Scaffold oriented synthesis. Part 4: Design, synthesis and biological evaluation of novel 5-substituted indazoles as potent and selective kinase inhibitors employing heterocycle forming and multicomponent reactions

One‐Pot Construction of Bis‐Heterocycles through Isocyanide Based Multicomponent Reactions

“…In 2011, I. Akritopoulou-Zanze and co-workers reported the synthesis of indazoles bound imidazopyridines/pyrimidines/ pyrazines (28) and indazoles bound imidazothiazoles (29) via Sc(OTf) 3 catalyzed GBBR. [47] The products were obtained by reacting amidines with 1H-indazole-5-carbaldehyde, and isocyanides in the presence of Sc(OTf) 3 catalyst in methanol solvent at room temperature (Scheme 15). Further, these compounds were evaluated against a panel of kinase assays and potent inhibitors for the identification of Gsk3b, Rock2, and EGFR.…”

Aminoazole-Based Diversity-Oriented Synthesis of Heterocycles

“…There are a lot of examples of using aminoazoles as an amine component in GBB-3CR resulting in the formation of heterocycles like 181 . The most studied ones are the processes involving 3-amino-1,2,4-triazoles (Bienaymé and Bouzid, 1998 ; Tyagi et al, 2012 ; Urich et al, 2013 ; Aouali et al, 2015 ), 2-amino(benzo)thiazoles (Bienaymé and Bouzid, 1998 ; Guchhait and Madaan, 2009 , 2010 ; Guchhait et al, 2009 ; Al-Tel et al, 2010 ; Akritopoulou-Zanze et al, 2011 ; Baviskar et al, 2011 ; Burchak et al, 2011 ; Hieke et al, 2012 ; Tyagi et al, 2012 ; Vidyacharan et al, 2014 ; Martinez-Ariza et al, 2015 ; Ansari et al, 2016 ; Shaabani and Hooshmand, 2016 ; Shao et al, 2017 ), 2-amino-1,3,4-thiadiazoles (Krasavin et al, 2008 ; Guchhait and Madaan, 2009 ; Guchhait et al, 2009 ; Wadhwa et al, 2015 ), 2-amino(benz)imidazoles (Lee et al, 2013 ; Pereshivko et al, 2013 ). GBB-3CR involving 2-aminooxazoles (Bienaymé and Bouzid, 1998 ) led to the formation of imidazoazoles while involving 1,2,5-oxadiazole-3,4-diamine (Kysil et al, 2010 ) gave oxadiazolopyrazines.…”

Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles

“…The heterocyclic nitrogen traps the nitrilium ion, which leads to the formation of an imidazole ring following a rearrangement ( Scheme 15 ). This reaction is widely used for the generation of highly diverse small molecule libraries [ 40 , 41 ]; the bioactive compounds synthesized this way include kinase inhibitors [ 42 ], topoisomerase II inhibitors [ 43 ], antibacterials effective against methicillin-resistant Staphylococcus aureus [ 44 ], fluorescent probes [ 45 ] and HIV-1 reverse transcriptase inhibitors ( Scheme 16 ) [ 46 , 47 ].…”