3‐Aminopyrazolo[3,4‐b]pyridine: Effective Precursor for Barium Hydroxide‐Mediated Three Components Synthesis of New Mono‐ and Bis(pyrimidines) with Potential Cytotoxic Activity

Abstract

In this study, an efficient one-pot procedure for preparing a new series of pyrazolo [3,4-b]pyridine-fused pyrimidines was described. The target hybrids were developed through a three-component reaction of 3-amino-1H-pyrazolo [3,4-b]pyridine, benzaldehydes, and acetophenones (molar ratio 1 : 1 : 1). The best conditions for the previous reaction were 2.5 equivalents of barium hydroxide in DMF at 150 °C for 6 h. New bis(pyrimidines) were synthesized in high yields using a similar one-pot reaction protocol with some modifications. Thus, two equivalents of each of the appropriate acetophenones and 3-aminopyrazolopyridine were reacted with one equivalent of the appropriate bis(aldehydes). The reaction was carried out at 150 °C for 8 h using 4.5 equivalents of barium hydroxide in DMF. Repeating the previous reaction with the appropriate bis(acetyl) derivatives and benzaldehydes resulted in good yields of the target bis(pyrimidines). The in vitro cytotoxic activity of new pyrimidines against the MCF-7, HEPG2, and Caco2 cell lines was evaluated using the reference doxorubicin (IC 50 values of 4.34 -6.97 μM). Hybrid 6h had the best activity against Caco2 and MCF-7 cell lines, IC 50 values of 12.62 and 14.50 μM, respectively. The IC 50 values for hybrids 6c, 6e, and 6f against MCF-7 and Caco2 cell lines were 23.99 -41.69 and 33.14 -43.33 μM, respectively. Furthermore, hybrid 6e displayed IC 50 value of 20.06 μM HEPG2 cell lines, while the hybrids 6c, 6f and 6h exhibited IC 50 values ranging between 26.29 -50.51 μM. Furthermore, hybrid 6e had an IC 50 value of 20.06 μM for the HEPG2 cell lines, whereas hybrids 6c, 6f, and 6h had IC 50 values ranging from 26.29 to 50.51 μM.

Chloramine Trihydrate‐Mediated Tandem Synthesis of New Pyrrole and/or Arene‐Linked Mono‐ and Bis(1,3,4‐Oxadiazole) Hybrids as Potential Bacterial Biofilm and MRSA Inhibitors

“…Recently, we discovered that bis‐analogs might display more effective bioactivity when compared to their mono‐analogs [3,33] . We compared the antibacterial activity of some new bis(1,3,4‐oxadiazoles) and their mono‐analogs in this study.…”

“…Recently, we discovered that bis-analogs might display more effective bioactivity when compared to their mono-analogs. [3,33] We compared the antibacterial activity of some new bis(1,3,4-oxadiazoles) and their mono-analogs in this study. Experimental results showed that bis(1,3,4-oxadiazoles) 11 and their monoanalogs 13, which are linked to an additional 4-(2,5dimethyl-1H-pyrrol-1-yl) unit, was found to be more effective than that of bis(1,3,4-oxadiazoles) 6 and their mono-analogs 12.…”

“…The previous synthons are typically produced by condensation of aldehydes or carboxylic acids with hydrazides [25,26] . In the context of our ongoing effort to prepare promising antibacterial azoles, [27–33] the goal of this study is to prepare new pyrrole and/or arene‐linked mono‐, and bis(1,3,4‐oxadiazole) hybrids using an efficient tandem protocol. The new hybrids were evaluated as potential bacterial biofilm and MRSA inhibitors.…”

[3+2] Cycloaddition Synthesis of New Piperazine‐Linked Bis(chromene) Hybrids Possessing Pyrazole Units as Potential Acetylcholinesterase Inhibitors

“…Furthermore, the promising AChE inhibitory activity of pyrazole‐based scaffolds has been investigated in numerous reports [19–22] . The previous hybrids also have a wide range of other biological activities, such as antibacterial, [23] antifungal, [24] antiviral, [25] anti‐inflammatory, [26] anticancer, [27] and antimalarial activity [28] . Additionally, they can act as promising inhibitors of HIV‐1, [29] and EGFR, [30] as well as COX‐2, [31] and MurB enzymes [32] .…”