1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidine-5,7(4H,6H)-dione | 109421-37-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidine-5,7(4H,6H)-dione
• 英文别名: 1,3-dimethylpyrazolo[4,3-d]pyrimidine-5,7-(4H, 6H)dione；1,3-dimethyl-4H-pyrazolo[4,3-d]pyrimidine-5,7-dione
• CAS: 109421-37-6
• 化学式: C₇H₈N₄O₂
• 分子量: 180.166
• InChiKey: POLDZKDQNFLQRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidine-5,7(4H,6H)-dione 在 N,N-二异丙基乙胺 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 (S)-4-(5-chloro-1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3-ethylmorpholine
  参考文献：
  名称：

  A hit to lead discovery of novel N-methylated imidazolo-, pyrrolo-, and pyrazolo-pyrimidines as potent and selective mTOR inhibitors

  摘要：

  A series of N-7-methyl-imidazolopyrimidine inhibitors of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-methyl substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3K alpha and delta kinases. The corresponding N-Me substituted pyrrolo[3,2-d]pyrimidines and pyrazolo[4,3-d]pyrimidines also show potent mTOR inhibition with selectivity toward both PI3 alpha and delta kinases. The most potent compound synthesized is pyrazolo[4,3-d]pyrimidine 21c. Compound 21c shows a K-i of 2 nM against mTOR inhibition, remarkable selectivity (>2900x) over PI3 kinases, and excellent potency in cell-based assays. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.027
• 作为产物：
  描述：

  2,5-二甲基-4-硝基吡唑-3-甲酰胺 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 、 乙腈 为溶剂， 100.0 ℃ 、344.75 kPa 条件下， 反应 24.0h， 生成 1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidine-5,7(4H,6H)-dione
  参考文献：
  名称：

  A hit to lead discovery of novel N-methylated imidazolo-, pyrrolo-, and pyrazolo-pyrimidines as potent and selective mTOR inhibitors

  摘要：

  A series of N-7-methyl-imidazolopyrimidine inhibitors of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-methyl substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3K alpha and delta kinases. The corresponding N-Me substituted pyrrolo[3,2-d]pyrimidines and pyrazolo[4,3-d]pyrimidines also show potent mTOR inhibition with selectivity toward both PI3 alpha and delta kinases. The most potent compound synthesized is pyrazolo[4,3-d]pyrimidine 21c. Compound 21c shows a K-i of 2 nM against mTOR inhibition, remarkable selectivity (>2900x) over PI3 kinases, and excellent potency in cell-based assays. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.027

文献信息

• N-7 SUBSTITUTED PURINE AND PYRAZOLOPYRIMINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Pei Zhonghua

  公开号：US20110086840A1

  公开（公告）日：2011-04-14

  The present invention relates to compounds of Formula I: wherein R 1 , R 2 , R 3 , A 1 , A 2 , A 3 , A 4 , Y 1 and Y 2 and D have the meaning described herein. The present invention also relates to pharmaceutical compositions comprising such compounds and therapeutic uses thereof.

  本发明涉及以下式I的化合物： 其中R1、R2、R3、A1、A2、A3、A4、Y1和Y2以及D具有本文所描述的含义。本发明还涉及包含此类化合物的药物组合物以及其治疗用途。
• Pyrazolo[4,3-d]pyrimidine-5,7-(4H,6H)dione or -5-thione-7-one analogs
  申请人：Warner-Lambert Company

  公开号：US04663326A1

  公开（公告）日：1987-05-05

  Various novel analogs of pyrazolo[4,3d]pyrimidine-5,7-(4H,6H)diones and also 5-thione-7-ones, novel methods of synthesis therefor, compositions and uses are the present invention. For example, the novel 5,7-diones and 5-thione-7-ones are useful for stimulating the central nervous system reversing bronchoconstriction, and as cardiac stimulants cardiotonic agents.

  本发明涉及吡唑并[4,3d]嘧啶-5,7-(4H,6H)二酮和5-硫代-7-酮的各种新型类似物，以及用于其合成的新方法、组合物和用途。例如，新型的5,7-二酮和5-硫代-7-酮可用于刺激中枢神经系统、逆转支气管痉挛，并作为心脏兴奋剂和心力衰竭药物。
• N-7 substituted purine and pyrazolopyrimine compounds, compositions and methods of use
  申请人：Pei Zhonghua

  公开号：US08828990B2

  公开（公告）日：2014-09-09

  The present invention relates to compounds of Formula I: wherein R1, R2, R3, A1, A2, A3, A4, Y1 and Y2 and D have the meaning described herein. The present invention also relates to pharmaceutical compositions comprising such compounds and therapeutic uses thereof.

  本发明涉及式I的化合物：其中R1，R2，R3，A1，A2，A3，A4，Y1和Y2以及D具有本文所述的含义。本发明还涉及包含这种化合物的制药组合物和其治疗用途。
• Substituted amino alkyl compounds
  申请人：CELL THERAPEUTICS, INC.

  公开号：EP1460074A1

  公开（公告）日：2004-09-22

  Compounds and pharmaceutical compositions thereof comprise the general formula:(R)j - (core moiety), including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, wherein j is an integer from one to three, the core moiety is non-cyclic or comprises at least one, five- to seven-membered ring structure, R may be selected from the group consisting of a hydrogen, halogen atom, hydroxyl, amino, substituted or unsubstituted benzyl, alkyl (C1-6) or alkenyl (C2-6) group, and at least one R has the general formula I: wherein n is an integer from four to eighteen; each R'1 and R'2 is independently a hydrogen atom, alkyl (C1-4) or alkenyl (C2-4) groups, the alkyl or alkenyl groups being preferably substituted by a halogen atom, hydroxyl, keto or dimethylamino group and/or may be interrupted by an oxygen atom; and each R'3 and R'4 is independently a hydrogen atom or methyl group. Preferably, n is an integer from six to ten, R'1 and R'2 are independently hydrogen atoms or methyl groups and R'3 and R'4 are hydrogen atoms. The compounds are useful in treating or preventing, for example, sepsis syndrome, hematopoietic or organ toxicity, baldness, hair loss or allopecia caused by cytotoxic therapies, and progression of an inflammatory or autoimmune disease.

  化合物及其药物组合物由通式组成：(R)j-(核心分子)，包括已解析的对映体和/或非对映异构体、水合物、盐、溶媒及其混合物，其中j为1至3的整数，核心分子为非环状或包括至少一个五至七元环结构，R可选自氢、卤素原子、羟基、氨基、取代或未取代的苄基、烷基(C1-6)或烯基(C2-6)所组成的组，且至少一个R具有通式I： 其中 n 是 4 到 18 的整数；每个 R'1 和 R'2 独立地为氢原子、烷基（C1-4）或烯基（C2-4），烷基或烯基最好被卤原子、羟基、酮基或二甲基氨基取代，和/或可被氧原子打断；每个 R'3 和 R'4 独立地为氢原子或甲基。优选地，n 是 6 到 10 的整数，R'1 和 R'2 独立地是氢原子或甲基，R'3 和 R'4 是氢原子。这些化合物可用于治疗或预防败血症综合征、造血或器官毒性、细胞毒性疗法引起的秃头、脱发或脱发症，以及炎症或自身免疫性疾病的恶化等。
• HAMILTON, H. W.
  作者：HAMILTON, H. W.

  DOI：——

  日期：——