ethyl 2-(2-oxo-3H-benzimidazol-1-yl)acetate | 27265-99-2

• 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: ethyl 2-(2-oxo-3H-benzimidazol-1-yl)acetate
• 英文别名: 2-Oxo-1-benzimidazolineacetic acid ethyl ester
• CAS: 27265-99-2
• 化学式: C₁₁H₁₂N₂O₃
• 分子量: 220.228
• InChiKey: CRGRDUPSCKCIBT-UHFFFAOYSA-N

物化性质

• 密度：
  1.249±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 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：

  ethyl 2-(2-oxo-3H-benzimidazol-1-yl)acetate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 以90 %的产率得到(9ci)-2,3-二氢-2-氧代-1H-苯并咪唑-1-乙酸
  参考文献：
  名称：

  PYRIDO-PYRAZOLES AS INHIBITORS OF DDR'S FOR THE TREATMENT OF FIBROTIC DISORDERS AND CANCER

  摘要：

  This invention relates to novel compounds and pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as inhibitors of discoidin domain receptor 1 (DDR1) and discoidin domain receptor 2 (DDR2). The compounds are particularly useful in the treatment of cancer and fibrotic diseases.5

  公开号：

  WO2024042316A1
• 作为产物：
  描述：

  Ethyl 2-[2-oxo-3-(prop-1-en-2-yl)-1,3-benzodiazol-1-yl]acetate 在 硫酸 作用下， 生成 ethyl 2-(2-oxo-3H-benzimidazol-1-yl)acetate
  参考文献：
  名称：

  Benzimidazoles as NMDA Glycine-Site Antagonists: Study on the Structural Requirements in 2-Position of the Ligand

  摘要：

  A series of different substituted benzimidazole derivatives has been synthesized and evaluated for the ability to displace [3H]MDL-105,519 to rat cortical membranes. Two benzimidazole-2-carboxylic acids 9 b and 9 c, in this substitution pattern not yet described as glycine antagonists, showed IC50 values of 0.89 microM (9 b) and 38.0 microM (9 c). Replacement of the carboxylate function in 2-position by a sulfonic acid moiety appreciably increased solubility, but decreased the affinity giving evidence for the strong need of the carboxylate group within the ligand. Further structure-activity studies using benzimidazole-2-one derivatives with an acetic acid moiety adjacent to a ring nitrogen revealed new insights into the importance of amide functionalities within the heterocycle for the affinity of antagonist glycine-site ligands.

  DOI：

  10.1002/(sici)1521-4184(20005)333:5<123::aid-ardp123>3.0.co;2-5

文献信息

• [EN] IL4I1 INHIBITORS AND METHODS OF USE<br/>[FR] INHIBITEURS D'IL4I1 ET PROCÉDÉS D'UTILISATION
  申请人：MERCK SHARP & DOHME

  公开号：WO2021226003A1

  公开（公告）日：2021-11-11

  Described herein are compounds of Formula I or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as IL4I1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for IL4I1-related diseases.

  本文描述了化合物I的结构或其药用盐。化合物I作为IL4I1抑制剂，可用于预防、治疗或作为IL4I1相关疾病的治疗剂。
• 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。
• Renin inhibitory peptides
  申请人：BEECHAM GROUP PLC

  公开号：EP0350163A2

  公开（公告）日：1990-01-10

  Compounds of formula (I), and pharmaceutically acceptable salts thereof: wherein Z₁, Z₂, Z₃ and the carbon atoms to which Z₁ and Z₃ are attached, form a 5-membered non-aromatic heterocyclic ring; E is absent or is (CH₂)n or CH(CH₂)n-1 wherein n is 1 to 4; A is -CONH-, -NHCO-, -COO-, -S(O)r- wherein r is 0, 1 or 2, or -CH₂-; p is 0, 1 or 2; q is 0 or 1; Rz is hydrogen, C₁₋₆ alkyl or, when A is -CH₂-, hydroxy; Ra and Rb are independently selected from hydrogen or a substituent; R₁ is CH₂R₉ wherein R₉ is optionally substituted aryl or heteroaryl; R₂ is CHR₁₀R₁₁ wherein R₁₀ is hydrogen or methyl and R₁₁ is C₁₋₆ alkyl, C₃₋₈ cycloalkyl, optionally substituted aryl or heteroaryl, or R₁₁ is amino, C₂₋₇ alkanoylamino, 2-oxopyrrolidinyl, 2-oxopiperidinyl or C₁₋₆ alkoxycarbonylamino; R₃ is CH₂R₁₂ wherein R₁₂ is C₁₋₆ alkyl or C₃₋₈ cycloalkyl; R₄ is C₁₋₆ alkyl or C₃₋₈ cycloalkyl; and the dashed line represents an optional bond (when E is present); which are renin inhibitors, useful in the treatment of hypertension.

  式 (I) 的化合物及其药学上可接受的盐类： 其中 Z₁、Z₂、Z₃ 和连接 Z₁ 和 Z₃ 的碳原子形成 5 元非芳杂环； E 不存在或为 (CH₂)n 或 CH(CH₂)n-1，其中 n 为 1 至 4； A 是-CONH-、-NHCO-、-COO-、-S(O)r-（其中 r 是 0、1 或 2）或-CH₂-； p 是 0、1 或 2 q 是 0 或 1； Rz 是氢、C₁₋₆烷基或（当 A 是-CH₂-时）羟基； Ra 和 Rb 分别独立地选自氢或取代基； R₁ 是 CH₂R₉，其中 R₉ 是任选取代的芳基或杂芳基； R₂ 是 CHR₁₀R₁₁ 其中 R₁₀ 是氢或甲基，R₁₁ 是 C₁₋₆ 烷基、C₃₋₈ 环烷基、任选取代的芳基或杂芳基、或 R₁₁ 是氨基、C₂₋₇ 烷酰氨基、2-氧代吡咯烷基、2-氧代哌啶基或 C₁₋₆ 烷氧羰基氨基； R₃ 是 CH₂R₁₂，其中 R₁₂ 是 C₁₋₆ 烷基或 C₃₋₈ 环烷基； R₄ 是 C₁₋₆ 烷基或 C₃₋₈ 环烷基；以及 虚线代表任选键（当 E 存在时）；它们是肾素抑制剂，可用于治疗高血压。
• 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.