A solid-phase synthetic route to substituted 7-azabenzimidazoles suitable for combinatorial library synthesis

Farrant, Elizabeth; Rahman, Shahzad S.

doi:10.1016/s0040-4039(00)00859-5

Cited by 16 publications

(13 citation statements)

References 7 publications

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“…Upon the aromatic nitro reduction, o ‐phenylendiamine on the solid support was subjected to the on‐resin cyclocondensation that is performed with variety of commercially available aldehydes in DMF. Initial conditions for the cyclocondensation included DDQ reagent (compounds 1–4 ), but later it was not used in the synthesis as it has been reported that overnight exposure to the air is enough to catalyze the oxidative cyclocondensation (56,72–74). Upon completion of the ligand synthesis, final cleavage and side chain deprotection was achieved using TFA.…”

Section: Discussionmentioning

confidence: 99%

Structure–Activity Relationships of Melanocortin Agonists Containing the Benzimidazole Scaffold

et al. 2007

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The melanocortin system has been implicated in regulating various physiological processes including pigmentation, energy homeostasis, obesity, steroidogenesis cardiovascular, and exocrine gland function. The five melanocortin receptors that belong to the super family of G protein-coupled receptors are stimulated by naturally occurring agonists. The aim of this research was focused on the design, synthesis, and pharmacological characterization of melanocortin ligands that contain the 1,2,5-trisubstituted benzimidazole scaffold. A series of benzimidazole analogues, with three points of diversity at positions 1, 2, and 5, were designed, synthesized, pharmacologically assayed at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R and resulted in ligands possessing a range of agonist activity from nm to no stimulation at up to 100 microM concentrations. This study demonstrates that the benzimidazole structure template can be appended with key melanocortin agonist amino acids for the design melanocortin receptor agonist ligands.

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Section: Discussionmentioning

confidence: 99%

Structure–Activity Relationships of Melanocortin Agonists Containing the Benzimidazole Scaffold

et al. 2007

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“…Recently, methods for the use of solid-phase to obtain imidazopyridines have been described. A novel route for the solid-phase synthesis of 1,2,5-substituted 7-azabenzimidazole derivatives has been developed by Farrant et al ( Scheme 28 ) [ 105 ]. In this method primary amines are attached to an aldehyde resin then coupled to 6-chloro-5-nitro-nicotinyl chloride.…”

Section: Synthetic Routes To Imidazo[45- B ]Pymentioning

confidence: 99%

Pharmacological Potential and Synthetic Approaches of Imidazo[4,5-b]pyridine and Imidazo[4,5-c]pyridine Derivatives

2017

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The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The discovery of their first bioactivity as GABAA receptor positive allosteric modulators divulged their medicinal potential. Proton pump inhibitors, aromatase inhibitors, and NSAIDs were also found in this chemical group. Imidazopyridines have the ability to influence many cellular pathways necessary for the proper functioning of cancerous cells, pathogens, components of the immune system, enzymes involved in carbohydrate metabolism, etc. The collective results of biochemical and biophysical properties foregrounded their medicinal significance in central nervous system, digestive system, cancer, inflammation, etc. In recent years, new preparative methods for the synthesis of imidazopyridines using various catalysts have been described. The present manuscript to the best of our knowledge is the complete compilation on the synthesis and medicinal aspects of imidazo[4,5-b]pyridines and imidazo[4,5-c]pyridines reported from the year 2000 to date, including structure–activity relationships.

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“…15 Prior to synthesis, the resin bound amines were prepared by reductive amination of primary amine monomers onto formyl resin (4-formyl-3-methoxyphenoxy resin). 16 These were then treated with an Pr 2 NEt to give the 4-amino-derivatives. The second chloride was displaced with piperazine.…”

Section: P Y R I M I D I N E Smentioning

confidence: 99%

“…In a similar fashion to the purine template, the resin bound amines were prepared by reductive amination of primary amine monomers onto a formyl resin prior to synthesis. 16 These resin-bound amines were then treated with an excess of dichloropurine in NMP at 80 C in the presence of i Pr 2 NEt to displace the chloro-group at the 6-position. The second chloride was displaced by a primary amine using higher temperatures as this is not as activated as the 6-position chloride.…”

Section: P Y R I M I D I N E Smentioning

confidence: 99%

Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets

Lai¹,

Langston²,

Adams³

et al. 2005

Med. Res. Rev.

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This work describes the preparation of approximately 13,000 compounds for rapid identification of hits in high-throughput screening (HTS). These compounds were designed as potential serine/threonine or tyrosine kinase inhibitors. The library consists of various scaffolds, e.g., purines, oxindoles, and imidazoles, whereby each core scaffold generally includes the hydrogen bond acceptor/donor properties known to be important for kinase binding. Several of these are based upon literature kinase templates, or adaptations of them to provide novelty. The routes to their preparation are outlined. A variety of automation techniques were used to prepare >500 compounds per scaffold. Where applicable, scavenger resins were employed to remove excess reagents and when necessary, preparative high performance liquid chromatography (HPLC) was used for purification. These compounds were screened against an 'in-house' kinase panel. The success rate in HTS was significantly higher than the corporate compound collection.

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A solid-phase synthetic route to substituted 7-azabenzimidazoles suitable for combinatorial library synthesis

Cited by 16 publications

References 7 publications

Structure–Activity Relationships of Melanocortin Agonists Containing the Benzimidazole Scaffold

Structure–Activity Relationships of Melanocortin Agonists Containing the Benzimidazole Scaffold

Pharmacological Potential and Synthetic Approaches of Imidazo[4,5-b]pyridine and Imidazo[4,5-c]pyridine Derivatives

Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets

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