2-(6-methoxychroman-3-yl)-6-(1H-pyrazol-4-yl)quinazolin-4(3H)-one | 1227360-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-(6-methoxychroman-3-yl)-6-(1H-pyrazol-4-yl)quinazolin-4(3H)-one
• 英文别名: 2-(6-methoxy-3,4-dihydro-2H-chromen-3-yl)-6-(1H-pyrazol-4-yl)-3H-quinazolin-4-one
• CAS: 1227360-23-7
• 化学式: C₂₁H₁₈N₄O₃
• 分子量: 374.399
• InChiKey: QLPMSDMAJQBZGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  88.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  卡普他明 、 2-(6-methoxychroman-3-yl)-6-(1H-pyrazol-4-yl)quinazolin-4(3H)-one 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2-(2-(6-methoxychroman-3-yl)-6-(1H-pyrazol-4-yl)quinazolin-4-ylthio)-N,N-dimethylethanamine
  参考文献：
  名称：

  Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors

  摘要：

  Rho kinase ( ROCK) is an attractive therapeutic target for various diseases including glaucoma, hypertension, and spinal cord injury. Herein, we report the development of a series of ROCK-II inhibitors based on 4-quinazolinone and quinazoline scaffolds. SAR studies at three positions of the quinazoline core led to the identification of analogs with high potency against ROCK-II and good selectivity over protein kinase A (PKA). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.039
• 作为产物：
  描述：

  4-吡唑硼酸频哪醇酯 、 N-(4-bromo-2-carbamoylphenyl)-6-methoxychromane-3-carboxamide 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 1.0h， 生成 2-(6-methoxychroman-3-yl)-6-(1H-pyrazol-4-yl)quinazolin-4(3H)-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors

  摘要：

  Rho kinase ( ROCK) is an attractive therapeutic target for various diseases including glaucoma, hypertension, and spinal cord injury. Herein, we report the development of a series of ROCK-II inhibitors based on 4-quinazolinone and quinazoline scaffolds. SAR studies at three positions of the quinazoline core led to the identification of analogs with high potency against ROCK-II and good selectivity over protein kinase A (PKA). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.039

文献信息

• [EN] QUINAZOLINE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE QUINAZOLINE EN TANT QU'INHIBITEURS DE KINASE
  申请人：FENG YANGBO

  公开号：WO2010056758A1

  公开（公告）日：2010-05-20

  The invention is directed to quinazoline compounds that can inhibit the bioactivity of one or more kinase enzymes, including a Rho kinase, an AKT kinase, a p70S6K kinase, a LIM kinase, an IKK kinase, a Fit kinase, an Aurora kinase, or a Src kinase, or any combination thereof; to methods of use of those compounds; and to methods of preparation of those compounds. The inventive compounds can be used in the treatment of malconditions including cardiovascular disease, neurogenic pain, hypertension, atherosclerosis, angina, stroke, arterial obstruction, peripheral arterial disease, erectile dysfunction, acute and chronic pain, dementia, Alzheimer's disease, Parkinson's disease, neuronal degeneration, asthma, amyotrophic lateral sclerosis, spinal cord injury, rheumatoid arthritis, osteoarthritis, osteoporosis, psoriasis, cerebral vasospasm, open angle glaucoma, multiple sclerosis, pulmonary hypertension, acute respiratory distress syndrome, inflammation, diabetes, urinary organ diseases and benign prostatic hypertrophy (BPH), metastasis, cancer, glaucoma, ocular hypertension, retinopathy, autoimmune disease, viral infection, or myocardial pathology.

  这项发明涉及能够抑制一个或多个激酶酶的生物活性的喹唑啉化合物，包括Rho激酶、AKT激酶、p70S6K激酶、LIM激酶、IKK激酶、Fit激酶、Aurora激酶或Src激酶，或其任意组合；这些化合物的使用方法；以及这些化合物的制备方法。这些创新化合物可用于治疗包括心血管疾病、神经性疼痛、高血压、动脉粥样硬化、心绞痛、中风、动脉阻塞、周围动脉疾病、勃起功能障碍、急性和慢性疼痛、痴呆症、阿尔茨海默病、帕金森病、神经元退化、哮喘、肌萎缩侧索硬化、脊髓损伤、类风湿性关节炎、骨关节炎、骨质疏松症、银屑病、脑血管痉挛、开角型青光眼、多发性硬化、肺动脉高压、急性呼吸窘迫综合征、炎症、糖尿病、泌尿器官疾病和良性前列腺增生（BPH）、转移、癌症、青光眼、眼压增高、视网膜病变、自身免疫疾病、病毒感染或心肌病理的恶性疾病的治疗。
• Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors
  作者：Xingang Fang、Yen Ting Chen、E. Hampton Sessions、Sarwat Chowdhury、Tomas Vojkovsky、Yan Yin、Jennifer R. Pocas、Wayne Grant、Thomas Schröter、Li Lin、Claudia Ruiz、Michael D. Cameron、Philip LoGrasso、Thomas D. Bannister、Yangbo Feng

  DOI：10.1016/j.bmcl.2011.01.039

  日期：2011.3

  Rho kinase ( ROCK) is an attractive therapeutic target for various diseases including glaucoma, hypertension, and spinal cord injury. Herein, we report the development of a series of ROCK-II inhibitors based on 4-quinazolinone and quinazoline scaffolds. SAR studies at three positions of the quinazoline core led to the identification of analogs with high potency against ROCK-II and good selectivity over protein kinase A (PKA). (C) 2011 Elsevier Ltd. All rights reserved.