4-chloro-2-cyclohexylquinazoline | 284486-58-4

• 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: 4-chloro-2-cyclohexylquinazoline
• 英文别名: 2-cyclohexyl-4-chloroquinazoline
• CAS: 284486-58-4
• 化学式: C₁₄H₁₅ClN₂
• 分子量: 246.739
• InChiKey: ZMCCPGKJLTWKNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  苯胺 、 4-chloro-2-cyclohexylquinazoline 以 四氢呋喃 为溶剂， 反应 17.0h， 以70%的产率得到(2-Cyclohexyl-quinazolin-4-yl)-phenyl-amine
  参考文献：
  名称：

  Discovery of Potent Cyclic GMP Phosphodiesterase Inhibitors. 2-Pyridyl- and 2-Imidazolylquinazolines Possessing Cyclic GMP Phosphodiesterase and Thromboxane Synthesis Inhibitory Activities

  摘要：

  Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2-phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP-PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3-pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.

  DOI：

  10.1021/jm00018a014
• 作为产物：
  描述：

  2-(cyclohexylcarbonylamino)benzamide 在 sodium methylate 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 36.5h， 生成 4-chloro-2-cyclohexylquinazoline
  参考文献：
  名称：

  Discovery of Potent Cyclic GMP Phosphodiesterase Inhibitors. 2-Pyridyl- and 2-Imidazolylquinazolines Possessing Cyclic GMP Phosphodiesterase and Thromboxane Synthesis Inhibitory Activities

  摘要：

  Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2-phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP-PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3-pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.

  DOI：

  10.1021/jm00018a014

文献信息

• A Facile and Versatile Route to 2-Substituted-4(3H)-Quinazolinones and Quinazolines
  作者：David J. Connolly、Patrick J. Guiry

  DOI：10.1055/s-2001-18080

  日期：——

  A range of 2-aryl and 2-alkyl quinazolinones have been prepared in moderate to good yields from the reaction of anthranilic acid and the appropriately substituted imidate in a facile, mild, one-pot procedure. Subsequent reaction with phosphorus oxychloride afforded the corresponding 4-chloro-2-substituted quinazolines, which are useful synthetic intermediates, in good to high yields. Product isolation was facilitated by the development of work up procedures for both reactions that did not include purification by column chromatography.

  通过简单、温和的一锅式反应，我们从蚁酸和适当取代的亚胺酯反应中制备出了一系列 2-芳基和 2-烷基喹唑啉酮，收率从中等到良好。随后与氧氯化磷反应，可以得到相应的 4-氯-2-取代喹唑啉类化合物，它们是有用的合成中间体，收率从好到高。为这两个反应开发的工作程序不包括柱层析纯化，从而促进了产品的分离。
• Novel Palladium-Free Synthesis of a Key Quinazolinap Precursor
  作者：Patrick Guiry、Ludovic Milhau

  DOI：10.1055/s-0030-1259507

  日期：2011.2

  A novel, short synthetic route has been successfully developed for a key precursor of Quinazolinap ligands. The key step is a Friedel-Crafts-type reaction between 2-naphthol and 4-chloroquinazoline, with moderate to quantitative yields recorded. A variation of this reaction allows for the introduction of an amine group on the naphthalene unit.

  针对喹唑啉配体的一种关键前体，我们成功开发出了一种新颖的短合成路线。关键步骤是 2-萘酚和 4-氯喹唑啉之间的 Friedel-Crafts 型反应，可获得中等至定量的产率。该反应的一个变体可以在萘单元上引入一个胺基。
• Fused ring heteroaryl and heterocyclic compounds which inhibit leukocyte adhesion mediated by VLA-4
  申请人：Elan Pharmaceuticals, Inc.

  公开号：US06545003B1

  公开（公告）日：2003-04-08

  Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

  揭示了能够结合VLA-4的化合物。其中某些化合物还能抑制白细胞粘附，特别是通过VLA-4介导的白细胞粘附。这些化合物在治疗哺乳动物患者（例如人类）的炎症性疾病方面非常有用，如哮喘、阿尔茨海默病、动脉粥样硬化、艾滋病痴呆、糖尿病、炎症性肠病、类风湿关节炎、组织移植、肿瘤转移和心肌缺血。这些化合物还可以用于治疗炎症性脑部疾病，如多发性硬化症。
• Metal- and photosensitizer-free cross-dehydrogenative coupling through photoinduced energy transfer
  作者：Bo Liu、Qiong Wang、Bin Cheng、Taimin Wang、Hongze Liao、Hou-Wen Lin

  DOI：10.1039/d3gc03983h

  日期：——

  photosensitizer-free cross-dehydrogenative coupling (CDC) systems to promote the cleavage of strong C(sp3)–H bonds through a distinct non-photoredox engaged hydrogen atom transfer (HAT) process. Mechanistic experiments indicate that this reaction predominantly proceeds through an energy transfer mechanism from excited-state heteroarenes to peroxides, with the direct irradiation of peroxides serving as a supplementary

  我们开发了不含金属和光敏剂的交叉脱氢偶联（CDC）系统，通过独特的非光氧化还原参与氢原子转移（HAT）过程促进强C（sp 3 ）–H键的裂解。机理实验表明，该反应主要通过从激发态杂芳烃到过氧化物的能量转移机制进行，过氧化物的直接照射作为促进O-O键均裂的补充和次要途径。生成的氧自由基从底物 C-H 键发生 HAT，然后将所得烷基加成到杂芳烃上，促进关键 C-C 键的形成。通过对一系列过氧化物的筛选，得出过苯甲酸叔丁酯（TBPB）和杂芳烃是最佳能量传递对的结论。除了效率和步骤经济性之外，这种方法还具有环境优势，使其适合药物和类药物分子的后期功能化，同时容纳广泛的官能团。
• FUSED RING HETEROARYL AND HETEROCYCLIC COMPOUNDS WHICH INHIBIT LEUKOCYTE ADHESION MEDIATED BY VLA-4
  申请人：Elan Pharmaceuticals, Inc.

  公开号：EP1147091A2

  公开（公告）日：2001-10-24