4-(3-quinolyl)-1,4-diazepane-1-carboxylic acid tert-butyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(3-quinolyl)-1,4-diazepane-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 4-quinolin-3-yl-1,4-diazepane-1-carboxylate
• 化学式: C₁₉H₂₅N₃O₂
• 分子量: 327.426
• InChiKey: ZIPDKTKPNANWES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3-quinolyl)-1,4-diazepane-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 1-(3-quinolinyl)homopiperazine
  参考文献：
  名称：

  Novel Potent Ligands for the Central Nicotinic Acetylcholine Receptor:  Synthesis, Receptor Binding, and 3D-QSAR Analysis

  摘要：

  In the past few years the focus on central acetylcholine receptors has shifted from compounds with affinity for muscarinic acetylcholine receptors (mAChR) to compounds with affinity for nicotinic acetylcholine receptors (nAChR). The therapeutic potential includes treatment of a variety of diseases, e.g., Alzheimer's disease, Parkinson's disease, and Tourette's syndrome. This work describes the synthesis of six novel series of potent ligands with nanomolar affinity for the alpha 4 beta 2 nAChR subtype. Structure-activity relationship (SAR) was evaluated by the calculation of a 3D-QSAR model. 3D-QSAR analysis of the compounds using the GRID/GOLPE methodology resulted in a model of high quality (R-2 = 0.97, Q(2) = 0.81). The coefficient plots reveal that the steric interactions between the target and our compounds are of major importance for the affinity. Bulky substituents in the B-position of the pyridine ring will reduce the affinity of the compounds, whereas bulky ring systems including a sp(3)-nitrogen will increase the affinity of the compounds.

  DOI：

  10.1021/jm990973d
• 作为产物：
  描述：

  3-溴喹啉 、 1,4-二氮杂环庚烷-1-甲酸叔丁酯 在 palladium diacetate 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲苯 、 叔丁醇 为溶剂， 反应 0.83h， 以94%的产率得到4-(3-quinolyl)-1,4-diazepane-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  An improved synthesis of N-aryl and N-heteroaryl substituted homopiperazines—from conventional thermal conditions to scaling-up using microwave heating

  摘要：

  An efficient Pd(0)-catalyzed Buchwald-Hartwig protocol for the facile preparation of N-aryl and N-heteroaryl substituted homopiperazines is described. The syntheses proceeded with aryl- and heteroaryl halides in high yields using X-Phos as best ligand. The C-N coupling products were prepared both under conventional as well as microwave heating conditions and examples for microwave-assisted upscaling are included in this study. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.07.086

文献信息

• Heteroaryl diazacycloalkanes, their preparation and use;
  申请人：Neurosearch A/S

  公开号：US20040072823A1

  公开（公告）日：2004-04-15

  The present invention discloses compounds of the formula 1 any of its enantiomers or any mixture thereof, isotopes thereof or a pharmaceutically acceptable salt thereof; wherein n is 1, 2 or 3; m is 0, 1 or 2; R represents hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, or aralkyl; and R 1 represents aminophenyl; nitrophenyl; hydroxyphenyl, alkoxyphenyl; a monocyclic 5 to 6 membered heterocyclic group which may be substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, alkynoxy, methylenedioxy, halogen, CF 3 , OCF 3 , CN, amino, nitro, —COOR 3 , —CONR 2 R 3 , —NH—CO 2 R 2 , NHCO—R 2 , —OCO—NR 2 R 3 ; wherein R 2 and R 3 independently represents hydrogen or alkyl; aryl optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, CF 3 , OCF 3 , CN, amino and nitro; —X-alkyl-Y-alkyl wherein X and Y independently represents O, S, NH, N-alkyl or Se; and alkyl is optionally substituted with alkoxy or thioalkoxy; —X-(alkyl) o -aryl wherein o is 0 or 1 and X represents O, S, NH, N-alkyl or Se; optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, CF 3 , OCF 3 , CN, amino and nitro; —X-(alkyl) o -Z wherein o is 0 or 1 and X represents O, S, NH, N-alkyl or Se and Z represents a 5- or 6-membered monocyclic heterocyclic group; optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, CF 3 , OCF 3 , CN, amino and nitro; a monocyclic 5 to 6 membered heterocyclic group optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, CF 3 , OCF 3 , CN, amino and nitro; or or R 1 represents a bicyclic heterocyclic group, composed of a 5 to 6 membered monocyclic heterocyclic group fused to a benzene ring, and which may be substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, alkoxy-alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, CF 3 , OCF 3 , CN, amino, nitro, aryl optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, CF 3 , OCF 3 , CN, amino and nitro; and a monocyclic 5 to 6 membered heterocyclic group optionally substituted one or more times with alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, alkenoxy, alkynoxy, methylenedioxy, halogen, CF 3 , OCF 3 , CN, amino and nitro; The compounds of the invention are useful as nicotinic ACh receptor ligands.

  本发明公开了以下式化合物的任一对映异构体或其混合物，同位素或其药学上可接受的盐；其中n为1、2或3；m为0、1或2；R代表氢、烷基、环烷基、环烷基烷基或芳基；以及R1代表氨基苯基；硝基苯基；羟基苯基、烷氧基苯基；一种单环5到6成员杂环基团，该基团可以被取代一次或多次，取代基选自烷基、环烷基、环烷基烷基、烯基、炔基、烷氧基、环烷氧基、烯氧基、炔氧基、烷氧基、亚甲二氧基、卤素、CF3、OCF3、CN、氨基、硝基、—COOR3、—CONR2R3、—NH—CO2R2、NHCO—R2、—OCO—NR2R3；其中R2和R3独立地代表氢或烷基；芳基可选择地被烷基、环烷基、环烷基烷基、烯基、炔基、烷氧基、环烷氧基、烯氧基、炔氧基、亚甲二氧基、卤素、CF3、OCF3、CN、氨基和硝基取代一次或多次；—X-烷基-Y-烷基，其中X和Y独立地代表O、S、NH、N-烷基或Se；烷基可选择地被烷氧基或硫代烷氧基取代；—X-(烷基)o-芳基，其中o为0或1，X代表O、S、NH、N-烷基或Se；可选择地被烷基、环烷基、环烷基烷基、烯基、炔基、烷氧基、环烷氧基、烯氧基、炔氧基、亚甲二氧基、卤素、CF3、OCF3、CN、氨基和硝基取代一次或多次；—X-(烷基)o-Z，其中o为0或1，X代表O、S、NH、N-烷基或Se，Z代表一个5-或6-成员单环杂环基团；可选择地被烷基、环烷基、环烷基烷基、烯基、炔基、烷氧基、环烷氧基、烯氧基、炔氧基、亚甲二氧基、卤素、CF3、OCF3、CN、氨基和硝基取代一次或多次；一种单环5到6成员杂环基团，可选择地被烷基、环烷基、环烷基烷基、烯基、炔基、烷氧基、环烷氧基、烯氧基、炔氧基、亚甲二氧基、卤素、CF3、OCF3、CN、氨基和硝基取代一次或多次；或者R1代表一个双环杂环基团，由一个5到6成员单环杂环基团与苯环融合而成，可选择地被烷基、环烷基、环烷基烷基烯基、炔基、烷氧基、烷氧基-烷氧基、环烷氧基、烯氧基、炔氧基、亚甲二氧基、卤素、CF3、OCF3、CN、氨基、硝基、芳基可选择地被烷基、环烷基、环烷基烷基烯基、炔基、烷氧基、环烷氧基、烯氧基、炔氧基、亚甲二氧基、卤素、CF3、OCF3、CN、氨基和硝基取代一次或多次；以及一种单环5到6成员杂环基团，可选择地被烷基、环烷基、环烷基烷基烯基、炔基、烷氧基、环烷氧基、烯氧基、炔氧基、亚甲二氧基、卤素、CF3、OCF3、CN、氨基和硝基取代一次或多次；本发明的化合物可用作尼古丁ACh受体配体。
• [EN] HETEROARYL DIAZACYCLOALKANES AS CHOLINERGIC LIGANDS AT NICOTINIC ACETYLCHOLINE RECEPTORS<br/>[FR] DIAZACYCLOALCANES D'HETERO-ARYLE UTILISES EN TANT QUE LIGANDS CHOLINERGIQUES DES RECEPTEURS NICOTINIQUES DE L'ACETYLCHOLINE
  申请人：NEUROSEARCH A/S

  公开号：WO1999021834A1

  公开（公告）日：1999-05-06

  (EN) The present invention discloses compounds of formula (I) any of its enantiomers or any mixture thereof, isotopes thereof or a pharmaceutically acceptable salt thereof; wherein n is 1, 2 or 3; m is 0, 1 or 2; R represents hydrogen, alkyl, cycloalkyl, cycloalkylalkyl or aralkyl; and R1 represents aminophenyl; nitrophenyl; hydroxyphenyl, alkoxyphenyl; a monocyclic 5 to 6 membered heterocyclic group which may be substituted one or more times with substituents or R1 represents a bicyclic heterocyclic group, composed of 5 to 6 membered monocyclic heterocyclic group fused to a benzene ring, and which may be substituted one or more times with substituents. The compounds of the invention are useful as nicotinic ACh receptor ligands.(FR) La présente invention se rapporte à des composés représentés par la formule (I), à tous les énantiomères de ces composés ou à un mélange de ces derniers, à des isotopes de ces composés ou à un de leurs sels pharmaceutiquement acceptables. Dans la formule (I), n est égal à 1, 2 ou 3; m est égal à 0, 1 ou 2; R représente l'hydrogène, un alkyle, un cycloalkyle, un cycloalkylalkyle ou un aralkyle et R1 représente un aminophényle, un nitrophényle, un hydroxyphényle, un alcoxyphényle, un groupe hétérocyclique monocyclique à 5 ou 6 éléments qui peut être substitué une ou plusieurs fois par des substituants ou R1 représente un groupe hétérocyclique bicyclique composé d'un groupe hétérocyclique monocyclique à 5 ou 6 éléments fusionné avec un noyau benzène, et qui peut être substitué une ou plusieurs fois par des substituants. Les composés de cette invention s'avèrent utiles en tant que ligands des récepteurs nicotiniques de l'acétylcholine (ACh).

  本发明揭示了公式（I）的化合物及其任何对映体或其混合物，同位素或其药学上可接受的盐；其中n为1、2或3；m为0、1或2；R代表氢、烷基、环烷基、环烷基烷基或芳基烷基；R1代表氨基苯基、硝基苯基、羟基苯基、烷氧基苯基、一个由5到6个成员的单环杂环基团，该基团可以被1个或多个取代基取代，或R1代表由5到6个成员的单环杂环基团与苯环融合而成的双环杂环基团，该基团可以被1个或多个取代基取代。本发明的化合物可用作尼古丁ACh受体配体。
• HETEROARYL DIAZACYCLOALKANES AS CHOLINERGIC LIGANDS AT NICOTINIC ACETYLCHOLINE RECEPTORS
  申请人：NEUROSEARCH A/S

  公开号：EP1027336B1

  公开（公告）日：2004-10-06
• US6825189B1
  申请人：——

  公开号：US6825189B1

  公开（公告）日：2004-11-30
• US6897219B2
  申请人：——

  公开号：US6897219B2

  公开（公告）日：2005-05-24