2-(5-chloropyridin-3-yloxy)ethanol | 223797-68-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(5-chloropyridin-3-yloxy)ethanol
• 英文别名: 3-chloro-5-(2-hydroxyethoxy)pyridine；2-(5-Chloro-3-pyridyloxy)ethanol；2-(5-chloropyridin-3-yl)oxyethanol
• CAS: 223797-68-0
• 化学式: C₇H₈ClNO₂
• 分子量: 173.599
• InChiKey: JZVMYCUQRVEHGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  42.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(5-chloropyridin-3-yloxy)ethanol 在 氢氧化钾 、 氯化亚砜 作用下， 以 四氢呋喃 、 叔丁醇 为溶剂， 反应 1.0h， 生成 3-chloro-5-ethenyloxypyridine
  参考文献：
  名称：

  对烟碱乙酰胆碱受体的alpha4beta2亚型具有亲和力的新配体。合成，受体结合和3D-QSAR建模。

  摘要：

  在以前的计算研究结果的基础上，合成了一系列对烟碱乙酰胆碱受体α4β2亚型具有亲和力的哌嗪，二氮杂pan，重氮azo，重氮杂双环壬烷和重氮杂双环癸烷。使用GRID / GOLPE方法开发了预测性3D-QSAR模型（​​R2 = 0.94，Q2 = 0.83，SDEP = 0.34）。SAR是根据PLS系数的轮廓图和烟碱型乙酰胆碱受体的alpha4beta2亚型的同源性模型来解释的。结果表明，从质子化胺上的氢和从吡啶氮到水分子的氢键以及带有质子化胺的取代基和受体之间的范德华相互作用对于配体亲和力都是重要的。

  DOI：

  10.1021/jm058058h
• 作为产物：
  描述：

  3,5-二氯吡啶 在 sodium hydroxide 、 sodium 、 二甲基亚砜 作用下， 以 乙二醇 为溶剂， 生成 2-(5-chloropyridin-3-yloxy)ethanol
  参考文献：
  名称：

  Heteroaryl diazabicycloalkanes, their preparation and use

  摘要：

  本发明涉及一种新颖的杂环二氮杂双环庚烷衍生物，其通式表示为（I），其任一对映异构体或其混合物，其N-氧化物，其药学上可接受的盐，以标记或非标记形式存在，发现它们在尼古丁乙酰胆碱受体上是胆碱能配体。由于其药理特性，本发明的化合物可能对治疗与中枢神经系统（CNS）的胆碱能系统相关的疾病或紊乱，平滑肌收缩相关的疾病或紊乱，内分泌疾病或紊乱，神经退行性疾病或紊乱，炎症相关的疾病或紊乱，疼痛以及因滥用化学物质而导致的戒断症状等各种疾病或紊乱可能有用。

  公开号：

  US20020037893A1

文献信息

• Certain aryl-aliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases
  申请人：Biovitrum AB

  公开号：US06465467B1

  公开（公告）日：2002-10-15

  Compounds of the general formula (I): wherein the variables are as defined in the specification are useful for the prophylaxis or treatment of serotonin-related, especially 5-HT2 receptor-related, diseases in human beings or animals, particularly diseases related to the 5-HT2c receptor, especially diseases such as eating disorders, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctionions, and urinary disorders.

  通式（I）的化合物： 其中变量如规范中定义的那样，对于预防或治疗人类或动物中与血清素相关，特别是5-HT2受体相关的疾病是有用的，特别是与5-HT2c受体相关的疾病，尤其是与进食障碍、记忆障碍、精神分裂症、情绪障碍、焦虑障碍、疼痛、性功能障碍和尿液障碍等疾病相关的疾病。
• [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。
• CERTAIN ARYLALIPHATIC AND HETEROARYL-ALIPHATIC PIPERAZINYL PYRAZINES AND THEIR USE IN THE TREATMENT OF SEROTONIN-RELATED DISEASES
  申请人：Biovitrum, AB, a Stockholm, Sweden corporation

  公开号：US20040242554A1

  公开（公告）日：2004-12-02

  The invention relates to compounds of the general formula (I): 1 wherein Ar is optionally substituted aryl or heteroaryl; A is (i) —O—, —S—, —SO 2 —, —NH—, (ii) a C 1-4 -alkyl- or C 1-6 -acyl-substituted nitrogen atom or (iii) a C 1-8 -alkylene chain or a heteroalkylene chain having 2 to 8 chain atoms, which optionally contains at least one unsaturation, and which may be substituted and/or contain a bridge to form a saturated or partially or fully unsaturated ring having 3-8 ring members; B is —C(R 4 )(R 5 )—, —OC(R 4 )(R 5 )—, —N(R 6 )C(R 4 )(R 5 )—, —N(R 6 )—, —O—, —S— or —SO 2 —; R is optionally substituted C 3-8 -cycloalkyl, aryl or heteroaryl; R 1 is (i) a saturated or unsaturated azacyclic or aminoazacyclic ring, or a saturated diazacyclic or aminodiazacyclic ring, which has 4 to 7 ring members, or a saturated aminoazabicyclic, azabicyclic or diazabicyclic ring which has 7 to 10 ring members, which rings optionally are substituted in one or more positions, or a group —[C(R 4 )(R 5 )] x N(R 2a )(R 3a )]; R 2a , R 3a , R 4 , R 5 , R 6 and x are as defined in the claims, and n is 0 or 1; and pharmaceutically acceptable salts, hydrates and prodrug forms thereof. The compounds may be prepared by per se conventional methods and can be used for treating a human or animal subject suffering from a serotonin-related disorder, such as eating disorders, especially obesity, memory, disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctions, and urinary disorders. The invention also relates to such use as well as to pharmaceutical compositions comprising a compound of formula (I).

  本发明涉及通式（I）的化合物：其中Ar是可选取代的芳基或杂芳基；A是（i）—O—，—S—，—SO2—，—NH—，（ii）C1-4烷基或C1-6酰基取代的氮原子，或（iii）C1-8烷基链或具有2-8链原子的杂烷基链，其可选包含至少一个不饱和度，并且可以取代和/或含有桥接以形成具有3-8环成员的饱和或部分或完全不饱和环；B是—C（R4）（R5）—，—OC（R4）（R5）—，—N（R6）C（R4）（R5）—，—N（R6）—，—O—，—S—或—SO2—；R是可选取代的C3-8环烷基，芳基或杂芳基；R1是（i）饱和或不饱和的氮杂环或氨基氮杂环，或饱和的二氮杂环或氨基二氮杂环，其具有4-7环成员，或饱和的氨基氮杂双环、氮杂双环或二氮杂双环，其具有7-10环成员，这些环在一个或多个位置上可选取代，或者是一个组—[C（R4）（R5）]xN（R2a）（R3a）；R2a，R3a，R4，R5，R6和x如权利要求中所定义，n为0或1；以及其药学上可接受的盐、水合物和前药形式。这些化合物可以通过常规方法制备，并可用于治疗患有血清素相关疾病的人或动物，例如进食障碍，尤其是肥胖症，记忆障碍，精神分裂症，情绪障碍，焦虑障碍，疼痛，性功能障碍和泌尿系统疾病。本发明还涉及这种用途以及包含通式（I）化合物的制药组合物。
• Certain arylaliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases
  申请人：Biovitrum, AB, a Stockholm, Sweden corporation

  公开号：US20030092694A1

  公开（公告）日：2003-05-15

  The invention relates to compounds of the general formula (I): 1 wherein Ar is optionally substituted aryl or heteroaryl; A is (i) —O—, —S—, —SO 2 —, —NH—, (ii) a C 1-4 -alkyl- or C 1-6 -acyl-substituted nitrogen atom or (iii) a C 1-8 -alkylene chain or a heteroalkylene chain having 2 to 8 chain atoms, which optionally contains at least one unsaturation, and which may be substituted and/or contain a bridge to form a saturated or partially or fully unsaturated ring having 3-8 ring members; B is —C(R 4 )(R 5 )—, —OC(R 4 )(R 5 )—, —N(R 6 )C(R 4 )(R 5 )—, —N(R 6 )—, —O—, —S— or —SO 2 —; R is optionally substituted C 3-8 -cycloalkyl, aryl or heteroaryl; R 1 is (i) a saturated or unsaturated azacyclic or aminoazacyclic ring, or a saturated diazacyclic or aminodiazacyclic ring, which has 4 to 7 ring members, or a saturated aminoazabicyclic, azabicyclic or diazabicyclic ring which has 7 to 10 ring members, which rings optionally are substituted in one or more positions, or a group —[C(R 4 )(R 5 )] x N(R 2a )(R 3a )]; R 2a , R 3a , R 4 , R 5 , R 6 and x are as defined in the claims, and n is 0 or 1; and pharmaceutically acceptable salts, hydrates and prodrug forms thereof The compounds may be prepared by per se conventional methods and can be used for treating a human or animal subject suffering from a serotonin-related disorder, such as eating disorders, especially obesity, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctions, and urinary disorders The invention also relates to such use as well as to pharmaceutical compositions comprising a compound of formula (I)

  本发明涉及一般式（I）的化合物：其中Ar是可选取代的芳基或杂环芳基；A是（i）-O-，-S-，-SO2-，-NH-，（ii）C1-4-烷基或C1-6-酰基取代的氮原子或（iii）C1-8-烷基链或具有2至8个链原子的杂烷基链，可选地含有至少一个不饱和度，并且可以取代和/或包含桥以形成具有3-8个环成员的饱和或部分或完全不饱和的环；B是-C（R4）（R5）-，-OC（R4）（R5）-，-N（R6）C（R4）（R5）-，-N（R6）-，-O-，-S-或-SO2-；R是可选取代的C3-8-环烷基，芳基或杂环芳基；R1是（i）饱和或不饱和的氮杂环或氨基氮杂环环，或具有4至7个环成员的饱和二氮杂环或氨基二氮杂环环，或具有7至10个环成员的饱和氨基氮杂双环、氮杂双环或二氮杂双环环，这些环可选地在一个或多个位置上取代，或一个组-［C（R4）（R5）］xN（R2a）（R3a）；其中R2a，R3a，R4，R5，R6和x如所述，n为0或1；以及其药学上可接受的盐、水合物和前药形式。这些化合物可以通过常规方法制备，并可用于治疗患有血清素相关疾病的人类或动物受试者，例如进食障碍，特别是肥胖，记忆障碍，精神分裂症，情绪障碍，焦虑症，疼痛，性功能障碍和泌尿系统疾病。本发明还涉及这种用途以及包含式（I）化合物的药物组合物。
• Novel Potent Ligands for the Central Nicotinic Acetylcholine Receptor:  Synthesis, Receptor Binding, and 3D-QSAR Analysis
  作者：Simon Feldbæk Nielsen、Elsebet Østergaard Nielsen、Gunnar M. Olsen、Tommy Liljefors、Dan Peters

  DOI：10.1021/jm990973d

  日期：2000.6.1

  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.