3-propyl-5-(pyridin-3-yl)pyrazin-2-ylhydrazine | 128972-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-propyl-5-(pyridin-3-yl)pyrazin-2-ylhydrazine
• 英文别名: 2-hydrazino-3-propyl-5-(pyridin-3-yl)pyrazine；3-propyl-5-(3-pyridyl)pyrazin-2-ylhydrazine；2-hydrazino-3-propyl-5-(3-pyridyl)pyrazine；(3-propyl-5-pyridin-3-ylpyrazin-2-yl)hydrazine
• CAS: 128972-05-4
• 化学式: C₁₂H₁₅N₅
• 分子量: 229.285
• InChiKey: RXKDHPHOFGUVNU-UHFFFAOYSA-N

物化性质

• 熔点：
  164-165 °C
• 沸点：
  421.0±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-propyl-5-(pyridin-3-yl)pyrazin-2-ylhydrazine 在 sodium hydroxide 、 sodium hydride 、 1-羟基苯并三唑 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 24.5h， 生成 N-[(1S,2S)-1,3-dicyclohexyl-1-hydroxypropan-2-yl]-2-[8-(2-methylpropyl)-6-phenyl-[1,2,4]triazolo[4,3-a]pyrazin-3-yl]-3-pyridin-3-ylpropanamide
  参考文献：
  名称：

  1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

  摘要：

  A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.

  DOI：

  10.1021/jm00171a005
• 作为产物：
  描述：

  3-(2-氨基乙酰基)吡啶 在 乙酸铵 、 一水合肼 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 10.5h， 生成 3-propyl-5-(pyridin-3-yl)pyrazin-2-ylhydrazine
  参考文献：
  名称：

  1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

  摘要：

  A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.

  DOI：

  10.1021/jm00171a005

文献信息

• Amino acid derivatives useful as renin inhibitors
  申请人：Hoffmann-La Roche Inc.

  公开号：US05278161A1

  公开（公告）日：1994-01-11

  Compounds of the formula ##STR1## wherein A, B, X, Y, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as set forth in the specification, in the form of optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diasteromeric racemates as well as pharmaceutically acceptable salts thereof which inhibit the activity of the natural enzyme renin and are useful in the control or prevention of high blood pressure and cardiac insufficiency are described.

  本文描述了式##STR1##的化合物，其中A、B、X、Y、R.sup.1、R.sup.2、R.sup.3、R.sup.4和R.sup.5如规范中所述，以光学纯的对映异构体形式、对映异构体混合物、对映异构体外消旋体或对映异构体外消旋体混合物的形式存在，以及其药学上可接受的盐，这些化合物抑制天然酶肾素的活性，对高血压和心脏衰竭的控制或预防有用。
• Aminosäurederivate
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0464572A2

  公开（公告）日：1992-01-08

  Die Verbindungen der Formel worin A, B, X, Y, R1, R2, R3, R4 und R5 die in Anspruch 1 angegebene Bedeutung besitzen, in Form von optisch reinen Diastereomeren, Diastereomerengemischen, diastereomeren Racematen oder Gemischen von diastereomeren Racematen sowie pharmazeutisch verwendbare Salze davon hemmen die Wirkung des natürlichen Enzyms Renin und können demnach in Form pharmazeutischer Präparate bei der Bekämpfung bzw. Verhütung von Bluthochdruck und Herzinsuffizienz verwendet werden. Sie können nach verschiedenen, an sich bekannten Verfahren hergestellt werden.

  式中的化合物 其中 A、B、X、Y、R1、R2、R3、R4 和 R5 具有权利要求 1 中给出的含义，以光学纯非对映异构体、非对映异构体混合物、非对映消旋体或非对映消旋体混合物的形式，以及它们的药用盐，可抑制天然肾素酶的作用，因此可以药物制剂的形式用于控制或预防高血压和心力衰竭。它们可以用各种已知的方法生产。
• ROBERTS, DAVID A.;BRADBURY, ROBERT H.;BROWN, DAVID;FAULL, ALAN;GRIFFITHS,+, J. MED. CHEM., 33,(1990) N, C. 2326-2334
  作者：ROBERTS, DAVID A.、BRADBURY, ROBERT H.、BROWN, DAVID、FAULL, ALAN、GRIFFITHS,+

  DOI：——

  日期：——
• Heterocyclic amides
  申请人：ZENECA LIMITED

  公开号：EP0369743B1

  公开（公告）日：1995-04-19
• US5091425A
  申请人：——

  公开号：US5091425A

  公开（公告）日：1992-02-25