[4-(3-Chloro-4-methoxy-benzylamino)-2-methylsulfanyl-pyrimidin-5-yl]-(1-methyl-1H-imidazol-2-yl)-methanone | 372113-70-7

• 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: [4-(3-Chloro-4-methoxy-benzylamino)-2-methylsulfanyl-pyrimidin-5-yl]-(1-methyl-1H-imidazol-2-yl)-methanone
• 英文别名: 2-methylthio-5-(1-methyl-2-imidazolylcarbonyl)-6-(3-chloro-4-methoxybenzylamino)pyrimidine；[4-[(3-chloro-4-methoxyphenyl)methylamino]-2-methylsulfanylpyrimidin-5-yl]-(1-methylimidazol-2-yl)methanone
• CAS: 372113-70-7
• 化学式: C₁₈H₁₈ClN₅O₂S
• 分子量: 403.892
• InChiKey: JRYBQHKOAHRKGU-UHFFFAOYSA-N

物化性质

• 沸点：
  638.3±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [4-(3-Chloro-4-methoxy-benzylamino)-2-methylsulfanyl-pyrimidin-5-yl]-(1-methyl-1H-imidazol-2-yl)-methanone 在 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 氯仿 、 甲苯 、 mineral oil 为溶剂， 生成 (S)-2-(2-Hydroxymethyl-1-pyrrolidinyl)-5-(1-methyl-2-imidazolyl)-8-(3-chloro-4-methoxybenzyl)-7,8-dihydro-7-oxo-pyrido[2,3-d]pyrimidine
  参考文献：
  名称：

  8-(3-Chloro-4-methoxybenzyl)-8H-pyrido[2,3-d]pyrimidin-7-one derivatives as potent and selective phosphodiesterase 5 inhibitors

  摘要：

  A novel series of highly selective phosphodiesterase 5 (PDE5) inhibitors was found. 8H-Pyrido[2,3-d]pyrimidin-7-one derivatives bearing an (S)-2-(hydroxymethyl)pyrrolidin-1-yl group at the 2-position and a 3-chloro-4-methoxybenzyl group at the 8-position exhibited potent PDE5 inhibitory activities and high PDE5 selectivity over PDE6. Among the synthesized compounds, the 5-methyl analogue (5b) showed the most potent relaxant effect on isolated rabbit corpus cavernosum with an EC30 value of 0.85 nM. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.02.041
• 作为产物：
  描述：

  3-氯-4-甲氧基苄胺 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 [4-(3-Chloro-4-methoxy-benzylamino)-2-methylsulfanyl-pyrimidin-5-yl]-(1-methyl-1H-imidazol-2-yl)-methanone
  参考文献：
  名称：

  8-(3-Chloro-4-methoxybenzyl)-8H-pyrido[2,3-d]pyrimidin-7-one derivatives as potent and selective phosphodiesterase 5 inhibitors

  摘要：

  A novel series of highly selective phosphodiesterase 5 (PDE5) inhibitors was found. 8H-Pyrido[2,3-d]pyrimidin-7-one derivatives bearing an (S)-2-(hydroxymethyl)pyrrolidin-1-yl group at the 2-position and a 3-chloro-4-methoxybenzyl group at the 8-position exhibited potent PDE5 inhibitory activities and high PDE5 selectivity over PDE6. Among the synthesized compounds, the 5-methyl analogue (5b) showed the most potent relaxant effect on isolated rabbit corpus cavernosum with an EC30 value of 0.85 nM. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.02.041

文献信息

• Pyridopyrimidine or naphthyridine derivative
  申请人：Yamada Koichiro

  公开号：US20050101615A1

  公开（公告）日：2005-05-12

  A pyridopyrimidine or a naphthyridine derivative of the formula (I): wherein R 1 is an optionally substituted nitrogen-containing heterocyclic group, etc.; R 2 is H or a lower alkyl group; R 3 is H or an optionally substituted lower alkyl group, etc.; R 4 is H, a lower alkyl group, COOH, etc.; R 5 is a lower alkyl group which may optionally be substituted by an optionally substituted aryl etc.; one of X and Y is CH and the other is nitrogen, or both of X and Y are nitrogen; or a pharmaceutically acceptable salt thereof, these compounds exhibiting excellent PDE V inhibitory activities, and being useful in the prophylaxis or treatment of penile erectile dysfunction, etc.

  公式（I）中的吡啶并嘧啶或萘啶衍生物，其中R1是可选取代的含氮杂环基团等；R2是氢或较低的烷基基团；R3是氢或可选取代的较低烷基基团等；R4是氢、较低的烷基基团、COOH等；R5是较低的烷基基团，其可以可选取代芳基等；X和Y中的一个是CH，另一个是氮，或者X和Y都是氮；或其药学上可接受的盐，这些化合物表现出优异的PDE V抑制活性，并且在预防或治疗阴茎勃起功能障碍等方面非常有用。
• PYRIDOPYRIMIDINE OR NAPHTHYRIDINE DERIVATIVE
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP1364950A1

  公开（公告）日：2003-11-26

  A pyridopyrimidine or a naphthyridine derivative of the formula (I): wherein R1 is an optionally substituted nitrogen-containing heterocyclic group, etc.; R2 is H or a lower alkyl group; R3 is H or an optionally substituted lower alkyl group, etc.; R4 is H, a lower alkyl group, COOH, etc.; R5 is H, an optionally substituted aryl, etc; one of X and Y is CH and the other is nitrogen, or both of X and Y are nitrogen; or a pharmaceutically acceptable salt thereof, these compounds exhibiting excellent PDE V inhibitory activities, and being useful in the prophylaxis or treatment of penile erectile dysfunction, etc.

  式（I）的吡啶嘧啶或萘啶衍生物： 其中 R1 是任选取代的含氮杂环基团等； R2 是 H 或低级烷基； R3 是 H 或任选取代的低级烷基等； R4 是 H、低级烷基、COOH 等； R5 是 H、任选取代的芳基等； X 和 Y 中的一个是 CH，另一个是氮。这些化合物具有优异的 PDE V 抑制活性，可用于预防或治疗阴茎勃起功能障碍等。
• EP1364950
  申请人：——

  公开号：——

  公开（公告）日：——
• US7078522B2
  申请人：——

  公开号：US7078522B2

  公开（公告）日：2006-07-18
• 8-(3-Chloro-4-methoxybenzyl)-8H-pyrido[2,3-d]pyrimidin-7-one derivatives as potent and selective phosphodiesterase 5 inhibitors
  作者：Toshiaki Sakamoto、Yuichi Koga、Masataka Hikota、Kenji Matsuki、Hideki Mochida、Kohei Kikkawa、Kotomi Fujishige、Jun Kotera、Kenji Omori、Hiroshi Morimoto、Koichiro Yamada

  DOI：10.1016/j.bmcl.2015.02.041

  日期：2015.4

  A novel series of highly selective phosphodiesterase 5 (PDE5) inhibitors was found. 8H-Pyrido[2,3-d]pyrimidin-7-one derivatives bearing an (S)-2-(hydroxymethyl)pyrrolidin-1-yl group at the 2-position and a 3-chloro-4-methoxybenzyl group at the 8-position exhibited potent PDE5 inhibitory activities and high PDE5 selectivity over PDE6. Among the synthesized compounds, the 5-methyl analogue (5b) showed the most potent relaxant effect on isolated rabbit corpus cavernosum with an EC30 value of 0.85 nM. (C) 2015 Elsevier Ltd. All rights reserved.