4-(5-methyl-[1,3,4]oxadiazol-2-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl
• 英文别名: 2-Methyl-5-(1-pyridin-2-ylpiperidin-4-yl)-1,3,4-oxadiazole
• 化学式: C₁₃H₁₆N₄O
• 分子量: 244.296
• InChiKey: DVYHQCVIORLAHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(5-methyl-[1,3,4]oxadiazol-2-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl 、 2-甲基-4-甲氧基苯胺 在 对甲苯磺酸 作用下， 以 xylene 为溶剂， 反应 18.0h， 生成 4-[4-(4-methoxy-2-methyl-phenyl)-5-methyl-4H-[1,2,4]triazol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl
  参考文献：
  名称：

  [EN] TRIAZOLE DERIVATIVES WHICH INHIBIT VASOPRESSIN ANTAGONISTIC ACTIVITY
  [FR] DERIVES DE TRIAZOLE INHIBANT L'ACTIVITE ANTAGONISTE DE LA VASOPRESSINE

  摘要：

  式(I)的化合物或其药用可接受的衍生物，其中：Het代表2-吡啶基或2-嘧啶基；R1代表H、C1-3烷基或含氮杂环环有5或6个原子的环；R2代表H、苄基或C1-3烷基；R3代表H、甲基、甲氧基或氯；适用于治疗焦虑、心血管疾病（包括心绞痛、动脉硬化、高血压、心力衰竭、水肿、高钠血症）、痛经（原发性和继发性）、子宫内膜异位症、呕吐（包括晕动病）、宫内生长迟缓、炎症（包括类风湿性关节炎）、米特尔施梅克氏综合征、子痫前症、早泄、早产、雷诺氏病。

  公开号：

  WO2005079808A1
• 作为产物：
  描述：

  N-(吡啶-2-基)哌啶-4-羧酸 在 N-甲基吗啉 、 草酰氯 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 19.5h， 生成 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl
  参考文献：
  名称：

  Discovery of PF-184563, a potent and selective V1a antagonist for the treatment of dysmenorrhoea. The influence of compound flexibility on microsomal stability

  摘要：

  The V1a receptor has emerged as an attractive target for a range of indications including Raynaud's disease and dysmenorrhoea. As part of an effort to discover a new class of orally active V1a antagonist, we optimised a highly lipophilic, metabolically unstable lead into a range of potent, selective and metabolically stable V1a antagonists. In this communication, we demonstrate the series-dependent effect of limiting the number of rotatable bonds in order to decrease Cytochrome P450-mediated metabolism. This effort culminated in the discovery of PF-184563, a novel, selective V1a antagonist with excellent in vitro and in vivo properties. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.038

文献信息

• Triazole derivatives which inhibit vasopressin antagonistic activity
  申请人：Bryans S. Justin

  公开号：US20070203132A1

  公开（公告）日：2007-08-30

  Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: Het represents 2-pyridinyl or 2-pyrimidinyl; R 1 represents H, C 1-3 alkyl or a nitrogen-containing heterocyclic ring having 5 or 6 ring atoms; R 2 represents H, benzyl or C 1-3 alkyl; and R 3 represents H, methyl, methoxy or chloro; are useful for treating anxiety, cardiovascular disease (including angina, atherosclerosis, hypertension, heart failure, edema, hypernatremia), dysmenorrhoea (primary and secondary), endometriosis, emesis (motion sickness), intrauterine growth retardation, inflammation (including rheumatoid arthritis), mittlesmerchz, preclampsia, premature ejaculation, premature (preterm) labor and Raynaud's disease.

  化合物式(I)或其药学可接受的衍生物，其中：Het代表2-吡啶基或2-嘧啶基；R1代表H、C1-3烷基或含有5或6个环原子的氮杂环；R2代表H、苄基或C1-3烷基；R3代表H、甲基、甲氧基或氯，用于治疗焦虑、心血管疾病（包括心绞痛、动脉硬化、高血压、心力衰竭、水肿、高钠血症）、痛经（原发性和继发性）、子宫内膜异位症、恶心（晕动病）、宫内生长迟缓、炎症（包括类风湿性关节炎）、月经痛、先兆子痫、早泄、早产和雷诺氏病。
• TRIAZOLE DERIVATIVES WHICH INHIBIT VASOPRESSIN ANTAGONISTIC ACTIVITY
  申请人：Pfizer Limited

  公开号：EP1708718A1

  公开（公告）日：2006-10-11
• US7449462B2
  申请人：——

  公开号：US7449462B2

  公开（公告）日：2008-11-11
• [EN] TRIAZOLE DERIVATIVES WHICH INHIBIT VASOPRESSIN ANTAGONISTIC ACTIVITY<br/>[FR] DERIVES DE TRIAZOLE INHIBANT L'ACTIVITE ANTAGONISTE DE LA VASOPRESSINE
  申请人：PFIZER LTD

  公开号：WO2005079808A1

  公开（公告）日：2005-09-01

  Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: Het represents 2-pyridinyl or 2-pyrimidinyl;R1 represents H, C1-3 alkyl or a nitrogen-containing heterocyclic ring having 5 or 6 ring atoms; R2 represents H, benzyl or C 1-3 alkyl; and R3 represents H, methyl, methoxy or chloro; are useful for treating anxiety, cardiovascular disease (including angina, atherosclerosis, hypertension, heart failure, edema, hypernatremia), dysmenorrhoea (primary and secondary), endometriosis, emesis (including motion sickness), intrauterine growth retardation, inflammation (including rheumatoid arthritis), mittlesmerchz, preclampsia, premature ejaculation, premature (preterm) labor and Raynaud's disease.

  式(I)的化合物或其药用可接受的衍生物，其中：Het代表2-吡啶基或2-嘧啶基；R1代表H、C1-3烷基或含氮杂环环有5或6个原子的环；R2代表H、苄基或C1-3烷基；R3代表H、甲基、甲氧基或氯；适用于治疗焦虑、心血管疾病（包括心绞痛、动脉硬化、高血压、心力衰竭、水肿、高钠血症）、痛经（原发性和继发性）、子宫内膜异位症、呕吐（包括晕动病）、宫内生长迟缓、炎症（包括类风湿性关节炎）、米特尔施梅克氏综合征、子痫前症、早泄、早产、雷诺氏病。
• Discovery of PF-184563, a potent and selective V1a antagonist for the treatment of dysmenorrhoea. The influence of compound flexibility on microsomal stability
  作者：Patrick S. Johnson、Thomas Ryckmans、Justin Bryans、Dave M. Beal、Kevin N. Dack、Neil Feeder、Anthony Harrison、Mark Lewis、Helen J. Mason、James Mills、Julie Newman、Christelle Pasquinet、Dave J. Rawson、Lee R. Roberts、Rachel Russell、Deborah Spark、Alan Stobie、Toby J. Underwood、Robin Ward、Simon Wheeler

  DOI：10.1016/j.bmcl.2011.08.038

  日期：2011.10

  The V1a receptor has emerged as an attractive target for a range of indications including Raynaud's disease and dysmenorrhoea. As part of an effort to discover a new class of orally active V1a antagonist, we optimised a highly lipophilic, metabolically unstable lead into a range of potent, selective and metabolically stable V1a antagonists. In this communication, we demonstrate the series-dependent effect of limiting the number of rotatable bonds in order to decrease Cytochrome P450-mediated metabolism. This effort culminated in the discovery of PF-184563, a novel, selective V1a antagonist with excellent in vitro and in vivo properties. (C) 2011 Elsevier Ltd. All rights reserved.