2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine | 329204-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine
• 英文别名: 2-chloro-5-(2-methylthiazol-4-ylethynyl)pyridine；2-Chloro-5-[(2-methyl-4-thiazolyl)ethynyl]pyridine；4-[2-(6-chloropyridin-3-yl)ethynyl]-2-methyl-1,3-thiazole
• CAS: 329204-13-9
• 化学式: C₁₁H₇ClN₂S
• 分子量: 234.709
• InChiKey: PYMPQHSJRUVZKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 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：

  2-甲基吡咯烷 、 2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine 在 盐酸 作用下， 以 N-甲基吡咯烷酮 、 乙醚 为溶剂， 反应 0.5h， 生成 L-001120970
  参考文献：
  名称：

  Thiazolyl mglur5 antagonists and methods for their use

  摘要：

  一系列独特化合物的鉴定，由于它们在药物样性方面具有优势特性，包括在效力、药代动力学、选择性和体内受体占有性质方面具有优势特性。具体来说，选择一个由乙炔基连接到吡啶环的3位或嘧啶环的5位的1,3-噻唑-2-基环成员，其中环被选定取代基取代，将导致一种具有优越药物样性的化合物。该发明包括这些杂环化合物的药用盐形式，特别是氯化盐和三氟乙酸盐。

  公开号：

  US20090203903A1
• 作为产物：
  描述：

  5-[(2-methyl-4-thiazolyl)ethynyl]-1H-pyridin-2-one 在 三氯氧磷 作用下， 反应 1.5h， 以62%的产率得到2-chloro-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

• [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。
• Thiazolyl Mglur5 Antagonists and Methods for Their Use
  申请人：Cosford Nicholas D.

  公开号：US20110230526A1

  公开（公告）日：2011-09-22

  The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

  本发明涉及一系列独特的化合物，由于它们具有优越的药物特性，因此具有优越的药物特性，包括效力和/或药代动力学和/或选择性和/或体内受体占有率特性。具体来说，选择一个1,3-噻唑-2-基环成员，通过乙炔基连接到吡啶环的3位或嘧啶环的5位，其中该环被选定的取代基取代，结果产生具有优越药物特性的化合物。本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯化物盐和三氟乙酸盐。
• THIAZOLYL MGLUR5 ANTAGONISTS AND METHODS FOR THEIR USE
  申请人：Cosford Nicholas D.

  公开号：US20120289696A1

  公开（公告）日：2012-11-15

  The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

  本发明涉及一种独特的化合物系列的鉴定，由于这些化合物具有优越的药物性质，因此具有优越的效力、药代动力学、选择性和/或体内受体占用性质。具体而言，选择将1,3-噻唑-2-基环成员与乙炔基连接到吡啶环的3位或嘧啶环的5位，其中该环被选定的取代基取代，可得到具有优越药物性质的化合物。本发明包括这些杂环化合物的药用可接受盐形式，特别是氯化物盐和三氟乙酸盐。
• Thiazolyl mGluR5 antagonists and methods for their use
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08242143B2

  公开（公告）日：2012-08-14

  The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

  该发明涉及一系列特殊优势化合物的鉴定，这些化合物具有药物特性，因为它们具有优越的药效、药代动力学、选择性和/或体内受体占位性能。具体而言，选择在吡啶环的3位或嘧啶环的5位上连接乙炔基的1,3-噻唑-2-基环成员，并在环上取代选定的取代基，结果得到一种具有优越药物特性的化合物。该发明包括这些杂环化合物的药用盐形式，特别是氯化物盐和三氟乙酸盐。
• Thiazolyl MGLUR5 antagonists and methods for their use
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2380889A2

  公开（公告）日：2011-10-26

  The identification of a unique series of 1,3 thiazoles which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.

  鉴定一系列独特的 1，3-噻唑，这些噻唑在药效和/或药代动力学和/或选择性和/或体内受体占据特性方面具有优势，因而在类药物特性方面具有特殊优势。具体地说，选择由乙炔连接到吡啶基环的 3 位或嘧啶基环的 5 位的 1，3-噻唑-2-基环成员，其中该环被选定的取代基取代，从而使化合物具有优异的类药物特性。本发明包括这些杂环化合物的药学上可接受的盐形式，特别是氯盐和三氟乙酸盐。