Synthesis and evaluation of the antiproliferative activity of novel isoindolo[2,1-a]quinoxaline and indolo[1,2-a]quinoxaline derivatives

Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2

“…The preparation of the N-aryl pyrrole 4 was obtained by nucleophilic substitution of the diethyl pyrrole-2,3-dicarboxylate 5, previously prepared according to the method of Röder et al [26], with 2-fluoronitrobenzene using cesium carbonate as the base in refluxing DMF solution (Scheme 1) [24,25]. Reduction of the nitro moiety of 4 with iron in hot glacial acetic acid produced the spontaneous ring closure onto the ester to afford the desired tricyclic pyrrolo[1,2-a]quinoxaline 2b through a one-pot reductionecyclization step [24,25]. Similar substitution of commercially the methyl pyrrole-2-carboxylate with various ethyl fluoro-nitrobenzenecarboxylate led to the methyl 1-(4-or 5-ethoxycarbonyl-2-nitrophenyl)pyrrole-2-carboxylates 6a,b.…”

Design, synthesis and antimalarial activity of novel bis{N-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives

“…Coupling chloro derivatives 7a-f with 3-or 4-formylphenylboronic acid in the presence of Pd(PPh 3 ) 4 as a catalyst under SuzukiMiyaura cross-coupling conditions proceeded to afford the substituted benzaldehydes 8a-h 22,27,28,30 . Reaction of primary amines, such as 3,3 0 -diamino-N-methyldipropylamine or N-(3-aminopropyl)-1,3-propanediamine or 1,4-bis(3-aminopropyl)piperazine), with the latter 7a-f gave the di-imines 9a-p, reduced into the bis{N-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amines 1a-p using sodium borohydride in methanol.…”

“…These compounds have been reported as key intermediates for the assembly of several heterocycles including antipsychotic agents, anti-HIV agents, adenosine A 3 receptor modulators 19 , antiparasitic agents [20][21][22][23][24][25] and antitumor agents [26][27][28][29][30] . In the course of our work devoted to discover new compounds employed in the antiparasitic chemotherapy, we previously identified some series of substituted pyrrolo[1,2-a]quinoxaline derivatives designed as interesting bioactive isosteres of quinoline derivatives [20][21][22][23][24] .Thus, taking into account our experience in the field of the synthesis of new antimalarial heterocyclic compounds based on our pyrrolo[1,2-a]quinoxaline heterocyclic core [20][21][22][23][24][27][28][29][30] , we decided to incorporate a benzyl group in position 4 of the heterocyclic skeletonof our previously described bispyrrolo [1,2-a]quinoxalines C 20 to broaden the structural diversity of these derivatives, and mainly to increase the aromatic surface of these designed compounds ( Figure 1). …”

Synthesis and Antiproliferative Effect of Ethyl 4‐[4‐(4‐Substituted Piperidin‐1‐yl)]benzylpyrrolo[1,2‐a]quinoxalinecarboxylate Derivatives on Human Leukemia Cells

“…The discovery of new therapeutic agents against cancer is one of the most important goals in medicinal chemistry. Thus, we recently published four series of new pyrrolo[1,2‐ a ]quinoxaline derivatives (Figure ) endowed with interesting activity toward human leukemia cells . These antileukemia pyrroloquinoxaline compounds have been previously reported as new structural analogues of derivative A6730, a reference Akt inhibitor that exhibits antiproliferative activity against various human leukemia cell lines …”

“…Taking into account the best results obtained in the previous series (A–B, Figure ), we decided to refer to the JG564 and JG572 pyrrolo[1,2‐ a ]quinoxaline pharmacophores as a template for the design of new compounds 1 a – o , in which the pyrrolo[1,2‐ a ]quinoxaline ring is replaced in various positions by an ethyl ester functionality (Figure ). In addition, further modulations on the piperidine core were also considered, such as the introduction of new substituted heterocyclic moieties (benzimidazolone, fluorobenzimidazole, and pyridinyltriazole substituents), in analogy to previously described antileukemia compounds . The antiproliferative activity of the resulting derivatives ( 1 a – o ) was then evaluated in vitro against various myeloid (U937, HL60, K562) or lymphoid (Jurkat, U266) leukemia cell lines.…”