Isoxazole Compounds: How Does a Five-Membered N,O-Heterocycle Influence the Performance of Drugs, Agrochemicals, and Functional Molecules?

1 What Are Isoxazole Compounds?

Isoxazole compounds refer to compounds that contain an isoxazole ring in their molecular structure. The isoxazole ring is a five-membered N,O-containing heteroaromatic ring composed of three carbon atoms, one nitrogen atom, and one oxygen atom, with the nitrogen and oxygen atoms positioned adjacent to each other in the ring.

 

The isoxazole ring itself is small, but its influence on molecular properties is not minor. It can alter molecular rigidity, polarity, hydrogen-bond acceptor distribution, substituent extension direction, metabolic stability, and reaction transformation pathways. Reviews in medicinal chemistry indicate that isoxazole compounds exhibit broad biological activities, with common research directions including antibacterial, anti-inflammatory, and antitumor activities. The introduction of an isoxazole ring may also improve the physicochemical properties of molecules.

Isoxazole should be distinguished from several structurally related motifs.

Type	Structural Feature	Main Difference
Isoxazole	Aromatic five-membered N,O-containing ring	Main focus of this article
Oxazole	Also contains nitrogen and oxygen, but with different N/O positions	Positional isomer with different electronic distribution
Isoxazoline	Partially saturated analogue of isoxazole	Different aromaticity, spatial shape, and target interaction
Isoxazolidine	More saturated five-membered N,O-containing ring	More flexible; commonly found in synthetic intermediates or structural transformation studies

This article focuses on aromatic isoxazole compounds; isoxazolines are discussed separately in the relevant application section.

2 Structural Features of the Isoxazole Ring

2.1 A Five-Membered Small Ring Brings Conformational Restriction

The isoxazole ring is smaller than a benzene ring and more rigid than a typical alkyl chain. It can fix substituents in relatively defined spatial directions and reduce local free rotation.

This is important in drug and agrochemical design. When active molecules bind to enzymes, receptors, ion channels, or plant targets, they require not only appropriate functional groups but also the proper orientation of these functional groups into the binding site. The isoxazole ring can serve as a small “spatial positioning unit”, helping a molecule form a more stable binding pose.

2.2 Adjacent Nitrogen and Oxygen Alter Polarity and Hydrogen-Bonding Patterns

In the isoxazole ring, the nitrogen and oxygen atoms are adjacent to each other, giving this five-membered ring a distinctive electronic distribution. The pyridine-like nitrogen in the ring is usually the main hydrogen-bond acceptor, while the oxygen atom may also participate in weaker hydrogen-bond acceptor interactions. The actual strength of these interactions depends on substituents, conformation, protonation state, and the binding environment. The five-membered aromatic ring may also participate in aromatic interactions and hydrophobic contacts.

It should be noted that isoxazole is not a strongly hydrophilic group. Whether an isoxazole-containing molecule has good water solubility depends on the hydrophobic fragments, ionizable groups, molecular weight, and crystal form of the entire molecule. If the molecule also contains multiple aromatic rings, halogens, trifluoromethyl groups, or long alkyl chains, it may still show relatively strong lipophilicity overall.

2.3 Substitution Position Determines the Direction of Molecular Extension

Common substitution patterns of isoxazole include 3-substitution, 4-substitution, 5-substitution, 3,5-disubstitution, 3,4,5-trisubstitution, and benzisoxazole structures. Different substitution positions change the spatial extension directions of different molecular fragments.

In research and development, the key question is not simply “whether the molecule contains an isoxazole ring”, but rather: at which position is the substituent attached? Does this position direct the hydrophobic group, hydrogen-bond acceptor, or reactive center in the correct direction?

Isoxazoles substituted at the 3-position and 5-position may have the same molecular weight, but their spatial orientation differs. Their activity, selectivity, solubility, and metabolic stability may all differ as a result.

2.4 The N–O Bond Provides Transformability

The isoxazole ring is not only a final structural motif but can also serve as a synthetic intermediate. Literature reports show that isoxazole structures can serve as precursors for the synthesis of β-hydroxy carbonyl compounds and γ-amino alcohols. Related N,O-containing five-membered rings such as isoxazolines and isoxazolidines are also commonly involved in reductive ring opening and structural transformations. Some aromatic isoxazole systems can also undergo ring opening, hydrolysis, reduction, or rearrangement under specific conditions.

This feature has two sides in synthetic design. On the one hand, isoxazole can be used as a tool for constructing complex molecules. On the other hand, its stability should also be evaluated under strongly reducing, strongly acidic, strongly basic, light-irradiation, or certain metal-mediated reaction conditions.

3 How Structure Influences Molecular Performance

Structural Feature of Isoxazole	Possible Performance Change	Practical Problem It May Help Solve
Five-membered aromatic small ring	Increases local rigidity	Reduces ineffective conformations and improves binding-pose stability
Adjacent nitrogen and oxygen	Alters dipole and hydrogen-bond acceptor distribution	Changes target recognition mode
Multiple substitution sites	Facilitates regulation of spatial orientation and electronic effects	Supports systematic structural optimization
Aromatic heterocycle feature	Provides aromatic interactions and a certain degree of stability	Improves binding affinity or molecular stability
Transformable N–O bond	Can be used for ring opening, reduction, or precursor transformation	Supports synthetic routes or prodrug/pro-pesticide design
Compact small-ring structure	Small size and strong directionality	Replaces larger structural fragments in limited binding pockets

The role of an isoxazole structure must be judged in the context of the specific molecule. It may sometimes improve activity, enhance selectivity, or increase stability, but it may also bring negative effects such as reduced solubility, altered metabolism, or poor target matching.

4 Representative Product Case: The Isoxazole Structure in Oxacillin

Oxacillin is a representative isoxazolyl penicillin antibiotic. Isoxazolyl penicillins are a class of semisynthetic antibiotics, with representative drugs including oxacillin, cloxacillin, dicloxacillin, and flucloxacillin. These drugs are formed by connecting an isoxazolyl group to the 6-aminopenicillanic acid nucleus. They are acid-resistant and show tolerance to penicillinases produced by Gram-positive bacteria.

4.1 Structural Division of Labor in Oxacillin

Oxacillin contains two key structural levels.

① β-Lactam core.

This is the key moiety responsible for the antibacterial action of penicillin antibiotics. Penicillins exert bactericidal effects by interfering with bacterial cell wall synthesis.

② Isoxazole side chain.

The isoxazole side chain is not the primary bactericidal site, but it changes the spatial shape of the molecule, making the β-lactam core less susceptible to destruction by certain penicillinases.

4.2 What Problem Does the Isoxazole Side Chain Solve?

Ordinary penicillin is readily destroyed by penicillinases produced by certain bacteria. Isoxazolyl penicillins such as oxacillin improve tolerance to certain penicillinases through the steric effect of the side chain. This case illustrates that the role of the isoxazole ring is not necessarily to directly enhance the pharmacologically active core. It may instead protect the active core, alter stability, or expand the effective application scenario.

4.3 Precautions for Oxacillin Use

Oxacillin is indicated for infections caused by penicillinase-producing staphylococci that have been confirmed to be susceptible to it. The prescribing information requires that cultures and susceptibility testing should be performed whenever possible before initial treatment. If susceptibility results show that the infection is not caused by the corresponding susceptible staphylococci, oxacillin should not be continued. Therefore, “penicillinase resistance” should not be understood as “suitable for all resistant infections”. Whether the drug is appropriate depends on the pathogen, susceptibility results, patient condition, and clinical diagnosis.

5 Agrochemical Case: The Isoxazole Structure in Isoxaflutole

Isoxaflutole is an herbicide containing an isoxazole structure. It is used to control certain grass and broadleaf weeds, and its mechanism of action is related to inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD). When this enzyme is inhibited, plant pigment formation is disrupted, and susceptible weeds develop bleaching symptoms. Evaluation materials from the Food and Agriculture Organization of the United Nations and the World Health Organization indicate that isoxaflutole can control various grass and broadleaf weeds after uptake through the root system.

5.1 Key Feature of Isoxaflutole: Precursor Transformation

The special value of isoxaflutole lies in the fact that it does not rely solely on the parent molecule for activity. Studies show that isoxaflutole can be rapidly converted in plants and soil into a diketonitrile derivative. This diketonitrile form is an important active form and can inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD). This indicates that, in agrochemical molecules, the isoxazole ring may sometimes be more than a stable structural fragment; it can also participate in the design logic of a “precursor–active form” relationship.

 

5.2 Agrochemical Problems It Addresses

The isoxaflutole case reflects three practical issues:

① Weed control.

It controls susceptible weeds by affecting pigment formation through a specific enzyme target.

② Application and uptake.

Properties related to soil behavior and root uptake influence its pre-emergence or early-stage treatment effects.

③ Activity release.

The parent molecule is converted into the active diketonitrile form, making structural transformation part of efficacy design.

5.3 Precautions for Use

Agrochemical products cannot be used solely based on structural judgment. The actual performance of isoxaflutole is related to crop species, soil conditions, organic matter, rainfall, application timing, weed species, and resistance management. Herbicides must be used according to registered labels and local regulations. Crop range, dose, or application timing should not be expanded arbitrarily.

6 Main Applications of Isoxazole Compounds

6.1 Pharmaceutical Field

In the pharmaceutical field, the isoxazole ring is often used to modulate molecular activity, selectivity, stability, and physicochemical properties. Review materials show that isoxazole compounds have been widely studied in antibacterial, anti-inflammatory, antitumor, and other research directions. Some compounds containing isoxazole structures have also entered clinical drugs or candidate drug research. In drug design, isoxazole is mainly used to address the following problems:

R&D Problem	Possible Role of Isoxazole
The molecule is too flexible	Increases rigidity and fixes substituent orientation
Hydrogen-bonding direction is unsuitable	Changes hydrogen-bond acceptor position and dipole direction
Functional groups are prone to hydrolysis	Serves as a replacement for certain amide, ester, or carbonyl fragments
Target selectivity is insufficient	Changes the spatial matching between the molecule and the binding pocket
Structural optimization space is limited	Enables series construction through 3-, 4-, and 5-substitution

Isoxazole does not guarantee improved activity. Any structural replacement must be validated using data on activity, selectivity, solubility, metabolic stability, safety, and in vivo exposure.

6.2 Agrochemical Field

In the agrochemical field, isoxazole or related structures can be used in herbicides, insecticides, and acaricides. Their value lies not only in improving activity but also in regulating crop selectivity, soil behavior, residual activity, uptake and transformation, and target action. In agrochemical selection, the following points should be emphasized:

Focus	Specific Question
Target mechanism	Whether it matches the main field weeds or pests
Crop safety	Whether it is suitable for the target crop and growth stage
Soil behavior	Whether there are risks of residue, leaching, or rotational crop injury
Application window	Whether it is suitable for pre-emergence, post-emergence, soil treatment, or foliar treatment
Resistance management	Whether the same mode of action is being used continuously over the long term

6.3 Veterinary-Related Field

Isoxazoline compounds are structurally related to isoxazole compounds, but they are not the same class as aromatic isoxazoles. Isoxazoline flea and tick products listed by the U.S. Food and Drug Administration include fluralaner, lotilaner, afoxolaner, and others. They are mainly used for flea and tick control in dogs and cats. The agency also notes that these products are safe and effective for most dogs and cats, but in some dogs and cats they have been associated with reports of neurological adverse events such as muscle tremors, ataxia, and seizures. Veterinary consultation should take the animal’s medical history into account before use.

6.4 Organic Synthesis Field

The isoxazole ring can be constructed through 1,3-dipolar cycloaddition between nitrile oxides and alkynes. Reactions between nitrile oxides and alkenes usually first give isoxazolines, which can subsequently be oxidized or otherwise converted into aromatic isoxazoles. Cyclization between hydroxylamine and suitable carbonyl compounds is also an important route for constructing isoxazoles and related N,O-containing five-membered heterocycles.

One study reported the preparation of 3,4,5-trisubstituted isoxazoles in water under mildly basic, room-temperature conditions through the reaction of nitrile oxides with 1,3-dicarbonyl compounds, β-ketoesters, or β-ketoamides. The study also noted that conditions need to be optimized to control selectivity and reduce competitive reactions such as nitrile oxide dimerization, O-trapping, or other side reactions.

In synthesis, isoxazole mainly addresses three problems:

① Rapid construction of five-membered N,O-containing heterocycles.

Suitable for preparing libraries of polysubstituted heterocyclic compounds.

② Fixing the spatial orientation of multiple substituents.

Suitable for lead structure optimization in drug and agrochemical research.

③ Serving as a transformable intermediate.

It can be converted under specific conditions into hydroxy carbonyl compounds, amino alcohols, and other structures.

6.5 Functional Molecule Field

In functional molecules, the isoxazole ring can be used to regulate rigidity, electronic distribution, coordination ability, and recognition mode. It may appear in fluorescent probes, ligands, molecular recognition units, or functional material molecules. The design focus in this field is overall structural matching rather than reliance on the isoxazole ring alone. Whether isoxazole is useful depends on whether it genuinely improves luminescence, recognition, coordination, stability, or assembly behavior.

7 How to Select Isoxazole Compounds

7.1 First Clarify the Problem to Be Solved

Before using an isoxazole structure, the target problem should first be identified.

Target Problem	Whether Isoxazole Is Worth Considering	Key Verification
The molecule is too flexible and the binding pose is unstable	Suitable	Conformation, activity, target binding
A hydrogen-bond acceptor in a specific direction is needed	Can be considered	Hydrogen-bond direction, binding mode
A hydrolysis-prone functional group needs to be replaced	Can be tested	Hydrolytic stability, metabolic stability
Selectivity needs to be changed	Can be considered	Selectivity profile and safety
Simply trying to improve water solubility	Should not be used blindly	Solubility, lipophilicity, salt form, or crystal form
A series of compounds needs to be constructed	Suitable	Comparison of different substitution positions and substituents
A transformable precursor is needed	Can be considered	Transformation conditions, transformation products, stability

7.2 Selection in Drug Discovery and Development

In drug discovery and development, the isoxazole ring is suitable as a structural optimization tool. A reasonable judgment sequence is as follows:

① Confirm the main defect of the original molecule.

Is the problem insufficient activity, poor selectivity, metabolic instability, low solubility, or excessive conformational flexibility?

② Assess whether isoxazole can address the defect.

For example, isoxazole may be used to increase rigidity, adjust hydrogen-bond acceptor direction, or replace a hydrolysis-prone fragment.

③ Validate with experimental data.

At minimum, activity, selectivity, solubility, metabolic stability, cellular performance, and safety should be compared.

7.3 Selection in Agrochemical Development and Use

Agrochemical selection cannot rely only on the structure of the active ingredient; field conditions must also be considered.

① Whether the crop is suitable.

The safety of the same active ingredient may differ among crops, varieties, and growth stages.

② Whether the target is suitable.

Different weed or pest species may show major differences in control efficacy.

③ Whether soil and climate are suitable.

Soil organic matter, humidity, rainfall, temperature, and light exposure all affect efficacy and residues.

④ Whether resistance management is suitable.

Long-term use of products with the same mode of action increases resistance risk. Rotation, mixtures, and nonchemical control measures should be integrated.

7.4 Selection of Synthetic Intermediates

Selection of synthetic intermediates should focus on route feasibility.

① Whether the starting materials are stable and readily available.

The stability and cost of starting materials such as nitrile oxides, hydroximoyl chlorides, alkynes, and dicarbonyl compounds affect scale-up.

② Whether regioselectivity is controllable.

Mixtures of isomers increase purification difficulty and may also affect subsequent activity evaluation.

③ Whether side reactions are controllable.

Nitrile oxides may undergo competitive reactions such as dimerization, O-trapping, and C-trapping. Related studies show that condition optimization is critical for obtaining the target isoxazole product.

④ Whether subsequent reactions will damage the isoxazole ring.

Strong reducing conditions, strong acids, strong bases, intense light exposure, or certain metal systems may cause ring opening or rearrangement.

8 Product Selection Navigation for Isoxazole Compounds: From Basic Scaffolds and Drug Structures to Agrochemical and Veterinary Applications

Research or Experimental Goal	Which Table to Consult First	Why Start with This Table	Suggested Linked Table(s)	Navigation Tip
Establish a basic structural understanding of isoxazole compounds	Table 3	Table 3 lists basic scaffolds such as isoxazole, benzisoxazole, methyl isoxazoles, isoxazole carboxylic acids, and amino isoxazoles. It helps readers first understand the five-membered N,O-containing heterocycle, substitution positions, and functionalization patterns	Tables 1 and 2	Start with the parent ring, substitution position, and functional group type, and then understand how these structures extend into drug, agrochemical, and veterinary active molecules
Compare how 3-, 4-, and 5-substitution affect structural orientation and reaction use	Table 3	Table 3 includes 3-, 4-, and 5-isoxazole carboxylic acids, as well as 3- and 5-methyl- and amino-substituted isoxazoles, making it suitable for comparing positional isomers and structural modification patterns	Table 1	First compare substitution positions, and then examine how isoxazole fragments influence drug structures in molecules such as sulfamethoxazole, isocarboxazid, and oxacillin
Design isoxazole drug fragments, amide coupling reactions, or heterocyclic derivative synthesis experiments	Table 3	Isoxazole carboxylic acids, amino isoxazoles, and aryl isoxazole carboxylic acids in Table 3 are commonly used linking units. They can be used for amidation, sulfonamidation, urea construction, and compound library preparation	Table 1	First identify the reactive functional group, and then determine from known drug structures whether the target fragment is intended for antibacterial, anti-inflammatory, central nervous system, or immunomodulatory research
Study how isoxazolyl penicillin side chains influence antibacterial drug stability	Table 1	Table 1 lists isoxazolyl penicillins such as oxacillin, dicloxacillin, and flucloxacillin, allowing direct comparison of side-chain structures and penicillinase-resistant characteristics	Table 3	Link to 5-methyl-3-phenylisoxazole-4-carboxylic acid to understand the side-chain source of oxacillin-type compounds and the isoxazole carboxamide structure
Compare isoxazole fragments in sulfonamide antibacterial drugs	Table 1	Table 1 includes sulfamethoxazole and sulfisoxazole, which can be used to compare methyl isoxazole fragments, sulfonamide structures, and antibacterial drug scaffolds	Table 3	Link to intermediates such as 3-amino-5-methylisoxazole and 3,5-dimethylisoxazole to understand the construction logic of isoxazole fragments in sulfonamide drugs
Study the role of isoxazole structures in anti-inflammatory and analgesic drugs	Table 1	Table 1 includes valdecoxib, parecoxib, and parecoxib sodium, which can be used to analyze diaryl isoxazole scaffolds, prodrug forms, and salt-form differences	Table 3	Combine with basic isoxazole and aryl isoxazole fragments to understand the role of the isoxazole ring in rigidity, aromatic substitution, and drug-fragment connection
Study the application of benzisoxazole structures in central nervous system drugs	Table 1	Table 1 includes zonisamide, risperidone, paliperidone, and iloperidone, which can be used to analyze the structural role of benzisoxazole in antiepileptic and antipsychotic drugs	Table 3	Link to 1,2-benzisoxazole to first understand the fused heterocyclic parent scaffold, and then compare substituents and functional directions in different drugs
Study isoxazole natural products or neuropharmacological research tools	Table 1	Table 1 includes ibotenic acid, muscimol, and acivicin, which can be used for experiments related to neuroactivity, amino acid analogues, and metabolic inhibition	Table 3	Link to the basic scaffold table to distinguish isoxazole, isoxazolol, isoxazole carboxylic acid, and isoxazoline structures in biological activity
Study the role of isoxazole structures in immunomodulation and metabolic transformation	Table 1	Table 1 includes leflunomide, which can be used for studies of isoxazole carboxamide structures, immunomodulatory drugs, and active metabolite formation	Table 3	Link to isoxazole carboxylic acid and amino isoxazole intermediates to understand the fragment-design basis of isoxazole carboxamide structures
Conduct pesticide residue analysis, calibration-curve establishment, or method validation for isoxazole agrochemicals	Table 2	Table 2 includes isoxaflutole standard solution and hymexazol standard solution, which can be used for instrumental analysis, residue detection, recovery validation, and quality control	Table 3	Link to the basic scaffold table to understand the isoxazole structural types corresponding to the standards, facilitating the selection of detection ions and separation conditions during method development
Study precursor transformation and target action of isoxazole herbicides	Table 2	Isoxaflutole in Table 2 is the agrochemical case discussed in the article. It can be used to study pro-herbicide design, the active diketonitrile form, and inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD)	Table 3	Link to isoxazole carboxylic acids and basic parent scaffolds to understand the stability, transformability, and spatial configuration of isoxazole structures in agrochemical molecules
Study pre-emergence herbicides, crop selectivity, and soil treatment systems	Table 2	Table 2 includes isoxaben and isoxaflutole, which can be used to compare different isoxazole herbicides in soil treatment, weed control, and residue analysis	Table 3	Link to the basic scaffold and intermediate table to distinguish aromatic isoxazoles, isoxazolines, and other related five-membered N,O-containing rings
Study crop safeners and herbicide detoxification metabolism	Table 2	Table 2 includes isoxadifen-ethyl, which can be used for studies of crop selectivity protection, herbicide detoxification metabolism, and agrochemical compatibility	Table 3	Link to the basic structure table to understand the differences between isoxazoline carboxylate esters and aromatic isoxazoles in structure and use
Study the ectoparasite-control activity of isoxazoline veterinary drugs	Table 2	Table 2 lists fluralaner, afoxolaner, sarolaner, and lotilaner, which can be used for flea and tick control activity, structure–activity relationship, and safety evaluation	Tables 1 and 3	First clarify that these products belong to isoxazoline-related structures, and then distinguish them from aromatic isoxazole drugs and basic scaffolds to avoid confusing five-membered N,O rings with different degrees of saturation
Select starting products for drug screening, agrochemical screening, or methodology research	Tables 1, 2, and 3	The three tables correspond to different starting points: Table 1 is suitable for active-molecule research, Table 2 for agrochemical and veterinary applications, and Table 3 for structural construction and intermediate synthesis	Select linked tables according to the experimental goal	For activity validation, consult Table 1 or Table 2 first; for synthesis, fragment modification, and structural comparison, consult Table 3 first

Table 1 | Pharmaceutical Active Molecules and Natural Product Research Tools

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
Isoxazolyl penicillin antibacterial drug	66-79-5	O612572	oxacillin	Moligand™, ≥98%	The isoxazole side chain can improve the tolerance of the penicillin nucleus to certain penicillinases. It is used in studies of β-lactam antibacterial drug structures, enzyme resistance, and antimicrobial susceptibility
Isoxazolyl penicillin antibacterial drug	3116-76-5	D609874	dicloxacillin	Moligand™	A representative isoxazolyl penicillin molecule, useful for comparing the effects of halogenated aryl side chains on penicillinase tolerance, antibacterial spectrum, and structural stability
Isoxazolyl penicillin antibacterial drug	5250-39-5	F610349	flucloxacillin	Moligand™	A penicillin drug containing a fluoro/chloro-substituted isoxazole side chain, useful for studying side-chain steric effects, antibacterial activity, and structural differences among β-lactam drugs
Sulfonamide antibacterial drug	723-46-6	S105341	Sulfamethoxazole	Moligand™, ≥98%	A classic sulfonamide antibacterial drug containing a methyl isoxazole fragment, useful for studies of sulfonamide drug structures, antibacterial mechanisms, and combination antibacterial systems
Sulfonamide antibacterial drug	127-69-5	S118593	Sulfisoxazole	≥98%	A sulfonamide antibacterial drug containing a dimethyl isoxazolyl group, useful for comparing the effects of isoxazole substituents on the physicochemical properties and antibacterial activity of sulfonamide drugs
Cyclooxygenase-2 inhibitor	181695-72-7	V125795	Valdecoxib	Moligand™, ≥99%	An anti-inflammatory and analgesic active molecule containing a diaryl isoxazole scaffold, useful for research on cyclooxygenase-2 inhibitors, aryl sulfone structures, and heterocyclic pharmacophores
Cyclooxygenase-2 inhibitor prodrug	198470-84-7	P135573	Parecoxib	Moligand™, ≥98%	A valdecoxib-related prodrug, useful for studying isoxazole aryl sulfone structures, injectable anti-inflammatory and analgesic drugs, and prodrug transformation behavior
Cyclooxygenase-2 inhibitor prodrug salt	198470-85-8	P302693	Parecoxib Sodium	≥99%	A commonly used sodium salt form of parecoxib, useful for studies of salt-form differences, solubility, prodrug release, and anti-inflammatory analgesic drug quality
Immunomodulatory drug	75706-12-6	L129518	Leflunomide	Moligand™, ≥98%	Contains a 5-methylisoxazole carboxamide fragment, useful for studies of immunomodulatory drugs, active metabolite formation, and isoxazole carboxamide structures
Antiepileptic drug	68291-97-4	Z276568	Zonisamide	Moligand™, ≥99%	Contains a benzisoxazole methanesulfonamide scaffold, useful for studies of antiepileptic drugs, neuronal excitability regulation, and sulfonamide heterocyclic drugs
Monoamine oxidase inhibitor	59-63-2	I339690	Isocarboxazid	Moligand™, ≥98%	Contains a methyl isoxazole carbohydrazide fragment, useful for studies of monoamine oxidase inhibitors, hydrazide drug structures, and central nervous system drugs
Benzisoxazole antipsychotic drug	106266-06-2	R127644	Risperidone	Moligand™, ≥98%	Contains a fluorinated benzisoxazole fragment, useful for studies of atypical antipsychotics, receptor-binding profiles, and central nervous system drug structures
Benzisoxazole antipsychotic drug	144598-75-4	P120141	Paliperidone	Moligand™, ≥98%	A risperidone-related active molecule retaining the benzisoxazole structure, useful for metabolite controls, receptor action studies, and long-acting formulation research
Benzisoxazole antipsychotic drug	133454-47-4	I125279	Iloperidone	Moligand™, ≥98%	Contains a fluorinated benzisoxazole structure, useful for antipsychotic drug structure studies, receptor selectivity evaluation, and central nervous system drug assessment
Fused isoxazole steroid drug	17230-88-5	D132177	danazol	Moligand™, ≥98%	Contains a fused isoxazole steroid scaffold, useful for studies of steroid drugs, endocrine regulation, and heterocycle-fused steroid structures
Isoxazoline natural product research tool	42228-92-2	A134970	Acivicin	Moligand™, ≥97%	A glutamine analogue containing an isoxazoline structure, useful for studies of glutamine metabolism, amidotransferase inhibition, and metabolic pathways
Isoxazole neuroactive natural product	2552-55-8	A137136	Ibotenic acid	Moligand™, ≥95%	Contains a hydroxyisoxazole-substituted α-amino acid structure, useful for studies of excitatory amino acid receptors, neurotoxicology, and neurolesion models
Isoxazole neuroactive research tool	2763-96-4	M1438210	Muscimol	≥99%	Contains an isoxazolol structure, useful for studies of γ-aminobutyric acid receptor activation, neural inhibitory pathways, and neuropharmacology

Table 2 | Compounds Related to Agrochemicals, Veterinary Drugs, and Parasite Control

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
Isoxazole herbicide standard	141112-29-0	BWY396507	Isoxaflutole Solution in Acetonitrile	100 μg/mL in Acetonitrile, uncertainty 3%	A standard solution of an isoxazole pro-herbicide, used for pesticide residue detection, method calibration, and studies related to 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibition
Isoxazole soil fungicide standard	10004-44-1	BWY397355	Hymexazol Solution in Methanol	100 μg/mL in Methanol, uncertainty 3%	A hymexazol standard solution, useful for soil fungicide residue analysis, seed-treatment agent detection, and method validation
Isoxazole herbicide	82558-50-7	I354299	Isoxaben	≥95%	A benzamide-type isoxazole herbicide, useful for pre-emergence broadleaf weed control, studies of plant cell wall formation, and pesticide residue analysis
Isoxazoline herbicide safener	163520-33-0	I331164	Isoxadifen-ethyl	≥98%	An isoxazoline carboxylate herbicide safener, useful for studies of crop selectivity protection, herbicide detoxification metabolism, and agrochemical compatibility
Isoxazoline ectoparasite-control active substance	864731-61-3	F413470	Fluralaner	≥99%	An isoxazoline insecticidal and acaricidal active molecule, useful for research on flea and tick control drugs and ligand-gated chloride channel-related mechanisms
Isoxazoline ectoparasite-control active substance	1093861-60-9	A649382	Afoxolaner	Moligand™, ≥99%	A representative isoxazoline ectoparasite-control molecule, useful for evaluating flea and tick control activity in dogs and studying insecticidal and acaricidal mechanisms
Isoxazoline ectoparasite-control active substance	1398609-39-6	S647577	Sarolaner	≥99%	An isoxazoline parasite-control active substance, useful for studies of ectoparasite efficacy, structure–activity relationships, and veterinary insecticidal/acaricidal drugs
Isoxazoline ectoparasite-control active substance	1369852-71-0	L651016	Lotilaner	≥99%	An isoxazoline flea and tick control active molecule, useful for studies of ectoparasite-control drugs, dose–exposure relationships, and safety evaluation

Table 3 | Basic Scaffolds, Key Intermediates, and Structural Modification Units

Category	CAS No.	Aladdin Cat. No.	Name	Specification or Purity	Product Features and Applications
Basic isoxazole parent scaffold	288-14-2	I133354	Isoxazole	Moligand™, ≥98%	The basic parent ring of isoxazole compounds, useful for studies of five-membered N,O-containing heteroaromatic ring properties, substitution reactions, and drug-fragment design
Basic benzisoxazole parent scaffold	271-95-4	B151955	1,2-Benzisoxazole	≥96% (GC)	A basic benzisoxazole scaffold, useful for studies of antipsychotic and antiepileptic drug-related fragments and fused heteroaromatic ring structures
Alkyl-substituted isoxazole intermediate	30842-90-1	M695223	3-Methylisoxazole	≥97%	A 3-methyl-substituted isoxazole building unit, useful for positional-effect comparison, heterocycle substitution reactions, and small-molecule fragment optimization
Alkyl-substituted isoxazole intermediate	5765-44-6	M158646	5-Methylisoxazole	≥95% (GC)	A 5-methyl-substituted isoxazole building unit, useful for isomer comparison, substituent-orientation regulation, and drug-fragment screening
Dialkyl-substituted isoxazole intermediate	300-87-8	D122898	3,5-Dimethylisoxazole	≥99%	A dimethyl-substituted isoxazole basic fragment, useful for polysubstituted isoxazole synthesis, comparison of dialkyl substitution positional effects, and heterocyclic electronic-effect studies
Isoxazole carboxylic acid intermediate	3209-71-0	I133309	Isoxazole-3-carboxylic acid	≥97%	A 3-carboxylated isoxazole, useful for amide coupling, esterification, drug-fragment connection, and studies of carboxylic acid bioisosteres
Isoxazole carboxylic acid intermediate	6436-62-0	I341530	Isoxazole-4-carboxylic acid	≥97%	A 4-carboxylated isoxazole, useful for constructing centrally linked isoxazole fragments, amide library synthesis, and substitution-position effect studies
Isoxazole carboxylic acid intermediate	21169-71-1	I121616	Isoxazole-5-carboxylic acid	≥98%	A 5-carboxylated isoxazole, useful for the synthesis of carboxamide candidate molecules, heterocyclic fragment assembly, and positional-isomer control studies
Isoxazolyl penicillin side-chain intermediate	1136-45-4	W134259	5-Methyl-3-phenylisoxazole-4-carboxylic acid	≥99%	A carboxylic acid related to oxacillin-type side chains, useful for studies of isoxazole aryl carboxamide fragments, β-lactam side-chain design, and amide coupling
Aminoisoxazole intermediate	1750-42-1	A124591	3-Aminoisoxazole	≥95%	A 3-aminoisoxazole building unit, useful for the synthesis of sulfonamide, urea, amide heterocyclic derivatives, and drug fragments
Aminoisoxazole intermediate	14678-05-8	I587306	Isoxazol-5-amine	≥98%	A 5-aminoisoxazole intermediate, useful for positional-isomer comparison, construction of nitrogen-substituted heterocycles, and coupling reactions
Methyl amino isoxazole intermediate	1072-67-9	A151654	3-Amino-5-methylisoxazole	≥97% (GC)	An important fragment related to sulfamethoxazole, useful for sulfonamide drug synthesis, antibacterial drug intermediates, and amino isoxazole derivative research
Methyl amino isoxazole intermediate	14678-02-5	A151656	5-Amino-3-methylisoxazole	≥97% (T)	A positional isomer of methyl amino isoxazole, useful for structure–activity relationship comparison, amino-substitution orientation regulation, and heterocyclic drug intermediate development

Note: The above are representative Aladdin products. For more product specifications, search by “product name/CAS/catalog number” on the Aladdin official website.

References

[1] PubChem. Isoxazole.

[2] Zhu, J.; Mo, J.; Lin, H.-Z.; Chen, Y.; Sun, H.-P. The recent progress of isoxazole in medicinal chemistry. Bioorganic & Medicinal Chemistry, 2018, 26, 3065–3075. DOI: 10.1016/j.bmc.2018.05.013.

[3] Wang, X.; Hu, Q.; Tang, H.; Pan, X. Isoxazole/Isoxazoline Skeleton in the Structural Modification of Natural Products: A Review. Pharmaceuticals, 2023, 16, 228. DOI: 10.3390/ph16020228.

[4] Gore, G.; Prester, A.; von Stetten, D.; Bartels, K.; Schulz, E. C. Binding mode of Isoxazolyl Penicillins to a Class-A β-lactamase at ambient conditions. Communications Chemistry, 2025, 8, 387. DOI: 10.1038/s42004-025-01801-x.

[5] DailyMed. Oxacillin for Injection, Prescribing Information.

[6] Viviani, F.; Little, J. P.; Pallett, K. E. The Mode of Action of Isoxaflutole II. Characterization of the Inhibition of Carrot 4-Hydroxyphenylpyruvate Dioxygenase by the Diketonitrile Derivative of Isoxaflutole. Pesticide Biochemistry and Physiology, 1998, 62, 125–134. DOI: 10.1006/pest.1998.2375.

[7] Food and Agriculture Organization of the United Nations; World Health Organization. Isoxaflutole Evaluation, Joint Meeting on Pesticide Residues, 2013.

[8] Hossain, M. I.; Khan, M. I. H.; Kim, S. J.; Le, H. V. Synthesis of 3,4,5-trisubstituted isoxazoles in water via a cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides. Beilstein Journal of Organic Chemistry, 2022, 18, 446–458. DOI: 10.3762/bjoc.18.47.

[9] U.S. Food and Drug Administration. Fact Sheet for Pet Owners and Veterinarians about Potential Adverse Events Associated with Isoxazoline Flea and Tick Products.

More related articles are listed below:

Oxazolines and Oxazolidines: A Selection Guide for Improving R&D Controllability with Small N,O Five-Membered Rings (Appendix Tables 1–4: Product Navigation)

Oxazole (Oxazole): A Guide to Property Tuning and Synthetic “Plug-In” Assembly for a Weakly Basic Five-Membered Heteroaromatic (with Product Navigation Tables 1–4)

C2-Symmetric Chiral BOX (Bis(oxazoline)) Ligands: How to Make Enantioselectivity (ee) Robust in Asymmetric Catalysis (Key Structural Points and Typical Applications)