4-羟基-2-苯基嘧啶-5-甲酸乙酯 | 55613-22-4

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-羟基-2-苯基嘧啶-5-甲酸乙酯
• 中文别名: 4-羟基-2-苯基嘧啶-5-羧酸乙酯；乙基-4-羟基-2-苯基嘧啶-5-羧酸乙酯
• 英文名称: ethyl 6-oxo-2-phenyl-1,6-dihydropyrimidine-5-carboxylate
• 英文别名: ethyl 4-oxo-2-phenyl-3,4-dihydropyrimidine-5-carboxylic acid；6-oxo-2-phenyl-1,6-dihydro-pyrimidine-5-carboxylic acid ethyl ester；6-Oxo-2-phenyl-1,6-dihydro-pyrimidin-5-carbonsaeure-aethylester；ethyl 3,4-dihydro-4-oxo-2-phenylpyrimidine-5-carboxylate；ethyl 6-oxo-2-phenyl-1H-pyrimidine-5-carboxylate
• CAS: 55613-22-4
• 化学式: C₁₃H₁₂N₂O₃
• 分子量: 244.25
• InChiKey: JSIHCFJCICVJHJ-UHFFFAOYSA-N

物化性质

• 熔点：
  209-212°
• 密度：
  1.25

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  4-羟基-2-苯基嘧啶-5-甲酸乙酯 在 ammonium hydroxide 、 三氯氧磷 作用下， 反应 7.5h， 生成 6-氧代-2-苯基-1,6-二氢-嘧啶-5-甲腈
  参考文献：
  名称：

  抗过敏剂。2.2-苯基-5-（1H-四唑-5-基）嘧啶-4（3H）-一个。

  摘要：

  DOI：

  10.1021/jm00352a009
• 作为产物：
  描述：

  苯甲脒 以88%的产率得到
  参考文献：
  名称：

  JUBY P. F.; HUDYMA T. W.; BROWN M.; ESSERY J. M.; PARTYKA R. A., J. MED. CHEM., 1979, 22, NO 3, 263-269

  摘要：

  DOI：

文献信息

• FIVE-MEMBERED HETEROCYCLIC COMPOUNDS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1541564A1

  公开（公告）日：2005-06-15

  The present invention provides a compound represented by the formula: wherein R1 is an optionally substituted 5-membered heterocyclic group; X, Y and V are the same or different and each is a bond, an oxygen atom, a sulfur atom and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is -(CH2)n-Z1- or -Z1-(CH2)n- (n is an integer of 0 to 8, Z1 is a bond, an oxygen atom, a sulfur atom and the like); ring B is a nitrogen-containing heterocycle optionally further having 1 to 3 substituents; W is a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; R2 is a hydrogen atom, a cyano group, -PO(OR9)(OR10) (R9 and R10 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, and R9 and R10 are optionally bonded to form an optionally substituted ring) and the like, or a salt thereof, which has a superior adipose tissue weight decreasing action, a hypoglycemic action and a hypolipidemic action, and which is useful as an agent for the prophylaxis or treatment of obesity, diabetes mellitus, hyperlipidemia, impaired glucose tolerance, hypertension and the like.

  本发明提供了一种由以下式表示的化合物： 其中R1是可选择地取代的5-成员杂环基团；X、Y和V相同或不同，每个都是键，氧原子，硫原子等；Q是具有1到20个碳原子的二价碳氢基团；环A是一个芳香环，可选择地进一步具有1到3个取代基；Z是-(CH2)n-Z1-或-Z1-(CH2)n-（n是0到8的整数，Z1是键，氧原子，硫原子等）；环B是一个含氮杂环，可选择地进一步具有1到3个取代基；W是键或具有1到20个碳原子的二价碳氢基团；R2是氢原子，氰基，-PO(OR9)(OR10)（R9和R10相同或不同，每个是氢原子或可选择地取代的碳氢基团，R9和R10可选择地结合形成可选择地取代的环）等，或其盐，具有优越的减少脂肪组织重量的作用，降糖作用和降脂作用，并且作为预防或治疗肥胖症，糖尿病，高脂血症，糖耐量受损，高血压等的药剂是有用的。
• Substituted heterocyclic compounds and methods of use
  申请人：Andersen Lyn Denise

  公开号：US20060069110A1

  公开（公告）日：2006-03-30

  The present invention relates to pyridines, pyrimidines and derivatives thereof, and pharmaceutically acceptable salts thereof. Also included is a method of treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic β cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

  本发明涉及吡啶、嘧啶及其衍生物，以及其药用盐。还包括一种治疗炎症、类风湿关节炎、帕盖特病、骨质疏松症、多发性骨髓瘤、葡萄膜炎、急性或慢性骨髓性白血病、胰岛素β细胞破坏、骨关节炎、类风湿脊柱炎、痛风性关节炎、炎症性肠病、成人呼吸窘迫综合征（ARDS）、牛皮癣、克罗恩病、过敏性鼻炎、溃疡性结肠炎、过敏反应、接触性皮炎、哮喘、肌肉退化、虚弱、赖特氏综合征、I型糖尿病、II型糖尿病、骨吸收性疾病、移植物抗宿主反应、阿尔茨海默病、中风、心肌梗塞、缺血再灌注损伤、动脉粥样硬化、脑外伤、多发性硬化、脑疟疾、败血症、脓毒性休克、中毒性休克综合征、发热、由HIV-1、HIV-2、HIV-3、巨细胞病毒（CMV）、流感病毒、腺病毒、疱疹病毒或带状疱疹感染引起的肌肉疼痛的方法，包括向哺乳动物施用上述化合物的有效量。
• Synthesis and biological evaluation of 5-carbamoyl-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors
  作者：Taiji Goto、Akiko Shiina、Toshiharu Yoshino、Kiyoshi Mizukami、Kazuki Hirahara、Osamu Suzuki、Yoshitaka Sogawa、Tomoko Takahashi、Tsuyoshi Mikkaichi、Naoki Nakao、Mizuki Takahashi、Masashi Hasegawa、Shigeki Sasaki

  DOI：10.1016/j.bmc.2013.09.013

  日期：2013.11

  5-Carbamoyl-2-phenylpyrimidine derivative 2 has been identified as a phosphodiesterase 4 (PDE4) inhibitor with moderate PDE4B inhibitory activity (IC50 = 200 nM). Modification of the carboxylic acid moiety of 2 gave N-neopentylacetamide derivative 10f, which had high in vitro PDE4B inhibitory activity (IC50 = 8.3 nM) and in vivo efficacy against lipopolysaccharide (LPS)-induced pulmonary neutrophilia

  5-氨基甲酰基-2-苯基嘧啶衍生物2被鉴定为具有中等PDE4B抑制活性（IC 50  = 200 nM）的磷酸二酯酶4（PDE4）抑制剂。的羧酸部分的修饰2得到Ñ -neopentylacetamide衍生物10f中，其具有在体外PDE4B抑制活性高（IC 50  = 8.3纳米）和体内抗内毒素效力（LPS）诱导的中性粒细胞增多肺小鼠（ID 50  = 16毫克/千克，ip）。此外，基于与人类PDE4B催化域结合的10f的X射线晶体学，我们设计了7,8-dihydro-6 H -pyrido [4,3- d] pyrimidin-5-one衍生物39，其具有稠合的双环内酰胺支架。化合物39对小鼠脾细胞中LPS诱导的肿瘤坏死因子α（TNF-α）的产生表现出优异的抑制活性（IC 50  = 0.21 nM），对小鼠LPS诱导的肺嗜中性粒细胞具有体内抗炎活性（在时抑制41％）剂量为1.0 mg /
• 2-aryl-8-oxodihydropurine derivative, process for the producing the same, medicinal compositions containing the same, and intermediates thereof
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US06372740B1

  公开（公告）日：2002-04-16

  2-Aryl-8-oxodihydropurine derivative of the following formula (I): wherein W is H, lower alkyl, halogen, lower alkoxy, amino, mono- or di-lower alkylamino, or substituted or unsubstituted phenyl; X is H, lower alkyl, cycloalkyl-lower alkyl, substituted or unsubstituted phenyl-lower alkyl, lower alkenyl, carbamoyl, di-lower alkylcarbamoyl, or a group of the formula (Q): —CH(R3)CON(R1)(R2); Y is H, lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, lower alkenyl, substituted or unsubstituted phenyl-lower alkyl, or a group of the formula (Q): —CH(R3)CON(R1)(R2); A is substituted or unsubstituted phenyl, or substituted or unsubstituted heteroaryl; provided that when one of X and Y of the above formula (I) is the group of the formula (Q), then the other is the same groups for X or Y as described above except for the group of the formula (Q), or a pharmaceutically acceptable acid addition salt thereof. These compounds are useful for the prophylaxis or treatment of central nervous disorders such as anxiety-related diseases (neurosis, somatoform disorders, anxiety disorders, and others), depression, epilepsy, etc., or circulatory organs disorders such as angina pectoris, hypertension.

  2-芳基-8-氧代嘌呤衍生物的结构式（I）如下：其中W为H、较低烷基、卤素、较低烷氧基、氨基、单或双较低烷基氨基，或取代或未取代的苯基；X为H、较低烷基、环烷基-较低烷基、取代或未取代的苯基-较低烷基、较低烯基、氨甲酰基、双较低烷基氨甲酰基，或具有以下结构的基团（Q）：—CH(R3)CON(R1)(R2)；Y为H、较低烷基、环烷基、环烷基-较低烷基、较低烯基、取代或未取代的苯基-较低烷基，或具有以下结构的基团（Q）：—CH(R3)CON(R1)(R2)；A为取代或未取代的苯基，或取代或未取代的杂环芳基；前提是当上述结构式（I）中的X和Y中的一个为具有以下结构的基团（Q）时，另一个为与上述描述相同的X或Y的相同基团，但不包括具有以下结构的基团（Q），或其药学上可接受的酸盐。这些化合物可用于预防或治疗中枢神经系统障碍，如焦虑相关疾病（神经症、躯体形式障碍、焦虑症等）、抑郁症、癫痫等，或循环器官障碍，如心绞痛、高血压等。
• Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives
  作者：Alexandra Lopes、Eduardo Miguez、Arthur Kümmerle、Victor Rumjanek、Carlos Fraga、Eliezer Barreiro

  DOI：10.3390/molecules181011683

  日期：——

  position on the pyrimidine ring with respect to the carbonyl group, as well as the electronic effects of pyrimidine by changing it to phenyl. The conformer equilibrium was attributed to the decoplanarization of the aromatic ring and carbonyl group (generated by an ortho-alkyl group) and/or the electron withdrawing character of the pyrimidine ring. Both effects increased the rotational barrier of the C-N

  在此，我们描述了 4-甲基-2-苯基嘧啶-N-酰基腙化合物（芳基-NAH）的 NMR 实验和结构修饰，以发现其 1H- 和 13C-NMR 光谱中某些信号的重复是否与以下物质的混合物有关亚胺双键立体异构体 (E/Z) 或 CO-NH 键构象异构体（syn 和 antiperiplanar）。来自不同温度下的 NOEdiff、2D-NOESY 和 1H-NMR 光谱的 NMR 数据，以及异丙叉腙的合成揭示了 4-甲基-2-苯基嘧啶-N-酰基腙衍生物作为两种构象异构体的混合物的重复信号的性质在解决方案中。此外，我们研究了嘧啶环邻位取代基相对于羰基的立体电子影响，以及将嘧啶变为苯基的电子效应。构象异构体平衡归因于芳香环和羰基（由邻烷基产生）的去平面化和/或嘧啶环的吸电子特性。这两种效应都增加了 CN 酰胺键的旋转势垒，正如从动态 NMR 计算的 ΔG≠ 值所证实的那样。据我们所知，这是对具有两个