3-Bromo-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine | 329204-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-Bromo-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine
• 英文别名: 3-Bromo-5-[(2-methyl-4-thiazolyl)ethynyl]pyridine；4-[2-(5-bromopyridin-3-yl)ethynyl]-2-methyl-1,3-thiazole
• CAS: 329204-97-9
• 化学式: C₁₁H₇BrN₂S
• 分子量: 279.16
• InChiKey: SLLMZMSYBFFSLX-UHFFFAOYSA-N

物化性质

• 沸点：
  400.0±32.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Bromo-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine 在 盐酸 、 copper(l) iodide 、 四(三苯基膦)钯 、 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 31.67h， 生成 3-(2-Methyl-thiazol-4-ylethynyl)-5-vinyl-pyridine
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]pyridine Analogues as Potent, Noncompetitive Metabotropic Glutamate Receptor Subtype 5 Antagonists; Search for Cocaine Medications

  摘要：

  Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to identifying ligands that bind to the allosteric modulatory site, distinct from the site for the primary agonist glutamate. Both 2-methyl-6-(phenylethynyl)pyridine (MPEP) and its analogue 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP) have been shown to be selective and potent noncompetitive antagonists of mGluR5. Because of results presented in this study showing that MTEP prevents the reinstatement of cocaine self-administration caused by the presentation of environmental cues previously associated with cocaine availability, we have prepared a series of analogues of MTEP with the aim of gaining a better understanding of the structural features relevant to its antagonist potency and with the ultimate aim of investigating the effects of such compounds in blunting the self-administration of cocaine. These efforts have led to the identification of compounds showing higher potency as mGluR5 antagonists than either MPEP or MTEP. Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP.

  DOI：

  10.1021/jm050570f
• 作为产物：
  描述：

  3,5-二溴吡啶 、 2-甲基-4-三甲基硅乙炔基噻唑 在 四丁基氟化铵 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 以76%的产率得到3-Bromo-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]pyridine Analogues as Potent, Noncompetitive Metabotropic Glutamate Receptor Subtype 5 Antagonists; Search for Cocaine Medications

  摘要：

  Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to identifying ligands that bind to the allosteric modulatory site, distinct from the site for the primary agonist glutamate. Both 2-methyl-6-(phenylethynyl)pyridine (MPEP) and its analogue 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP) have been shown to be selective and potent noncompetitive antagonists of mGluR5. Because of results presented in this study showing that MTEP prevents the reinstatement of cocaine self-administration caused by the presentation of environmental cues previously associated with cocaine availability, we have prepared a series of analogues of MTEP with the aim of gaining a better understanding of the structural features relevant to its antagonist potency and with the ultimate aim of investigating the effects of such compounds in blunting the self-administration of cocaine. These efforts have led to the identification of compounds showing higher potency as mGluR5 antagonists than either MPEP or MTEP. Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP.

  DOI：

  10.1021/jm050570f

文献信息

• Alkyne derivatives as tracers for metabotropic glutamate receptor binding
  申请人：Cosford Peter Nicholas David

  公开号：US20070060618A1

  公开（公告）日：2007-03-15

  The present invention is directed to isotopically labeled alkyne derivative compounds, particularly 11 C, 13 C, 14 C, 18 F, 15 O, 13 N, 35 S, 2 H, and 3 H labeled compounds. In particular, the present invention is directed to 11 C, 13 C, 14 C, 18 F, 15 O, 13 N, 35 S, 2 H, and 3 H labeled heterocyclic alkynes and methods of their preparation. The present invention further includes a method of use of the 11 C, 18 F, 15 O, or 13 N labeled heterocyclic alkyne compounds as tracers in positron emission tomography (PET) imaging, particularly in the study of metabolic conditions in mammals, specifically conditions modulated by metabotropic glutamate receptors subtype 5 (mGluR5).

  本发明涉及同位素标记的炔基衍生物化合物，特别是11C、13C、14C、18F、15O、13N、35S、2H和3H标记的化合物。具体而言，本发明涉及11C、13C、14C、18F、15O、13N、35S、2H和3H标记的杂环炔烃及其制备方法。本发明还包括将11C、18F、15O或13N标记的杂环炔烃化合物用作正电子发射断层扫描（PET）成像中的示踪剂的使用方法，特别是在哺乳动物代谢状况的研究中，特别是通过代谢型谷氨酸受体亚型5（mGluR5）调节的状况。
• [EN] HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSES HETEROCYCLIQUES ET PROCEDES D'UTILISATION DE CEUX-CI
  申请人：MERCK & CO INC

  公开号：WO2001016121A1

  公开（公告）日：2001-03-08

  In accordance with the present invention, there are provided novel class of heterocyclic compounds and methods of use thereof. Compounds of the invention contain a substituted, unsaturated five, six or seven membered heterocyclic ring that includes at least one nitrogen atom and at least one carbon atom. At a ring position adjacent to a ring nitrogen atom, the heterocyclic ring has at least one substituent which includes a moiety, linked to the heterocyclic ring via an alkylene moiety, an alkynylene moiety or an azo group. Invention compounds are capable of a wide variety of uses including modulating physiological processes by functioning as agonists and antagonists of receptors in the nervous system, as insecticides, and as fungicides. The invention further provides methods of modulating the activity of excitatory amino acid receptors using a specifically defined class of heterocyclic compounds including the novel compounds referred to above. In one embodiment, there are provided methods of modulating metabotropic glutamate receptors. The present invention also discloses methods of treating disease using heterocyclic compounds. The invention further discloses methods of preventing disease conditions related to diseases of the pulmonary system, diseases of the nervous system, diseases of the cardiovascular system, diseases of the gastrointestinal system, diseases of the endocrine system, diseases of the exocrine system, diseases of the skin, cancer and diseases of the ophthalmic system. The invention also discloses pharmaceutically acceptable salt forms of the above-described heterocyclic compounds.

  根据本发明，提供了一类新型的杂环化合物及其使用方法。该发明的化合物包含一个取代的、不饱和的五、六或七元杂环环，其中至少包含一个氮原子和至少一个碳原子。在靠近环氮原子的环位置上，杂环环有至少一个取代基，包括一个官能团，通过烷基官能团、炔基官能团或偶氮基团连接到杂环环上。发明的化合物能够广泛应用，包括通过作为神经系统受体的激动剂和拮抗剂来调节生理过程，作为杀虫剂和杀菌剂。本发明还提供了使用特定定义的杂环化合物类来调节兴奋性氨基酸受体活性的方法，包括上述新型化合物。在一种实施例中，提供了调节代谢性谷氨酸受体的方法。本发明还揭示了使用杂环化合物治疗疾病的方法。本发明还揭示了预防与肺系统疾病、神经系统疾病、心血管系统疾病、胃肠系统疾病、内分泌系统疾病、外分泌系统疾病、皮肤疾病、癌症和眼科系统疾病相关的疾病状态的方法。本发明还揭示了上述杂环化合物的药物可接受的盐形式。
• [3H]-Methoxymethyl-MTEP and [3H]-Methoxy-PEPy: potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor
  作者：Nicholas D.P Cosford、Jeffrey Roppe、Lida Tehrani、Edwin J Schweiger、T.Jon Seiders、Ashok Chaudary、Sara Rao、Mark A Varney

  DOI：10.1016/s0960-894x(02)00997-6

  日期：2003.2

  The design, synthesis, and characterization of two potent, non-competitive radioligands, [H-3]-methoxymethyl-MTEP and [H-3]-methoxy-PEPy, that are selective for the mGlu5 receptor are described. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 5-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-2,3′-bipyridine: a highly potent, orally active metabotropic glutamate subtype 5 (mGlu5) receptor antagonist with anxiolytic activity
  作者：Jeffrey R Roppe、Bowei Wang、Dehua Huang、Lida Tehrani、Theodore Kamenecka、Edwin J Schweiger、Jeffery J Anderson、Jesse Brodkin、Xiaohui Jiang、Merryl Cramer、Janice Chung、Grace Reyes-Manalo、Benito Munoz、Nicholas D.P Cosford

  DOI：10.1016/j.bmcl.2004.05.037

  日期：2004.8

  Structure-activity relationship studies leading to the discovery of a new, orally active mGlu5 receptor antagonist are described. The title compound, 5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-2,3'-bipyridine, is highly potent in vitro, has good in vivo receptor occupancy, and is efficacious in the rat fear-potentiated startle model of anxiety following oral dosing. (C) 2004 Elsevier Ltd. All rights reserved.
• HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Merck & Co., Inc.

  公开号：EP1214303A1

  公开（公告）日：2002-06-19