4-amino-3-(2-bromo-4-isopropylphenyl)-2-thioxo-2,3-dihydrothiazole-5-carboxamide | 228254-23-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-amino-3-(2-bromo-4-isopropylphenyl)-2-thioxo-2,3-dihydrothiazole-5-carboxamide
• CAS: 228254-23-7
• 化学式: C₁₃H₁₄BrN₃OS₂
• 分子量: 372.31
• InChiKey: GDBJXNDNPBVBMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  74.04
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-amino-3-(2-bromo-4-isopropylphenyl)-2-thioxo-2,3-dihydrothiazole-5-carboxamide 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-(2-bromo-4-isopropylphenyl)-2-methyl-5-(methylthio)-N⁶,N⁶-dipropylpyrimidine-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：

  2-溴-4-异丙基苯胺 在 sodium carbonate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.33h， 生成 4-amino-3-(2-bromo-4-isopropylphenyl)-2-thioxo-2,3-dihydrothiazole-5-carboxamide
  参考文献：
  名称：

  Thiazolo[4,5-d]pyrimidine thiones and -ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(99)00159-6

文献信息

• Design, Synthesis, and Biological Evaluations of Novel Thiazolo[4,5-d]pyrimidine Corticotropin Releasing Factor (CRF) Receptor Antagonists as Potential Treatments for Stress Related Disorders and Congenital Adrenal Hyperplasia (CAH)
  作者：Md Rabiul Islam、Christos Markatos、Ioannis Pirmettis、Minas Papadopoulos、Vlasios Karageorgos、George Liapakis、Hesham Fahmy

  DOI：10.3390/molecules29153647

  日期：——

  with CRF receptor binding may be of value to treat neuropsychiatric stress-related disorders. Also, CRF1R antagonists have recently emerged as potential treatment options for congenital adrenal hyperplasia. Previously, several series of CRF1 receptor antagonists were developed by our group. In continuation of our efforts in this direction, herein we report the synthesis and biological evaluation of a new

  促肾上腺皮质激素释放因子（CRF）是下丘脑分泌的一种关键神经肽激素。它是 HPA 轴的主要激素，协调对压力的生理和行为反应。许多疾病，包括焦虑、抑郁、成瘾复发等，都与该系统的过度激活有关。因此，可能干扰 CRF 受体结合的新分子可能对治疗神经精神应激相关疾病有价值。此外，CRF1R 拮抗剂最近已成为先天性肾上腺增生症的潜在治疗选择。此前，我们课题组已开发了多个系列的CRF1受体拮抗剂。为了继续我们在这个方向上的努力，我们在此报告了一系列新的 CRF1R 拮抗剂的合成和生物学评价。与安塔拉明相比，评估了代表性化合物的结合亲和力。四种化合物（2、5、20 和 21）的 log IC50 值分别为 -8.22、-7.95、-8.04 和 -7.88，而安塔拉明的 log IC50 值为 -7.78。该结果表明这四种化合物分别优于antalarmin 2.5、1.4、1.7和1.25倍。值得一提的