2-甲基-3-[[(2S)-吡咯烷-2-基]甲氧基]吡啶 | 161417-03-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-甲基-3-[[(2S)-吡咯烷-2-基]甲氧基]吡啶
• 英文名称: 2-methyl-3-[(2S)-2-pyrrolidinylmethoxy]pyridine
• 英文别名: ABT-089；Pozanicline；2-methyl-3-[[(2S)-pyrrolidin-2-yl]methoxy]pyridine
• CAS: 161417-03-4
• 化学式: C₁₁H₁₆N₂O
• 分子量: 192.261
• InChiKey: YRVIKLBSVVNSHF-JTQLQIEISA-N

物化性质

• 沸点：
  302.7±22.0 °C(Predicted)
• 密度：
  1.046±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  3

制备方法与用途

生物活性

Pozanicline（ABT-089）是一种新型的胆碱能药物，是 α4β2 烟碱乙酰胆碱受体（nAChRs）的部分激动剂，并显示出对 α6β2 和 α4α5β2 nAChR 亚型的高度选择性。

Pozanicline 与 [3H] 剧痒毒素位点的结合亲和力 (Ki) 为 16.7 nM（大鼠）。

Pozanicline 能逆转尼古丁戒断引起的认知缺陷，适用于尼古丁成瘾的研究。

靶点

• Ki: 16 nM (α4β2* 烟碱乙酰胆碱受体)

反应信息

• 作为反应物：
  描述：

  2-甲基-3-[[(2S)-吡咯烷-2-基]甲氧基]吡啶 生成 2-Methyl-3-(pyrrolidin-2-ylmethoxy)pyridine dihydrochloride
  参考文献：
  名称：

  J. Med. Chem. 1997, 40, 385-390

  摘要：

  DOI：
• 作为产物：
  描述：

  2-methyl-3-((1-t-butoxycarbonyl-2-(S)-pyrrolidinyl)methoxy)pyridine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 以88%的产率得到2-甲基-3-[[(2S)-吡咯烷-2-基]甲氧基]吡啶
  参考文献：
  名称：

  Structure−Activity Studies on 2-Methyl-3-(2(S)-pyrrolidinylmethoxy)pyridine (ABT-089):  An Orally Bioavailable 3-Pyridyl Ether Nicotinic Acetylcholine Receptor Ligand with Cognition-Enhancing Properties

  摘要：

  2-Methyl-3-(2(S)-pyrrolidinylmethoxy)pyridine, ABT-089 (S-4), a member of the 3-pyridyl ether class of nicotinic acetylcholine receptor (nAChR) ligands, shows positive effects in rodent and primate models of cognitive enhancement and a rodent model of anxiolytic activity and possesses a reduced propensity to activate peripheral ganglionic type receptors. The profiles of S-4, its N-methyl analogue, and the corresponding enantiomers across several measures of cholinergic channel function in vitro and in vivo are presented, together with in vitro. metabolism and in vivo bioavailability data. On the basis of its biological activities and favorable oral bioavailability, S-4 is an attractive candidate for further evaluation as a treatment for cognitive disorders.

  DOI：

  10.1021/jm960233u

文献信息

• [EN] ARYL IMIDAZOLE COMPOUNDS AND THEIR USE AS BETA AMYLOID PRODUCTION INHIBITORS<br/>[FR] COMPOSÉ ARYLIMIDAZOLE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PRODUCTION DE LA PROTÉINE AMYLOÏDE BÊTA
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098488A1

  公开（公告）日：2010-09-02

  A compound represented by the formula (I): or a pharmacologically acceptable salt or ester thereof, wherein Ring A represents a triazolyl group or the like which may be substituted, Ring B represents a phenyl group or the like which may be substituted, X1 represents a single bond or the like, R1 and R2 each represent a C1-6 alkyl group or the like, m represents an integer of 0 to 3, and n represents an integer of 0 to 2, is effective as a therapeutic agent for a disease caused by Aβ.

  一种由化学式(I)表示的化合物，或其药理学上可接受的盐或酯，其中环A代表可能被取代的三唑基团或类似物，环B代表可能被取代的苯基团或类似物，X1代表单键或类似物，R1和R2分别代表C1-6烷基或类似物，m代表0到3的整数，n代表0到2的整数，对于由Aβ引起的疾病具有治疗作用。
• MULTI-CYCLIC COMPOUNDS
  申请人：KIMURA Teiji

  公开号：US20090062529A1

  公开（公告）日：2009-03-05

  A compound represented by the formula (I): or a pharmacologically acceptable salt thereof, wherein Ar 1 represents an imidazolyl group or the like which may be substituted with a C1-6 alkyl group, Ar 2 represents a phenyl group or the like which may be substituted with a C1-6 alkoxy group, X 1 represents a double bond or the like and Het represents a triazolyl group or the like which may be substituted with a C1-6 alkyl group or the like, is effective as a therapeutic or prophylactic agent for a disease caused by Aβ.

  一种由化学式(I)表示的化合物或其药理学可接受的盐，其中Ar1代表可用C1-6烷基基团取代的咪唑基团或类似基团，Ar2代表可用C1-6烷氧基团取代的苯基团或类似基团，X1代表双键或类似基团，Het代表可用C1-6烷基基团或类似基团取代的三唑基团或类似基团，对由Aβ引起的疾病具有治疗或预防作用。
• [EN] NITROGEN-CONTAINING FUSED HETEROCYCLIC COMPOUNDS AND THEIR USE AS BETA AMYLOID PRODUCTION INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES CONDENSÉS CONTENANT DE L'AZOTE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PRODUCTION DE LA BÊTA-AMYLOÏDE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098487A1

  公开（公告）日：2010-09-02

  A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein Ring A represents a five-membered aromatic heterocyclic group or the like fused with a non-aromatic ring group, which may be substituted, Ring B represents a phenyl group or the like which may be substituted, X1 represents a single bond or the like, R1 and R2 each represent a C1-6 alkyl group or the like, m represents an integer of 0 to 3, and n represents an integer of 0 to 2, is effective as a therapeutic agent for a disease caused by Aβ.

  化合物的分子式为[I]：或其药理学可接受的盐或酯，其中环A代表一个五元芳香杂环基团或类似于非芳香环基团的融合物，可以被取代，环B代表一个苯基或类似的基团，可以被取代，X1代表一个单键或类似物，R1和R2分别代表一个C1-6烷基基团或类似物，m表示0到3的整数，n表示0到2的整数，对由Aβ引起的疾病具有治疗作用。
• [EN] IMIDAZOLYLPYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS D'IMIDAZOLYLPYRAZINE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098495A1

  公开（公告）日：2010-09-02

  To provide a novel low-molecular-weight compound that inhibits the production of amyloid-β (Aβ ). A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein R1 and R2 are the same or different and each represent a substituent selected from the following Substituent Group a1; m represents an integer of 0 to 3; n represents an integer of 0 to 2; X1 represents a single bond or the like; X2 represents a single bond or the like; Ring A represents a five-membered aromatic heterocyclic group or the like which contains two or more nitrogen atoms and may have 1 to 3 substituents selected from the following Substituent Group b1; and Ring B represents a monocyclic or fused cyclic aromatic ring group such as the formula [2] which may have 1 to 3 substituents selected from the following Substituent Group c1, is effective as a therapeutic agent for a disease such as Alzheimer's disease. Substituent Group a1: a C1-6 alkyl group and the like Substituent Group b1: a C1-6 alkyl group and the like Substituent Group c1: an amino group and the like

  提供一种新型低分子量化合物，该化合物能够抑制淀粉样蛋白-β（Aβ）的产生。表示为化学式[I]的化合物，或其药理学上可接受的盐或酯，其中R1和R2相同或不同，每个代表以下取代基团a1中选择的取代基；m代表0到3的整数；n代表0到2的整数；X1代表单键或类似物；X2代表单键或类似物；环A代表含有两个或更多氮原子并且可能具有1到3个取代基团b1中选择的取代基的五元芳香杂环基团或类似物；环B代表可能具有1到3个取代基团c1中选择的取代基的单环或融合环芳香环基团，如化学式[2]所示，对于阿尔茨海默病等疾病具有治疗作用。取代基团a1：C1-6烷基基团等；取代基团b1：C1-6烷基基团等；取代基团c1：氨基团等。
• [EN] MORPHOLINO COMPOUNDS, USES AND METHODS<br/>[FR] COMPOSÉS MORPHOLINO, UTILISATIONS ET PROCÉDÉS
  申请人：UNIV DUNDEE

  公开号：WO2012160392A1

  公开（公告）日：2012-11-29

  The invention relates to morpholino-derivatives according to Formula (I) or stereoisomers or pharmaceutically acceptable salts or solvate thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, m and n are as defined in the specification. The compounds are antagonists, reverse agonists or agonists of G-protein coupled receptors, such as dopamine D4 and 5HT1a. The inventions also relates to pharmaceutical compositions comprising the compounds and methods involving the compounds and compositions. The compounds and compositions of the invention may in particular be used in the treatment of diseases and disorders, such as neurological and neurodegenerative diseases; or as lead compounds for the design and selection of further therapeutic compounds.

  该发明涉及根据式（I）的吗啡啉衍生物或其立体异构体或药用可接受的盐或溶剂化物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、m和n如规范中定义。这些化合物是G蛋白偶联受体的拮抗剂、逆向激动剂或激动剂，例如多巴胺D4和5HT1a。该发明还涉及包括这些化合物的药物组合物和涉及这些化合物和组合物的方法。该发明的化合物和组合物特别可用于治疗疾病和疾病，如神经和神经退行性疾病；或作为设计和选择更多治疗化合物的引导化合物。