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Synlett 2025; 36(05): 459-463
DOI: 10.1055/a-2384-6983
letter

Synthesis, Characterization, and Biological Applications of Tetramethylpiperidinyl Triazolopyridazine Derivatives

Srinivasa Reddy Keesara
a   Department of Chemistry, Koneru Lakshmaiah Education Foundation, RVS Nagar, Aziz Nagar (PO), Moinabad Road, Hyderabad, Telangana, 500075, India
,
Ratnasekhar Bolla
a   Department of Chemistry, Koneru Lakshmaiah Education Foundation, RVS Nagar, Aziz Nagar (PO), Moinabad Road, Hyderabad, Telangana, 500075, India
,
Hanumantharayappa Bharathkumar 
b   Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, India-500007, India
,
Sai Balaji Andugulapati
c   Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India
,
Sreedhar Gundekari
,
Mohan Varkolu∗
a   Department of Chemistry, Koneru Lakshmaiah Education Foundation, RVS Nagar, Aziz Nagar (PO), Moinabad Road, Hyderabad, Telangana, 500075, India
› Author AffiliationsThe authors thank Koneru Lakshmaiah Education Foundation (KL Deemed to be University) for support and for providing the research facilities to carry out the work.
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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 drugs

Supporting 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

© 2024. Thieme. All rights reserved

Georg Thieme Verlag KG
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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]+.