{
  "abstract": "Herein, we developed a highly efficient palladium-catalyzed, oxidant-promoted, chelation-assisted, regioselective strategy to introduce the nitro group directly at the ortho-position of the pendant aryl ring of the 1-aryl-1H-indazoles. The newly developed methodology is bench-stable and exclusively furnishes the C2' (ortho)-substituted 1-(2-nitroaryl)-1H-indazoles 2a-z/2aa-ad in up to 87% yield. The nitrated product serves as a versatile precursor and is reduced to a key amine functionality, which paves the path for several transformed pharmacologically and medicinally relevant derivatives, such as sulfonamide, N-benzylated compound, amide, thiourea, etc. To shed light on the underlying mechanistic pathway, several control experiments were conducted. The free-radical scavengers (TEMPO and BHT) successfully trapped the in situ formed free radical in the reaction mixture, and the TEMPO-nitro adduct was detected by HRMS analysis, thereby confirming the involvement of the free-radical pathway in our developed protocol. The key features of this methodology involve an operationally simple regioselective protocol, a wide substrate scope, excellent functional group tolerance, high yields, scalable gram-scale synthesis, and direct access to N-containing congeners via post-functional modifications. Furthermore, the antiproliferative activity of selected derivatives has been evaluated against the human glioblastoma U-87 MG cancer cell line. Among the tested derivatives, compound 2k exhibited the most potent antiproliferative activity against the cancer cells, with an IC₅₀ value of 51.99 ± 14.96 µM compared to the standard drug dihydroartemisinin (DHA) 80.44 ± 7.5 µM.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Bioactive Heterocycles and Catalysis (BHC lab), Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Raebareli (Transit Campus) Bijnor-Sisendi Road, Near CRPF Base Camp, Sarojini Nagar Lucknow-226002 India schaudhary.chy@niperraebareli.edu.in sandeep.chaudhary2311@gmail.com.",
    "Laboratory of Molecular Neurotherapeutics, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli (Transit Campus) Bijnor-Sisendi Road, Near CRPF Base Camp, Sarojini Nagar Lucknow-226002 India."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Janmejaya Sen",
      "orcid": "0009-0002-1750-1357"
    },
    {
      "affs": [
        0
      ],
      "name": "Shivani",
      "orcid": "0009-0001-6173-4652"
    },
    {
      "affs": [
        1
      ],
      "name": "Pushpendra Kumar"
    },
    {
      "affs": [
        1
      ],
      "name": "Ashok Kumar Datusalia",
      "orcid": "0000-0002-7499-1658"
    },
    {
      "affs": [
        0
      ],
      "name": "Sandeep Chaudhary",
      "orcid": "0000-0002-1444-3895"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6qaqs606edhds.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra08657h",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13726133/?tool=EBI",
  "id": "6qaqs606edhds",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13726133",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1605|Catalytic C–H Functionalization Methods"
    ]
  ],
  "openalex": "W7225076306",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13726133/pdf/?tool=EBI",
  "pmcid": "PMC13726133",
  "pmid": "42974101",
  "published": "2026-11-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6qaqs606edhds.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:50Z",
      "native_id": "PMC:PMC13726133",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13726133"
    },
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "MED:42974101",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42974101"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Catalytic C–H Functionalization Methods",
      "subfield": "organic"
    }
  ],
  "title": "Pd-catalyzed, oxidant-promoted, chelation-assisted, regioselective direct ortho-nitration of 1-aryl-1H-indazoles via C–H bond activation: direct access to novel indazole-based antiproliferative agents",
  "title_text": "Pd-catalyzed, oxidant-promoted, chelation-assisted, regioselective direct ortho-nitration of 1-aryl-1H-indazoles via C–H bond activation: direct access to novel indazole-based antiproliferative agents",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T03:20:59Z",
  "url": "https://research.draconitic.com/paper/6qaqs606edhds",
  "venue": "RSC advances",
  "versions": []
}