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Synlett 2025; 36(05): 459-463
DOI: 10.1055/a-2384-6983
DOI: 10.1055/a-2384-6983
letter
Synthesis, Characterization, and Biological Applications of Tetramethylpiperidinyl Triazolopyridazine Derivatives
The authors thank Koneru Lakshmaiah Education Foundation (KL Deemed to be University) for support and for providing the research facilities to carry out the work.
Abstract
We have synthesized a series of tetramethylpiperidinyl triazolopyridazine derivatives and screened the molecules for their biological activity against a cancer (NCI-H460) cell line. Among the tested molecules, 2-[3-(2,2,6,6-tetramethylpiperidin-4-yl)-3H-[1,2,3]triazolo[4,5-c]pyridazin-6-yl]-5-(2H-1,2,3-triazol-2-yl)phenol significantly inhibited cell growth with an IC50 value of 5.2 μM. We hope that this study will help in the development of better candidates for the treatment of lung cancer.
Key words
triazolopyridazines - lung cancer - medicinal chemistry - biological activity - anticancer drugsSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2384-6983.
- Supporting Information
Publication History
Received: 10 January 2024
Accepted after revision: 12 August 2024
Accepted Manuscript online:
12 August 2024
Article published online:
20 September 2024
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- 29 Products 9a–d; General Procedure A mixture of compound 7 (1.0 equiv), the appropriate boronic acid 8a–d (1.2 equiv), and K2CO3 (2.0 equiv) in 10:4 1,4-dioxane–H2O was degassed with N2 for 15 min at r.t., then Pd(dppf)Cl2 (0.15 equiv) was added at r.t. under N2. The mixture was stirred for 6 h at 75–80 °C under N2 until 7 was completely consumed (TLC), then cooled to r.t. The reaction was quenched with ice-water and the mixture was extracted with EtOAc. The organic phase was separated, and the aqueous layer was extracted with EtOAc. The combined organic phase was dried (Na2SO4) and concentrated, and the crude product was purified by column chromatography. 2-[3-(2,2,6,6-Tetramethylpiperidin-4-yl)-3H-[1,2,3]triazolo[4,5-c]pyridazin-6-yl]-5-(2H-1,2,3-triazol-2-yl)phenol (9a) Off-white solid; yield: 0.80 g (53%). 1H NMR (400 MHz, DMSO-d 6): δ = 9.22 (s, 1 H), 8.23 (d, J = 7.2 Hz, 1 H), 8.12 (s, 2 H), 7.71 (s, 1 H), 7.54 (d, J = 7.4 Hz, 1 H), 5.63 (m, 1 H), 2.20 (m, 2 H), 1.99 (m, 2 H), 1.35 (s, 6 H), 1.15 (s, 6 H). 13C NMR (100 MHz, DMSO-d 6): δ = 157.3 (C5), 153.6 (C21), 148.6 (C23), 141.2 (C29), 137.8 (C30), 137.3 (C2), 132.0 (C1), 121.7 (C25), 117.4 (C6, C24), 109.9 (C7), 106.9 (C22), 56.9 (C12 & C14), 51.9 (C10), 30.2 (C11 & C15), 24.7 (C16–C19). LC/MS: m/z = 419 [M + H]+.