7-Hydroxy-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-thiazolo[4,5-d]pyrimidine-2-thione | 246166-37-0

• 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: 7-Hydroxy-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-thiazolo[4,5-d]pyrimidine-2-thione
• 英文别名: 3-mesityl-5-methyl-2-thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-one
• CAS: 246166-37-0
• 化学式: C₁₅H₁₅N₃OS₂
• 分子量: 317.436
• InChiKey: OXBMYBPFZXMGEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.74
• 重原子数：
  21.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  50.68
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  7-Hydroxy-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-thiazolo[4,5-d]pyrimidine-2-thione 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 sodium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 、 三氯氧磷 作用下， 反应 2.0h， 生成 N⁴-butyl-N⁴-ethyl-N⁶-mesityl-2-methyl-5-(methylthio)pyrimidine-4,6-diamine
  参考文献：
  名称：

  Synthesis of substituted pyrimidines as corticotropin releasing factor (CRF) receptor ligands

  摘要：

  Corticotropin releasing factor (CRF) is a neuropeptide hormone produced from the hypothalamus that controls the secretion of corticotropin (ACTH) from the anterior pituitary gland that, in turn, prompts the adrenal glands to secrete glucocorticoids. This involvement in the hypothalamic-pituitary-adrenal axis (HPA) in response to stress and also playing a key role in behavioral, cardiovascular, immune and gastrointestinal systems made CRF binding to its receptors an important target in drug discovery aiming to develop lead compounds with the potential to treat various stress-related disorders including depression, anxiety and addictive disorders. Several non-peptide CRF1 receptor antagonists were developed by pharmaceutical companies and are currently in clinical trials with the aim of improving the health consequences of chronic stress and for use in the clinical management of anxiety and stress. Many showed promising results not only in treatment of anxiety and depression but also in treatment of CRF-induced hypertension, as well as in treatment of arthritis, irritable bowel syndrome and peptic ulcers. In this manuscript, we describe the synthesis of substituted pyrimidines with close structural similarities to reported lead compounds with promising CRF1 receptor affinities and carrying groups known to be associated with optimum affinity to CRF1 receptors. The affinity of the newly prepared compounds in comparison to antalarmin, a potent CRF1 receptor antagonist in clinical trials as a standard, is also described. Four compounds from the new series showed promising CRF1 receptor affinity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.040
• 作为产物：
  描述：

  N-mesitylthioformamide 在 sulfur 作用下， 生成 7-Hydroxy-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-thiazolo[4,5-d]pyrimidine-2-thione
  参考文献：
  名称：

  合成2-亚氨基和2-肼基噻唑并[4,5- d ]嘧啶类药物作为促肾上腺皮质激素释放因子（CRF）拮抗剂

  摘要：

  促肾上腺皮质激素释放因子（CRF）是一种重要的神经肽激素，它控制人体对压力的整体反应。它在调节行为，心血管，免疫和胃肠系统中起着至关重要的作用。CRF系统的过度激活与许多疾病有关，包括焦虑症，抑郁症，药物成瘾，高血压，肠易激综合症（IBS），消化性溃疡，炎症等。因此，CRF与其受体的结合是开发用于治疗与慢性应激有关的疾病的新药物的有吸引力的靶标。已开发出许多小分子非肽CRF受体拮抗剂，许多处于临床试验的不同阶段。许多人在治疗焦虑症，抑郁症，消化性溃疡，炎症，IBS和药物成瘾方面显示出巨大希望。在我们最近的先前工作中，描述了两个系列的嘧啶和融合的嘧啶CRF拮抗剂的开发。为了继续朝这个方向努力，在本手稿中，描述了第三系列CRF受体拮抗剂的合成。选择化合物对CRF（CRF）1型受体的结合亲和力确定1 R）并与标准CRF拮抗剂药物antalarmin进行比较。鉴定了先导化合物，并通过测量其对激动剂

  DOI：

  10.1016/j.ejmech.2017.07.016

文献信息

• Thiazolo[4,5-d]pyrimidine thiones and -ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists
  作者：James P. Beck、Matt A. Curry、Robert J. Chorvat、Larry W. Fitzgerald、Paul J. Gilligan、Robert Zaczek、George L. Trainor

  DOI：10.1016/s0960-894x(99)00159-6

  日期：1999.4

  A series of thiazolo[4,5-d]pyrimidine thiones and -ones was prepared and discovered to have good binding affinity to the CRH-R1 receptor, thus showing promise as a new class of potential anxiolytics and/or antidepressants. (C) 1999 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.