Quinazoline (Quinazoline, 1,3-Diazanaphthalene) Research Selection Guide: Structural Features, Application Scenarios, and Key Reagent Navigation (Tables 1–4)

1.Introduction

Quinazoline is a fused, aromatic nitrogen-containing heterocyclic core scaffold. In research and medicinal chemistry, compounds derived from this core are commonly referred to collectively as “quinazoline derivatives.” Structurally, quinazoline can be understood as a bicyclic system formed by fusion of a benzene ring with a pyrimidine ring. It can also be described as a naphthalene framework in which the carbon atoms at the 1 and 3 positions are replaced by nitrogen atoms. Accordingly, commonly used alternative names include 1,3-benzodiazine, 1,3-diazanaphthalene, and 5,6-benzopyrimidine.

2.Why Does Quinazoline Appear So Often?

Quinazoline appears frequently in chemistry and drug discovery, typically for three main reasons:

1. A tunable nitrogen-containing aromatic scaffold

The fused bicyclic system with two ring nitrogens retains aromatic stability and rigidity, while allowing fine modulation of electronic properties and polarity through substitution patterns and changes in oxidation state. This makes it a practical platform for synthesis and property optimization.

2. A highly reusable “privileged scaffold” in medicinal chemistry

Many reviews recognize quinazoline/quinazolinone frameworks as important drug scaffolds. They recur across anticancer, antibacterial, and anti-inflammatory research, often because they provide a stable aromatic framework and key recognition elements for biological targets.

3. Momentum from landmark drugs and mechanistic tool compounds

For example, 4-anilinoquinazoline is a classic “hinge-binding” core in protein kinase inhibitors, especially those targeting the EGFR pathway. In structural biology, EGFR kinase structures complexed with ligands such as erlotinib (a 4-anilinoquinazoline-class inhibitor) are widely used representative examples.

3.Basic Concepts

3.1 Name Interpretation

1. 1,3-Diazanaphthalene (1,3-diazanaphthalene): highlights that it shares the fused bicyclic framework of naphthalene, except that two carbon atoms are replaced by nitrogen atoms.

2. Benzopyrimidine (benzopyrimidine / 5,6-benzopyrimidine): emphasizes that it is equivalent to a benzene ring fused to a pyrimidine ring.

3.2 How Is Quinazoline Related to “Isomeric Diazanaphthalenes”?

Quinazoline, together with quinoxaline, phthalazine, and cinnoline, belongs to the family of diazanaphthalene isomers (constitutional isomers of fused diazabicyclic systems). Their essential difference lies in the positions of the two nitrogen atoms within the fused ring system, which leads to distinct electronic characteristics and reactivity profiles.

Where Quinazoline Sits Within the “Diazanaphthalene Family”

Common English name	Key structural description	Typical appearances in research
Quinazoline	Benzene fused to pyrimidine (= 1,3-diazanaphthalene)	Kinase-inhibitor core; SNAr electrophilic heteroarene; quinazolinone natural-product scaffold
Quinoxaline	Benzene fused to pyrazine (also a diazanaphthalene isomer)	Electron-acceptor scaffold; common fused heterocycle in medicinal and materials chemistry
Phthalazine	Benzene fused to pyridazine (one isomer in the family)	Drug scaffold; functional heterocycle synthesis intermediate
Cinnoline	Another diazanaphthalene fused isomer	Occasionally encountered in heterocyclic chemistry and lead discovery

4.Structural Features

4.1 Recognition Enabled by Two “Pyridine-Type” Nitrogens

The two nitrogens in the quinazoline ring typically act as hydrogen-bond acceptors in molecular recognition:

1. In protein targets, they are often used to form directional hydrogen-bond networks (for example, hinge-binding interactions in kinase active sites commonly leverage this feature).

2. In coordination chemistry, they can also serve as N-donor coordination sites to construct metal complexes (often discussed from the perspective of “benzopyrimidine-fused N-heteroaromatic ligands”).

4.2 Weak Basicity and Salt Formation Upon Acidification: Governing Aqueous Solubility and Speciation

1. Quinazoline is a weakly basic, fused aromatic diazine. In aqueous solution, its tendency to be protonated is commonly described using the pKa of its conjugate acid (pKaH). Measurements consistent with a strict acid–base definition indicate that quinazoline has an aqueous pKaH of ~1.95. This implies that under neutral conditions (e.g., pH ≈ 7) it exists almost entirely as the neutral molecular form, whereas under more strongly acidic conditions it more readily forms salts, thereby altering solubility and reactivity.

2. It is also worth noting that a higher value frequently cited in the literature (pKa ≈ 3.51) often corresponds to an apparent equilibrium in which protonation is conflated with additional processes such as reversible hydration (“water addition”) on the ring. This value should therefore not be used directly to estimate the true ionization fraction or solubility behavior of quinazoline in water.

3. Practical implication for research selection: when water solubility, salt forms, or controlled charge state are required, these properties are typically achieved through substituent design, salt formation, or by selecting more readily ionizable quinazoline derivatives (e.g., drug-like scaffolds bearing amine side chains), rather than assuming the parent core will be intrinsically water-soluble.

5.Common Application Areas: What Problems Does Quinazoline Help Solve?

5.1 Drug Discovery & Chemical Biology: Making “Recognition” More Stable and Reusable

(1) Core scaffold for protein kinase inhibitors

4-Anilinoquinazoline is one of the classic kinase-inhibitor scaffold families. Many widely used EGFR-pathway inhibitors in both clinical and research settings belong to this class. Structural biology also features representative structures of EGFR kinase in complex with 4-anilinoquinazoline inhibitors (e.g., erlotinib, which is a 4-anilinoquinazoline-class inhibitor).

(2) An “expandable platform” for multi-target / dual-target strategies

For example, some reviews discuss quinazoline-based dual EGFR/VEGFR-2 inhibitors, using compounds such as vandetanib to illustrate their role in cancer therapy.

(3) Tool compounds in receptor pharmacology

“α1-receptor antagonists bearing a quinazoline scaffold” are a classic category in pharmacology. For instance, prazosin is widely used as a prototype drug and tool compound, and clinical pharmacology literature explicitly refers to it as a “quinazoline derivative.”

5.2 Synthetic Chemistry: Rapid Construction Enabled by Differences in Reactivity

When the quinazoline ring carries an appropriate leaving group (commonly a 2- or 4-position halogen or other activating group), quinazoline can serve as an electrophilic heteroarene building block for SNAr. This enables rapid installation of fragments such as amines, alcohols, and thiols, facilitating the generation of heteroaromatic derivative libraries that are scalable and amenable to parallel synthesis (construction of 4-aminoquinazoline frameworks is particularly common).

5.3 N-Oxides: Intermediate Value for Accessing More Complex Frameworks

Quinazoline N-oxides (e.g., 1-oxide / 3-oxide) represent more than an “oxidation-state change.” They are often used as reactive intermediates for downstream transformations. Dedicated reviews summarize the synthesis and reactions of quinazoline 3-oxides and highlight their key value as intermediates for preparing quinazoline analogues and ring-expanded derivatives.

5.4 Quinazolinones: A High-Frequency Natural-Product Motif and a Commonly Used Core in Drug Development

(1) Quinazolinones—especially quinazolin-4(3H)-one—appear frequently in natural products. Studies have noted that this motif is a shared core scaffold across more than 200 natural alkaloids, and it is therefore often regarded as an important natural-product structural unit.

(2) In pharmaceutical and agrochemical R&D, quinazolin-4(3H)-one is repeatedly used as an “expandable core scaffold.” This is largely because its fused lactam (amide-like) framework is generally synthetically tractable. The literature also discusses that this scaffold is relatively stable under mild acid/base conditions and can be systematically optimized—via substituent design—for both biological activity and physicochemical properties.

6.How to Classify Quinazoline: By “Scaffold Oxidation State / Functional Form”

Category	Representative form	Structural differences	Common research-use keywords
Quinazoline (aromatic core)	Quinazoline	Fully aromatic fused system; two N atoms as acceptor sites; overall weak basicity	Kinase hinge-binding core; SNAr electrophilic heteroarene; coordination site
Reduced quinazoline	Dihydro-/Tetrahydro-quinazoline	Partial saturation → greater conformational and electronic variation	SAR exploration; property-tuning intermediates
Quinazolinone	Quinazolin-4(3H)-one / Quinazolin-2(1H)-one	Introduction of an amide-type carbonyl → changes H-bond donor/acceptor pattern; tautomerism may occur	Natural-product/drug scaffold; stable bioactive core
Quinazolinedione	Quinazoline-2,4-dione	Two carbonyls → higher polarity and different ionization features	Enzyme inhibition; interaction-mode expansion; synthetic platform
Quinazoline N-oxides	Quinazoline N-oxides (1-oxide/3-oxide)	N→O alters electron distribution and reaction pathways	Intermediate chemistry; ring expansion/rearrangement; access to more complex frameworks

7.When Should You Choose Quinazoline?

Research task / experimental need	Why quinazoline is suitable	Recommended quinazoline category/form
Lead discovery or mechanistic tools for EGFR/other kinases	Two N atoms enable stable H-bond recognition; 4-anilinoquinazoline is a classic hinge-binding framework	4-Anilinoquinazoline and its derivatives
Rapid construction of substituted heteroarene libraries (parallel synthesis)	Halogen/activated sites enable fast SNAr installation of amine/alcohol/thiol fragments	Quinazoline derivatives with leaving groups at C2 or C4
“Natural-product-like” stable scaffold for activity exploration	Quinazolinones are common in natural products and drugs; richer tautomerism and H-bond patterns	Quinazolinones and derivatives
Accessing more complex fused/ring-expanded frameworks via N-oxides	N-oxides open distinct transformation channels and serve as synthetic strategy nodes	Quinazoline 1-oxide/3-oxide
Receptor pharmacology tools or classic reference compounds	Quinazoline derivatives are well-established in α1-receptor antagonists	Drug-like quinazoline scaffolds bearing side chains

8.Selection and Practical Considerations

1. Do not assume the “quinazoline core” is intrinsically highly water-soluble

a) Quinazoline is a weakly basic aromatic diazine, and the pKaH of its conjugate acid in water is low (reported around ~1.95 in the literature). Therefore, under common neutral conditions (e.g., pH 6–8) it is largely uncharged, and its aqueous solubility is often limited.

b) If better aqueous usability is required, typical approaches include:

(i) introducing ionizable side chains (e.g., amines/quaternary ammonium groups), or

(ii) preparing acid-addition salts and using them at an appropriate pH, or

(iii) employing co-solvents/formulation strategies to improve solubility and handling.

2. Clarify the “reactive position” in advance: SNAr substitution, or coupling/electrophilic substitution?

a) Quinazolines bearing leaving groups (commonly Cl/Br/I), especially 2- or 4-halogenated quinazolines, are often used as electrophilic building blocks for SNAr. Nucleophiles such as amines can replace the 4-position halogen under relatively mild conditions, rapidly affording 4-amino/4-anilinoquinazolines. For 2,4-dihalo substrates, the 4-position often shows higher substitutability; a common strategy is therefore to perform SNAr at C4 first, then continue functionalization as needed (e.g., further SNAr or switching to Pd-catalyzed cross-coupling).

b) If your goal is to introduce aryl/alkenyl fragments on the benzene ring portion (C5–C8), or to enable more modular fragment assembly, it is often more appropriate to choose starting materials bearing cross-coupling handles (e.g., Br/I or boronate esters) and use Suzuki/Buchwald and related coupling routes.

c) In practice, selection should start from the route: decide which position you need to modify and whether to use SNAr or coupling, then work backward to the required leaving group/handle and reaction conditions. This approach typically delivers more reliable regioselectivity and yields.

3. For quinazolinones/quinazolinediones, consider tautomerism and H-bond pattern changes

a) Introducing carbonyl groups can substantially change molecular recognition and polarity. In control experiments or SAR analyses, avoid treating “quinazoline” and “quinazolinone” as directly interchangeable equivalents.

4. N-oxides are more than “just more polar”: they alter reactivity and often serve as key intermediates

a) N-oxidation markedly changes the electron distribution of the quinazoline ring. As a result, quinazoline N-oxides are not merely “more polar / more soluble” derivatives; they are often used as reactive intermediates for further transformations, including the synthesis of quinazoline analogues and ring-expanded/fused derivatives.

b) Because the N-oxidation step and subsequent transformations may involve side reactions such as hydrolysis, ring opening, or decomposition, route design should explicitly address:

“how to obtain the target N-oxide → how to leverage its reactivity in the next step → whether (and how) to perform a mild deoxygenation back to the quinazoline core.”

The literature also includes examples in which quinazoline N-oxides are reduced (deoxygenated) back to quinazoline.

5. In biological experiments: choose compounds based on the “scaffold–target–mechanistic evidence chain”

a) For example, in EGFR-focused studies, it is often preferable to prioritize 4-anilinoquinazoline frameworks that are supported by established structural and mechanistic evidence (with a mature structural-biology and literature base). This can reduce trial-and-error costs caused by unstable activity or unclear mechanisms of action.

9.Quinazoline-Related Reagent Selection Navigation: Locate Tables 1–4 by Research Task

Scenario tag	Research task / key experiment	Recommended table(s) to consult first	Table-selection logic	Representative products
Pathway validation / mechanistic research	Verify whether a cellular phenotype depends on EGFR/ERBB signaling (e.g., p-EGFR / p-ERK / p-AKT; inhibitor-treatment group setup)	Table 1	Table 1 compiles quinazoline-based kinase inhibitors and classic EGFR tool compounds, suitable for causal validation and positive controls via a “pathway shutoff → phenotype reversal” logic.	PD153035 (P125741 / P129384), Gefitinib (G125799), Erlotinib HCl (E129310)
Efficacy evaluation / drug sensitivity & resistance	Evaluate sensitivity to EGFR-targeted drugs and benchmark resistance models (compare inhibition mechanisms/target spectra)	Table 1	Table 1 covers multiple EGFR/ERBB inhibitors commonly used in research and the clinic, enabling horizontal comparisons across “generation/target spectrum/mechanism.”	Gefitinib (G125799), Icotinib (I129405), Lapatinib (L126696)
Covalent inhibition mechanism	Irreversible inhibition, target engagement, and sustained inhibition effects (signal recovery differences after washout; time-dependent inhibition)	Table 1	Table 1 includes multiple covalent, irreversible ERBB inhibitors, making it ideal for “washout–recovery / time-dependence” experiments comparing reversible vs irreversible inhibitors.	Afatinib (A401422), Dacomitinib (D129347), Canertinib (C125447)
Multi-target / angiogenesis	Intervene in cross-talk pathways such as VEGFR/RET/EGFR and validate angiogenesis-related phenotypes	Table 1	Multi-target quinazoline inhibitors better match experimental needs where multiple pathways are modulated in parallel for phenotype validation.	Vandetanib (V125180)
Receptor pharmacology / smooth muscle function	Validate α1-receptor antagonism (binding/functional assays; smooth muscle contraction; Ca²⁺ signaling)	Table 2	Table 2 focuses on α1-receptor antagonists with a quinazoline scaffold, widely used as standard references in receptor pharmacology and functional assays.	Prazosin HCl (P160142), Terazosin HCl dihydrate (T129895), Doxazosin (D334301)
Pharmacological reference / analytical methodology	References related to anti-inflammatory analgesics or diuretics; quantitative method development/validation by HPLC/LC-MS	Table 2	Table 2 includes quinazolinone pharmacological references, suitable for efficacy benchmarking and establishing/validating analytical quantification methods.	Proquazone (P693912), Fenquizone (F351066), Quinethazone (Q338241)
Scaffold fundamentals / property benchmarking	Compare physicochemical properties, tautomerism, and H-bonding features of the quinazoline core and simple derivatives (scaffold understanding)	Table 3	Table 3 provides the parent core and simple functionalized derivatives—ideal as a starting point for building understanding and selection logic from “scaffold → properties → modifiable positions.”	Quinazoline (Q107983), 4-Hydroxyquinazoline (H157172), 2-Aminoquinazoline (Q635684)
Lead synthesis / SAR optimization	Substitution scanning around quinazoline (especially 4-anilinoquinazoline): amine fragments at C4, substitutions at C6/7/8, fragment assembly	Tables 3 + 4	Table 3 provides the core/critical fragments to lock in the “core recognition unit”; Table 4 provides halogenated electrophilic platforms to rapidly expand the substitution library.	4-Quinazolinamine (Q167437), N-(3-Chlorophenyl)quinazolin-4-amine (N668056), 4-Chloroquinazoline (C123527)
SNAr loading of amine fragments	Rapidly introduce arylamines/aliphatic amines using a 4-Cl (or 2,4-diCl) platform; stepwise substitution to build a compound series	Table 4	Table 4 is centered on halogenated quinazoline electrophiles, matching workflows of “electrophilic platform → amine loading → rapid iteration” and condition screening.	4-Chloroquinazoline (C123527), 2,4-Dichloroquinazoline (D185530), 2-Chloroquinazoline (C185573)
Cross-coupling library expansion	Expansion via Suzuki/Sonogashira/Buchwald and related couplings (I/Br as coupling handles; multi-position parallel optimization)	Table 4	Table 4 contains multi-position building blocks combining I/Br/Cl handles, enabling rapid library construction via “coupling + SNAr” combination strategies.	4-Chloro-6-iodoquinazoline (C153623), 7-Bromo-4-chloroquinazoline (B176828), 8-Bromo-4-chloroquinazoline (B340848)
Ring construction / starting-material selection	Build quinazoline/quinazolinone cores via cyclization from anthranilonitrile/anthranilamide (route starting point and starting-material choice)	Table 4	Table 4 includes key precursors and a formamidine source, suitable for planning routes from “starting materials → cyclization → core that can be further halogenated/aminated.”	Anthranilonitrile (A107481), 2-Aminobenzamide (A107203), Formamidine acetate (F100557)

Table 1｜Kinase Inhibitors and Pathway Tools (EGFR/ERBB, etc.: drugs/probes/positive controls)

Category	CAS No.	Aladdin Cat. No.	Name	Specification or purity	Key features & applications
Kinase inhibitor (EGFR-targeted; quinazoline-class targeted drug/reference)	184475-35-2	G125799	Gefitinib (ZD1839)	Moligand™, ≥99%	Classic quinazoline-class EGFR inhibitor; commonly used as a reference for efficacy validation in EGFR-dependent cell lines, pathway inhibition (p-EGFR), and combination-therapy mechanism studies.
Kinase inhibitor (EGFR-targeted; quinazoline-class targeted drug/reference)	183319-69-9	E129310	Erlotinib HCl (OSI-774)	Moligand™, ≥99%	Classic 4-anilinoquinazoline-class EGFR inhibitor; widely used as a positive control for EGF/EGFR pathway blockade (p-EGFR/p-ERK/p-AKT), antiproliferative assays, and resistance mechanism studies.
Kinase inhibitor (EGFR-targeted; quinazoline-class targeted drug/reference)	610798-31-7	I129405	Icotinib	Moligand™, ≥99%	Quinazoline-class EGFR inhibitor; used for EGFR signaling inhibition validation, drug sensitivity/resistance comparisons, and SAR reference studies.
Kinase inhibitor (EGFR/HER2; quinazoline-class targeted drug/reference)	231277-92-2	L126696	Lapatinib	Moligand™, ≥99%	Dual-target inhibitor (commonly EGFR/HER2) for pathway studies; used in HER2-relevant models for inhibition validation, downstream phosphorylation assays, and proliferation/apoptosis reference experiments.
Kinase inhibitor (irreversible; EGFR/HER family)	439081-18-2	A401422	Afatinib	Moligand™, ≥98%	Irreversible (covalent) EGFR/HER family inhibitor; used for covalent-inhibition mechanism studies, target engagement, and pathway inhibition assays in resistance-mutation contexts.
Kinase inhibitor (irreversible; EGFR/HER family)	1110813-31-4	D129347	Dacomitinib (PF299804, PF299)	≥99%	Irreversible (covalent) EGFR/HER family inhibitor; commonly used to compare reversible vs irreversible inhibition, inhibition durability, and resistance mechanisms.
Kinase inhibitor (irreversible; EGFR/HER family)	267243-28-7	C125447	Canertinib (CI-1033)	Moligand™, ≥98%	Prototype covalent ERBB-family inhibitor; used for ERBB signaling network analysis, covalent-inhibitor design, and cellular pathway inhibition benchmarking.
Kinase inhibitor (multi-target; quinazoline-class targeted drug/reference)	443913-73-3	V125180	Vandetanib	Moligand™, ≥99%	Quinazoline-scaffold multi-target inhibitor (commonly used in VEGFR/EGFR/RET-related studies); used for angiogenesis/signal-transduction inhibition validation, tumor-cell phenotypes, and pathway cross-talk studies.
EGFR inhibitor (research tool/positive control)	153436-54-5	P125741	PD153035	≥98%	Classic EGFR inhibitor tool compound; used for EGFR-dependent phenotype validation, pathway deconvolution, and inhibitor-control group setup.
EGFR inhibitor (research tool/positive control)	183322-45-4	P129384	PD153035 HCl	≥98% (HPLC)	Highly selective EGFR inhibitor tool compound; used to rapidly “shut down” EGFR signaling to test whether a phenotype depends on EGFR (WB/ELISA/cell proliferation, etc.).
EGFR inhibitor (research tool/cellular pathway validation)	194423-15-9	P129447	PD168393	≥98%	Cell-permeable EGFR inhibitor; commonly used for rapid, cell-based validation of EGFR signaling contributions to phenotypes such as proliferation/migration/differentiation, as a pathway-inhibition control.

Table 2｜Receptor Pharmacology Tools and Non-Kinase Pharmacological References (α1 Antagonists; Quinazolinone Diuretics/Anti-Inflammatories)

Category	CAS No.	Aladdin Cat. No.	Name	Specification or purity	Key features & applications
Quinazoline-scaffold α1 receptor antagonist (receptor pharmacology tool)	74191-85-8	D334301	Doxazosin	Moligand™, ≥98%	α1-adrenergic receptor antagonist bearing a quinazoline scaffold; used in receptor binding/functional assays (Ca²⁺ signaling/contractile responses), smooth muscle–related pathways, and pharmacology benchmarking.
Quinazoline-scaffold α1 receptor antagonist (receptor pharmacology tool)	19237-84-4	P160142	Prazosin Hydrochloride	≥98%	Classic quinazoline-class α1 receptor antagonist; commonly used as a standard reference in α1 receptor binding/functional assays and signaling studies related to vascular smooth muscle.
Quinazoline-scaffold α1 receptor antagonist (receptor pharmacology tool)	70024-40-7	T129895	Terazosin Hydrochloride Dihydrate	≥98%	Quinazoline-class α1 receptor antagonist; widely used as a reference compound in receptor pharmacology, smooth muscle functional assays, and BPH/urinary-function mechanism studies.
Quinazoline-scaffold α1 receptor antagonist (receptor pharmacology tool)	81403-68-1	A129804	Alfuzosin hydrochloride	≥98%	α1 receptor antagonist containing a quinazoline scaffold; commonly used in α1 receptor–related binding/antagonism functional assays and as a pharmacological reference.
Quinazolinone pharmacological reference (anti-inflammatory/analgesic)	22760-18-5	P693912	proquazone	Moligand™, ≥98%	Quinazolinone-class anti-inflammatory/analgesic reference; often used as a control in inflammation/COX-related mechanism studies and for analytical method development (quantitation/impurity profiling).
Quinazolinone pharmacological reference (diuretic; structure–mechanism studies)	20287-37-0	F351066	Fenquizone	Moligand™, ≥97%	Sulfonamide-type quinazolinone diuretic reference; used in studies on renal ion transport/diuretic mechanisms and as a reference for analytical detection methodology.
Quinazolinone pharmacological reference (diuretic; structure–mechanism studies)	73-49-4	Q338241	Quinethazone	Moligand™	Diuretic reference compound containing a quinazolinone scaffold; used for diuretic mechanism studies, renal tubular transport–related experiments, and quantitative drug-analysis benchmarking.

Table 3｜Quinazoline Core and Non-Halogenated Derivatives (Core/Quinazolinone/Quinazolinedione; Key Fragments Included)

Category	CAS No.	Aladdin Cat. No.	Name	Specification or purity	Key features & applications
Quinazoline parent core (basic scaffold/reference)	253-82-7	Q107983	Quinazoline	≥98%	Standard quinazoline core scaffold; used for heteroarene property studies (N acceptor behavior/coordination/basicity) and as a starting point for subsequent functionalization and lead-scaffold optimization.
Quinazoline core / simple functionalized derivative (common amino core)	1687-51-0	Q635684	2-Aminoquinazoline	≥97%	Widely used amino-quinazoline core; used to build amino-substituted series (salt formation/H-bond network tuning), and also serves as a starting material for further coupling, amidation, or sulfonylation.
Quinazoline core / simple functionalized derivative (4-amino core)	15018-66-3	Q167437	4-Quinazolinamine	≥97%	4-Aminoquinazoline is a common “core recognition unit” in kinase inhibitors; used to build 4-substituted/4-anilino derivatives and to support SAR and pathway-inhibition activity screening.
Quinazoline core / simple functionalized derivative (tautomerism / synthetic starting point)	491-36-1	H157172	4-Hydroxyquinazoline	≥98% (HPLC)	Representative 4-oxygen-functionalized quinazoline core (may exhibit keto/enol tautomerism); used to access quinazolinone derivatives, tune H-bond donor/acceptor properties, and enable lead-scaffold modification.
Quinazolinone functional building block (thiol derivative / ligand modification)	13906-09-7	M158467	2-Mercapto-4(3H)-quinazolinone	≥98%	Combines a quinazolinone scaffold with a thiol reactive handle; used to build thioether/thio-substituted derivatives and introduce a “sulfur handle” for further coupling/modification, supporting SAR and functional probe design.
Quinazolinone core (simple substitution; structure–property studies)	1769-24-0	M158468	2-Methyl-4(1H)-quinazolinone	≥98%	Classic quinazolinone core representative; used to study how substitution affects electronic effects/tautomerism/solubility, and can also serve as a starting scaffold for further halogenation, coupling, or functionalization.
Quinazolinone core (reduced form / synthetic intermediate)	7471-58-1	D1073384	1,2-Dihydroquinazolin-2-one	≥95%	Common dihydro-quinazolinone intermediate; used to explore synthetic routes to quinazolinone derivatives (oxidation/substitution/ring modification) and to compare scaffold conformation and properties.
Quinazolinedione / hydantoin-like scaffold (lead structure / synthetic core)	86-96-4	B152549	Benzoyleneurea	≥98% (HPLC)	Quinazoline-2,4-dione (quinazolinedione) scaffold; used for quinazolinedione derivative synthesis and enzyme/receptor lead exploration, as a derivatizable heterocyclic platform.
4-Anilinoquinazoline fragment (kinase-inhibitor scaffold/intermediate)	88404-44-8	N668056	N-(3-chlorophenyl)quinazolin-4-amine	—	Typical “core fragment” of 4-anilinoquinazoline; used to build/benchmark 4-anilinoquinazoline series (common parent motif for EGFR and other kinase inhibitors), facilitating substituent optimization and SAR studies.

Table 4｜Synthetic Precursors and Halogenated Electrophilic Building Blocks (SNAr/Coupling: Stepwise Substitution Platforms)

Category	CAS No.	Aladdin Cat. No.	Name	Specification or purity	Key features & applications
Quinazoline synthetic precursor / cyclization reagent (formamidine source)	3473-63-0	F100557	Formamidine acetate	≥99%	Common donor of the “formamidine (C(=NH)NH₂)” unit; a key reagent for condensation–cyclization with anthranilonitrile/anthranilamide to build quinazoline or 4-aminoquinazoline cores.
Quinazoline synthetic precursor (anthranilonitrile)	1885-29-6	A107481	Anthranilonitrile	≥98%	Important precursor for building quinazoline/4-aminoquinazoline; often cyclized with a formamidine source and related reagents to quickly enter routes of “quinazoline core → C4 amine installation.”
Quinazoline synthetic precursor (anthranilamide)	88-68-6	A107203	Anthranilamide	≥98%	Common precursor for quinazolinone/quinazoline derivatives; used in cyclization with formamidine sources, acyl chlorides/amidation reagents, etc., to rapidly construct quinazolinone cores and support substituent optimization.
Halogenated quinazoline electrophilic building block (SNAr/coupling)	6141-13-5	C185573	2-Chloroquinazoline	≥98%	Activated electrophile at C2; commonly used for SNAr installation of amines/alcohols/thiols to afford 2-substituted quinazolines, supporting scaffold expansion and positional scanning in medicinal chemistry.
Halogenated quinazoline electrophilic building block (SNAr/coupling)	5190-68-1	C123527	4-Chloroquinazoline	≥97%	Strong electrophilic site at C4; facilitates SNAr with arylamines/aliphatic amines to form 4-amino/4-anilinoquinazolines; a high-frequency starting material for EGFR-inhibitor scaffold construction.
Halogenated quinazoline electrophilic building block (multi-position, stepwise substitution)	607-68-1	D185530	2,4-Dichloroquinazoline	≥95%	Dual activation at C2/C4 enables selective “stepwise SNAr” for disubstitution; commonly used to rapidly assemble multi-substituted quinazolines (especially kinase-scaffold routes where C4 amine installation is performed first).
Halogenated quinazoline electrophilic building block (coupling site)	354574-59-7	B573435	4-Bromoquinazoline	≥98%	C4 halogen can be used in Pd-catalyzed cross-coupling or further functionalization; suitable for building 4-substituted quinazolines and for fragment assembly in medicinal chemistry.
Halogenated quinazoline electrophilic building block (common kinase-inhibitor intermediate)	13790-39-1	C123528	4-Chloro-6,7-dimethoxyquinazoline	≥98%	C4-Cl enables SNAr installation of anilines/amines; 6,7-dimethoxy is a classic feature in kinase-inhibitor scaffolds; commonly used to synthesize 4-anilinoquinazoline-type EGFR inhibitor analogues.
Halogenated quinazoline electrophilic building block (dual-function site: coupling + SNAr)	98556-31-1	C153623	4-Chloro-6-iodoquinazoline	≥98%	The I substituent is favorable for Pd-catalyzed cross-coupling (Suzuki/Sonogashira, etc.), while C4-Cl supports SNAr amination; used to rapidly build multi-substituted quinazoline libraries and perform SAR scanning.
Functionalized halogenated derivative (coupling handle)	32084-59-6	B152546	6-Bromo-4-hydroxyquinazoline	≥98%	C6-Br enables coupling-based substituent expansion; the C4 oxygen functionality can be further activated/transformed; used to build multi-position-tunable quinazoline scaffolds to optimize binding and physicochemical properties.
Halogenated quinazoline electrophilic building block (dual-function site: coupling + SNAr)	573675-55-5	B176828	7-bromo-4-chloroquinazoline	≥97%	C4-Cl for SNAr amination plus C7-Br for Pd-catalyzed coupling; suitable for rapid construction of 4,7-disubstituted quinazoline libraries.
Halogenated quinazoline electrophilic building block (dual-function site: coupling + SNAr)	125096-72-2	B340848	8-bromo-4-chloroquinazoline	≥97%	Combination of C4-Cl (SNAr) and C8-Br (coupling); used to build 4,8-disubstituted quinazolines and systematically assess positional substitution effects on activity/selectivity.

Note: The above are representative Aladdin products. For additional specifications, please refer to the product list at the end of the document, or search the Aladdin website using the compound name/CAS number/catalog number.

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