2-(5,7-dichloropyrazolo[1,5-a]pyrimidin-2-yl)-3,5-dimethylquinoxaline | 1332729-62-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-(5,7-dichloropyrazolo[1,5-a]pyrimidin-2-yl)-3,5-dimethylquinoxaline
• 英文别名: 2-(5,7-Dichloropyrazolo[1,5-a]pyrimidin-2-yl)-3,5-dimethylquinoxaline
• CAS: 1332729-62-0
• 化学式: C₁₆H₁₁Cl₂N₅
• 分子量: 344.203
• InChiKey: VHWPDUBGVWTEJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(5,7-dichloropyrazolo[1,5-a]pyrimidin-2-yl)-3,5-dimethylquinoxaline 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 35.5h， 生成 2-(3,5-dimethylquinoxalin-2-yl)-5-pyrrolidin-1-yl-N-tetrahydropyran-4-yl-pyrazolo[1,5-a]pyrimidin-7-amine hydrochloride
  参考文献：
  名称：

  Discovery of a pyrazolo[1,5-a]pyrimidine derivative (MT-3014) as a highly selective PDE10A inhibitor via core structure transformation from the stilbene moiety

  摘要：

  We have developed a new class of PDE10A inhibitor, a pyrazolo[1,5-a] pyrimidine derivative MT-3014 (1). A previous compound introduced was deprioritized due to concerns for E/Z-isomerization and glutathione-adduct formation at the core stilbene structure. We discovered pyrazolo [1,5-a] pyrimidine as a new lead scaffold by structure-based drug design utilizing a co-crystal structure with PDE10A. The lead compound was optimized for in vitro activity, solubility, and selectivity against human ether-a-go-go related gene cardiac channel binding. We observed that MT-3014 shows excellent efficacy in rat conditioned avoidance response test and suitable pharmacokinetic properties in rats, especially high brain penetration.

  DOI：

  10.1016/j.bmc.2019.06.021
• 作为产物：
  描述：

  3-(3,5-dimethylquinoxalin-2-yl)-1H-pyrazol-5-amine 在 吡啶 、 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 10.0h， 生成 2-(5,7-dichloropyrazolo[1,5-a]pyrimidin-2-yl)-3,5-dimethylquinoxaline
  参考文献：
  名称：

  Discovery of a pyrazolo[1,5-a]pyrimidine derivative (MT-3014) as a highly selective PDE10A inhibitor via core structure transformation from the stilbene moiety

  摘要：

  We have developed a new class of PDE10A inhibitor, a pyrazolo[1,5-a] pyrimidine derivative MT-3014 (1). A previous compound introduced was deprioritized due to concerns for E/Z-isomerization and glutathione-adduct formation at the core stilbene structure. We discovered pyrazolo [1,5-a] pyrimidine as a new lead scaffold by structure-based drug design utilizing a co-crystal structure with PDE10A. The lead compound was optimized for in vitro activity, solubility, and selectivity against human ether-a-go-go related gene cardiac channel binding. We observed that MT-3014 shows excellent efficacy in rat conditioned avoidance response test and suitable pharmacokinetic properties in rats, especially high brain penetration.

  DOI：

  10.1016/j.bmc.2019.06.021

文献信息

• [EN] PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS PDE10 INHIBITORS<br/>[FR] COMPOSÉS PYRAZOLOPYRIMIDINES ET LEUR UTILISATION COMME INHIBITEUR DE LA PDE10
  申请人：MITSUBISHI TANABE PHARMA CORP

  公开号：WO2011105628A1

  公开（公告）日：2011-09-01

  The present invention relates to a compound represented by formula [I]: wherein: R1 is hydrogen, halogen, lower alkyl or cyano; Ring A is an optionally substituted heterocyclic group; Ring B is an optionally substituted 3 to 6-membered monocyclic group; and Y is optionally substituted amino, optionally substituted cyclic amino, optionally substituted aliphatic 3 to 6-membered monocyclyloxy, optionally substituted lower alkyl or optionally substituted lower alkyl-O-, or a pharmaceutically acceptable salt thereof, and to their use as PDE10 inhibitor.

  本发明涉及一种由式[I]表示的化合物，其中：R1是氢、卤素、较低的烷基或氰基；环A是可选择取代的杂环基团；环B是可选择取代的3至6元杂环基团；Y是可选择取代的氨基、可选择取代的环氨基、可选择取代的脂肪族3至6元单环氧基、可选择取代的较低的烷基或可选择取代的较低的烷基-O-，或其药学上可接受的盐，以及它们作为PDE10抑制剂的用途。
• PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS PDE10 INHIBITORS
  申请人：Kawanishi Eiji

  公开号：US20120309754A1

  公开（公告）日：2012-12-06

  The present invention relates to a compound represented by formula [I]: wherein: R 1 is hydrogen, halogen, lower alkyl or cyano; Ring A is an optionally substituted heterocyclic group; Ring B is an optionally substituted 3 to 6-membered monocyclic group; and Y is optionally substituted amino, optionally substituted cyclic amino, optionally substituted aliphatic 3 to 6-membered monocyclyloxy, optionally substituted lower alkyl or optionally substituted lower alkyl-O—, or a pharmaceutically acceptable salt thereof, and to their use as PDE10 inhibitor.

  本发明涉及一种由式[I]表示的化合物： 其中：R1是氢、卤素、较低的烷基或氰基；环A是可选取代的杂环基团；环B是可选取代的3至6成员的单环基团；以及Y是可选取代的氨基、可选取代的环状氨基、可选取代的脂肪族3至6成员的单环氧基、可选取代的较低烷基或可选取代的较低烷基-O-，或其药学上可接受的盐，并且作为PDE10抑制剂使用。
• US8969376B2
  申请人：——

  公开号：US8969376B2

  公开（公告）日：2015-03-03
• Discovery of a pyrazolo[1,5-a]pyrimidine derivative (MT-3014) as a highly selective PDE10A inhibitor via core structure transformation from the stilbene moiety
  作者：Yuuki Koizumi、Yoshihito Tanaka、Takehiko Matsumura、Yoichi Kadoh、Haruko Miyoshi、Mitsuya Hongu、Kei Takedomi、Jun Kotera、Takashi Sasaki、Hiroyuki Taniguchi、Yumi Watanabe、Misae Takakuwa、Koki Kojima、Nobuyuki Baba、Itsuko Nakamura、Eiji Kawanishi

  DOI：10.1016/j.bmc.2019.06.021

  日期：2019.8

  We have developed a new class of PDE10A inhibitor, a pyrazolo[1,5-a] pyrimidine derivative MT-3014 (1). A previous compound introduced was deprioritized due to concerns for E/Z-isomerization and glutathione-adduct formation at the core stilbene structure. We discovered pyrazolo [1,5-a] pyrimidine as a new lead scaffold by structure-based drug design utilizing a co-crystal structure with PDE10A. The lead compound was optimized for in vitro activity, solubility, and selectivity against human ether-a-go-go related gene cardiac channel binding. We observed that MT-3014 shows excellent efficacy in rat conditioned avoidance response test and suitable pharmacokinetic properties in rats, especially high brain penetration.