N-[6-chloro-2-(3,5-dimethylpyrazol-1-yl)pyrimidin-4-yl]acetamide | 1014720-89-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[6-chloro-2-(3,5-dimethylpyrazol-1-yl)pyrimidin-4-yl]acetamide
• 英文别名: N-(6-Chloro-2-(3,5-dimethyl-1H-pyrazol-1-yl)pyrimidin-4-yl)acetamide
• CAS: 1014720-89-8
• 化学式: C₁₁H₁₂ClN₅O
• 分子量: 265.702
• InChiKey: XQGAYHZIANBQQZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  72.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[6-chloro-2-(3,5-dimethylpyrazol-1-yl)pyrimidin-4-yl]acetamide 在 四(三苯基膦)钯 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 22.0h， 生成 (S)-3-{3-[6-acetylamino-2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidin-4-yl]-5-fluoro-phenoxy}-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  WO2008/116185

  摘要：

  公开号：
• 作为产物：
  描述：

  乙酰丙酮 在 肼 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 2.5h， 生成 N-[6-chloro-2-(3,5-dimethylpyrazol-1-yl)pyrimidin-4-yl]acetamide
  参考文献：
  名称：

  WO2008/116185

  摘要：

  公开号：

文献信息

• SUBSTITUTED PYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS
  申请人：Lanier Marion

  公开号：US20100234341A1

  公开（公告）日：2010-09-16

  Compounds of formula (I) including pharmaceutically acceptable salts, esters, solvates and stereoisomers thereof, R 1 , R 2 and R 3 are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.

  公式（I）的化合物，包括药学上可接受的盐、酯、溶剂和立体异构体，其中R1、R2和R3的定义如本文所述。本发明还公开了含有结构（I）化合物的制药组合物，以及与其使用相关的方法。
• 2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A2A antagonists with improved solubility and metabolic stability
  作者：Manisha Moorjani、Zhiyong Luo、Emily Lin、Binh G. Vong、Yongsheng Chen、Xiaohu Zhang、Jaimie K. Rueter、Raymond S. Gross、Marion C. Lanier、John E. Tellew、John P. Williams、Sandra M. Lechner、Siobhan Malany、Mark Santos、María I. Crespo、José-Luis Díaz、John Saunders、Deborah H. Slee

  DOI：10.1016/j.bmcl.2008.09.048

  日期：2008.10

  In this report, the strategy and outcome of expanding SAR exploration to improve solubility and metabolic stability are discussed. Compound 35 exhibited excellent potency, selectivity over A(1) and improved solubility of >4 mg/mL at pH 8.0. In addition, compound 35 had good metabolic stability with a scaled intrinsic clearance of 3 mL/min/kg (HLM) and demonstrated efficacy in the haloperidol induced catalepsy model. (C) 2008 Elsevier Ltd. All rights reserved.
• 2-Amino-<i>N</i>-pyrimidin-4-ylacetamides as A_2A Receptor Antagonists: 1. Structure−Activity Relationships and Optimization of Heterocyclic Substituents
  作者：Deborah H. Slee、Yongsheng Chen、Xiaohu Zhang、Manisha Moorjani、Marion C. Lanier、Emily Lin、Jaimie K. Rueter、John P. Williams、Sandra M. Lechner、Stacy Markison、Siobhan Malany、Mark Santos、Raymond S. Gross、Kayvon Jalali、Yang Sai、Zhiyang Zuo、Chun Yang、Julio C. Castro-Palomino、María I. Crespo、Maria Prat、Silvia Gual、José-Luis Díaz、John Saunders

  DOI：10.1021/jm701185v

  日期：2008.3.1

  Previously we have described a novel series of potent and selective A(2A) receptor antagonists (e.g., 1) with excellent aqueous solubility.(1) While these compounds are efficacious A(2A) antagonists in vivo, the presence of an unsubstituted furyl moiety was a cause of some concern. In order to avoid the potential metabolic liabilities that could arise from an unsubstituted fury] moiety, an optimization effort was undertaken with the aim of replacing the unsubstituted furan with a more metabolically stable group while maintaining potency and selectivity. Herein, we describe the synthesis and SAR of a range of novel heterocyclic systems and the successful identification of a replacement for the unsubstituted furan moiety with a methylfuran or thiazole moiety while maintaining potency and selectivity.
• Lead Optimization of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A_2A Adenosine Receptor Antagonists for the Treatment of Parkinson’s Disease
  作者：Xiaohu Zhang、John E. Tellew、Zhiyong Luo、Manisha Moorjani、Emily Lin、Marion C. Lanier、Yongsheng Chen、John P. Williams、John Saunders、Sandra M. Lechner、Stacy Markison、Tanya Joswig、Robert Petroski、Jaime Piercey、William Kargo、Siobhan Malany、Mark Santos、Raymond S. Gross、Jenny Wen、Kayvon Jalali、Zhihong O’Brien、Carol E. Stotz、María I. Crespo、José-Luis Díaz、Deborah H. Slee

  DOI：10.1021/jm800851u

  日期：2008.11.27

  4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-pyrimidines bearing substituted pyridyl groups as C-6 substituents were prepared as selective adenosine hA(2A) receptor antagonists for the treatment of Parkinson's disease. The 5-methoxy-3-pyridyl derivative 6g (hA(2A) K-i 2.3 nM, hA(1) K-i 190 nM) was orally active at 3 mg/kg in a rat HIC model but exposure was poor in nonrodent species, presumably due to poor aqueous solubility. Follow-on compound 16a (hA(2A) K-i 0.83 nM, hA(1) K-i 130 nM), bearing a 6-(morpholin-4-yl)-2-pyridyl substituent at C-6, had improved solubility and was orally efficacious (3 mg/kg, HIC) but showed time-dependent cytochrome P450 3A4 inhibition, possibly related to morpholine ring metabolism. Compound 16j (hA(2A) K-i 0.44 nM, hA(1) K-i 80 nM), bearing a 6-(4-methoxypiperidin-1-yl)-2-pyridyl substituent at C-6, was sparingly soluble but had good oral exposure in rodent and nonrodent species, had no cytochrome P450 or human ether-a-go-go related gene channel issues, and was orally efficacious at 1 mg/kg in HIC and at 3 mg/kg for potentiation Of L-dopa-induced contralateral rotations in 6-hydroxydopamine-lesioned rats.
• WO2008/70661
  申请人：——

  公开号：——

  公开（公告）日：——