• 1. An atom efficient route to N-aryl and N-alkyl pyrrolines by transition metal catalysis?
  Supaporn Sawadjoon,Joseph S. M. Samec Org. Biomol. Chem., 2011,9, 2548-2554
• 2. An artificial enzyme cascade amplification strategy for highly sensitive and specific detection of breast cancer-derived exosomes?
  Huiying Xu,Lu Zheng,Yu Zhou,Bang-Ce Ye Analyst, 2021,146, 5542-5549
• 3. An algal process treatment combined with the Fenton reaction for high concentrations of amoxicillin and cefradine
  Haitao Li,Yu Pan,Zhizhi Wang,Shan Chen,Ruixin Guo,Jianqiu Chen RSC Adv., 2015,5, 100775-100782
• 4. An automatic determination of thoria in thoria-urania mixtures
  Analyst, 1966,91, 208-210
• 5. An antioxidant self-healing hydrogel for 3D cell cultures?
  Lei Yang,Yuan Zeng,Haibo Wu,Chunwu Zhou,Lei Tao J. Mater. Chem. B, 2020,8, 1383-1388

3-(1H-Pyrazol-1-yl)propanohydrazide (CAS No. 1177300-40-1): A Versatile Scaffold in Chemical Biology and Drug Discovery

3-(1H-Pyrazol-1-yl)propanohydrazide, a compound with the CAS registry number 1177300-40-1, represents a unique chemical entity that has garnered significant attention in recent years due to its structural versatility and potential applications in medicinal chemistry. This molecule combines the pharmacophoric features of the pyrazole ring system, known for its ability to modulate protein-protein interactions, with the hydrazide functional group, which exhibits inherent reactivity and tunable physicochemical properties. The combination of these elements positions it as a promising lead compound for developing novel therapeutics targeting diverse biological pathways.

The core structure of 3-(1H-Pyrazol-1-yl)propanohydrazide consists of a central pyridine-derived N'-propylhydrazide moiety attached to a substituted pyrazole ring via an ethylene bridge. This architecture allows for strategic functionalization at multiple sites, enabling the design of derivatives with enhanced specificity and bioavailability. Recent studies published in Nature Communications (2023) highlight its utility as a building block in covalent inhibitor development, where the hydrazide group can form Michael-type adducts with cysteine residues on target proteins. Researchers demonstrated that analogs of this compound exhibit submicromolar potency against bromodomain-containing proteins, which are implicated in cancer epigenetic regulation.

In terms of synthetic accessibility, this compound can be prepared through optimized routes involving the condensation of 5-substituted pyrazoles with propionyl chloride followed by hydrazine treatment. A 2022 study in Journal of Medicinal Chemistry introduced a one-pot methodology achieving 89% yield under mild conditions using microwave-assisted synthesis. Such advancements underscore its feasibility as an intermediate for large-scale pharmaceutical applications. The hydrazide functionality also facilitates further derivatization via carbodiimide coupling or click chemistry approaches, enabling the attachment of targeting ligands or fluorescent probes for diagnostic purposes.

Biochemical evaluations reveal intriguing properties: when tested against a panel of kinases in high-throughput screening (HTS), this compound showed selective inhibition of DYRK family kinases associated with Alzheimer's disease progression. Follow-up mechanistic studies using X-ray crystallography confirmed that it binds to the ATP pocket through π-stacking interactions with aromatic residues while forming hydrogen bonds via its terminal amine group. These findings were corroborated by molecular dynamics simulations published in Bioorganic & Medicinal Chemistry Letters, which predicted favorable binding energies (-8.5 kcal/mol) under physiological conditions.

Clinical translation potential is evident from ongoing investigations into its anti-inflammatory effects mediated through COX enzyme inhibition pathways. Preclinical models using LPS-stimulated macrophages demonstrated dose-dependent suppression of pro-inflammatory cytokines like TNF-alpha and IL-6 at concentrations below 5 μM without significant cytotoxicity up to 50 μM (data from Inflammation Research, 2024). Its dual mechanism involving both enzymatic inhibition and modulation of NF-kB signaling pathways distinguishes it from conventional nonsteroidal anti-inflammatory drugs (NSAIDs), potentially overcoming limitations related to gastrointestinal side effects.

Spectroscopic characterization confirms its molecular formula C₈H₉N₅O and molecular weight of 696 g/mol (calculated based on latest NMR data). IR spectroscopy identifies characteristic peaks at 3456 cm?1 (N-H stretch), 2965 cm?1 (C-H stretch), and 889 cm?1 (C-N bending), while mass spectrometry reveals [M+H]⁺+ at m/z 696. Recent computational studies using density functional theory (DFT) have mapped its electronic distribution, showing high electrophilicity indices at the α-carbon adjacent to the hydrazide group—a critical insight for designing irreversible inhibitors targeting cysteine proteases such as cathepsin K involved in osteoporosis pathogenesis.

The compound's amphiphilic nature arises from its polar hydrazide end and hydrophobic pyridine ring system, resulting in logP values between 4.5–5.8 depending on substituents according to recent solubility assays reported in Molecular Pharmaceutics. This balance between hydrophilicity and lipophilicity enhances cellular permeability while maintaining solubility requirements for formulation development—a key factor highlighted by FDA guidelines on drug-like properties outlined in their recent white paper on QSPR modeling approaches.

Innovative applications include its use as a chelating agent for metalloenzyme modulation, particularly targeting zinc-dependent matrix metalloproteinases (MMPs). A collaborative study between MIT and Pfizer researchers demonstrated that when complexed with copper ions (Nature Chemistry, March 2024), this compound inhibits MMP activity more effectively than conventional inhibitors like marimastat, showing promise for treating fibrotic diseases where extracellular matrix remodeling plays a central role.

Safety profiles derived from recent toxicology studies indicate low acute toxicity when administered orally to murine models at doses up to 5 g/kg body weight (Toxicological Sciences, July 2024). Long-term subchronic toxicity evaluations over four weeks revealed no significant organ damage or mutagenic effects according to Ames test results conducted under OECD guidelines. These findings align with regulatory standards required for advancing compounds into preclinical development stages.

Ongoing research explores its role as an immunomodulatory agent through toll-like receptor (TLR) pathway interference documented in Biochemical Pharmacology. In vitro assays showed suppression of TLR4 signaling cascades by competitively inhibiting MyD88 adapter protein recruitment, suggesting therapeutic potential for autoimmune disorders such as rheumatoid arthritis where excessive inflammatory responses are pathogenic hallmarks.

This compound's structural flexibility has also enabled exploration as a prodrug carrier system when conjugated with polyethylene glycol chains (JACS Au, January 2024). Such conjugates demonstrated extended half-lives in plasma while maintaining target engagement efficacy when evaluated against pancreatic cancer cell lines expressing specific folate receptors—a critical advancement toward overcoming pharmacokinetic challenges common among small molecule therapies.

In material science applications, researchers at Stanford recently synthesized hybrid materials incorporating this compound's hydrazone derivatives into porous frameworks (Angewandte Chemie, May 2024). These materials exhibit pH-responsive drug release profiles suitable for targeted delivery systems, achieving controlled release over seven days when exposed to physiological pH levels—a breakthrough for sustained-release formulations requiring precise temporal control mechanisms.

The growing interest in this molecule stems from its ability to bridge organic synthesis innovations with emerging biological targets identified through CRISPR-based phenotypic screens (Nature Reviews Drug Discovery, June 2024). Its modular structure allows rapid iterative optimization using modern medicinal chemistry strategies such as fragment-based drug design and structure-based virtual screening approaches now standard across pharmaceutical R&D pipelines worldwide.

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