1354413-66-3

Upstream product

• 1354413-58-3 1-phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde 
• 7409-31-6 4-bromo-3-hydroxy-1-phenyl-1H-pyrazole 
• 1008-79-3 1-phenyl-1H-pyrazol-3-ol 
• 1354413-51-6 4-formyl-1-phenyl-1H-pyrazol-3-yl trifluoromethanesulfonate 
• 1354413-50-5 3-(benzyloxy)-1-phenyl-1H-pyrazol 
• 464185-13-5 3-(benzyloxy)-1-phenyl-1H-pyrazole-4-carbaldehyde 
• 1354413-49-2 3-(benzyloxy)-4-bromo-1-phenyl-1H-pyrazole 

Relevant academic research and scientific papers

Synthesis and antiproliferative activity of 2,4,6,7-tetrasubstituted-2h-pyrazolo[4,3-c]pyridines

A library of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines was prepared from easily accessible 1-phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde via an iodine-mediated elec-trophilic cyclization of intermediate 4-(azidomethyl)-1-phenyl-3-(phenylethynyl)-1H-pyrazoles to 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridines followed by Suzuki cross-couplings with various boronic acids and alkylation reactions. The compounds were evaluated for their antiproliferative activity against K562, MV4-11, and MCF-7 cancer cell lines. The most potent compounds displayed low micromolar GI50 values. 4-(2,6-Diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol proved to be the most active, induced poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, activated the initiator enzyme of apoptotic cascade caspase 9, induced a fragmentation of microtubule-associated protein 1-light chain 3 (LC3), and reduced the expression levels of proliferating cell nuclear antigen (PCNA). The obtained results suggest a complex action of 4-(2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol that combines antiproliferative effects with the induction of cell death. Moreover, investigations of the fluorescence properties of the final compounds revealed 7-(4-methoxyphenyl)-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine as the most potent pH indicator that enables both fluorescence intensity-based and ratiometric pH sensing.

Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6-trisubstituted-2H-pyrazolo[4,3-c]pyridines

An efficient synthetic route for the synthesis of 2H-pyrazolo[4,3-c]pyridines, primarily varying by the substituents at the 2-, 4- and 6-positions, is described here. A Sonogashira-type cross-coupling reaction was employed to yield 3-alkynyl-1H-pyrazole-4-carbaldehydes, ethanones and propanones from the corresponding 1H-pyrazol-3-yl trifluoromethanesulfonates. Subsequent treatment of the coupling products with dry ammonia afforded a versatile library of 2H-pyrazolo[4,3-c]pyridines, which were then evaluated for their cytotoxicity against K562 and MCF-7 cancer cell lines. The most potent of these compounds displayed low micromolar GI50 values in both cell lines. Active compounds induced dose-dependent cell-cycle arrest in mitosis, as shown by flow cytometric analysis of DNA content and phosphorylation of histone H3 at serine-10. Moreover, biochemical assays revealed increased activities of caspases-3/7 in treated cells, specific fragmentation of PARP-1, and phosphorylation of Bcl-2, collectively confirming apoptosis as the mechanism of cell death.

Synthesis of 3-substituted 1-phenyl-1H-pyrazole-4-carbaldehydes and the corresponding ethanones by Pd-catalysed cross-coupling reactions

An efficient synthetic route to construct ortho-substituted 1-phenyl-1H-pyrazole-4-carboxaldehydes and the corresponding ethanones starting from 1-phenyl-1H-pyrazol-3-ol is described. Carbon-carbon bond-forming Pd-catalysed cross-coupling reactions were applied for the functionalisation of the intermediate pyrazole triflates. Detailed NMR spectroscopic investigations were undertaken with all obtained products. ARKAT-USA, Inc.