1-acetyl-3-(3,4-dichloro-α-methylbenzyl)oxindole | 114727-56-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-acetyl-3-(3,4-dichloro-α-methylbenzyl)oxindole
• 英文别名: 1-acetyl-3-[1-(3,4-dichlorophenyl)ethyl]-3H-indol-2-one
• CAS: 114727-56-9
• 化学式: C₁₈H₁₅Cl₂NO₂
• 分子量: 348.229
• InChiKey: IZAJPRSPEPQLAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-acetyl-3-(3,4-dichloro-α-methylbenzyl)oxindole 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 sodium hydride 、 溶剂黄146 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 22.5h， 生成 {3-[1-(3,4-Dichloro-phenyl)-ethyl]-3-methyl-2-oxo-2,3-dihydro-indol-1-yl}-acetic acid
  参考文献：
  名称：

  Synthesis and aldose reductase inhibitory activity of substituted 2(1H)-benzimidazolone- and oxindole-1-acetic acids

  摘要：

  Potent in vitro inhibition of the enzyme aldose reductase (AR) was observed with several members of a series of 3-alkylated 2(1H)-benzimidazolone-1-acetic acids, as well as with analogs from a structurally-related series of oxindole-1-acetic acids with 3-alkyl or 3-alkylidene substituents. Intrinsic activity against AR was, in general, greatest in compounds from the second series, especially with analogs which contain alkylidene side chains, with typical IC50 values of less-than-or-equal-to 1 muM. However, in a streptozotocin-diabetic rat model, the best compounds from either series failed to prevent sorbitol accumulation in lens or sciatic nerve to the degree observed with AR inhibitors such as ponalrestat or zopolrestat.

  DOI：

  10.1016/0223-5234(92)90112-e
• 作为产物：
  描述：

  3,4-二氯苯乙酮 在 palladium on activated charcoal 四氢吡咯 、 氢气 作用下， 以 甲醇 、 乙醇 、 乙酸乙酯 为溶剂， 反应 9.25h， 生成 1-acetyl-3-(3,4-dichloro-α-methylbenzyl)oxindole
  参考文献：
  名称：

  Synthesis and aldose reductase inhibitory activity of substituted 2(1H)-benzimidazolone- and oxindole-1-acetic acids

  摘要：

  Potent in vitro inhibition of the enzyme aldose reductase (AR) was observed with several members of a series of 3-alkylated 2(1H)-benzimidazolone-1-acetic acids, as well as with analogs from a structurally-related series of oxindole-1-acetic acids with 3-alkyl or 3-alkylidene substituents. Intrinsic activity against AR was, in general, greatest in compounds from the second series, especially with analogs which contain alkylidene side chains, with typical IC50 values of less-than-or-equal-to 1 muM. However, in a streptozotocin-diabetic rat model, the best compounds from either series failed to prevent sorbitol accumulation in lens or sciatic nerve to the degree observed with AR inhibitors such as ponalrestat or zopolrestat.

  DOI：

  10.1016/0223-5234(92)90112-e

文献信息

• Indolinone derivatives
  申请人：PFIZER INC.

  公开号：EP0252713A1

  公开（公告）日：1988-01-13

  A series of novel 3-mono(substituted methyl)- and 3,3-di(substituted methyl)-2-oxo-indoline-1-alkanoic acid compounds have been prepared, including their lower alkyl esters and unsubstituted amide derivatives, as well as the base salts of said acids with pharm­acologically acceptable cations. These compounds are useful in therapy as aldose reductase inhibitors for the control of certain chronic diabetic complications. Typical members include those compounds derived from 2-oxo-indoline-1-acetic acid wherein a 3,4-dichloro­benzyl or 3,4-dichloro-α-methylbenzyl moiety is substituted at 3-position of the molecule. Preferred member compounds include 3-(3,4-dichlorobenzyl)-2-oxo-­indoline-1-acetic acid, 5-chloro-3-(3,4-dichloro­benzyl)-2-oxo-indoline-1-acetic acid, 3-(3,4-dichloro­benzyl)-6-methoxy-2-oxo-indoline-1-acetic acid, 3-(3,4-dichlorobenzyl)-6-hydroxy-2-oxo-indoline-1-­acetic acid and 3-(3,4-dichloro-α-methylbenzyl)-2-­oxo-indoline-1-acetic acid. Methods for preparing these compounds from known starting materials are provided.

  我们制备了一系列新型 3-单（取代甲基）-和 3,3-二（取代甲基）-2-氧代吲哚啉-1-烷酸化合物，包括它们的低级烷基酯和未取代的酰胺衍生物，以及上述酸与药理学上可接受的阳离子的碱式盐。这些化合物可作为醛糖还原酶抑制剂用于治疗，以控制某些慢性糖尿病并发症。典型的成员包括由 2-氧代吲哚啉-1-乙酸衍生的化合物，其中 3,4-二氯苄基或 3,4-二氯-α-甲基苄基在分子的 3 位被取代。优选的成员化合物包括 3-(3,4-二氯苄基)-2-氧代吲哚啉-1-乙酸、5-氯-3-(3,4-二氯苄基)-2-氧代吲哚啉-1-乙酸、3-(3、3-(3,4-二氯苄基)-6-甲氧基-2-氧代-吲哚啉-1-乙酸、3-(3,4-二氯苄基)-6-羟基-2-氧代-吲哚啉-1-乙酸和 3-(3,4-二氯-α-甲基苄基)-2-氧代-吲哚啉-1-乙酸。提供了用已知起始原料制备这些化合物的方法。
• US4960785A
  申请人：——

  公开号：US4960785A

  公开（公告）日：1990-10-02
• US5064852A
  申请人：——

  公开号：US5064852A

  公开（公告）日：1991-11-12
• Synthesis and aldose reductase inhibitory activity of substituted 2(1H)-benzimidazolone- and oxindole-1-acetic acids
  作者：HR Howard、R Sarges、TW Siegel、TA Beyer

  DOI：10.1016/0223-5234(92)90112-e

  日期：1992.11

  Potent in vitro inhibition of the enzyme aldose reductase (AR) was observed with several members of a series of 3-alkylated 2(1H)-benzimidazolone-1-acetic acids, as well as with analogs from a structurally-related series of oxindole-1-acetic acids with 3-alkyl or 3-alkylidene substituents. Intrinsic activity against AR was, in general, greatest in compounds from the second series, especially with analogs which contain alkylidene side chains, with typical IC50 values of less-than-or-equal-to 1 muM. However, in a streptozotocin-diabetic rat model, the best compounds from either series failed to prevent sorbitol accumulation in lens or sciatic nerve to the degree observed with AR inhibitors such as ponalrestat or zopolrestat.