5,6-dichloro-2-oxo-1-benzimidazolineacetate | 75389-52-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5,6-dichloro-2-oxo-1-benzimidazolineacetate
• 英文别名: 5,6-dichloro-2-oxo-1-benzimidazolineacetic acid ethyl ester；ethyl 2-(5,6-dichloro-2-oxo-3H-benzimidazol-1-yl)acetate
• CAS: 75389-52-5
• 化学式: C₁₁H₁₀Cl₂N₂O₃
• 分子量: 289.118
• InChiKey: UMCKWKSYQXPKHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,6-dichloro-2-oxo-1-benzimidazolineacetate 在 sodium hydroxide 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 1.25h， 生成 3-(3,4-dichlorobenzyl)-5,6-dichloro-2-oxo-1-benzimidazolineacetic 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：

  4,5-二氯邻苯二胺 在 sodium ethanolate 作用下， 以 xylene 为溶剂， 反应 6.5h， 生成 5,6-dichloro-2-oxo-1-benzimidazolineacetate
  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

• Benzimidazolone derivatives
  申请人：Pfizer Inc.

  公开号：US04209527A1

  公开（公告）日：1980-06-24

  A series of novel 3-(substituted methyl)-2-oxo-1-benzimidazolinalkanoic acid compounds has 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 particular 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-1-benzimidazoline-acetic acid wherein a benzyl moiety is substituted at the 3-position of the molecule. Methods for preparing these compounds from known starting materials are provided.

  已经制备了一系列新颖的3-(取代甲基)-2-氧代-1-苯并咪唑烷羧酸化合物，包括它们的较低烷基酯和未取代酰胺衍生物，以及所述酸的碱盐与药理学上可接受的阳离子。这些特定化合物在治疗中作为醛糖还原酶抑制剂对某些慢性糖尿病并发症的控制是有用的。典型成员包括从2-氧代-1-苯并咪唑烷乙酸衍生的化合物，其中苯甲基基团取代于分子的3位。提供了从已知起始材料制备这些化合物的方法。
• Benzimidazolone derivatives, process for their preparation and pharmaceutical compositions containing them
  申请人：PFIZER INC.

  公开号：EP0019440A1

  公开（公告）日：1980-11-26

  A series of novel 3-(substituted methyl)-2-oxo-1-benzimidazolinalkanoic acids of the formula: and the lower alkyl esters and unsubstituted amide derivatives thereof, and the base salts of said acids with pharmacologically acceptable cations, wherein X is hydrogen and X' is hydrogen, fluorine, chlorine, bromine, lower alkyl or lower alkoxy; or X and X', when taken separately, are each chlorine, lower alkyl or lower alkoxy, and when taken together are -QCH2(CH2)nO- wherein n is zero or one; Y is alkylene having from one to three carbon atoms arranged in a straight or branched chain; and Z is naphthylmethyl, furfuryl, thenyl, phenylalkyl having up to three carbon atoms in the alkyl moiety or benzoylmethyl, said phenylalkyl and benzoylmethyl being optionally mono or di-substituted in the phenyl ring by fluorine, chlorine, bromine, trifluoromethyl, lower alkyl or lower alkoxy, or when two different substituents are present by chlorine, methyl, methoxy or trifluoromethyl. These particular compounds are useful in therapy as aldose reductase inhibitorsforthe control of certain chronic diabetic complications. Typical members include those compounds derived from 2-oxo-1-benzimidazolineacetic acid wherein a benzyl moiety is substituted at the 3-position of the molecule. Methods for preparing these compounds from known starting materials are provided.

  一系列新型 3-(取代甲基)-2-氧代-1-苯并咪唑啉烷酸，其式如下 及其低级烷基酯和未取代的酰胺衍生物，以及上述酸与药学上可接受的阳离子的碱式盐，其中 X 是氢，X'是氢、氟、氯、溴、低级烷基或低级烷氧基；或 X 和 X'，当分开时，各自是氯、低级烷基或低级烷氧基，当合在一起时，是-QCH2(CH2)nO-，其中 n 是零或一；Y 是具有一至三个碳原子的直链或支链亚烷基；Z 是萘甲基、糠基、然后基、烷基中最多有三个碳原子的苯基烷基或苯甲酰甲基，所述苯基烷基和苯甲酰甲基在苯基环上可选择被氟、氯、溴、三氟甲基、低级烷基或低级烷氧基单取代或二取代，或者当存在两个不同的取代基时被氯、甲基、甲氧基或三氟甲基取代。这些特殊化合物可作为醛糖还原酶抑制剂用于控制某些慢性糖尿病并发症的治疗。典型的成员包括由 2-氧代-1-苯并咪唑啉乙酸衍生的化合物，其中苄基在分子的 3 位被取代。提供了从已知起始原料制备这些化合物的方法。
• US4209527A
  申请人：——

  公开号：US4209527A

  公开（公告）日：1980-06-24
• 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.