2-chloro-N-(2-furan-2-yl-6-thiazol-2-yl-pyramidin-4-yl)-acetamide | 1006381-06-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-N-(2-furan-2-yl-6-thiazol-2-yl-pyramidin-4-yl)-acetamide
• 英文别名: 2-chloro-N-(2-furan-2-yl-6-thiazol-2-yl-pyrimidin-4-yl)-acetamide；2-chloro-N-[2-(furan-2-yl)-6-(1,3-thiazol-2-yl)pyrimidin-4-yl]acetamide
• CAS: 1006381-06-1
• 化学式: C₁₃H₉ClN₄O₂S
• 分子量: 320.759
• InChiKey: HDKVMWAGVHTGRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 2-chloro-N-(2-furan-2-yl-6-thiazol-2-yl-pyramidin-4-yl)-acetamide 生成 N-(2-furan-2-yl-6-thiazol-2-yl-pyrimidin-4-yl)-2-(4-methyl-piperazin-1-yl)acetamide
  参考文献：
  名称：

  [EN] 2, 6-DI (HETERO) ARYL -4-AMIDO-PYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS
  [FR] PYRIMIDINES SUBSTITUEES UTILISEES COMME ANTAGONISTES DU RECEPTEUR D'ADENOSINE

  摘要：

  公开号：

  WO2006110884A3
• 作为产物：
  描述：

  2-chloro-N-[2-(5-methyl-furan-2-yl)-6-thiazol-2-yl-pyrimidin-4-yl]-acetamide 、 2-呋喃羧酰胺 生成 2-chloro-N-(2-furan-2-yl-6-thiazol-2-yl-pyramidin-4-yl)-acetamide
  参考文献：
  名称：

  Substituted Pyrimidines as Adenosine Receptor Antagonists

  摘要：

  式(I)的化合物，包括药学上可接受的盐、酯、溶剂合物和立体异构体，其中R1、R2和R3的定义如本文所述。含有式(I)化合物的制药组合物，以及与其使用作为腺苷受体拮抗剂相关的方法，特别是A2A腺苷受体亚型的拮抗剂。

  公开号：

  US20080275064A1

文献信息

• [EN] 2, 6-DI (HETERO) ARYL -4-AMIDO-PYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS<br/>[FR] PYRIMIDINES SUBSTITUEES UTILISEES COMME ANTAGONISTES DU RECEPTEUR D'ADENOSINE
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2006110884A3

  公开（公告）日：2006-11-23
• Identification of Novel, Water-Soluble, 2-Amino-<i>N</i>-pyrimidin-4-yl Acetamides as A_2A Receptor Antagonists with In Vivo Efficacy
  作者：Deborah H. Slee、Xiaohu Zhang、Manisha Moorjani、Emily Lin、Marion C. Lanier、Yongsheng Chen、Jaimie K. Rueter、Sandra M. Lechner、Stacy Markison、Siobhan Malany、Tanya Joswig、Mark Santos、Raymond S. Gross、John P. Williams、Julio C. Castro-Palomino、María I. Crespo、Maria Prat、Silvia Gual、José-Luis Díaz、Jenny Wen、Zhihong O’Brien、John Saunders

  DOI：10.1021/jm070623o

  日期：2008.2.1

  Potent adenosine hA(2A) receptor antagonists are often accompanied by poor aqueous solubility, which presents issues for drug development. Herein we describe the early exploration of the structure-activity relationships of a lead pyrimidin-4-yl acetamide series to provide potent and selective 2-amino-N-pyrimidin4-yl acetamides as hA(2A) receptor antagonists with excellent aqueous solubility. In addition, this series of compounds has demonstrated good bioavailability and in vivo efficacy in a rodent model of Parkinson's disease, despite having reduced potency for the rat A(2A) receptor versus the human A2A receptor.
• 2, 6-DI (HETERO) ARYL -4-AMIDO-PYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS
  申请人：Almirall, S.A.

  公开号：EP1888565B1

  公开（公告）日：2011-03-23
• [EN] SUBSTITUTED PYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS<br/>[FR] PYRIMIDINES SUBSTITUEES UTILISEES COMME ANTAGONISTES DU RECEPTEUR D'ADENOSINE
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2006110884A2

  公开（公告）日：2006-10-19

  (EN) Compounds of formula (I), including pharmaceutically acceptable salts, esters, solvates and stereoisomers thereof, Rl, R2 and R3 are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof as antagonists of adenosine receptors, in particular antagonists of the A2A adenosine receptor subtype.(FR) Cette invention concerne des composés représentés par la formule (I), y compris des sels, esters, solvates, stéréo-isomères et promédicaments de ceux-ci, R1, R2 and R3 étant définis dans la demande. Des compositions pharmaceutiques contenant un composé de structure (I) ainsi que des procédés relatifs à l'utilisation de ces compositions sont également décrits.
• 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.