4-(pyridin-2-yl)tetrahydro-2H-pyran-4-carbonitrile | 1368615-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(pyridin-2-yl)tetrahydro-2H-pyran-4-carbonitrile
• 英文别名: 4-pyridin-2-yloxane-4-carbonitrile
• CAS: 1368615-99-9
• 化学式: C₁₁H₁₂N₂O
• 分子量: 188.229
• InChiKey: GUGBUMPRAFZQTD-UHFFFAOYSA-N

物化性质

• 沸点：
  367.1±42.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  45.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(pyridin-2-yl)tetrahydro-2H-pyran-4-carbonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以32%的产率得到(4-(pyridin-2-yl)tetrahydro-2H-pyran-4-yl)methanamine
  参考文献：
  名称：

  New direct inhibitors of InhA with antimycobacterial activity based on a tetrahydropyran scaffold

  摘要：

  Tetrahydropyran derivative 1 was discovered in a high-throughput screening campaign to find new inhibitors of mycobacterial InhA. Following initial in-vitro profiling, a structure-activity relationship study was initiated and a focused library of analogs was synthesized and evaluated. This yielded compound 42 with improved antimycobacterial activity and low cytotoxicity. Additionally, the crystal structure of InhA in complex with inhibitor 1 was resolved, to reveal the binding mode and provide hints for further optimization. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.02.008
• 作为产物：
  描述：

  4-氰基四氢吡喃 、 2-氰基吡啶 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以62%的产率得到4-(pyridin-2-yl)tetrahydro-2H-pyran-4-carbonitrile
  参考文献：
  名称：

  氰阴离子作为亲核芳香取代中的一个离去基团：叠氮杂环上的季铵盐中心的合成

  摘要：

  用衍生自脂族α，α-二取代的酯和腈的阴离子对2-或4-氰基嗪进行亲核芳族取代会导致氰化物官能团的置换。使氰化物能够在S N Ar反应中用作高活性离去基团，为合成原料提供了额外的灵活性。我们表明，在许多情况下，氰化物离去基团在卤素存在下优先被取代。所得的杂芳基碘化物，溴化物和氯化物随后可用作进一步化学多样化的处理方法。

  DOI：

  10.1021/jo302307y

文献信息

• [EN] BENZYL-, (PYRIDIN-3-YL)METHYL- OR (PYRIDIN-4-YL)METHYL-SUBSTITUTED OXADIAZOLOPYRIDINE DERIVATIVES AS GHRELIN O-ACYL TRANSFERASE (GOAT) INHIBITORS<br/>[FR] DÉRIVÉS D'OXADIAZOLOPYRIDINE À SUBSTITUTION BENZYLE, (PYRIDIN-3-YL)MÉTHYLE OU (PYRIDIN-4-YL)MÉTHYLE UTILISÉS EN TANT QU'INHIBITEURS DE LA GHRÉLINE O-ACYLTRANSFÉRASE (GOAT)
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2019149657A1

  公开（公告）日：2019-08-08

  The present invention relates to compounds of general formula (I), wherein the groups R1 and R2 are defined as in claim 1, which have valuable pharmacological properties, in particular bind to ghrelin O-acyl transferase (GOAT) and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular obesity.

  本发明涉及一般式（I）的化合物，其中基团R1和R2的定义如权利要求1中所述，该化合物具有有价值的药理特性，特别是与胃饥饿素O-酰基转移酶（GOAT）结合并调节其活性。这些化合物适用于治疗和预防可以受到该受体影响的疾病，如代谢性疾病，特别是肥胖症。
• Benzyl-, (pyridin-3-yl)methyl -or (pyridin-4-yl)-methyl-substituted oxadiazolopyridine derivatives as ghrelin O-acyl transferase (GOAT) inhibitors
  申请人：Boehringer Ingelheim International GmbH

  公开号：US11254688B2

  公开（公告）日：2022-02-22

  The present invention relates to compounds of general formula (I), wherein the groups R1 and R2 are defined as in claim 1, which have valuable pharmacological properties, in particular bind to ghrelin O-acyl transferase (GOAT) and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular obesity.

  本发明涉及通式(I)的化合物，其中基团 R1 和 R2 的定义如权利要求 1 所述，这些化合物具有重要的药理特性，特别是能与胃泌素 O-酰基转移酶（GOAT）结合并调节其活性。这些化合物适用于治疗和预防受该受体影响的疾病，如代谢性疾病，特别是肥胖症。
• BENZYL-, (PYRIDIN-3-YL)METHYL -OR (PYRIDIN-4-YL)-METHYL-SUBSTIITUTED OXADIAZOLOPYRIDINE DERIVATIVES AS GHRELIN O-ACYL TRANSFERASE (GOAT) INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20210053985A1

  公开（公告）日：2021-02-25

  The present invention relates to compounds of general formula (I), wherein the groups R 1 and R 2 are defined as in claim 1 , which have valuable pharmacological properties, in particular bind to ghrelin O-acyl transferase (GOAT) and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular obesity.
• Cyanide Anion as a Leaving Group in Nucleophilic Aromatic Substitution: Synthesis of Quaternary Centers at Azine Heterocycles
  作者：Alexander D. Thompson、Malcolm P. Huestis

  DOI：10.1021/jo302307y

  日期：2013.1.18

  Nucleophilic aromatic substitution of 2- or 4-cyanoazines with the anions derived from aliphatic α,α-disubstituted esters and nitriles leads to displacement of the cyanide function. Enabling cyanides to be used as highly active leaving groups in SNAr reactions provides additional flexibility in starting materials for synthesis. We show that, in many cases, the cyanide leaving group is displaced preferentially

  用衍生自脂族α，α-二取代的酯和腈的阴离子对2-或4-氰基嗪进行亲核芳族取代会导致氰化物官能团的置换。使氰化物能够在S N Ar反应中用作高活性离去基团，为合成原料提供了额外的灵活性。我们表明，在许多情况下，氰化物离去基团在卤素存在下优先被取代。所得的杂芳基碘化物，溴化物和氯化物随后可用作进一步化学多样化的处理方法。
• New direct inhibitors of InhA with antimycobacterial activity based on a tetrahydropyran scaffold
  作者：Stane Pajk、Matej Živec、Roman Šink、Izidor Sosič、Margarete Neu、Chun-wa Chung、María Martínez-Hoyos、Esther Pérez-Herrán、Daniel Álvarez-Gómez、Emilio Álvarez-Ruíz、Alfonso Mendoza-Losana、Julia Castro-Pichel、David Barros、Lluís Ballell-Pages、Robert J. Young、Maire A. Convery、Lourdes Encinas、Stanislav Gobec

  DOI：10.1016/j.ejmech.2016.02.008

  日期：2016.4

  Tetrahydropyran derivative 1 was discovered in a high-throughput screening campaign to find new inhibitors of mycobacterial InhA. Following initial in-vitro profiling, a structure-activity relationship study was initiated and a focused library of analogs was synthesized and evaluated. This yielded compound 42 with improved antimycobacterial activity and low cytotoxicity. Additionally, the crystal structure of InhA in complex with inhibitor 1 was resolved, to reveal the binding mode and provide hints for further optimization. (C) 2016 Elsevier Masson SAS. All rights reserved.