Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines

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 of New Pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxaline Derivatives in One Step

“…Quinolino[3,4‐ b ]quinoxalines showed high activity as topoisomerase II a inhibitors and cytotoxic properties against two human cancer cell lines (HeLa and MCF‐7) . The pyrrolo[1,2‐ a ]quinoxaline is an important central core in many of biological systems including antipsychotic agents , anti‐HIV agents , adenosine A3 receptor modulators and has also demonstrated cytotoxic activity against lymphoid leukemia cell lines . Whereas imidazoquinoxalines exhibited significant biological activities like inhibitory effects on radicals and DNA oxidation .…”

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.…”