5-氯-6-吡嗪基-1-烟酸 | 889953-74-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 5-氯-6-吡嗪基-1-烟酸
• 英文名称: 5-chloro-6-(piperazin-1-yl)nicotinic acid
• 英文别名: 5-Chloro-6-piperazin-4-ium-1-ylpyridine-3-carboxylate
• CAS: 889953-74-6
• 化学式: C₁₀H₁₂ClN₃O₂
• 分子量: 241.677
• InChiKey: YWIMUHQNVJTAKH-UHFFFAOYSA-N

物化性质

• 沸点：
  460.1±45.0 °C(Predicted)
• 密度：
  1.377±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  65.5
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  5-氯-6-吡嗪基-1-烟酸 在 硫酸 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 3-methylbutyl 5-chloro-6-[4-({[(5-chloro-2-thienyl)sulfonyl]amino}carbonyl)-piperazin-1-yl]nicotinate
  参考文献：
  名称：

  Synthesis, structure–property relationships and pharmacokinetic evaluation of ethyl 6-aminonicotinate sulfonylureas as antagonists of the P2Y12 receptor

  摘要：

  The present paper describes the development of a new series of P2Y(12) receptor antagonists based on our previously reported piperazinyl urea series 1 (IC50 binding affinity = 0.33 mu M, aq solubility <0.1 mu M, microsomal CLint (HLM) >= 300 mu M/min/mg). By replacement of the urea functionality with a sulfonylurea group we observed increased affinity along with improved stability and solubility as exemplified by 47 (IC50 binding affinity = 0.042 mu M, aq solubility = 90 mu M, microsomal CLint (HLM) = 70 mu M/min/mg). Further improvements in affinity and metabolic stability were achieved by replacing the central piperazine ring with a 3-aminoazetidine as exemplified by 3 (IC50 binding affinity = 0.0062 mu M, aq solubility = 83 mu M, microsomal CLint (HLM) = 28 mu M/min/mg). The improved affinity observed in the in vitro binding assay also translated to the potency observed in the WPA aggregation assay (47: 19 nM and 3: 9.5 nM) and the observed in vitro ADME properties translates to the in vivo PK properties observed in rat. In addition, we found that the chemical stability of the sulfonylureas during prolonged storage in solution was related to the sulfonyl urea linker and depended on the type of solvent and the substitution pattern of the sulfonyl urea functionality. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.007
• 作为产物：
  描述：

  哌嗪 、 5,6-二氯烟酸 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 生成 5-氯-6-吡嗪基-1-烟酸
  参考文献：
  名称：

  Synthesis, structure–property relationships and pharmacokinetic evaluation of ethyl 6-aminonicotinate sulfonylureas as antagonists of the P2Y12 receptor

  摘要：

  The present paper describes the development of a new series of P2Y(12) receptor antagonists based on our previously reported piperazinyl urea series 1 (IC50 binding affinity = 0.33 mu M, aq solubility <0.1 mu M, microsomal CLint (HLM) >= 300 mu M/min/mg). By replacement of the urea functionality with a sulfonylurea group we observed increased affinity along with improved stability and solubility as exemplified by 47 (IC50 binding affinity = 0.042 mu M, aq solubility = 90 mu M, microsomal CLint (HLM) = 70 mu M/min/mg). Further improvements in affinity and metabolic stability were achieved by replacing the central piperazine ring with a 3-aminoazetidine as exemplified by 3 (IC50 binding affinity = 0.0062 mu M, aq solubility = 83 mu M, microsomal CLint (HLM) = 28 mu M/min/mg). The improved affinity observed in the in vitro binding assay also translated to the potency observed in the WPA aggregation assay (47: 19 nM and 3: 9.5 nM) and the observed in vitro ADME properties translates to the in vivo PK properties observed in rat. In addition, we found that the chemical stability of the sulfonylureas during prolonged storage in solution was related to the sulfonyl urea linker and depended on the type of solvent and the substitution pattern of the sulfonyl urea functionality. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.007

文献信息

• New Pyridine Analogues II
  申请人：Brickmann Kay

  公开号：US20070244088A1

  公开（公告）日：2007-10-18

  The present invention relates to certain new pyridin analogues of Formula (I) to processes for preparing such compounds, to their utility in medicine in general and especially as P2Y 12 inhibitors and as anti-thrombotic agents, etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新的Formula (I)的吡啶类似物，涉及制备这类化合物的方法，它们在医学上的用途，特别是作为P2Y12受体拮抗剂和抗血栓药物等，它们在心血管疾病中作为药物的用途，以及含有它们的药物组合物。
• Pyridine Analogues II
  申请人：Brickmann Kay

  公开号：US20090186876A1

  公开（公告）日：2009-07-23

  The present invention relates to certain new pyridin analogues of Formula (I) [Chemical formula should be inserted here. Please see paper copy] Formula (I) to processes for preparing such compounds, to their utility in medicine in general and especially as P2Y 12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新的Formula (I) [化学式应在此处插入。请参阅纸质副本]的吡啶类似物，以及制备这些化合物的过程，它们在医学上的用途，特别是作为P2Y12抑制剂和抗血栓药物等，它们在心血管疾病中用作药物以及包含它们的制药组合物。
• NEW PYRIDINE ANALOGUES
  申请人：AstraZeneca AB

  公开号：EP2041111A1

  公开（公告）日：2009-04-01
• [EN] NEW PYRIDINE ANALOGUES<br/>[FR] NOUVEAUX ANALOGUES DE PYRIDINE
  申请人：ASTRAZENECA AB

  公开号：WO2008002247A1

  公开（公告）日：2008-01-03

  [EN] The present invention relates to certain new pyridin analogues of Formula ( I ) [Chemical formula should be inserted here. Please see paper copy] Formula ( I ) to processes for preparing such compounds, to their utility in medicine in general and especially as P2Y₁₂ inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
  [FR] La présente invention porte sur certains nouveaux analogues de pyridine de formule (I) et sur des procédés de préparation de ces composés, sur leur utilité dans le domaine médical, en général, et notamment comme inhibiteurs de P2Y₁₂ et comme agents anti-thrombotiques, etc., sur leur utilisation comme médicaments dans le traitement de maladies cardio-vasculaires, et sur des compositions pharmaceutiques les contenant.
• [EN] PHARMACEUTICAL COMPOSITION FOR PREVENTION AND/OR TREATMENT OF HEARING LOSS<br/>[FR] COMPOSITION DESTINÉE À LA PRÉVENTION, ET/OU AU TRAITEMENT D'UNE PERTE D'AUDITION<br/>[JA] 難聴の予防および／または治療用医薬組成物
  申请人：UNIV OSAKA

  公开号：WO2021079962A1

  公开（公告）日：2021-04-29

  本発明は、難聴の予防および／または治療用医薬組成物の提供を課題とする。　本発明は、一般式（１）［式中、 Ａは、置換されていてもよいベンゼン環である。 Ｂは、置換されていてもよいアリールまたは置換されていてもよいヘテロアリールである。 Ｘは、酸素原子または硫黄原子である。 Ｙは、窒素原子または炭素原子である。 一般式（２）において、一般式（３）は、Ｙが炭素原子のときは一重結合または二重結合であり、Ｙが窒素原子のときは一重結合である。Ｒ１は、互いに独立して低級アルキルであるか、２個のＲ１が互いに結合して、スピロ環または架橋構造を形成していてもよい、あるいは２個のＲ１が互いに結合して、Ｙを含む環を構成する炭素原子および窒素原子と共に飽和縮合複素環を形成していてもよい。 ｐは、０、１、または２である。 あるいは、（Ｒ１）ｐはオキソである。］ で表される化合物、その塩、またはそのプロドラッグを含有する難聴の予防および／または治療用医薬組成物に関する。