6-bromo-2-(chroman-3-yl)-1H-benzo[d]imidazole | 1162696-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-bromo-2-(chroman-3-yl)-1H-benzo[d]imidazole
• 英文别名: 5-bromo-2-(chroman-3-yl)-1H-benzo[d]imidazole；6-bromo-2-(3,4-dihydro-2H-chromen-3-yl)-1H-benzimidazole
• CAS: 1162696-26-5
• 化学式: C₁₆H₁₃BrN₂O
• 分子量: 329.196
• InChiKey: INUVSNUEXYNGJM-UHFFFAOYSA-N

物化性质

• 沸点：
  555.7±45.0 °C(predicted)
• 密度：
  1.543±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-2-(chroman-3-yl)-1H-benzo[d]imidazole 、 2-氨基-4-氯嘧啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 联硼酸频那醇酯 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 生成 4-(2-(chroman-3-yl)-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine
  参考文献：
  名称：

  The development of benzimidazoles as selective rho kinase inhibitors

  摘要：

  Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC50 < 10 nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.124
• 作为产物：
  描述：

  N-(2-amino-4-bromophenyl)-3,4-dihydro-2H-chromene-3-carboxamide 在 溶剂黄146 作用下， 生成 6-bromo-2-(chroman-3-yl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Benzimidazole- and benzoxazole-based inhibitors of Rho kinase

  摘要：

  Inhibitors of Rho kinase have been developed based on two distinct scaffolds, benzimidazoles, and benzoxazoles. SAR studies and efforts to optimize the initial lead compounds are described. Novel selective inhibitors of ROCK-II with excellent potency in both enzyme and cell-based assays were obtained. These inhibitors possess good microsomal stability, low cytochrome P-450 inhibitions and good oral bioavailability. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.095

文献信息

• NEW COMPOUNDS AND THEIR USE AS THERAPEUTICALLY ACTIVE SUBSTANCES IN THE TREATMENT AND/OR PREVENTION OF DISEASES INVOLVING THE RETINAL PIGMENT EPITHELIUM
  申请人：ENDOGENA THERAPEUTICS, INC.

  公开号：US20220110921A1

  公开（公告）日：2022-04-14

  A method of treating and/or preventing disease wherein retinal pigment epithelium, including administering compound of formula (I) or pharmaceutically acceptable salt, racemic mixture, corresponding enantiomer or, if applicable, corresponding diastereomer, wherein: X is either NH or O, R 11 , R 12 and R 13 are independently selected from consisting hydrogen group, fluoro, chloro, trifluoromethyl, methyl and difluoromethoxy, A is selected from consisting residue group of formula (II)-(VII) or (VIII) “*” denotes point of attachment to molecule remainder, and R 2 , R 3 , R 4 , R 5 , R 2 I , R 3 I , R 4 I , R 5 I , R 2 II , R 3 II , R 4 II , R 5 II , R 2 III , R 3 III , R 4 III , R 5 III , R 2 IV , R 3 IV , R 4 IV , R 5 IV , R 2 V , R 3 V , R 4 V , R 5 V , R 2 VI , R 3 VI , R 4 VI and R 5 VI are independently selected from hydrogen consisting group, linear or branched alkyl having 1-3 carbon atoms, fluoro, chloro, bromo, methoxy, ethoxy, propoxy, trifluoromethyl, 2,2,2-trifluoroethyl and difluoromethoxy and R 6 is selected from hydrogen consisting group, linear or branched alkyl having 1-3 carbon atoms, trifluoromethyl, and 2,2,2-trifluoroethyl.

  一种治疗和/或预防疾病的方法，其中包括给予式（I）化合物或药学上可接受的盐、外消旋体混合物、对映体或相应的对映异构体的视网膜色素上皮，其中：X为NH或O，R11、R12和R13独立地选择自氢原子、氟、氯、三氟甲基、甲基和二氟甲氧基的群；A从由式（II）-（VII）或（VIII）的残基群中选择；“*”表示附加到分子残基的点，而R2、R3、R4、R5、R2I、R3I、R4I、R5I、R2II、R3II、R4II、R5II、R2III、R3III、R4III、R5III、R2IV、R3IV、R4IV、R5IV、R2V、R3V、R4V、R5V、R2VI、R3VI、R4VI和R5VI独立地选择自氢原子、线性或支链烷基，其中碳原子数为1-3，氟、氯、溴、甲氧基、乙氧基、丙氧基、三氟甲基、2,2,2-三氟乙基和二氟甲氧基，而R6从氢原子、线性或支链烷基，其中碳原子数为1-3，三氟甲基和2,2,2-三氟乙基中选择。
• BENZIMIDAZOLES AND ANALOGS AS RHO KINASE INHIBITORS
  申请人：Feng Yangbo

  公开号：US20110052562A1

  公开（公告）日：2011-03-03

  Compounds useful as Rho kinase inhibitors according to formula IA or IB: wherein A, B, D, E, R 1 , R 2 and Ar 1 are as defined herein, and any tautomer, salt, stereoisomer, hydrate, solvent, or prodrug thereof, pharmaceutical compositions, methods of treatment, and synthetic methods are provided.

  提供公式IA或IB所示的有用的Rho激酶抑制剂化合物：其中A、B、D、E、R1、R2和Ar1的定义如本文所述，并提供任何互变异构体、盐、立体异构体、水合物、溶剂或前药，以及制药组合物、治疗方法和合成方法。
• [EN] BENZIMIDAZOLES AND ANALOGS AS RHO KINASE INHIBITORS<br/>[FR] BENZIMIDAZOLES ET ANALOGUES COMME INHIBITEURS DE LA RHO-KINASE
  申请人：FENG YANGBO

  公开号：WO2009079011A1

  公开（公告）日：2009-06-25

  Compounds useful as Rho kinase inhibitors according to formula IA or IB: wherein A, B, D, E, R1, R2 and Ar1 are as defined herein, and any tautomer, salt, stereoisomer, hydrate, solvent, or prodrug thereof, pharmaceutical compositions, methods of treatment, and synthetic methods are provided.
• The development of benzimidazoles as selective rho kinase inhibitors
  作者：E. Hampton Sessions、Michael Smolinski、Bo Wang、Bozena Frackowiak、Sarwat Chowdhury、Yan Yin、Yen Ting Chen、Claudia Ruiz、Li Lin、Jennifer Pocas、Thomas Schröter、Michael D. Cameron、Philip LoGrasso、Yangbo Feng、Thomas D. Bannister

  DOI：10.1016/j.bmcl.2010.01.124

  日期：2010.3

  Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC50 < 10 nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA). (C) 2010 Elsevier Ltd. All rights reserved.
• Benzimidazole- and benzoxazole-based inhibitors of Rho kinase
  作者：E. Hampton Sessions、Yan Yin、Thomas D. Bannister、Amiee Weiser、Evelyn Griffin、Jennifer Pocas、Michael D. Cameron、Claudia Ruiz、Li Lin、Stephan C. Schürer、Thomas Schröter、Philip LoGrasso、Yangbo Feng

  DOI：10.1016/j.bmcl.2008.10.095

  日期：2008.12

  Inhibitors of Rho kinase have been developed based on two distinct scaffolds, benzimidazoles, and benzoxazoles. SAR studies and efforts to optimize the initial lead compounds are described. Novel selective inhibitors of ROCK-II with excellent potency in both enzyme and cell-based assays were obtained. These inhibitors possess good microsomal stability, low cytochrome P-450 inhibitions and good oral bioavailability. (C) 2008 Elsevier Ltd. All rights reserved.