54855-81-1

Usage

Chemical Class

Quinazolinone derivatives

Physical Appearance

Yellow powder

Molecular Weight

212.25 g/mol

Common Uses

Building block in the synthesis of pharmaceuticals and bioactive compounds

Therapeutic Activities

Anti-inflammatory, antimicrobial, and anticancer properties

Potential Applications

Treatment of cancer, inflammation, and microbial infections

Value in Drug Discovery

Valuable chemical for drug discovery and development due to its potential therapeutic activities.

InChI:InChI=1/C9H8N2OS/c1-13-9-10-7-5-3-2-4-6(7)8(12)11-9/h2-5H,1H3,(H,10,11,12)

Upstream product

• 13906-09-7 2-thioxo-2,3-dihydro-1H-quinazolin-4-one 
• 77-78-1 dimethyl sulfate 
• 74-88-4 methyl iodide 
• 74-83-9 methyl bromide 
• 74-87-3 methylene chloride 
• 80-48-8 methyl p-toluene sulfonate 
• 13906-09-7 2-mercapto-3,4-dihydro-4-quinazolone 
• 13906-09-7 2-thio-4-ketotetrahydroquinazoline 
• 118-92-3 anthranilic acid 
• 13277-24-2 N-benzoyl-N'-(2-carboxyphenyl)thiourea 
• 28144-70-9 anthranilic acid amide 
• 118-48-9 isatoic anhydride 
• 48141-61-3 2,4-bis(methylthio)quinazoline 
• 13906-09-7 2-mercapto-3H-quinazolin-4-one 

Downstream Products

• 4248-15-1 2-anilinoquinazolin-4(3H)-one 
• 58803-74-0 4-chloro-2-(methylthio)quinazoline 
• 212143-48-1 2-Methanesulfinyl-3H-quinazolin-4-one 
• 16822-65-4 2-(4-methylpiperazin-1-yl)quinazolin-4(3H)-one 
• 61741-47-7 2-[2-(3,4-dimethoxy-phenyl)-ethylamino]-3H-quinazolin-4-one 
• 1791-50-0 2-(benzylamino)-4-Quinazolinol 
• 86-96-4 1,2,3,4-tetrahydro-quinazoline-2,4-dione 
• 1356922-71-8 2-methylthio-4-(4'-methylselenobenzyl)aminoquinazoline 
• 124309-88-2 2-<(4-chloro-2-methylphenyl)amino>-4-quinazolinone 
• 124309-86-0 4-chloro-2-<(4-chloro-2-methylphenyl)amino>quinazoline 
• 124309-81-5 4-chloro-2-(2-methylphenylamino)quinazoline 

Relevant academic research and scientific papers

Synthesis and intramolecular cyclization of 2-methylsulfanyl-4-oxo-3(4H)- quinazolinylacetohydrazide

Treatment of ambident sodium salt of 2-methylsulfanyl-4(3H)-quinazolinone with methyl bromoacetate resulted in N3-alkyl ester formation. Reaction of the resulted ester with hydrazine hydrate gave 2-methylsulfanyl-4- oxo-3(4H)-quinazolinyl)aceto

2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and Mycobacterium tuberculosis: Structure-Activity Relationships, Mechanism of Action and Absorption, Distribution, Metabolism, and Excretion Characterization

Mycobacterium tuberculosis (MTb) possesses two nonproton pumping type II NADH dehydrogenase (NDH-2) enzymes which are predicted to be jointly essential for respiratory metabolism. Furthermore, the structure of a closely related bacterial NDH-2 has been reported recently, allowing for the structure-based design of small-molecule inhibitors. Herein, we disclose MTb whole-cell structure-activity relationships (SARs) for a series of 2-mercapto-quinazolinones which target the ndh encoded NDH-2 with nanomolar potencies. The compounds were inactivated by glutathione-dependent adduct formation as well as quinazolinone oxidation in microsomes. Pharmacokinetic studies demonstrated modest bioavailability and compound exposures. Resistance to the compounds in MTb was conferred by promoter mutations in the alternative nonessential NDH-2 encoded by ndhA in MTb. Bioenergetic analyses revealed a decrease in oxygen consumption rates in response to inhibitor in cells in which membrane potential was uncoupled from ATP production, while inverted membrane vesicles showed mercapto-quinazolinone-dependent inhibition of ATP production when NADH was the electron donor to the respiratory chain. Enzyme kinetic studies further demonstrated noncompetitive inhibition, suggesting binding of this scaffold to an allosteric site. In summary, while the initial MTb SAR showed limited improvement in potency, these results, combined with structural information on the bacterial protein, will aid in the future discovery of new and improved NDH-2 inhibitors.

Regioselective sulfonylation and N- to O-sulfonyl migration of quinazolin-4(3H)-ones and analogous thienopyrimidin-4(3H)-ones

The sulfonylation of quinazolin-4(3H)-ones and related tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones with mesyl, tosyl, and p-cyanobenzenesulfonyl chloride was studied. A hydrogen substituent at 2-position directed the sulfonyl group to the N-3 position, while alkylsulfanyl or amino substituents led to sulfonylation of the carbonyl oxygen. The latter effect was attributed to steric influence and the positive mesomeric effect of the 2-substituent. An access to N-sulfonylated 2-substituted regioisomers was established. An unexpected 1,3-sulfonyl migration was observed and further analyzed. This process occurred as an intramolecular N- to O-shift as verified by kinetic and crossover experiments.

A green and facile synthesis of 2-alkylsulfanyl-3H-quinazolin-4-one

Reaction of 2-thioquinazolinone (1) with various alkylating agents like dimethyl sulphate, diethyl sulphate and benzyl chloride in the presence of K2CO3 as a mild base, by a simple physical grinding, microwave irradiation and PEG-600 under solvent-free conditions for 10-15 min at room temperature, followed by processing, gave respectively 2-methylsulfanyl-3H-quinazolin-4-one (2a, i.e., R = CH3), 2-ethylsulfanyl-3H-quinazolin-4-one (2b, i.e., R = C2H5) and 2-benzyl sulfanyl-3H-quinazolin-4-one (2c, i.e., R = PhCH2Cl). It appears from this study that green syntheses such as solid phase synthesis (physical grinding) and microwave irradiation gives better yields, quality and in less reaction time the products over conventional methods involving green solvents like ethanol, PEG-600 etc. The entire sequences of reactions have been carried out using eco-friendly solvents and green conditions.

Design, synthesis, and structure-activity relationships of highly potent 5-HT3 receptor ligands

The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3R hit fragment. Here we describe the synthesis and structure-activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT3R affinity using a [3H]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pKi > 10) for the 5-HT3 receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT3 ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches.

Sulfur and selenium derivatives of quinazoline and pyrido[2,3-d]pyrimidine: Synthesis and study of their potential cytotoxic activity in vitro

The synthesis, cytotoxic activities and selectivities of 35 derivatives related to quinazoline and pyrido[2,3-d]pyrimidine are described. The synthesized compounds were screened in vitro against four tumoral cell lines - leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54) and breast (MCF-7) - and two cell lines derived from non-malignant cell lines, one mammary (184B5) and one from bronchial epithelium (BEAS-2B). MCF-7 and HTB-54 were the most sensitive cell lines with GI50 values below 10 μM for eleven and ten compounds, respectively. Two compounds (2o and 3a) were identified that evoked a marked cytotoxic effect in all cell lines tested and one compound, 7h, was potent and selective against MCF-7. A preliminary study into the mechanism of the potent derivatives 2o, 3a and 7h indicated that the cytotoxic activities of these compounds might be mediated by inducing cell death without affecting cell cycle phases.

PIPERIDINE DERIVATIVES HAVING CCR3 ANTAGONISM

The invention provides low molecular compounds having activity which inhibits binding of CCR3 ligands to CCR3 on target cells, i.e. CCR3 antagonists. The invention also provides compounds represented by formula (I) below, pharmaceutically acceptable acid adducts thereof, or pharmaceutically acceptable C1-C6 alkyl adducts thereof, as well as pharmaceutical compositions comprising them as effective ingredients, which are useful for treatment or prevention of diseases associated with CCR3, such as asthma and allergic rhinitis.

Kilogram-scale synthesis of a highly selective α1-adrenoceptor antagonist (DL-028A)

This work presents an improved eight-step process, leading to kilogram quantities of high-quality DL-028A, an antihypertensive agent. The improvements include reducing the levels of toxic reagents and the removal of dangerous processes and waste gas treatment. Moreover, specification and impurity profiles were determined.

Synthesis of 2-aminoquinazoline-4(3H)-one derivatives as potential potassium channel openers

Starting from 2-thioxoquinazolin-4-one, the synthesis of 2-amino-4(3H)- one derivatives, structurally related to potassium channels openers pinacidil and diazoxide, is described.