7-methoxy-2-phenyl-3H-benzimidazole-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 7-methoxy-2-phenyl-3H-benzimidazole-4-carboxylic acid
• 英文别名: 7-methoxy-2-phenyl-1H-benzoimidazole-4-carboxylic acid；7-methoxy-2-phenyl-1H-benzimidazole-4-carboxylic acid
• 化学式: C₁₅H₁₂N₂O₃
• 分子量: 268.272
• InChiKey: KBBQBUFJJAMRPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  苯胺 、 7-methoxy-2-phenyl-3H-benzimidazole-4-carboxylic acid 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  Design and synthesis of 7-hydroxy-1H-benzoimidazole derivatives as novel inhibitors of glycogen synthase kinase-3β

  摘要：

  A hydroxy functional group was introduced as the hydrogen bond donor and acceptor at the hinge region of protein kinase in order to develop novel ATP-competitive inhibitors. Several derivatives of 7-hydroxyl-1H-benzoimidazole were designed as inhibitors of glycogen synthase kinase-3 beta with the help of ab initio calculations and a docking study. Enzymatic assay and an X-ray complex study showed that these designed compounds were highly potent ATP-competitive inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.056
• 作为产物：
  描述：

  methyl 7-methoxy-2-phenyl-3H-benzimidazole-4-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 生成 7-methoxy-2-phenyl-3H-benzimidazole-4-carboxylic acid
  参考文献：
  名称：

  Design and synthesis of 7-hydroxy-1H-benzoimidazole derivatives as novel inhibitors of glycogen synthase kinase-3β

  摘要：

  A hydroxy functional group was introduced as the hydrogen bond donor and acceptor at the hinge region of protein kinase in order to develop novel ATP-competitive inhibitors. Several derivatives of 7-hydroxyl-1H-benzoimidazole were designed as inhibitors of glycogen synthase kinase-3 beta with the help of ab initio calculations and a docking study. Enzymatic assay and an X-ray complex study showed that these designed compounds were highly potent ATP-competitive inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.056

文献信息

• [EN] 7-HYDROXY-BENZOIMIDAZOLE-4-YL-METHANONE DERIVATIVES AND PBK INHIBITORS CONTAINING THE SAME<br/>[FR] DÉRIVÉS DE 7-HYDROXY-BENZO-IMIDAZOLE-4-YL-MÉTHANONE ET INHIBITEURS DE PBK LES CONTENANT
  申请人：ONCOTHERAPY SCIENCE INC

  公开号：WO2010051085A1

  公开（公告）日：2010-05-06

  7-Hydroxy-benzoimidazole-4-yl-methanone Derivatives, which are useful for PBK inhibitors, are provided.

  7-羟基苯并咪唑-4-基甲酮衍生物，用于PBK抑制剂。
• [EN] GLYCOGEN SYNTHASE KINASE 3BETA INHIBITOR, COMPOSITION AND PROCESS FOR THE PREPARATION THEREOF<br/>[FR] INHIBITEUR DE GLYCOGENE SYNTHASE KINASE 3 DOLLAR G(B), COMPOSITION ET PROCEDE DE PREPARATION ASSOCIE
  申请人：CRYSTALGENOMICS INC

  公开号：WO2004065370A1

  公开（公告）日：2004-08-05

  Novel compounds having hydroxybenzoimidazole carboxylic amide are useful for inhibiting glycogen synthase kinase 3β (GSK-3β).

  具有羟基苯并咪唑羧酰胺的新化合物对抑制糖原合成酶激酶3β（GSK-3β）具有用处。
• [EN] SUBSTITUTED AZABICYLIC COMPOUNDS AND THEIR USE AS INHIBITORS OF THE PRODUCTION OF TNF AND CYCLIC AMP PHOSPHODIESTERASE<br/>[FR] COMPOSES AZABICYCLIQUES SUBSTITUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA PRODUCTION DE TNF ET DE LA PHOTODIESTERASE CYCLIQUE D'AMP
  申请人：RHONE-POULENC RORER LIMITED

  公开号：WO1997048697A1

  公开（公告）日：1997-12-24

  (EN) This invention is directed to physiologically active compounds of formula (I) wherein (i) represents a bicyclic ring system, of about 10 to about 13 ring members, in which the ring (ii) is an azaheterocycle, and the ring (iii) represents an azaheteroaryl ring, or an optionally halo substituted benzene ring; wherein R1-R3, A1, Z1, m and n are as defined herein. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.(FR) L'invention concerne des composés efficaces sur le plan physiologique représentés par la formule (I), dans laquelle (i) représente un système de noyaux bicyclique comportant de 10 à 13 éléments, dans lequel le noyau (ii) représente un azahétérocycle et le noyau (iii) représente un noyau azahétéroaryle, ou le noyau de benzène éventuellement substitué par halo; R1, R3, A1, Z1, m et n sont tels qu'ils sont définis dans le descriptif. Ces compositions inhibent la production ou les effets physiologiques de TNF, ainsi que la phosphodiestérase cyclique d'AMP. L'invention concerne également des compositions pharmaceutiques contenant ces composés représentés par la formule (I), leur utilisation pharmaceutique et leurs procédés de préparation.

  该发明涉及具有以下式子(I)的生理活性化合物，其中(i)代表一个具有大约10到13个环成员的双环环系统，在该环(ii)为一个氮杂环，环(iii)代表一个氮杂芳基环或可选地卤代苯环；其中R1-R3，A1，Z1，m和n如本文所定义。这些化合物抑制TNF的产生或生理效应，并抑制环磷酸腺苷酶。该发明还涉及包含式(I)化合物的制药组合物，它们的制药用途以及制备它们的方法。
• Substituted azabicyclic compounds
  申请人：——

  公开号：US20020173527A1

  公开（公告）日：2002-11-21

  This invention is directed to physiologically active compounds of formula (I) 1 wherein 2 represents a bicyclic ring, system, of 9 ring members, in which the ring 3 is an oxazole, and the ring 4 is a benzene ring; R 1 represents hydrogen or a straight- or branched-chain alkyl group of 1 to about 4 carbon atoms, optionally substituted by hydroxy or one or more halogen atoms, or when Z 1 represents a direct bond R 1 may also represent a lower alkenyl or lower alkynyl group, or a formyl group; R 2 represents hydrogen, alkenyl, alkoxy, alkyl, alkylsulphinyl, alkylsulphonyl, alkylthio, aryl, arylalkyloxy, arylalkylsulphinyl, arylalkylsulphonyl, arylalkylthio, aryloxy, arylsulphinyl, arylsulphonyl, arylthio, cyano, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, hydroxy, —SO 2 NR 4 R 5 , —NR 4 SO 2 R 5 , —NR 4 R 5 , —C(═O)R 5 , —C(═O)C(═O)R 5 , —C(═O)NR 4 R 5 , —C(═O)OR 5 , —O(C═O)NR 4 R 5 , or —NR 4 C(═O)R 5 ; R 3 represents —C(═Z)—N(R 7 )R 6 ; A 1 represents a straight or branched C 1-6 alkylene chain optionally substituted by hydroxyl, alkoxy, oxo, cycloalkyl, aryl or heteroaryl; Z 1 represents a direct bond, an oxygen or sulphur atom or NH; n is zero; and mis 1; and N-oxides thereof, and their prodrugs, and pharmaceutically acceptable salts and solvates of the compounds of formula (I) and N-oxides thereof, and their prodrugs. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.

  本发明涉及公式（I）的生理活性化合物，其中2表示一个由9个环成的双环环系统，在该环3中为噁唑环，环4为苯环; R1表示氢或1至约4个碳原子的直链或支链烷基，可选地被羟基或一个或多个卤素原子取代，或当Z1表示直接键时，R1也可以表示低烯基或低炔基或甲酰基; R2表示氢、烯基、烷氧基、烷基、烷基磺酰基、烷基磺酰基、烷基硫基、芳基、芳基烷氧基、芳基烷基磺酰基、芳基烷基磺酰基、芳基烷基硫基、芳氧基、芳基磺酰基、芳基磺酰基、芳基硫基、氰基、环烯基、环烯基氧基、环烷基、环烷基氧基、羟基、-SO2NR4R5、-NR4SO2R5、-NR4R5、-C(═O)R5、-C(═O)C(═O)R5、-C(═O)NR4R5、-C(═O)OR5、-O(C═O)NR4R5或-NR4C(═O)R5; R3表示-C(═Z)-N(R7)R6; A1表示一条直链或支链C1-6烷基链，可选地被羟基、烷氧基、氧代、环烷基、芳基或杂环芳基取代; Z1表示直接键、氧原子或硫原子或NH; n为零; m为1;及其N-氧化物，以及公式（I）化合物和其N-氧化物的前药体，以及它们的制药可接受的盐和溶剂。这些化合物抑制TNF的产生或生理效应，并抑制环磷酸腺苷磷酸二酯酶。本发明还涉及包括公式（I）化合物的制药组合物，其制药用途和制备方法。
• Glycogen synthase kinase 3beta inhibitor, composition and process for the preparation thereof
  申请人：Cho Myung Joong

  公开号：US20060079521A1

  公开（公告）日：2006-04-13

  Novel compounds having hydroxybenzoimidazole carboxylic amide are useful for inhibiting glycogen synthase kinase 3β (GSK-3β).

  含有羟基苯并咪唑羧酰胺的新化合物可用于抑制糖原合酶激酶3β (GSK-3β)。