Vinylic amino group activation: a new and general strategy leading to functionalized fused heteroaromatics

Abstract

A conceptually new and general strategy has been developed for the construction of a benzimidazole or a benzoxazole ring fused with isoquinolinone affording a diverse and unique class of small molecules as potential and novel inhibitors of PDE4.

Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells

“…8–10 Benzimidazole-isoquinolinone derivatives have been synthesized as potential inhibitors of phosphodiesterase 4 (PDE4) employing an innovative amberlyst-15 catalyst. 11 Similar derivatives were developed with antimicrobial activity against Trypanosoma cruzi (T. cruzi) epimastigotes (GI 50 value is 0.5 μM). 12 These compounds also exhibited anti-inflammatory properties and anticancer activity against ovary (IGROV-1), breast (MCF-7) and CNS (SF-295) human cancer cell lines.…”

An Efficient and Facile Method for the Synthesis of Benzimidazoisoquinoline Derivatives via a Multicomponent Reaction

“…This use of this leaving group effectively generated more space for the modification of this structure (see the Supporting Information for details). This newly developed process provides facile access to a wide range of benzimidazoisoquinoline derivatives in good yields via a selective one-pot procedure and could therefore be used to synthesize numerous compounds for use in high through-put screening assays …”

Rh-Catalyzed Annulations of N-Methoxybenzamides and Ketenimines: Sterically and Electronically Controlled Synthesis of Isoquinolinones and Isoindolinones

“…Both benzimidazole and isoquinolinone are well-known structural motifs in medicinal chemistry. Benzo­[4,5]­imidazo­[1,2- b ]­isoquinolin-11-one derivatives, the fused form of isoquinolinone and benzimidazole frameworks, exhibited diverse bioactivities, and some of them have been demostrated as potential anti- Trypanosoma cruzi agents, PDE4 inhibitors, and anticancer agents (Figure ). However, most biological properties of this class of compounds remain unexplored due to the lack of accessible synthetic methods for these skeletons.…”

“…Consequently, developing convenient methods for the synthesis of such molecules has attracted much attention from medicinal and synthetic chemists. The published approaches to the benzo- [4,5]imidazo [1,2-b]isoquinolin-11-one ring system include the condesention of benzene-1,2-diamines with 2-(carboxymethyl)benzoic acids or their analogues (Scheme 1, route a), 7 the copper(I)-catalyzed cross-coupling of 2-halo-N-(2halophenyl)benzamides with alkyl 2-cyanoacetates or malononitrile (Scheme 1, route b), 8 the Ugi-type multicomponent reaction (Scheme 1, route c), 9 and the Amberlyst-15 mediated intramolecular cyclization of 3-amino-2-(2-aminophenyl)isoquinolin-1(2H)-ones (Scheme 1, route d). 5 Ketenimines have been demonstrated as an important and vesatile synthesis intermediate in organic synthesis.…”

“…The published approaches to the benzo- [4,5]imidazo [1,2-b]isoquinolin-11-one ring system include the condesention of benzene-1,2-diamines with 2-(carboxymethyl)benzoic acids or their analogues (Scheme 1, route a), 7 the copper(I)-catalyzed cross-coupling of 2-halo-N-(2halophenyl)benzamides with alkyl 2-cyanoacetates or malononitrile (Scheme 1, route b), 8 the Ugi-type multicomponent reaction (Scheme 1, route c), 9 and the Amberlyst-15 mediated intramolecular cyclization of 3-amino-2-(2-aminophenyl)isoquinolin-1(2H)-ones (Scheme 1, route d). 5 Ketenimines have been demonstrated as an important and vesatile synthesis intermediate in organic synthesis. 10 Their chemical properties have been widely explored, and they can undergo various reactions such as nucleophilic/electronphilic additions, cycloadditions, and sigmatropic rearrangements.…”