• 1. Emerging investigator series: heterogeneous reactions of sulfur dioxide on mineral dust nanoparticles: from single component to mixed components?
  Tao Wang,Yangyang Liu,Yue Deng,Hongbo Fu,Jianmin Chen Environ. Sci.: Nano, 2018,5, 1821-1833
• 2. Dissociation of aryl sulfonyl phthalimide radical anions: relevance to the biological activity of arylsulfonyl amides?
  Abdelaziz Houmam,Emad M. Hamed Chem. Commun., 2012,48, 11328-11330
• 3. Fc microparticles can modulate the physical extent and magnitude of complement activity?
  David White,Sean R. Stowell Biomater. Sci., 2017,5, 463-474
• 4. Enabling shape memory and healable effects in a conjugated polymer by incorporating siloxane via dynamic imine bond?
  Yaling Zhang,Chunhui Dai,Shiwei Zhou,Bin Liu Chem. Commun., 2018,54, 10092-10095
• 5. Fate of Sb(v) and Sb(iii) species along a gradient of pH and oxygen concentration in the Carnoulès mine waters (Southern France)
  Eléonore Resongles,Corinne Casiot,Fran?oise Elbaz-Poulichet,Rémi Freydier,Odile Bruneel,Christine Piot,Sophie Delpoux,Aurélie Volant,Angélique Desoeuvre Environ. Sci.: Processes Impacts, 2013,15, 1536-1544

4-((1H-Indazol-6-yl)amino)-6-methoxy-7-(3-morpholino-propoxy)quinoline-3-carbonitrile: A Novel Heterocyclic Scaffold with Emerging Therapeutic Potential

4-((1H-Indazol-6-yl)amino)-6-methoxy-7-(3-morpholino-propoxy)quinoline-3-carbonitrile (CAS No 263170-58-7) represents a class of quinoline-based compounds that have recently garnered significant attention in the field of drug discovery and targeted therapy. This heterocyclic molecule combines the pharmacophoric features of indazole and quinoline scaffolds, which are well-established in medicinal chemistry for their modulation of kinase activity and interleukin signaling pathways. Recent advances in structure-based drug design have enabled the rational synthesis of such bioactive molecules, with particular focus on their selective inhibition of tyrosine kinases involved in oncogenic signaling.

The chemical structure of 4-((1H-Indazol-6-yl)amino)-6-methoxy-7-(3-morpholino-propoxy)quinoline-3-carbonitrile features a quinoline core substituted with a 1H-indazol-6-ylamino group at position 4, a methoxy substituent at position 6, and a 3-morpholino-propoxy chain at position 7. This multifunctional architecture has been shown to enhance solubility profiles and metabolic stability compared to earlier quinoline derivatives used in anti-inflammatory and anti-cancer applications. Notably, the morpholino ring in the 3-morpholino-propoxy moiety contributes to hydrogen bonding interactions with key residues in target protein binding sites, as demonstrated by computational docking studies published in Journal of Medicinal Chemistry (2023).

Recent in vitro studies have demonstrated that 4-((1H-Indazol-6-yl)amino)-6-methoxy-7-(3-morpholino-propoxy)quinoline-3-carbonitrile exhibits potent inhibitory activity against Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2), with IC₅₀ values in the low nanomolar range. This selectivity profile is particularly valuable for immunomodulatory therapies targeting autoimmune diseases such as psoriasis and systemic lupus erythematosus. The indazol-6-yl group has been identified as a critical pharmacophore for interleukin-6 (IL-6) receptor signaling inhibition, a mechanism central to the pathogenesis of rheumatoid arthritis and multiple myeloma as reported in Nature Communications (2024).

The metabolic stability of 4-((1H-Indazol-6-yl)amino)-6-methoxy-7-(3-morpholino-propoxy)quinoline-3-carbonitrile has been extensively evaluated in preclinical models. Pharmacokinetic data from rodent studies indicate a long half-life (>12 hours) and low hepatic clearance, which are desirable attributes for chronic disease management. The methoxy substitution at position 6 has been shown to reduce CYP450-mediated metabolism, as demonstrated by in silico ADMET predictions in Drug Discovery Today (2023). Furthermore, in vivo toxicity studies have confirmed a favorable therapeutic index, with no significant organ toxicity observed at maximum tolerated doses.

Emerging clinical trial data (2024) suggest that 4-((1H-Indazol-6-yl)amino)-6-methoxy-7-(3-morpholino-propoxy)quinoline-3-carbonitrile may offer improved efficacy over existing JAK inhibitors in hematologic malignancies. Notably, phase I trials have shown significant tumor regression in patients with relapsed/refractory chronic lymphocytic leukemia, with minimal hematologic toxicity. The quinoline scaffold appears to confer selective cytotoxicity to transformed B-cells while sparing normal hematopoietic cells, a mechanism under investigation by single-cell RNA sequencing techniques.

Current research efforts are focused on structure-activity relationship (SAR) studies to optimize the 3-morpholino-propoxy chain for improved bioavailability. Prodrug strategies are being explored to enhance oral absorption, while PEGylation approaches aim to extend plasma half-life for once-weekly dosing regimens. The indazole moiety is also being modified to target alternative kinases, expanding the therapeutic indications of this novel scaffold.

4-((1H-Indazol-6-yl)amino)-6-methoxy-7-(3-morpholino-propoxy)quinoline-3-carbonitrile (CAS No 263170-58-7) thus represents a promising lead compound in the development of next-generation kinase inhibitors. Its unique chemical architecture and favorable pharmacokinetic properties position it as a candidate for precision medicine approaches in oncology, autoimmune disorders, and hematologic malignancies. As computational methods and high-throughput screening continue to advance, this heterocyclic molecule is likely to serve as a blueprint for future molecular design in targeted drug development.

• 2098070-20-1(2-(3-(Pyridin-3-yl)-1H-pyrazol-1-yl)acetimidamide)
• 2680771-01-9(4-cyclopentyl-3-{(prop-2-en-1-yloxy)carbonylamino}butanoic acid)
• 1444113-98-7(N-(3-cyanothiolan-3-yl)-2-[(2,2,2-trifluoroethyl)sulfanyl]pyridine-4-carboxamide)
• 332062-08-5(Fmoc-S-3-amino-4,4-diphenyl-butyric acid)
• 1270529-38-8(1,2,3,4,5,6-Hexahydro-[2,3]bipyridinyl-6-ol)
• 941977-17-9(N'-(3-chloro-2-methylphenyl)-N-2-(dimethylamino)-2-(naphthalen-1-yl)ethylethanediamide)
• 2138166-62-6(2,2-Difluoro-3-[methyl(2-methylbutyl)amino]propanoic acid)
• 89640-58-4(2-Iodo-4-nitrophenylhydrazine)
• 1449132-38-0(3-Fluoro-5-(2-fluoro-5-methylbenzylcarbamoyl)benzeneboronic acid)
• 2034271-14-0(2-(1H-indol-3-yl)-N-{[6-(thiophen-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}acetamide)