4-[(5-bromo-2-naphthalenyl)methyl]-1,2-dihydro-5-(trifluoromethyl)-3H-pyrazole-3-one | 148135-14-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-[(5-bromo-2-naphthalenyl)methyl]-1,2-dihydro-5-(trifluoromethyl)-3H-pyrazole-3-one
• 英文别名: 4-[(5-bromonaphthalen-2-yl)methyl]-5-(trifluoromethyl)-1,2-dihydropyrazol-3-one
• CAS: 148135-14-2
• 化学式: C₁₅H₁₀BrF₃N₂O
• 分子量: 371.156
• InChiKey: VQFKRACRWUYEAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(5-Bromo-naphthalen-2-ylmethyl)-4,4,4-trifluoro-3-oxo-butyric acid ethyl ester 在 肼 作用下， 以 乙二醇二甲醚 为溶剂， 以5%的产率得到4-[(5-bromo-2-naphthalenyl)methyl]-1,2-dihydro-5-(trifluoromethyl)-3H-pyrazole-3-one
  参考文献：
  名称：

  Studies on New Acidic Azoles as Glucose-Lowering Agents in Obese, Diabetic db/db Mice

  摘要：

  Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles isoxazol-3- and -5-ones and a pyrazol-3-one, showed significant plasma glucose-lowering activity (17-42% reduction) in genetically obese, diabetic db/db mice at a dose of 100 mg/kg/day x 4. Structure-activity relationship studies determined that 5-alkyl-4-(arylmethyl)pyrazol-3-ones, which exist in solution as aromatic enol/iminol tautomers, were the most promising new class of potential antidiabetic agent (32-45% reduction at 20 mg/kg/d x 4). Included in this work are convenient syntheses for several types of acidic azoles that may find use as new acidic bioisosteres in medicinal chemistry such as the antidiabetic lead 5-(trifluoromethyl)pyrazol-3-one (hydroxy tautomer) and aza homologs of the pyrazolones, 1,2,3-triazol-5-ones (hydroxy tautomer) and 1,2,3,4-tetrazol-5-one heterocycles. log P and pK(a) data for 15 potential acidic bioisosteres, all appended to a 2-naphthalenylmethyl residue so as to maintain a similar distance between the acidic hydrogen and arene nucleus, are presented. This new data set allows comparison of a wide variety of potential acid mimetics (pK(a) 3.78-10.66; log P -0.21 to 2.76) for future drug design.

  DOI：

  10.1021/jm00004a008

文献信息

• 4-arylmethyl-5-alkyl-3H-pyrazol-3-ones and hypoglycemic use
  申请人：American Home Products Corporation

  公开号：US05183825A1

  公开（公告）日：1993-02-02

  The compounds of the formula: ##STR1## in which the dotted lines represent optional unsaturation when X is CR.sup.5, Y is CR.sup.6 or X or Y are N; R.sup.1 is hydrogen, alkyl, aryl or arylalkyl; R.sup.2 is hydrogen, alkyl, aryl or arylalkyl; R.sup.3 is alkyl, perfluoromethyl or alkoxy; R.sup.4 is halogen, alkyl or alkoxy; X is CR.sup.5, O, S or N, in which R.sup.5 is hydrogen, halogen, alkyl, or alkoxy; Y is CR.sup.6, O, S or N, in which R.sup.6 is hydrogen, halogen, alkyl or alkoxy; n is one of the integers 0, 1 or 2; m is one of the integers 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof, are useful hypoglycemic agents in the treatment of non-insulin dependent diabetes mellitus.

  该化合物的化学式为：##STR1## 其中虚线代表当X为CR.sup.5时可选的不饱和度，Y为CR.sup.6或X或Y为N；R.sup.1为氢、烷基、芳基或芳基烷基；R.sup.2为氢、烷基、芳基或芳基烷基；R.sup.3为烷基、全氟甲基或烷氧基；R.sup.4为卤素、烷基或烷氧基；X为CR.sup.5、O、S或N，其中R.sup.5为氢、卤素、烷基或烷氧基；Y为CR.sup.6、O、S或N，其中R.sup.6为氢、卤素、烷基或烷氧基；n为0、1或2中的一个整数；m为0、1、2或3中的一个整数；或其药用可接受的盐，在治疗非胰岛素依赖性糖尿病中是有用的降糖药物。
• US5183825A
  申请人：——

  公开号：US5183825A

  公开（公告）日：1993-02-02