2-chloro-3-propyl-5-(pyridin-3-yl)pyrazine | 130227-97-3

• 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: 2-chloro-3-propyl-5-(pyridin-3-yl)pyrazine
• 英文别名: 2-chloro-3-propyl-5-(3-pyridyl)pyrazine；2-Chloro-3-propyl-5-pyridin-3-ylpyrazine
• CAS: 130227-97-3
• 化学式: C₁₂H₁₂ClN₃
• 分子量: 233.7
• InChiKey: WIFUKERNOSJISJ-UHFFFAOYSA-N

物化性质

• 沸点：
  339.6±37.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-3-propyl-5-(pyridin-3-yl)pyrazine 在 sodium hydroxide 、 sodium hydride 、 1-羟基苯并三唑 、 对甲苯磺酸 、 一水合肼 、 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 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 27.5h， 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 、 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 、 甲苯 为溶剂， 反应 7.5h， 生成 2-chloro-3-propyl-5-(pyridin-3-yl)pyrazine
  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

• 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。
• 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
• US5278161A
  申请人：——

  公开号：US5278161A

  公开（公告）日：1994-01-11
• 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
  作者：David A. Roberts、Robert H. Bradbury、David Brown、Alan Faull、David Griffiths、John S. Major、Alec A. Oldham、Robert J. Pearce、Arnold H. Ratcliffe

  DOI：10.1021/jm00171a005

  日期：1990.9

  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.