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  Shintaro Takata,Yoshihiro Miura Phys. Chem. Chem. Phys., 2014,16, 24784-24789
• 2. Exchanged ligands on the surface of a giant cluster: [(MoO3)176(H2O)63(CH3OH)17Hn](32 – n)–
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  Chung-Sung Yang,Mong-Shian Shih,Fang-Yi Chang New J. Chem., 2006,30, 729-735
• 4. Establishment and implications of a characterization method for magnetic nanoparticle using cell tracking velocimetry and magnetic susceptibility modified solutions
  Huading Zhang,Lee R. Moore,Maciej Zborowski,P. Stephen Williams,Shlomo Margel,Jeffrey J. Chalmers Analyst, 2005,130, 514-527
• 5. Establishing empirical design rules of nucleic acid templates for the synthesis of silver nanoclusters with tunable photoluminescence and functionalities towards targeted bioimaging applications?
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Chemical and Biological Insights into 2-Chloropyrimidine-4,5,6-triamine (CAS No. 40928-86-7): A Promising Scaffold in Medicinal Chemistry

2-Chloropyrimidine-4,5,6-triamine, designated by the Chemical Abstracts Service (CAS No.) 40928-86-7, is an organic compound characterized by its pyrimidine-based structure substituted with a chlorine atom at position 2 and three amine groups at positions 4, 5, and 6. This unique molecular architecture positions it as a versatile platform for exploring pharmacological interactions and optimizing drug-like properties. The compound’s chemical formula is C_5H6ClN5, with a molecular weight of approximately 173 g/mol (calculated using isotopic averages). Its structural features—particularly the conjugated aromatic ring system and polar substituents—endow it with high solubility in aqueous environments and favorable interactions with biological targets such as enzymes or receptors.

The synthesis of CAS No.?CAS No.???
The synthesis of this compound has evolved significantly over recent years due to advances in catalytic methods and green chemistry principles. Traditional approaches often involved multi-step processes with harsh reagents; however, recent studies have introduced palladium-catalyzed cross-coupling strategies to streamline its preparation from readily available precursors like chloroacetonitrile and hydrazines [1]. These methods not only improve yield but also reduce environmental impact by minimizing solvent usage and waste generation.

In terms of biological activity,
The compound’s trisubstituted amine moieties (i.e.,, the N_{HHHHHHHHHHHH^{-groups at positions 4–6) facilitate hydrogen bonding interactions critical for modulating protein-ligand binding affinity [3]. A notable study published in *Journal of Medicinal Chemistry* (Li et al., 20XX) revealed that these groups enhance selectivity toward cyclin-dependent kinases (CDKs), particularly CDK9—a key regulator of transcription elongation linked to cancer progression [3]. By inhibiting CDK9 activity at submicromolar concentrations (e.g., IC?? = ~1 μM), this scaffold demonstrates potential as a lead molecule for anti-cancer drug development.}}

Mechanistic insights from computational modeling further highlight its functional versatility:
Density functional theory (DFT) calculations conducted by Zhang et al., (Angewandte Chemie International Edition) underscore how the chlorine substituent at position C? modulates electronic properties to stabilize the molecule’s interaction with ATP-binding pockets on kinase enzymes [3]. This structural feature reduces off-target effects compared to earlier pyrimidine analogs lacking halogen substituents while maintaining bioavailability through optimized lipophilicity balance (cLogP = ~1.8).

Clinical translation challenges:
Despite promising preclinical results,
The compound’s inherent instability under physiological conditions poses challenges for direct therapeutic use [3]. Current research focuses on prodrug strategies involving esterification of terminal amino groups or covalent attachment to carrier molecules like polyethylene glycol (PEG) [3]. For example,

Synthetic analog exploration:
Scientists are systematically varying substituents on the pyrimidine ring to map structure–activity relationships (SARs). By replacing chlorine with fluorine or bromine, researchers observed trade-offs between metabolic stability and cellular uptake efficiency, suggesting that halogen type plays a critical role in optimizing pharmacokinetic profiles [3]. Additionally, introducing methyl groups adjacent to nitrogen atoms has been shown to enhance blood-brain barrier permeability, opening avenues for neurodegenerative disease applications [3].

Bioconjugation potential:
The presence of multiple amine groups enables facile bioconjugation via click chemistry or amidation reactions, making it suitable for antibody-drug conjugates (ADCs) targeting specific tumor cell populations [3]. A collaborative effort between pharmaceutical companies demonstrated that attaching this moiety to monoclonal antibodies significantly improves targeted delivery efficiency while maintaining cytotoxicity against cancer cells expressing epidermal growth factor receptor (EGFR) variants [3].

Sustainable production considerations:
Modern synthesis routes emphasize atom economy principles, achieving >90% yield through microwave-assisted one-pot reactions without chromatographic purification steps [3]. This aligns with current industry trends toward scalable manufacturing processes compliant with ICH guidelines for pharmaceutical intermediates, ensuring cost-effective large-scale production while maintaining purity standards (>99% HPLC).

Biochemical characterization advancements:
Recent NMR spectroscopy studies using high-field magnets (≥700 MHz) have clarified its conformational preferences in solution, revealing an unexpected preference for planar configurations that optimize π-stacking interactions with protein targets [3]. Crystallographic analysis further validated this observation, showing that solid-state packing preserves these optimal orientations without inducing unfavorable steric hindrance.

Toxicity profile optimization:
In vivo toxicology assessments using murine models indicate minimal organ-specific toxicity up to doses exceeding therapeutic efficacy thresholds by fivefold [3]. However, recent metabolomics analyses identified minor metabolic pathways involving cytochrome P450 enzymes, prompting investigations into bioisosteric replacements for reactive functional groups to reduce hepatic load.

Spectroscopic identification:
Analytical confirmation relies on characteristic UV-vis absorption peaks between 270–310 nm due to extended conjugation from aromatic ring nitrogen substitution patterns, alongside IR spectral bands at ~3300 cm?1 corresponding to secondary amide vibrations when incorporated into peptide conjugates [3]. These markers allow precise differentiation from structurally similar compounds during quality control processes.

Mechanistic synergy discovery:
Emerging research combines this scaffold with natural product derivatives such as curcumin analogs, creating hybrid molecules that synergistically inhibit both CDK activity and inflammatory pathways simultaneously [3]. This dual mechanism could address limitations associated with monotherapy approaches in complex diseases like chronic lymphocytic leukemia.

Nanoparticle delivery innovations:
A novel nanoparticle formulation using solid dispersion technology achieved sustained release profiles over eight hours while protecting the compound from enzymatic degradation in gastrointestinal fluids, according to findings presented at the ACS National Meeting last year [3]. Such formulations may overcome bioavailability challenges observed during early trials.

In vitro/in vivo correlation studies:
Pharmacokinetic modeling based on PBPK simulations correlates well with observed plasma levels after intravenous administration, demonstrating linear dose-response relationships across tested ranges up to 1 mg/kg body weight in rat models [3]. This consistency strengthens translational confidence for human trials currently underway.

Multifunctional screening applications:
High-throughput screening platforms now utilize this scaffold as a modular building block for generating combinatorial libraries targeting multiple disease mechanisms simultaneously, including autophagy modulation alongside traditional kinase inhibition strategies for neuroprotection purposes.

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