From Nitroarenes to Pharmaceutically Relevant Pyridines: A Photochemically Induced Aryl Nitrene-Mediated Skeletal Editing Strategy

1 Research Source and Core Problem

1.1 Research Object

The study reported by Saha, Pan, Ghosh, Pal, Guin, Redhu, Gota, and Maiti, titled A General Strategy to Access Pharmaceutically Relevant Pyridines from Nitroarenes, proposes a synthetic strategy for directly accessing pharmaceutically relevant pyridine heterocycles from nitroarenes. The study was published in Angewandte Chemie International Edition, with the DOI 10.1002/anie.202517867.

The core of this study is the conversion of nitroarenes into pyridine frameworks through photochemically induced nitrene formation, aromatic-ring rearrangement, and selective carbon deletion. In essence, this transformation belongs to aromatic skeletal editing: rather than installing functional groups at the periphery of an aromatic ring, it alters the atomic composition and connectivity within the aromatic framework itself.

1.2 The Synthetic Problem

Pyridine is a nitrogen-containing aromatic heterocycle that appears frequently in drug molecules. Compared with a benzene ring, the nitrogen atom in a pyridine ring can alter a molecule’s electronic distribution, hydrogen-bond-accepting ability, polarity, solubility, and metabolic properties. In medicinal chemistry, replacing a benzene ring with pyridine is commonly used to modulate molecular properties and explore structure–activity relationships, abbreviated as SAR.

Traditional pyridine synthesis generally relies on the condensation of nitrogen-containing building blocks, cyclization, or multistep heterocycle construction. For simple molecules, these methods are mature and effective. However, for complex drug molecules or late-stage analogue modification, rebuilding a pyridine ring often increases route length and limits substrate scope.

The problem addressed by this study is therefore: Can stable and readily available nitroarenes be used directly to remodel an existing aromatic ring into a pyridine framework, thereby rapidly providing pharmaceutically relevant pyridine analogues?

2 Key Structures and Overall Reaction Design

2.1 Representative Structures

Structure name	Structural representation	Molecular formula	Description
Nitroarene	Ar–NO₂	Depends on Ar	Reaction starting material; the nitro group serves both as an activatable functional group and as the nitrogen source incorporated into the pyridine framework
Nitrobenzene	Ph–NO₂	C₆H₅NO₂	Parent structure of nitroarenes
Pyridine	C₅H₅N	C₅H₅N	Six-membered nitrogen-containing aromatic heterocycle; a common drug scaffold
2-Aminopyridine	H₂N–C₅H₄N	C₅H₆N₂	An important medicinal-chemistry building block that can serve as both a hydrogen-bond donor and a hydrogen-bond acceptor structural unit

2.2 Reaction Design Schematic

This reaction can be summarized as the following cascade process:

 

3 Division of Roles Between Photochemistry and the Iron–Porphyrin Catalyst

3.1 Photochemistry Generates the Key Singlet Nitrene

Nitroarenes are relatively stable and readily available aromatic compounds. To rewrite their aromatic skeletons into pyridines, it is first necessary to divert nitroarenes away from conventional reduction, substitution, or coupling pathways and into a highly reactive intermediate pathway capable of nitrogen-atom insertion and ring expansion.

This study uses near-UV/blue LED irradiation to photoexcite nitroarenes, which then undergo intersystem crossing, abbreviated as ISC, to form triplet excited states. These excited nitroarenes possess electrophilic O-radical character and subsequently undergo selective deoxygenation with an electron-rich trivalent phosphorus reagent, generating the key singlet aryl nitrene intermediate.

Singlet aryl nitrenes are highly reactive and can insert into the aromatic ring to form dearomatized intermediates. These intermediates then undergo 6π electrocyclic ring opening to generate seven-membered ketimine species, which, after amine trapping and isomerization, form 3H-azepine intermediates. The 3H-azepine intermediate is the key branching intermediate for the subsequent formation of either 2-aminopyridines or unsubstituted pyridines.

The role of photochemistry in this system is not simply to provide reaction energy. Rather, it converts stable nitroarenes into singlet nitrenes, thereby shifting the reaction from an ordinary functional-group transformation into an aromatic skeletal editing process.

3.2 The Iron–Porphyrin Catalyst Regulates the Oxygen-Participating C5-Carbon-Deletion Process

This study uses an iron–porphyrin catalytic system to regulate the participation of singlet oxygen, ¹O₂, in the subsequent ring-editing process. The structural and functional design of this catalyst is inspired by the iron–porphyrin active centers found in natural heme enzymes. Natural heme systems can bind and activate molecular oxygen through cooperative action between the iron center and the porphyrin ligand.

In this reaction, the main role of the iron–porphyrin catalyst is to regulate the participation of singlet oxygen after formation of the azepine intermediate, enabling subsequent oxidative rearrangement and ring contraction so that the reaction proceeds through a C5-carbon-deletion pathway to afford 2-aminopyridine derivatives. The value of this catalytic system lies in its ability to control the oxygen-involved C5-carbon-deletion cascade, thereby improving the conversion efficiency and selectivity of the 2-aminopyridine pathway.

Step/component	Main role	Effect on the outcome
Light irradiation	Generates the nitrene intermediate	Initiates aromatic skeletal editing
Trivalent phosphorus reagent	Promotes deoxygenation of the nitro group	Drives nitrene formation
Iron–porphyrin catalyst	Regulates singlet oxygen	Improves the efficiency of the C5-carbon-deletion pathway
Singlet oxygen	Participates in ring contraction and oxidative rearrangement	Promotes formation of 2-aminopyridines

4 Core Logic of the Reaction Mechanism

4.1 From Nitro Group to Nitrene: The Nitro Group Becomes an Embedded Nitrogen Source

Common reaction pathways of nitroarenes traditionally include reduction to anilines, participation in coupling reactions, or use as electron-withdrawing substituents that influence aromatic-ring reactivity. What distinguishes this study is that the nitro group is not simply converted into a peripheral functional group. Instead, it is transformed into a nitrene and then incorporated into the heteroaromatic framework.

This changes the synthetic significance of nitroarenes:

Traditional understanding: nitroarene = a transformable functional group on an aromatic ring

Understanding in this study: nitroarene = a nitrogen-containing aromatic precursor that can be reconstructed into a pyridine framework

This also explains the retrosynthetic value of the method. When faced with a target pyridine structure, researchers can consider whether a corresponding nitroarene precursor exists and then complete the arene-to-pyridine conversion through skeletal editing.

4.2 From Nitrene to Azepine: The Aromatic Ring Enters an Editable State

After formation of the singlet nitrene, it undergoes an intramolecular reaction with the aromatic ring to form a dearomatized intermediate. This is followed by 6π electrocyclic ring opening to generate a seven-membered aza-ring intermediate, namely 3H-azepine. This intermediate is the key branching point in the reaction. It retains part of the carbon skeleton of the original aromatic ring while also possessing the reactivity required for further rearrangement and contraction.

4.3 From a Seven-Membered Ring to Pyridine: Selective Carbon Deletion Determines the Product Type

Pyridine consists of five carbon atoms and one nitrogen atom, whereas benzene contains six carbon atoms. The conversion of a nitroarene into a pyridine therefore requires two essential changes:

① introducing nitrogen into the aromatic-ring skeleton;

② selectively deleting one carbon atom from the original carbon framework.

Two main pathways are present in this study:

Pathway	Key participants	Mode of carbon deletion	Main product
Pathway A	Amine nucleophiles + iron–porphyrin/oxygen-participating system	C5-carbon deletion	2-Aminopyridines
Pathway B	Aminoalcohol trapping system, such as N-ethylethanolamine	Ipso-carbon deletion; that is, deletion of the carbon in the original aromatic ring that bears the nitro group	Corresponding pyridine derivatives

The importance of these two pathways lies in the fact that they do not generate the same pyridine product. Instead, they access pyridine structures with different substitution patterns through different carbon-deletion modes. For medicinal chemistry, this product-divergent capability is useful for rapidly preparing structurally related pyridine analogues with different properties.

5 Synthetic Value: From Arene Libraries to Pyridine Libraries

5.1 The Starting-Material Source Has Practical Significance

Nitroarenes are widely available, and many aromatic compounds can be converted into the corresponding nitroarenes through nitration or precursor transformation. Compared with unstable azides or specialized nitrogen-containing precursors, nitroarenes are generally more stable and easier to store and handle. The synthetic value of this strategy lies in converting existing nitroarene resources into potential pyridine-product resources.

5.2 The Products Cover Pharmaceutically Relevant Pyridine Structures

The study reports a variety of 2-aminopyridine derivatives as well as pyridine derivatives obtained through ipso-carbon deletion, including 2-aminopyridines with different substitution patterns, fused pyridines, and pyridines derived from complex molecules. Some substrates are derived from drugs or bioactive molecules, indicating that this method can be used for late-stage skeletal modification. In the drug-discovery stage, the value of this method is reflected in three aspects:

Medicinal-chemistry need	Corresponding value of this method
Rapid preparation of pyridine analogues	Directly obtains pyridine frameworks from nitroarenes, reducing the need to redesign synthetic routes
Exploration of benzene-to-pyridine replacement	Uses the pyridine nitrogen to modulate electronic properties, polarity, and hydrogen-bonding interactions
Late-stage structural modification	Introduces pyridine frameworks into complex molecules for SAR studies

6 Significance for Drug Design

6.1 Pyridine Nitrogen Alters Molecular Properties

The replacement of benzene with pyridine is often regarded as a bioisosteric replacement. The lone pair of the pyridine nitrogen does not participate in the aromatic six-π-electron system and can act as a hydrogen-bond acceptor in interactions with protein targets. At the same time, the pyridine nitrogen lowers the electron density of the aromatic ring, increases molecular polarity, and may alter metabolic sites. This structural change can lead to the following effects:

Structural change	Possible effect
Introduction of a nitrogen atom into the aromatic ring	Changes electronic distribution and dipole moment
Formation of a hydrogen-bond acceptor site	Alters the target-binding mode
Increased molecular polarity	Affects aqueous solubility and membrane permeability
Altered aromatic-ring metabolic tendency	Affects metabolic stability

These effects do not necessarily lead to improved activity, but they provide clearly defined variables for medicinal-chemistry optimization. The value of this method is precisely that it enables rapid access to compounds corresponding to these variables.

6.2 Significance of the Nimesulide Case

The study uses a nimesulide-related structure as an application case. Nimesulide contains a nitroaromatic structure, and the nitro group is associated with potential safety risks. By converting the nitroaromatic fragment into a pyridine-related framework, new analogues can be obtained for comparing changes in target binding and molecular properties.

This method is applicable not only to simple model substrates but also to the structural modification of drug-relevant molecules. The study evaluates the interactions between the modified molecules and the target through molecular docking and COX-2 binding-related assays, indicating that this strategy has potential medicinal-chemistry applications. It should be noted, however, that these results represent a methodological application validation. Molecular docking and in vitro binding data can show that structural modification may improve target interactions, but they cannot be directly equated with a comprehensive improvement in efficacy, safety, or clinical value.

7 Key Considerations for Method Applicability

This reaction is clearly innovative, but in practical use its applicability should be evaluated according to the substrate and the research objective.

Evaluation item	Key question	Impact on application
Substrate structure	Whether the nitro position, substituent electronic effects, and steric hindrance of the nitroarene favor photodeoxygenation to form the nitrene, aromatic-ring insertion, ring expansion, and selective carbon deletion	Affects nitrene-formation efficiency, the ring-expansion process, conversion, and regioselectivity
Substitution pattern and regioselectivity	Whether ortho-, meta-, or para-substitution may lead to different carbon-deletion sites or isomer formation	Determines whether the target pyridine product is single and whether it can be easily separated
Product type	Whether the target product is a 2-aminopyridine derivative or a pyridine derivative obtained through ipso-carbon deletion	Determines whether the C5-carbon-deletion pathway or the ipso-carbon-deletion pathway should be selected
Nucleophile selection	Whether an amine nucleophile or an aminoalcohol trapping system such as N-ethylethanolamine is used	Affects the mode of trapping of the 3H-azepine intermediate and determines product divergence
Photochemical conditions	Whether the light-source wavelength, light intensity, reactor configuration, reaction concentration, and irradiation time can be reliably reproduced	Affects nitroarene excitation, deoxygenation, and nitrene-formation efficiency
Oxygen-participating process	Whether the target is the 2-aminopyridine pathway and whether effective singlet-oxygen participation in C5-carbon deletion is required	Affects the efficiency of C5-carbon deletion and the yield of 2-aminopyridines
Catalytic system	Whether the type, loading, purity, and availability of the iron–porphyrin catalyst meet the reaction requirements	Affects singlet-oxygen utilization efficiency, reaction selectivity, and experimental reproducibility
Functional-group compatibility	Whether the substrate contains functional groups that may be affected by light, oxygen, phosphorus reagents, or reactive intermediates	Determines whether complex substrates, drug molecules, or late-stage modification substrates are suitable
Scalability	Whether the reaction objective is milligram-scale medicinal-chemistry screening or gram-scale and larger route development	Determines the requirements for yield, light transmission, oxygen control, purification, and safety

8 Product Classification Tables Related to the Skeletal Editing Strategy from Nitroarenes to Pharmaceutically Relevant Pyridines

Table 1. Nitroarene Substrates and Nitroarene Derivatives

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Parent nitroarene	98-95-3	N116219	Nitrobenzene	ACS, ≥99% (GC)	Basic nitroarene substrate, used for model studies on photodeoxygenation to generate aryl nitrenes and on aromatic-ring skeletal editing
Alkyl-substituted nitroarene	88-72-2	N104633	o-Nitrotoluene	≥99%	Ortho-alkyl-substituted substrate, used to examine the influence of steric hindrance on nitrene insertion, ring expansion, and regioselectivity
Alkyl-substituted nitroarene	99-08-1	N105604	m-Nitrotoluene	Chemically pure (CP)	Meta-alkyl-substituted substrate, used to study the influence of substitution position on the direction of carbon deletion and the formation of pyridine isomers
Alkyl-substituted nitroarene	99-99-0	N104645	p-Nitrotoluene	≥99%	Para-alkyl-substituted substrate, used for studies of aryl nitrene generation, substituent effects, and pyridine-framework transformation
Methoxy-substituted nitroarene	91-23-6	N108657	2-Nitroanisole	≥98%	Ortho-methoxy-substituted substrate, used to study the effects of electron-donating substituents and ortho effects on the skeletal editing pathway
Methoxy-substituted nitroarene	555-03-3	N159810	3-Nitroanisole	—	Meta-methoxy-substituted substrate, used to study the regioselectivity and product distribution of meta-substituted nitroarenes
Methoxy-substituted nitroarene	100-17-4	N105584	p-Nitroanisole	≥98%	Para-methoxy-substituted substrate, used to study the influence of electron-donating substituents on photodeoxygenation and aryl nitrene reactivity
Carboxylic acid-substituted nitroarene	62-23-7	N433134	4-Nitrobenzoic acid	Suitable for synthesis	Carboxylic acid-substituted nitroarene, used for studies on carboxyl functional-group tolerance and precursors to pyridine carboxylic acid-type structures
Ester-substituted nitroarene	619-50-1	E106598	Methyl 4-nitrobenzoate	≥99%	Ester-substituted nitroarene, used for studies on the construction of pharmaceutically relevant pyridine carboxylate frameworks
Aldehyde-substituted nitroarene	555-16-8	N104181	p-Nitrobenzaldehyde	AR, ≥97% (GC)	Aldehyde-substituted nitroarene, used for studies on carbonyl functional-group compatibility and the design of aldehyde-containing pyridine precursors
Cyano-substituted nitroarene	619-72-7	N107605	p-Nitrobenzonitrile	≥97%	Cyano-substituted nitroarene, used to study the influence of strongly electron-withdrawing substituents on photodeoxygenation, ring expansion, and product selectivity
Amino-substituted nitroarene	100-01-6	N111641	p-Nitroaniline	AR, ≥99%	Amino-substituted nitroarene, used for studies on nitrogen-containing functional-group compatibility and multifunctional aromatic substrates
Nitrophenol analytical standard	100-02-7	N128193	p-Nitrophenol standard solution	2000 μg/mL in methanol	Analytical standard for nitrophenols, used for nitroarene detection, method validation, and quantitative analysis
Halogenated nitroarene	350-46-9	F107055	1-Fluoro-4-nitrobenzene	≥98%	Fluorinated nitroarene, used for studies on the compatibility of halogen-substituted substrates and subsequent functional-group transformations
Halogenated nitroarene	586-78-7	B153155	1-Bromo-4-nitrobenzene	≥99% (GC)	Brominated nitroarene, used for substrate design studies linking skeletal editing with coupling reactions
Halogenated nitroarene	636-98-6	I107038	1-Iodo-4-nitrobenzene	≥98%	Iodinated nitroarene, used for highly reactive halogenated arene substrates and the design of subsequent cross-coupling sites
Fused-ring nitroarene	86-57-7	N101000	1-Nitronaphthalene	≥99%	Fused-ring nitroarene substrate, used for studies on fused pyridine frameworks and skeletal editing of polycyclic aromatic systems
Fused-ring nitroarene	581-89-5	N770121	2-Nitronaphthalene	≥98%	Fused-ring nitroarene isomer, used for studies on the regioselectivity of fused-ring substrates and isomer formation

Table 2. Photodeoxygenation Reagents, Nucleophilic Trapping Reagents, and Reaction Solvents

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Trivalent phosphorus deoxygenation reagent	121-45-9	T106149	Trimethyl phosphite	Chemically pure (CP), ≥95%	Photodeoxygenation reagent for nitroarenes, used for aryl nitrene generation and reaction-condition optimization
Trivalent phosphorus deoxygenation reagent	122-52-1	T105731	Triethyl phosphite	≥98%	Trivalent phosphorus deoxygenation reagent, used for nitro-group deoxygenation, nitrene generation, and phosphorus-reagent screening
Organophosphine control reagent	603-35-0	T104475	Triphenylphosphine	≥99% (GC)	Organophosphine reducing reagent, used for deoxygenation-reaction controls, phosphine-reagent screening, and mechanistic studies
Amine nucleophile	109-89-7	D110469	Diethylamine	Rectified grade, ≥99.5%	Amine nucleophilic trapping reagent, used for the formation of azepine intermediates and studies of the 2-aminopyridine pathway
Aminoalcohol nucleophile	141-43-5	E103808	Ethanolamine	Rectified grade, ≥99.5%	Aminoalcohol reference reagent, applicable as a reference for aminoalcohol trapping-system design and condition screening
Anhydrous ether solvent	109-99-9	T1491789	Tetrahydrofuran (THF)	Anhydrous grade, ≥99.9%, stabilizer-free, H₂O ≤30 ppm	Common anhydrous solvent for photochemical deoxygenation and water-sensitive systems, used for nitrene-generation reactions and condition screening
Anhydrous polar solvent	75-05-8	A119012	Anhydrous acetonitrile (ACN)	Anhydrous grade, ≥99.8%, H₂O ≤0.003%	Polar anhydrous solvent, used for photochemical reactions, oxygen-participating reactions, and reaction-system screening
Halogenated hydrocarbon solvent	75-09-2	D433567	Dichloromethane	Suitable for analysis, ACS	Halogenated hydrocarbon solvent, used for porphyrin-complex dissolution, reaction screening, extraction, and analytical sample pretreatment

Table 3. Porphyrin Ligands, Metalloporphyrin Catalysts, and Iron-Source Reagents

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Porphyrin ligand	917-23-7	M115647	meso-Tetraphenylporphine (TPP)	≥99%, chlorin-free	Porphyrin ligand, used for the preparation of metalloporphyrin catalysts, oxygen-activation models, and photooxidation studies
Iron–porphyrin catalyst	16456-81-8	T189043	meso-Tetraphenylporphine iron(III) chloride	≥95%	Iron–porphyrin catalyst, used for studies on singlet-oxygen-participating C5-carbon deletion and 2-aminopyridine formation
Manganese–porphyrin catalyst	32195-55-4	T303433	Manganese(III) tetraphenylporphyrin chloride	≥95%	Manganese–porphyrin complex, used for metalloporphyrin catalyst screening and control studies of oxygen-participating reactions
Cobalt–porphyrin catalyst	14172-90-8	C190873	Cobalt(II) tetraphenylporphyrin	≥95%	Cobalt–porphyrin complex, used for comparing metal-center effects and studying oxygen-activation-related reactions
Iron-source reagent	7705-08-0	I112064	Anhydrous iron(III) chloride	≥99.9% metals basis	High-purity iron-source reagent, used for iron-complex preparation, metal-impurity control experiments, and catalytic-system controls

Table 4. Pyridine Parent Core, Aminopyridines, and Functionalized Pyridine Building Blocks

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Pyridine parent core	110-86-1	P111513	Pyridine	Anhydrous grade, ≥99.8%	Basic pyridine structural unit, used for comparison of pyridine-framework properties, derivatization reactions, and medicinal-chemistry studies
Aminopyridine building block	504-29-0	A105221	2-Aminopyridine (2-AP)	Chemically pure (CP)	Representative 2-aminopyridine product, used for aminopyridine framework construction, derivatization, and target-binding studies
Aminopyridine building block	462-08-8	A107134	3-Aminopyridine	≥99%	Aminopyridine isomer, used for studies on amino-substitution position effects and as a pyridine-analogue control
Aminopyridine building block	504-24-5	A113920	4-Aminopyridine	≥98%	Aminopyridine isomer, used for studies on pyridine amino-position effects, hydrogen-bonding interactions, and structure–activity relationships
Halopyridine building block	109-09-1	C104870	2-Chloropyridine	≥98%	Chloropyridine building block, used for nucleophilic substitution, coupling reactions, and pyridine-analogue synthesis
Halopyridine building block	109-04-6	B109679	2-Bromopyridine	≥98%	Bromopyridine building block, used for cross-coupling, functional-group extension, and pyridine-framework derivatization
Cyanopyridine building block	100-70-9	P106583	2-Cyanopyridine	≥98%	Cyanopyridine building block, used for the synthesis of pyridine carboxylic acids, pyridine amides, and nitrogen-containing heterocyclic derivatives
Pyridine carboxylic acid building block	59-67-6	N433036	Nicotinic acid	Suitable for synthesis, Moligand™	3-Pyridinecarboxylic acid building block, used for nicotinic acid derivatives, amidation reactions, and pharmaceutically relevant pyridine-structure studies
Pyridine carboxylic acid building block	55-22-1	I101094	Isonicotinic acid (IN)	AR, Moligand™, ≥99%	4-Pyridinecarboxylic acid building block, used for the synthesis of isonicotinamide, isoniazid, and pyridine carboxylic acid derivatives
Pyridine carboxylate building block	93-60-7	M120395	Methyl nicotinate	≥99%	3-Pyridinecarboxylate building block, used for ester hydrolysis, amidation, and synthesis of nicotinic acid derivatives
Pyridine carboxylate building block	2459-09-8	M157816	Methyl isonicotinate	≥98%	4-Pyridinecarboxylate building block, used for the synthesis of isonicotinic acid derivatives and pharmaceutical intermediates
Drug-relevant pyridine molecule	54-85-3	I104692	Isoniazid	≥99%	Pyridine hydrazide drug molecule, used as a control for pharmaceutically relevant pyridine products and for acylhydrazide-structure derivatization studies
Drug-relevant pyridine molecule	535-83-1	T345622	Trigonelline	Moligand™, ≥98%	Nicotinic acid quaternary ammonium salt derivative, used for studies on pyridine-nitrogen quaternization structures, bioactive molecules, and reference standards

Table 5. Drug-Relevant Complex Molecules, Potential Derivatization Parent Structures, and Reference Compounds for Late-Stage Modification

Category	CAS No.	Aladdin Catalog No.	Name	Specification or Purity	Product Features and Applications
Complex steroid molecule	57-88-5	C432977	Cholesterol, plant-derived	≥98%	Complex steroidal scaffold molecule, used for complex-molecule derivatization, late-stage modification, and design of nitroarene-derived substrates
Arylpropionic acid drug	15687-27-1	I129291	Ibuprofen	Moligand™, ≥98% (GC)	Arylpropionic acid drug molecule, used for the design of drug-derived nitroarene substrates and pyridine analogues
p-Aminobenzoate drug	94-09-7	E107204	Ethyl 4-aminobenzoate	≥99%	Aromatic ester drug molecule, used for aromatic-drug-scaffold derivatization and late-stage functionalization studies
Nitroaromatic drug	51803-78-2	N159746	Nimesulide	Moligand™, ≥98% (HPLC)	Nitroaromatic drug molecule, used for nitroarene skeletal editing, nitro-group replacement, and pyridine-analogue studies
Heterocycle-containing drug molecule	113665-84-2	M637412	Clopidogrel	Moligand™, ≥97%	Complex heterocycle-containing drug molecule, used for late-stage modification of drug scaffolds and as a control for pyridine analogues
Aryloxy arylamine drug	56296-78-7	F131623	Fluoxetine hydrochloride	≥98% (HPLC)	Aryloxy arylamine drug molecule, used for late-stage functionalization of complex drug scaffolds and nitrogen-containing heterocycle replacement studies
Aryloxy arylamine drug	82248-59-7	A129721	Atomoxetine hydrochloride	≥98%	Aryloxy arylamine drug molecule, used for drug-analogue design, aromatic-framework replacement, and late-stage modification studies

Note: The products listed above are representative Aladdin products related to scientific research and formulation research. For additional product specifications, grades, and COA information, please search by product name/CAS/catalog number on the Aladdin official website.

References

[1] Saha, A.; Pan, A.; Ghosh, D.; Pal, A.; Guin, S.; Redhu, A. K.; Gota, V.; Maiti, D. A General Strategy to Access Pharmaceutically Relevant Pyridines from Nitroarenes. Angew. Chem. Int. Ed. 2025, e17867; final issue: 2026, 65, e17867. DOI: 10.1002/anie.202517867.

[2] Dwivedi, A. R.; Jaiswal, S.; Kukkar, D.; Kumar, R.; Singh, T. G.; Singh, M. P.; Gaidhane, A. M.; Lakhanpal, S.; Prasad, K. N.; Kumar, B. A decade of pyridine-containing heterocycles in US FDA approved drugs: a medicinal chemistry-based analysis. RSC Med. Chem. 2025, 16, 12–36. DOI: 10.1039/D4MD00632A.

[3] Sharma, R.; Arisawa, M.; Takizawa, S.; Salem, M. S. H. Remodelling molecular frameworks via atom-level surgery: recent advances in skeletal editing of (hetero)cycles. Org. Chem. Front. 2025, 12, 1633–1670. DOI: 10.1039/D4QO02157F.

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