

  公开号：

  US20130137679A1

文献信息

• 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] THERAPEUTICALLY ACTIVE COMPOUNDS FOR USE IN THE TREATMENT OF CANCER CHARACTERIZED AS HAVING AN IDH MUTATION<br/>[FR] COMPOSÉS THÉRAPEUTIQUEMENT ACTIFS DESTINÉS AU TRAITEMENT D'UN CANCER CARACTÉRISÉ PAR UNE MUTATION IDH
  申请人：AGIOS PHARMACEUTICALS INC

  公开号：WO2011072174A1

  公开（公告）日：2011-06-16

  Compounds and compositions comprising compounds useful in the treatment of cancer are described herein. The compounds and compositions can be used to modulate an isocitrate dehydrogenase (IDH) mutant (e.g., IDHIm or IDH2m) having alpha hydroxyl neoactivity.

  本文描述了用于治疗癌症的化合物和组合物。这些化合物和组合物可用于调节具有α-羟基新活性的异柠檬酸脱氢酶（IDH）突变体（例如IDH1m或IDH2m）。
• N-aryl-(homopiperazinyl)-cyclohexyl amines
  申请人：American Home Products Corporation

  公开号：US06337326B1

  公开（公告）日：2002-01-08

  This invention provides novel compounds and methods and compositions using them in the treatment of central nervous system disorders, including depression and anxiety, the compounds having the formula: wherein Ar is an aryl group of 4 to 10 carbon atoms or a heteraryl group of 4 to 10 carbon atoms; R1 and R2 are independently selected from hydrogen, straight chain alkyl of 1 to 12 carbon atoms, branched alkyls of 3 to 10 carbon atoms or cycloalkyl of 3 to 10 carbon atoms; R3 is H, straight chain, branched or cyclic alkyl, halogen, alkoxy, haloalkyl, OH, nitro, nitrile, amino, CN, carboxy, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl and alkylaminocarbonyl; or a pharmaceutically acceptable salt thereof.

  本发明提供了一些新颖的化合物、方法和组合物，用于治疗中枢神经系统疾病，包括抑郁症和焦虑症，其中所述化合物的化学式为：其中Ar为4至10个碳原子的芳基基团或4至10个碳原子的杂环基团；R1和R2独立地选自氢、1至12个碳原子的直链烷基、3至10个碳原子的支链烷基或3至10个碳原子的环烷基；R3为H、直链、支链或环烷基、卤素、烷氧基、卤代烷基、羟基、硝基、腈基、氰基、羧基、烷氧羰基、烷基羰基、氨基羰基和烷基氨基羰基；或其药学上可接受的盐。
• Thienopyridine Derivatives
  申请人：Oizumi Kiyoshi

  公开号：US20070219234A1

  公开（公告）日：2007-09-20

  [Problem to be Solved]The present invention provides a compound promoting osteogenesis. [Solution] The present invention provides a compound having the following general formula (I) wherein R 1 is H or alkyl, R 2 is R a S—, R a O—, R a NH—, R a (R b )N— or cyclic amino, and R a and R b are alkyl which may be substituted, cycloalkyl which may be substituted, or the like, or a pharmacologically acceptable salt thereof.

  【待解决的问题】本发明提供了一种促进成骨作用的化合物。 【解决方案】本发明提供了一种具有以下通式（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，而Ra和Rb为可被取代的烷基、可被取代的环烷基等，或其药理学上可接受的盐。