Discovery of pyrimidine benzimidazoles as Lck inhibitors: Part I

Potent and Selective Aminopyrimidine-Based B-Raf Inhibitors with Favorable Physicochemical and Pharmacokinetic Properties

“…This led us to the design of urea-linked pyrimidine scaffolds that are geometrically held in place via an intramolecular hydrogen bond (Figure ). A similar pseudoring approach has been employed by others to replace a bicyclic core framework (e.g., pyrido[2,3- d ]pyrimidin-7-one), , but to our knowledge, this approach had not been attempted to mimic an acylated aniline moiety.…”

Copper-catalysed C–H functionalisation gives access to 2-aminobenzimidazoles

“…The isolated guanidines were then reacted under our optimised reaction conditions. We were pleased to discover that a range of functional groups were tolerated in the transformation, including esters (11,12), nitriles (13) and halogens (14-18) which could be used in subsequent transformations. It is interesting to note the tolerance of halogens on the arene backbone, in particular bromine, as this shows the C-H functionalisation event is favoured over Ullmann-type insertion of copper into the carbon-halogen bond under the reaction conditions.…”

“…2-Amino benzimidazoles represent an important class of heterocycle due to their antibacterial, 11 immunosupressive, 12 antidiabetic, 13 antiviral 14 and analgesic 15,16 properties. For example, their use in the treatment and prevention of parasitic worm infections (Albendazole 1) and prevalence in second generation antihistamines (Emedastine 2, Figure 1) highlight this.…”

Benzimidazoles: From Antiproliferative to Multitargeted Anticancer Agents

“…And proton pump inhibitors [8,33], anticoagulants [40,41], immunomodulators [42], hormone modulators [43,44], antidepressants [45], lipid level modulators [46][47][48][49], and antidiabetics [50][51][52] are partial list of therapeutic effects of benzimidazole containing comprising compounds. Benzimidazole derivatives exert their actions by interacting with vital biological targets including β-tubulin [52][53][54][55], DNA minor groove [56][57][58], serotonin receptors (5-hydroxytryptamine receptors; 5-HT) [59][60][61][62], histamine receptors 4 (H4H) [63], dopamine receptor 2 (D2R) [64], chemokine receptor (CXCR3) [65], interleukin 2-inducible T-cell kinase (ITK) [66], lymphocyte tyrosine kinase (Lck) [67], phosphatidylinositol 3-kinase (PI3K) [68], activated protein kinase (MEK1) [69,70], anaplastic lymphoma kinase (ALK) [71], polo-like kinase 1 (PLK1) [72,73], breakpoint cluster region-Abelson kinase (BCR-Abl) [74], casein kinase 2 (CK2) [75], telangiectasia and Rad3-related protein kinase (ATR) [76], tyrosine kinase receptors [fibroblast growth factor receptors (FGFR-1/FGFR-2/FGFR-3)], vascular endothelial growth factor receptor (VEGFR-1/VEGFR-2/VEGFR-3), platelet-derived growth factor receptor (PDGFR-α/PDGFR-β), stem cell factor receptor (c-KIT), FMS-like tyrosine kinase 3 (FLT3) ...…”