5-(bromomethyl)-4-isopropyl-1-methyl-2-phenyl-1H-pyrazol-3(2H)-one | 53616-28-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(bromomethyl)-4-isopropyl-1-methyl-2-phenyl-1H-pyrazol-3(2H)-one
• 英文别名: 3-Bromomethyl-4-isopropyl-2-methyl-1-phenyl-3-pyrazolin-5-on；3-Brommethyl-4-isopropyl-2-methyl-1-phenyl-3-pyrazolin-5-on；3-bromomethyl propyphenazone；3-bromomethylpropyphenazone；5-bromomethyl-4-isopropyl-1-methyl-2-phenyl-1,2-dihydro-pyrazol-3-one；5-(Bromomethyl)-4-isopropyl-1-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one；5-(bromomethyl)-1-methyl-2-phenyl-4-propan-2-ylpyrazol-3-one
• CAS: 53616-28-7
• 化学式: C₁₄H₁₇BrN₂O
• 分子量: 309.206
• InChiKey: XBESMQIHFLWKGS-UHFFFAOYSA-N

物化性质

• 沸点：
  360.8±44.0 °C(Predicted)
• 密度：
  1.361±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(bromomethyl)-4-isopropyl-1-methyl-2-phenyl-1H-pyrazol-3(2H)-one 在 4-二甲氨基吡啶 、 水 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Biological and metabolic study of naproxen–propyphenazone mutual prodrug

  摘要：

  Naproxen-propyphenazone (NAP-PP) esters were synthesized as prodrugs with the aim of improving the therapeutic index through prevention of gastrointestinal irritation and bleeding. The structures of the synthesized NAP-PP hybrid esters were confirmed by IR and H-1 NMR spectroscopy and their purity was established by elemental analysis, HPLC and TLC. The release of NAP as well as PP derivatives. from the ester prodrugs was studied. A validated analytical HPLC method for the estimation of the NAP, and the prodrugs was developed, Also the enzymatic hydrolysis products of the ester were identified by GC-MS and in conjugation with HPLC. The kinetics of ester hydrolysis was studied in two different non-enzymatic buffer solutions, at pH 1.2, and 7.4 as well as in liver homogenates. Study of analgesic and anti-inflammatory properties in comparison with the reference compounds has shown that both analgesic and anti-inflammatory activities were present at the same doses of the investigated compounds, The ester III was found to be less irritating to gastric mucosal membrane than the parent drugs. These results suggest that the synthesized prodrugs are characterized by better therapeutic index than the parent drugs. (C) 2002 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0928-0987(02)00159-8
• 作为产物：
  描述：

  异丙安替比林 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以87.86%的产率得到5-(bromomethyl)-4-isopropyl-1-methyl-2-phenyl-1H-pyrazol-3(2H)-one
  参考文献：
  名称：

  N-（2,3-二甲苯基邻氨基苯甲酸）潜在的新型互药的合成，表征，体外水解和药效学特征

  摘要：

  在目前的研究工作中，我们报告了甲芬那酸（MA）和1,2二氢-1,5-二甲基-4-（1-甲基乙基）-2-苯基吡唑的新互药的合成，体外水解研究和药理学评价-3-一种旨在提高治疗效力并延缓胃肠源性不良反应的药物。合成的互酯前药（MP1和MP2）的结构通过IR，1 H NMR，13确认。通过TLC确认13 C NMR，质谱及其形成。通过元素分析确定了合成化合物的纯度。用乙酸诱导的扭体法测试标题化合物的镇痛活性。通过角叉菜胶诱导的大鼠爪水肿方法和致溃疡性测试抗炎活性。对镇痛活性的研究表明，与母体药物MA（61.10％）相比，前药（MP1和MP2）均显示出乙酸产生的扭体反应显着降低（81.67，63.90％）。与母体药物MA（53.14％）相比，两种互用前药均显示出更好的最大抗炎作用（71.43，85.71％），并且具有更长的时间。还发现合成的前药比母体药物对胃粘膜的刺激​​性小得多。在pH 1.2的模拟胃液（SGF）和pH

  DOI：

  10.1007/s00044-013-0516-5

文献信息

• New pyrazolones as 11b-HSD1 inhibitors for diabetes
  申请人：Amrein Kurt

  公开号：US20070049574A1

  公开（公告）日：2007-03-01

  Compounds of formula as well as pharmaceutically acceptable salts and esters thereof, wherein R 1 to R 4 have the significance given in claim 1 can be used in the form of pharmaceutical compositions.

  公式化合物以及医药可接受的它们的盐和酯，其中R1至R4的意义如权利要求1中所给出，可以用作药物组合物。
• Gastric ulcerogenic and biological activities of N-3'a-propyphenazonyl-2-acetoxybenzamide.
  作者：SHIGERU AONUMA、YASUHIRO KOHAMA、YUTAKA KOMIYAMA、SHIGEKO FUJIMOTO

  DOI：10.1248/cpb.28.1237

  日期：——

  A new derivative of aspirin, N-3'a-propyphenazonyl-2-acetoxybenzamide (aspirin-isopropylantipyrine, AIA) was synthesized, and its gastric ulcerogenic and biological activities were investigated together with those of related compounds. AIA (100, 200 mg/kg, p. o., i. p.) showed much less gastric ulcerogenic activity than aspirin in pylorus-ligated rats. The effect of AIA on the stomach was also weaker than those of salicylate-IA (SIA), salicyloyl leucine (SL), salicyloyl methionine (SM) and IA. AIA (200 mg/kg, p. o.) did not injure the stomachs of adjuvant arthritis rats given the drug daily for 21 days, unlike aspirin. However, AIA (100 mg/kg, i. p.) did not improve the gastric ulcerations induced by pylorus ligation, histamine, acetic acid and stress in rats. AIA showed analgetic activity (100, 200 mg/kg, s. c.) in the acetic acid method and the D'Amour-Smith method in mice, antipyretic activity (100 mg/kg, s. c.) in rats treated with E. coli, inhibitory activity (100 mg/kg, s. c.) on carrageenin edema formation in rats and inhibitory activity (200 mg/kg/day×21, p. o.) on adjuvant arthritis in rats. SL (100 mg/kg, s.c.) showed analgetic and antipyretic activities, while SIA (100 mg/kg, s. c.) showed only analgetic activity, and SM (100 mg/kg, s. c.) did not show any activity. These compounds were inactive on carrageenin edema formation, unlike AIA and aspirin. AIA (10-4g/ml) inhibited the contraction of isolated ileum preparations stimulated by histamine, anetyl-choline and barium chloride, but had no effect on anaphylactic shock of the ileum sensitized by egg albumin, AIA had no effect on increased vascular permeability in mice, rabbit blood pressure and the beating of perfused frog heart. The acute toxicity of AIA in mice was much less than that of aspirin, as shown by the LD50 values which were more than 5g/kg p.o., s.c. and 3.68 g/kg i.p. for AIA.

  合成了一种阿司匹林新衍生物N－3”－丙酰苯腙基－2－乙酰氧基苯甲酰胺（阿司匹林异丙基安替比林，AIA）。AIA和一些相关化合物的致胃溃疡作用及其生物活性也进行了研究。在幽门结扎大鼠，AIA（100，200mg／kg，灌胃和腹腔注射）的致胃溃疡作用比阿司匹林小得多。AIA对胃的作用也比水杨酸－异丙基安替比林（SIA），水杨酰亮氨酸（SL），水杨酰蛋氨酸（SM）和异丙基安替比林（IA）的作用弱。在佐剂型关节炎大鼠，AIA（200mg／kg，口饲）每日给药21天不引起胃损伤，阿司匹林则引起损伤。然而与阿司匹林不同，AIA（100mg／kg，腹腔注射）对幽门结扎，组胺，醋酸和应激引起的胃溃疡无治疗作用。AIA在醋酸扭体法及D’Amour－Smith小鼠热板法有镇痛作用（100，200mg／kg，皮下注射），在大肠杆菌所致发热大鼠有解热作用（100mg／kg，皮下注射），抑制大鼠卡拉胶足肿胀（100mg／kg，皮下注射）和佐剂病（200mg／kg／天×21，口饲）。SL（100mg／kg，皮下注射）有镇痛和解热作用，SI（100mg／kg，皮下注射）仅显示镇痛作用，而SM（100mg／kg，皮下注射）无任何作用。与AIA和阿司匹林不同，这些化合物对卡拉胶所致大鼠足肿胀无抑制作用。AIA（10￣4g／ml）对于离体组织胺，乙酰胆碱和氯化钡刺激的回肠制备显示抑制收缩作用，但对用卵白蛋白致敏的回肠的过敏性休克无抑制作用，AIA对小鼠和免的增加血管通透性，兔血压和离体蛙心收缩无作用。从LD50值比较，AIA急性毒性远小于阿司匹林，AIA的LD50值大于5g／kg，灌胃皮下注射和3.68g／kg，腹腔注射。
• Stabilitätsuntersuchungen an Phenylethylaminsubstituierten Pyrazolonen
  作者：Gerhard Rücker、Robert Mrongovius、Michael Neugebauer

  DOI：10.1002/ardp.19823151005

  日期：——

  Morazon (5a) und Famprofazon (7a) wurden weitere Pyrazolonderivate synthetisiert, die an C‐4 bzw. C‐3 über eine Methylenbrücke mit psychostimulierenden Phenylethylaminderivaten verknüpft sind. Stabilitätsuntersuchungen in‐vitro zeigten bei den C‐4 substituierten Pyrazolonen A eine Abhängigkeit der Zersetzungsgeschwindigkeit von der Basizität der Amine. Die C‐3 substituierten Verbindungen B sind in vitro

  从镇痛物质莫拉宗 (5a) 和氨丙磺脲 (7a) 开始，进一步合成了吡唑啉酮衍生物，这些衍生物通过亚甲基桥在 C-4 和 C-3 处与刺激精神的苯乙胺衍生物相连。体外稳定性研究表明，C-4 取代的吡唑啉酮 A 的分解速率取决于胺的碱度。C-3 取代的化合物 B 在体外比 C-4 取代的化合物更稳定。
• Pyrazolone Compounds As Metabotropic Glutamate Receptor Agonists For The Treatment Of Neurological And Psychiatric Disorders
  申请人：Balestra Michael

  公开号：US20090069340A1

  公开（公告）日：2009-03-12

  Compounds of Formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, and n are as defined for Formula (I) in the description, processes for the preparation of the compounds and new intermediates employed in the preparation, pharmaceutical compositions containing the compounds, and the use of the compounds in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction.

  公式（I）的化合物，其中R1，R2，R3，R4，R5，R6，X和n的定义如描述中的公式（I），制备该化合物的过程以及用于制备的新中间体，含有该化合物的制药组合物以及在治疗或预防与谷氨酸功能障碍有关的神经系统和精神障碍中使用该化合物。
• Pyrazolones as 11b-HSD1 inhibitors for diabetes
  申请人：Hoffman-La Roche Inc.

  公开号：US07652057B2

  公开（公告）日：2010-01-26

  Compounds of formula as well as pharmaceutically acceptable salts and esters thereof, wherein R1 to R4 have the significance given in claim 1 can be used in the form of pharmaceutical compositions.

  公式为的化合物及其药学上可接受的盐和酯，其中R1到R4具有权利要求1中所给出的意义，可以用作制药组合物的形式。