2,2-dimethyl-N-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)propanamide | 868374-67-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 2,2-dimethyl-N-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)propanamide
• 英文别名: 2,2-Dimethyl-N-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)propanamide；2,2-dimethyl-N-(7-methyl-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-2-yl)propanamide
• CAS: 868374-67-8
• 化学式: C₁₂H₁₆N₄O₂
• 分子量: 248.285
• InChiKey: YJOXTJGOPNYURH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  75.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-N-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)propanamide 在 N-碘代丁二酰亚胺 、 水 、 sodium hydride 、 溶剂黄146 、 sodium hydroxide 、 锌 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-amino-5-iodo-3,7-dimethyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  Discovery of pyrrolo[2,3-d]pyrimidin-4-ones as corticotropin-releasing factor 1 receptor antagonists with a carbonyl-based hydrogen bonding acceptor

  摘要：

  A new class of pyrrolo[2,3-d]pyrimidin-4-one corticotropin-releasing factor 1 (CRF1) receptor antagonists has been designed and synthesized. In general, reported CRF1 receptor antagonists possess a sp(2)-nitrogen atom as hydrogen bonding acceptor (HBA) on their core scaffolds. We proposed to use a carbonyl group of pyrrolo[2,3-d]pyrimidin-4-one derivatives as a replacement for the sp(2)-nitrogen atom as HBA in classical CRF1 receptor antagonists. As a result, several pyrrolo[2,3-d]pyrimidin-4-one derivatives showed CRF1 receptor binding affinity with IC50 values in the submicromolar range. Ex vivo I-125-sauvagine binding studies showed that 2-(dipropylamino)-3,7-dimethyl-5-(2,4,6-trimethylphenyl)-3,7-dihydro-4H-pyrrolo [2,3-d]pyrimidin-4-one (16b) (30 mg/kg, po) was able to penetrate into the brain and inhibit radioligand binding to CRF1 receptors (frontal cortex, olfactory bulb, and pituitary) in mice. We identified pyrrolo[2,3-d] pyrimidin-4-one derivatives as the first CRF1 antagonists with a carbonyl-based HBA. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.086
• 作为产物：
  描述：

  2-氨基-6-(甲基氨基)-4-嘧啶醇 在 吡啶 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 2,2-dimethyl-N-(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)propanamide
  参考文献：
  名称：

  Discovery of pyrrolo[2,3-d]pyrimidin-4-ones as corticotropin-releasing factor 1 receptor antagonists with a carbonyl-based hydrogen bonding acceptor

  摘要：

  A new class of pyrrolo[2,3-d]pyrimidin-4-one corticotropin-releasing factor 1 (CRF1) receptor antagonists has been designed and synthesized. In general, reported CRF1 receptor antagonists possess a sp(2)-nitrogen atom as hydrogen bonding acceptor (HBA) on their core scaffolds. We proposed to use a carbonyl group of pyrrolo[2,3-d]pyrimidin-4-one derivatives as a replacement for the sp(2)-nitrogen atom as HBA in classical CRF1 receptor antagonists. As a result, several pyrrolo[2,3-d]pyrimidin-4-one derivatives showed CRF1 receptor binding affinity with IC50 values in the submicromolar range. Ex vivo I-125-sauvagine binding studies showed that 2-(dipropylamino)-3,7-dimethyl-5-(2,4,6-trimethylphenyl)-3,7-dihydro-4H-pyrrolo [2,3-d]pyrimidin-4-one (16b) (30 mg/kg, po) was able to penetrate into the brain and inhibit radioligand binding to CRF1 receptors (frontal cortex, olfactory bulb, and pituitary) in mice. We identified pyrrolo[2,3-d] pyrimidin-4-one derivatives as the first CRF1 antagonists with a carbonyl-based HBA. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.086

文献信息

• Cyclic compounds
  申请人：Gyorkos Charles Albert

  公开号：US20070179165A1

  公开（公告）日：2007-08-02

  There is provided a CRF receptor antagonist comprising a compound of the formula (I): A-W—Ar  (I) wherein, A is a group represented by the formula (A1) or (A2): (wherein, ring Aa is a 5- or 6-membered ring which may be further substituted; ring Ab is a 5- or 6-membered ring which may be further substituted; ring Ac is a 5- or 6-membered ring which may be substituted; R 1 is optionally substituted alkyl, substituted amino, substituted hydroxy, etc.; X is carbonyl, —O—, —S—, etc.; Y 1 , Y 2 and Q are independently optionally substituted carbon or nitrogen; is a single or double bond); W is a bond, optionally substituted methylene, optionally substituted imino, —O—, —S—, etc.; Ar is optionally substituted aryl or optionally substituted heteroaryl; or a salt thereof or a prodrug thereof.

  提供了一种CRF受体拮抗剂，包括式(I)的化合物：A-W-Ar(I)，其中，A是由式(A1)或(A2)表示的基团：（其中，环Aa是一个可以进一步取代的5-或6成员环；环Ab是一个可以进一步取代的5-或6成员环；环Ac是一个可以取代的5-或6成员环；R1是可选的取代基的烷基，取代的氨基，取代的羟基等；X是羰基，-O-，-S-等；Y1，Y2和Q独立地是可选取代的碳或氮；是单键或双键）；W是键，可选取代的亚甲基，可选取代的亚胺基，-O-，-S-等；Ar是可选取代的芳基或可选取代的杂芳基；或其盐或前药。
• Heterocyclic CRF receptor antagonists
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2522670A1

  公开（公告）日：2012-11-14

  There is provided a CRF receptor antagonist comprising a compound of the formula (I) : A-W-Ar wherein, A is a group represented by the formula (A2), wherein ring Ab is a 5- or 6- membered ring which may be further substituted in addition to R1; ring Ac is a 5- or 6- membered ring which may be substituted; R1 is an optionally substituted hydrocarbyl, a substituted amino, an optionally substituted cyclic amino, a substituted hydroxy, a substituted sulfanyl, an optionally substituted sulfinyl, or an optionally substituted sulfonyl; X is carbonyl, -O-, -S-, -SO-, or -SO2-; Y1, Y2 and Q are independently optionally substituted carbon or nitrogen; ... is a single or double bond; W is a bond, an optionally substituted methylene, an optionally substituted ethylene, an optionally substituted imino, -O-, -S-, -SO-, or -SO2-; Ar is an optionally substituted aryl or an optionally substituted heteroaryl; or a salt thereof or a prodrug thereof.

  本发明提供了一种 CRF 受体拮抗剂，包括式 (I) ：A-W-Ar 其中，A 是由式(A2)代表的基团，其中环 Ab 是除 R1 之外可进一步取代的 5 或 6 分子环；环 Ac 是可被取代的 5 或 6 分子环；R1 是任选取代的烃基、取代的氨基、任选取代的环氨基、取代的羟基、取代的硫基、任选取代的亚磺酰基或任选取代的磺酰基； X是羰基、-O-、-S-、-SO-或-SO2-；Y1、Y2和Q独立地是任选取代的碳或氮；...是单键或双键；W是键、任选取代的亚甲基、任选取代的亚乙基、任选取代的亚氨基、-O-、-S-、-SO-或-SO2-；Ar是任选取代的芳基或任选取代的杂芳基；或其盐或其原药。
• [EN] CYCLIC COMPOUNDS<br/>[FR] COMPOSES CYCLIQUES
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2005099688A3

  公开（公告）日：2007-05-31
• CYCLIC COMPOUNDS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1732541A2

  公开（公告）日：2006-12-20
• EP1732541A4
  申请人：——

  公开号：EP1732541A4

  公开（公告）日：2008-03-05