Ethyl-α-(2-naphthalenylmethyl)-butyrylacetate | 148135-21-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: Ethyl-α-(2-naphthalenylmethyl)-butyrylacetate
• 英文别名: Ethyl-alpha-(2-naphthalenylmethyl)-butyrylacetate；ethyl 2-(naphthalen-2-ylmethyl)-3-oxohexanoate
• CAS: 148135-21-1
• 化学式: C₁₉H₂₂O₃
• 分子量: 298.382
• InChiKey: RKPHDPDGPHOXRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Ethyl-α-(2-naphthalenylmethyl)-butyrylacetate 在 盐酸 、 sodium hydroxide 、 盐酸羟胺 作用下， 生成 4-Naphthalen-2-ylmethyl-5-propyl-isoxazol-3-ol
  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
• 作为产物：
  描述：

  丁酰乙酸乙酯 、 2-溴甲基萘 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 Ethyl-α-(2-naphthalenylmethyl)-butyrylacetate
  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.

  式子为：##STR1## 其中点线表示当X为CR.sup.5，Y为CR.sup.6或X或Y为N时，可选的不饱和度; 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是0、1或2之一的整数; m是0、1、2或3之一的整数; 或其药学上可接受的盐，在非胰岛素依赖性糖尿病的治疗中是有用的降血糖药物。
• US5183825A
  申请人：——

  公开号：US5183825A

  公开（公告）日：1993-02-02
• Studies on New Acidic Azoles as Glucose-Lowering Agents in Obese, Diabetic db/db Mice
  作者：Kenneth L. Kees、Thomas J. Caggiano、Kurt E. Steiner、John J. Fitzgerald、Michael J. Kates、Thomas E. Christos、John M. Kulishoff、Robin D. Moore、Michael L. McCaleb

  DOI：10.1021/jm00004a008

  日期：1995.2

  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.