6-chloro-2-(thiazol-2-yl)pyrimidin-4-ylamine | 856173-72-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-chloro-2-(thiazol-2-yl)pyrimidin-4-ylamine
• 英文别名: 6-chloro-2-(1,3-thiazol-2-yl)pyrimidin-4-amine；6-chloro-2-(thiazol-2-yl)pyrimidin-4-amine
• CAS: 856173-72-3
• 化学式: C₇H₅ClN₄S
• 分子量: 212.662
• InChiKey: ZYKZJRNKOHKHEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-chloro-2-(thiazol-2-yl)pyrimidin-4-ylamine 在 肼 作用下， 以 乙醇 为溶剂， 生成 6-Hydrazinyl-2-(1,3-thiazol-2-yl)pyrimidin-4-amine
  参考文献：
  名称：

  2-Amino-N-pyrimidin-4-ylacetamides as A_2A Receptor Antagonists: 1. Structure−Activity Relationships and Optimization of Heterocyclic Substituents

  摘要：

  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.

  DOI：

  10.1021/jm701185v
• 作为产物：
  描述：

  6-hydroxy-2-(1,3-thiazol-2-yl)pyrimidin-4-amine 在 三氯氧磷 作用下， 反应 2.0h， 以16%的产率得到6-chloro-2-(thiazol-2-yl)pyrimidin-4-ylamine
  参考文献：
  名称：

  [EN] 2, 6 BISHETEROARYL-4-AMINOPYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS
  [FR] 2, 6-BISHETEROARYL-4-AMINOPYRIMIDINES UTILISEES EN TANT QU'ANTAGONISTES DES RECEPTEURS DE L'ADENOSINE

  摘要：

  公式（I）的4-氨基嘧啶衍生物，包括其药学上可接受的盐，其中R1和R2是阿多诺苷A2A受体拮抗剂，可用于治疗帕金森病等运动障碍。

  公开号：

  WO2005058883A1

文献信息

• [EN] 4 - AMINOPYRIMIDINE DERIVATIVES AND THEIR AS AS ADENOSINE A2A RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE 4-AMINOPYRIMIDINE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DES RÉCEPTEURS DE L'ADÉNOSINE A2A
  申请人：PALOBIOFARMA SL

  公开号：WO2011121418A1

  公开（公告）日：2011-10-06

  New 4-amino-pyrimidine derivatives as potent antagonists of the adenosine A2a receptor formula (I): (I) The invention provides as well a method for preparing such compounds, pharmaceutical compositions comprising an effective amount of these compounds and the use of such compounds in the manufacture of a medicament to treat pathological affections that can be improved by antagonism of the adenosine A2a receptor.

  新的4-氨基嘧啶衍生物作为强效腺苷A2a受体拮抗剂，化学式（I）：（I）。本发明还提供一种制备这些化合物的方法，包括有效量的这些化合物的药物组合物以及利用这些化合物制造药物治疗可以通过拮抗腺苷A2a受体改善的病理情况的用途。
• 2,6 Bisheteroaryl-4-Aminopyrimidines as Adenosine Receptor Antagonists
  申请人：Crespo Crespo Maria Isabel

  公开号：US20080058356A1

  公开（公告）日：2008-03-06

  4-Aminopyrimidine derivatives of formula (I) FORMULA heteroaryl groups, including pharmaceutically acceptable salts thereof, wherein R 1 and R 2 are adenosine A 2A receptor antagonists useful in the treatment of movement disorders such as Parkinson's disease.

  公式（I）的4-氨基嘧啶衍生物，其中包括杂环基团，以及其药学上可接受的盐，其中R1和R2是阿多诺西嗪A2受体拮抗剂，适用于治疗运动障碍，如帕金森病。
• 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。
• 4-AMINOPYRIMIDINE DERIVATIVES AND THEIR AS AS ADENOSINE A2a RECEPTOR ANTAGONISTS
  申请人：Camacho Gomez Juan Alberto

  公开号：US20130053308A1

  公开（公告）日：2013-02-28

  New 4-amino-pyrimidine derivatives as potent antagonists of the adenosine Aza receptor formula (I): (I) The invention provides as well a method for preparing such compounds, pharmaceutical compositions comprising an effective amount of these compounds and the use of such compounds in the manufacture of a medicament to treat pathological affections that can be improved by antagonism of the adenosine Aza receptor.

  新的4-氨基嘧啶衍生物作为强效腺苷Aza受体拮抗剂的公式（I）：（I）。本发明还提供了一种制备这些化合物的方法，包括有效量的这些化合物的制药组合物以及使用这些化合物制造治疗可以通过拮抗腺苷Aza受体改善的病理情况的药物的用途。
• <i>N</i>-[6-Amino-2-(heteroaryl)pyrimidin-4-yl]acetamides as A_2A Receptor Antagonists with Improved Drug Like Properties and in Vivo Efficacy
  作者：Marion C. Lanier、Manisha Moorjani、Zhiyong Luo、Yongsheng Chen、Emily Lin、John E. Tellew、Xiaohu Zhang、John P. Williams、Raymond S. Gross、Sandra M. Lechner、Stacy Markison、Tanya Joswig、William Kargo、Jaime Piercey、Mark Santos、Siobhan Malany、Marilyn Zhao、Robert Petroski、María I. Crespo、José-Luis Díaz、John Saunders、Jenny Wen、Zhihong O’Brien、Kayvon Jalali、Ajay Madan、Deborah H. Slee

  DOI：10.1021/jm800908d

  日期：2009.2.12

  In the present article, we report on a strategy to improve the physical properties of a series of small molecule human adenosine 2A (hA(2A)) antagonists. One of the aromatic rings typical of this series of antagonists is replaced with a series of aliphatic groups, with the aim of disrupting crystal packing of the molecule to lower the melting point and in turn to improve the solubility. Herein, we describe the SAR of a new series of water-soluble 2,4,6-trisubstituted pyrimidines where R-1 is an aromatic heterocycle, R-2 is a short-chain alkyl amide, and the typical R-3 aromatic heterocyclic substituent is replaced with an aliphatic amino substituent. This approach significantly enhanced aqueous solubility and lowered the log P of the system to provide molecules without significant hERG or CYP liabilities and robust in vivo efficacy.