tert-butyl 4-prop-2-ynylidenepiperidine-1-carboxylate | 1107620-21-2

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-prop-2-ynylidenepiperidine-1-carboxylate
• 英文别名: tert-butyl 4-(prop-2-yn-1-ylidene)piperidine-1-carboxylate；tert-butyl 4-prop-2-ynylidenepiperidine-1-carboxyate；1-(t-butoxycarbonyl)-4-(prop-2-ynylidene)piperidine；1-(t-Butoxycarbonyl)-4-(prop-2-ynylidene)-piperidine
• CAS: 1107620-21-2
• 化学式: C₁₃H₁₉NO₂
• 分子量: 221.299
• InChiKey: AAZBPDRUQHQIQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-prop-2-ynylidenepiperidine-1-carboxylate 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 、 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 2.25h， 生成 2-methyl-6-[3-(piperidin-4-ylidene)prop-1-yn-1-yl]pyridine
  参考文献：
  名称：

  Insights into the interaction of negative allosteric modulators with the metabotropic glutamate receptor 5: Discovery and computational modeling of a new series of ligands with nanomolar affinity

  摘要：

  Metabotropic glutamate receptor 5 (mGlu(5)) is a biological target implicated in major neurological and psychiatric disorders. In the present study, we have investigated structural determinants of the interaction of negative allosteric modulators (NAMs) with the seven-transmembrane (7TM) domain of mGlu(5). A homology model of the 7TM receptor domain built on the crystal structure of the mGlu(1) template was obtained, and the binding modes of known NAMs, namely MPEP and fenobam, were investigated by docking and molecular dynamics simulations. The results were validated by comparison with mutagenesis data available in the literature for these two ligands, and subsequently corroborated by the recently described mGlu(5) crystal structure. Moreover, a new series of NAMs was synthesized and tested, providing compounds with nanomolar affinity. Several structural modifications were sequentially introduced with the aim of identifying structural features important for receptor binding. The synthesized NAMs were docked in the validated homology model and binding modes were used to interpret and discuss structure-activity relationships within this new series of compounds. Finally, the models of the interaction of NAMs with mGlu(5) were extended to include important non-aryl alkyne mGlu(5) NAMs taken from the literature. Overall, the results provide useful insights into the molecular interaction of negative allosteric modulators with mGlu(5) and may facilitate the design of new modulators for this class of receptors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.008
• 作为产物：
  描述：

  tert-butyl 4-[3-(trimethylsilyl)prop-2-yn-1-ylidene]piperidine-1-carboxylate 在 甲醇 、 sodium hydroxide 作用下， 生成 tert-butyl 4-prop-2-ynylidenepiperidine-1-carboxylate
  参考文献：
  名称：

  Exploiting the hydrophobic channel of the NNIBP: Discovery of novel diarylpyrimidines as HIV-1 NNRTIs against wild-type and K103N mutant viruses

  摘要：

  DOI：

  10.1016/j.bmc.2021.116239

文献信息

• [EN] HETEROCYCLIC MGLU5 ANTAGONISTS<br/>[FR] ANTAGONISTES HÉTÉROCYCLIQUES DE MGLU5
  申请人：RECORDATI IRELAND LTD

  公开号：WO2011029633A1

  公开（公告）日：2011-03-17

  Compounds (I) (R1 is an optionally substituted C1-C13 heteromonocyclic, heterobicyclic or heterotri cyclic group containing from 1 to 5 heteroatoms selected from N, O and S; R2 is H, an optionally substituted monocyclic aromatic group, or a C1-C5 heteroaromatic group containing from 1 to 4 heteroatoms selected from N, O and S; R3 is an optionally substituted C1-C13 heteromonocyclic, heterobicyclic or heterotri cyclic group containing from 1 to 5 heteroatoms selected from N, O and S; an optionally substituted mono-, bi- or tricyclic C6-C14 aryl group, an optionally substituted C3-C6 cycloalkyl group, or an optionally substituted C3-C6 cycloalkenyl group; each R4, independently for each position capable of substitution, is H or C1-C6 alkyl; R5 is H, halogen or C1-C6 alkyl; m is 0, 1 or 2; n is 0, 1 or 2; p is 0, 1, 2, 3, 4, 5, or 6; and --- is an optional double bond) and their enantiomers, diastereomers, N-oxides and pharmaceutically acceptable salts, and pharmaceutical compositions containing them, are useful for the treatment of neuromuscular dysfunction of the lower urinary tract and also for the treatment of gastrooesophageal reflux disease; anxiety disorder; abuse, substance dependence and substance withdrawal disorders; neuropathic pain disorder, migraine and fragile X syndrome disorders.

  化合物（I）（其中R1为任选取代的含1至5个选自N、O和S的杂原子的C1-C13杂单环、杂双环或杂三环基团；R2为H、任选取代的单环芳香基团或含1至4个选自N、O和S的杂原子的C1-C5杂芳香基团；R3为任选取代的含1至5个选自N、O和S的杂原子的C1-C13杂单环、杂双环或杂三环基团，任选取代的单环、双环或三环C6-C14芳基团，任选取代的C3-C6环烷基团，或任选取代的C3-C6环烯基团；每个R4独立地为每个可取代位置上的H或C1-C6烷基；R5为H、卤素或C1-C6烷基；m为0、1或2；n为0、1或2；p为0、1、2、3、4、5或6；---为任选的双键）及其对映体、非对映体、N-氧化物和药学上可接受的盐，以及含有它们的药物组合物，可用于治疗下尿路神经肌肉功能障碍以及胃食管反流病；焦虑障碍；滥用、物质依赖和物质戒断障碍；神经性疼痛障碍、偏头痛和脆性X综合征障碍。
• NOVEL HETEROCYCLIC DERIVATIVES AS M-GLU5 ANTAGONISTS
  申请人：Leonardi Amedeo

  公开号：US20090042841A1

  公开（公告）日：2009-02-12

  This invention relates to novel heterocyclic compounds having selective affinity for the mGlu5 subtype of metabotropic receptors, pharmaceutical compositions thereof and uses for such compounds and compositions in the treatment of lower urinary tract disorders, such as neuromuscular dysfunction of the lower urinary tract, and in the treatment of migraine and gastroesophagael reflux disease (GERD).

  本发明涉及一种新型杂环化合物，其具有选择性亲和力，适用于代谢型受体mGlu5亚型，以及该类化合物的制药组合物及其在治疗下尿路障碍（例如下尿路神经肌肉功能障碍）、偏头痛和胃食管反流病（GERD）方面的用途。
• HETEROCYCLIC M-GLU5 ANTAGONISTS
  申请人：Leonardi Amedeo

  公开号：US20120028931A1

  公开（公告）日：2012-02-02

  Compounds I (R 1 is an optionally substituted C 1 -C 13 heteromonocyclic, heterobicyclic or heterotricyclic group containing from 1 to 5 heteroatoms selected from N, O and S; R 2 is H, an optionally substituted monocyclic aromatic group, or a C 1 -C 5 heteroaromatic group containing from 1 to 4 heteroatoms selected from N, O and S; R 3 is an optionally substituted C 1 -C 13 heteromonocyclic, heterobicyclic or heterotricyclic group containing from 1 to 5 heteroatoms selected from N, O and S; an optionally substituted mono-, bi- or tricyclic C 6 -C 14 aryl group, an optionally substituted C 3 -C 6 cycloalkyl group, or an optionally substituted C 3 -C 6 cycloalkenyl group; each R 4 , independently for each position capable of substitution, is H or C 1 -C 6 alkyl; R 5 is H, halogen or C 1 -C 6 alkyl; m is 0, 1 or 2; n is 0, 1 or 2; p is 0, 1, 2, 3, 4, 5, or 6; and is an optional double bond) and their enantiomers, diastereomers, N-oxides and pharmaceutically acceptable salts, and pharmaceutical compositions containing them, are useful for the treatment of neuromuscular dysfunction of the lower urinary tract and also for the treatment of gastrooesophageal reflux disease; anxiety disorder; abuse, substance dependence and substance withdrawal disorders; neuropathic pain disorder, migraine and fragile X syndrome disorders.

  化合物I（其中R1是可选取代的C1-C13杂环单环、杂环双环或杂环三环基团，包含1-5个从N、O和S中选取的杂原子；R2是H、可选取代的单环芳香基团，或包含1-4个从N、O和S中选取的杂原子的C1-C5杂环芳香基团；R3是可选取代的C1-C13杂环单环、杂环双环或杂环三环基团，包含1-5个从N、O和S中选取的杂原子；可选取代的单环、双环或三环C6-C14芳基基团，可选取代的C3-C6环烷基基团或可选取代的C3-C6环烯基基团；每个R4，在可取代的每个位置上，独立地是H或C1-C6烷基；R5是H、卤素或C1-C6烷基；m为0、1或2；n为0、1或2；p为0、1、2、3、4、5或6；并且是可选的双键），它们的对映异构体、顺反异构体、N-氧化物和药学上可接受的盐，以及含有它们的制药组合物，对于治疗下泌尿道神经肌肉功能障碍和胃食管反流病，焦虑症、滥用、物质依赖和物质戒断障碍，神经病性疼痛障碍、偏头痛和脆性X综合症障碍有用。
• Heterocyclic derivatives as M-GLU5 antagonists
  申请人：Leonardi Amedeo

  公开号：US08518916B2

  公开（公告）日：2013-08-27

  This invention relates to novel heterocyclic compounds having selective affinity for the mGlu5 subtype of metabotropic receptors, pharmaceutical compositions thereof and uses for such compounds and compositions in the treatment of lower urinary tract disorders, such as neuromuscular dysfunction of the lower urinary tract, and in the treatment of migraine and gastroesophagael reflux disease (GERD).

  本发明涉及新型杂环化合物，具有对代谢型受体mGlu5亚型的选择性亲和力，其制药组合物以及在治疗下尿路障碍，如下尿路神经肌肉功能障碍，以及治疗偏头痛和胃食管反流病（GERD）中使用这些化合物和组合物的用途。
• NOVEL HETEROCYCLIC COMPOUNDS AS MGLU5 ANTAGONISTS
  申请人：Recordati Ireland Limited

  公开号：EP2178858B1

  公开（公告）日：2011-12-28