Quinazolinone Moiety Research Articles

Synthesis and antibacterial evaluation of novel Schiff base derivatives containing 4(3H)-quinazolinone moiety

AbstractA series of novel Schiff base derivatives containing 4(3

γ-Fe2O3-HAp-(CH2)3-NHSO3H] nanoparticles as a highly efficient and magnetically separable catalyst for green one-pot synthesis of 4(3H)-Quinazolinones

Quinazolinone derivatives are essential units in a wide range of relevant pharmacophores with a broad spectrum of abilities. Due to their wide range of pharmacological and therapeutic activities including anticonvulsant, anti-inflammatory, hypolipidemic, anticancer, and anti-ulcer, the synthesis of quinazolinone moieties as a privileged class of fused heterocyclic compounds, have received much attention. An efficient and one-pot three components route was developed for the synthesis of 4(3H)-quinazolinones using commercially available starting materials. In order to synthesis of target compounds in good to excellent yields, a reaction between isatoic anhydride, acylchlorides, and amines in the presence of propylsulfamic acid functionalized magnetic hydroxyapatite nanoparticle (a-Fe 2 O 3 -HAp- (CH 2 ) 3 -NHSO 3 H), as a highly efficient and magnetically separable Bronsted acid catalyst, was performed. The organic layer was dried over anhydrous Na 2 SO 4 and filtered. The filtrate was concentrated under vacuum and the residue was recrystallized from 96% EtOH to give 2, 3-disubstituted 4-(3H)-quinazolinone derivatives in high yield. The reaction condition including the solvents, the amount of (a-Fe 2 O 3 -HAp-(CH 2 ) 3 -NHSO 3 H), reaction time and required temperature was optimized.

Design of novel potential aromatase inhibitors via hybrid pharmacophore approach: docking improvement using the QM/MM method

QM/MM and docking methods were used for designing novel hybrid aromatase inhibitors incorporating benzofuran, imidazole and quinazolinone moieties.

Design, synthesis, and antibacterial activity of novel Schiff base derivatives of quinazolin-4(3H)-one

Novel imine derivatives of quinazolin-4(3H)-one were designed and synthesized by using aminoethyl moieties to increase the amine bridge of quinazolin-4(3H)-one amine and then introducing various aromatic aldehydes. The target compounds were characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR), mass spectrometry (MS), infrared spectroscopy (IR), elemental analysis, and X-ray diffraction crystallography. Bioassay results indicated that some of the compounds showed good to excellent antibacterial activities against tobacco bacterial wilt and tomato bacterial wilt. The 50% effective concentrations (EC50) of the compounds against tobacco and tomato bacterial wilts ranged from 63.73 μg/mL to 201.52 μg/mL and 38.64 μg/mL to 81.39 μg/mL, respectively, which are lower than that the positive control thiodiazole copper (216.70 and 99.80 μg/mL). These results indicated that novel Schiff base derivatives containing the 4(3H)-quinazolinone moiety can effectively control tobacco and tomato bacterial wilts.

Synthesis and Bioactivity Evaluation of Novel Arylimines Containing a 3-Aminoethyl-2-[(p-trifluoromethoxy)anilino]-4(3H)-quinazolinone Moiety

Twenty-seven novel (E)-3-[2-arylideneaminoethyl]-2-[4-(trifluoromethoxy)anilino]-4(3H)-quinazolinone derivatives were synthesized by reacting various aromatic aldehydes with intermediate 6. The target compounds were characterized by (1)H NMR, (3)C NMR, IR, and elemental analysis. Bioassay results revealed that some of the compounds have strong antifungal activities against six fungi ( Gibberella zeae , Fusarium oxysporum , Clematis mandshurica , Paralepetopsis sasakii , Phytophthora infestans , and Sclerotinia sclerotiorum ) and three bacteria ( Xanthomonas oryzae , tomato bacterial wilt, and tobacco bacterial wilt). Notably, these compounds exhibited the highest activity against tomato bacterial wilt and X. oryzae, with 50% effective concentration (EC50) values ranging from 45.96 to 93.31 μg/mL and from 20.09 to 21.33 μg/mL, respectively, which are superior to those of the commercial antibacterial agents thiodiazole-copper (99.80 μg/mL) and bismerthiazol (92.61 μg/mL). These results indicate that novel arylimine derivatives containing the 4(3H)-quinazolinone moiety can effectively control tobacco bacterial wilt, tomato bacterial wilt, and X. oryzae. Evaluation of their bactericidal properties in field studies as well as the mechanisms underlying their enhanced antibacterial activity should be interesting topics for future investigations.

High-performance copolyimide fibers containing quinazolinone moiety: Preparation, structure and properties

Copolyimide (co-PI) fibers with superior mechanical properties and high thermal stability were developed via a two-step polymerization/imidization process based on a new design of introducing an aromatic heterocyclic diamine monomer, 2-(4-aminophenyl)-6-amino-4(3H)-quinazolinone (AAQ) into rigid homopolyimide backbones of 3,3′,4,4′-biphenyltetracarboxylic dianhydride (BPDA) and p-phenylenediamine (p-PDA). Effects of the incorporated AAQ moieties on the micro-structure and properties of the prepared fibers were investigated. Fourier transform infrared (FTIR) results indicated that hydrogen bonding is formed between the AAQ and cyclic imide units that effectively strengthens the intermolecular interactions. This has been considered to be the key factor responsible for the significantly enhanced mechanical properties of the co-PI fibers. Two-dimensional wide angle X-ray diffraction (2D WAXD) spectra showed that the co-PI fibers are highly oriented with well-ordered 2D structures along both the fiber and transverse directions. The co-PI fibers reached the optimum tensile strength and modulus of 2.8 GPa and 115 GPa, respectively, at the AAQ/p-PDA molar ratio of 5/5. The fiber also exhibited high thermal stability, with a 5%-weight-loss temperature of 599 °C under N2 and 564 °C in air.

Synthesis, characterization and in vitro antimicrobial screening of some new MCT reactive dyes bearing nitro quinazolinone moiety

A series of some new quinazolinone based MCT reactive dyes (7a–j) were successfully and easily synthesized by the coupling route of diazotized 3-{4-[4-amino-2, 6-difluorobenzyl]-3,5-difluorophenyl}-6-nitro-2-phenylquinazolin-4(3H)-one (4) with a diverse range of o-chloro-p-nitro anilino cyanurated coupling components (6a–j). The structures of all dyes were confirmed by UV–Vis, IR, 1H and 13C NMR spectroscopies. All the newly synthesized dyes were tested for their in vitro antimicrobial screening (antibacterial and antifungal) against several bacteria and fungi. Some of the compounds showed significant antibacterial as well as antifungal activities. Furthermore colorimetric study (L∗, a∗, b∗, C∗, H∗, K/S), Fastness properties and thermogravimetric analysis (TGA) data were also discussed.

Quinazolinone linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates: Design, synthesis and biological evaluation as potential anticancer agents

A series of novel quinazolinone linked pyrrolobenzodiazepine (PBD) conjugates were synthesized. These compounds 4a-f and 5a-f were prepared in good yields by linking C-8 of DC-81 with quinazolinone moiety through different alkane spacers. These conjugates were tested for anticancer activity against 11 human cancer cell lines and found to be very potent anticancer agents with GI(50) values in the range of <0.1-26.2microM. Among all the PBD conjugates, one of the conjugate 5c was tested against a panel of 60 human cancer cells. This compound showed activity for individual cancer cell lines with GI(50) values of <0.1microM. The thermal denaturation studies exhibited effective DNA binding ability compared to DC-81 and these results are further supported by molecular modeling studies. The detailed biological aspects of these conjugates on A375 cell line were studied. It was observed that compounds 4b and 5c induced the release of cytochrome c, activation of caspase-3, cleavage of PARP and subsequent cell death. Further, these compounds when treated with A375 cells showed the characteristic features of apoptosis like enhancement in the levels of p53, p21 and p27 inhibition of cyclin dependent kinase-2 (CDK2) and suppression of NF-kappaB. Moreover, these two compounds 4b and 5c control the cell proliferation by regulating anti-apoptotic genes like (B-cell lymphoma 2) Bcl-2. Therefore, the data generated suggests that these PBD conjugates activate p53 and inhibit NF-kappaB and thereby these compounds could be promising anticancer agents with better therapeutic potential for the suppression of tumours.

A Straightforward Total Synthesis of (−)‐Chaetominine

A total synthesis of the tripeptide alkaloid (-)-chaetominine (1) was achieved in 9.3% overall yield starting from commercially available D-tryptophan methyl ester, based on a short and straightforward (nine steps) sequence. The early stage introduction (first step) of the quinazolinone moiety and the late stage introduction (penultimate step) of the hydroxy group allowed a synthetic strategy devoid of protective groups. The key step of the process is the a-c tricyclic ring construction via an unprecedented NCS-mediated N-acyl cyclization on an indole ring to give tetrahydro-1H-pyrido[2,3-b]indole 11. In the penultimate step, oxidation of the tetracyclic intermediate 14 with oxaziridine 15 gave only one of the four possible diastereoisomers, the cis-diastereoisomer 16 resulting from the attack of the oxaziridine to the double bond face opposite to the c-d ring substituents. In the last step, the complete stereocontrol of the Et(3)SiH/TFA reduction of compound 16, probably involving a N-acyliminium ion, can be attributed to ring constrain, which forces the b-c ring junction in the more stable cis-orientation. (-)-Chaetominine (1) showed a negligible inhibitory activity on several cancer cell lines.

Design and Synthesis of Heterocyclic Conjugated Peptides as Novel Antimicrobial Agents

Antimicrobial peptides have been recognized as a novel class of antibiotics and several candidates are currently in clinical trials. In the present study, new antimicrobial compounds were synthesized by coupling quinazolinone moiety with the fragments of elastin sequences VP, GVP, VGVP and GVGVP. They were evaluated for their antibacterial activity against both gram positive and gram negative bacterial strains. We are here reporting that heterocyclic conjugated tetra peptide and penta peptide showed enhanced antibacterial activity compare to the conventional antimicrobial drugs.

Characterization of in vitro metabolites of rutaecarpine in rat liver microsomes using liquid chromatography/tandem mass spectrometry.

Following incubation of rutaecarpine, a new cyclooxygenase-2 inhibitor, with rat liver microsomes, the structures of the metabolites were characterized by liquid chromatography with tandem mass spectrometry. Nine metabolites corresponding to mono- or dihydroxylated rutaecarpine were formed. Characteristic product ions for the identification of rutaecarpine metabolites were observed at m/z 136, 158 and 286. The loss of water led to the fragment ion at m/z 286, indicating the hydroxylation of the aliphatic ring. The fragment ion at m/z 136 indicated the hydroxylated form of the phenyl group of the quinazolinone moiety, while that at m/z 158 indicated the hydroxylated form of the aromatic ring of the indole moiety.

Solid-phase synthesis of 2,6- and 2,7-diamino-4(3 H)-quinazolinones via palladium-catalyzed amination

A new procedure for the solid-phase synthesis of 2,6- and 2,7-diamino-4(3 H)-quinazolinones is described. The method involves coupling of 2,4,6- and 2,4,7-trichloroquinazoline to a solid support via benzyl alcohol type linkers, subsequent displacement of chlorine at C-2 then at the C-6 or C-7 positions by amines ( Fig. 1) and the cleavage of the products from the resin. The palladium-catalyzed amination of C-6 and C-7 positions with a representative set of amines in the presence of 2-(di- t-butylphosphino)biphenyl (DTBPBP), P( t-Bu) 3 and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) ligands has been investigated. This method should prove to be a useful tool for constructing combinatorial libraries containing the 4(3 H)-quinazolinone moiety.

Polyimides Containing a Quinazolinone Moiety

A novel heterocyclic diamine monomer, 2-(4-aminophenyl)-6-amino-4(3H)-quinazolinone was synthesized from readily available compounds in three steps in high yield. A series of novel polyimides containing the quinazolinone moiety were synthesized either by a one-step solution polymerization reaction or by a two-step procedure that included a ring-opening polyadddition to give poly(amic acid)s, followed by cyclodehydration to polyimides. In the one-step method in m-cresol or p-chlorophenol with isoquinoline catalyst, polyimides with inherent viscosities of 0.44−0.63 dL/g were obtained. Polyimides 4f and 4g from dianhydrides which have a flexible linkage, hexafluoroisopropylidene dianhydride (2f) and BPA dianhydride (2g), were soluble in hot m-cresol and could be cast into tough films from m-cresol solution. In the two-step method, poly(amic acid)s with inherent viscosity between 0.63 and 1.40 dL/g were obtained in DMAc at room temperature. The poly(amic acid)s were converted to the corresponding polyimide fi...

Quinazoline antifolate thymidylate synthase inhibitors: replacement of glutamic acid in the C2-methyl series.

The synthesis of a series of analogues of the potent thymidylate synthase (TS) inhibitor N-[4-[N-[(3,4-dihydro-2-methyl-4-oxo-6- quinazolinyl)methyl]-N-prop-2-ynylamino]benzoyl]-L-glutamic acid (ICI 198583, 1) is described in which the glutamic acid residue has been replaced by other alpha-amino acids. Most of these analogues were prepared by coupling of tert-butyl-4-(prop-2-ynylamino)benzoate (37) with 6-(bromomethyl)-3,4-dihydro-2-methyl-4-oxoquinazoline (34) followed by deprotection of the tert-butyl ester to the acid and azide-mediated coupling to the appropriate amino acid or amino acid ester. In cases where the amino acid ester was unreactive with the acid azide, a modification was used in which the quinazolinone moiety was protected as its 3-(pivaloyloxy)methyl derivative. This permitted the generation of the more reactive acid chloride of the p-aminobenzoate unit. In general these modifications result in compounds that have equivalent potency to 1 as inhibitors of isolated TS except where the amino acid lacks a lipophilic alpha-substituent. These compounds appear to require the reduced folate carrier (RFC) for transport into cells, but since they are not converted intracellularly into polyglutamated forms, they have a lower level of cytotoxicity compared to 1. The removal of the alpha-carboxylic acid has given a second set of analogues of 1 which contain simple alkyl amide, benzyl, substituted benzyl, and heterocyclic benzyl amide derivatives. These are considerably less potent than 1 as TS inhibitors but display 1-10 microM cytotoxicities due to the fact that they do not require RFC transport and can presumably readily enter cells by passive diffusion through the cell membrane. Molecular modeling and NMR studies indicated that the incorporation of, respectively, 7-methyl and 2'-fluoro substituents would favor the optimum conformation of these molecules for interaction with the TS enzyme. Accordingly, these substituents were incorporated into selected examples to give the series of analogues 47-55. These all show enhanced (approximately 10-fold) inhibition of TS compared to their unsubstituted counterparts. In the substituted benzylamides (51, 52) and heterocyclic benzyl amides (53-55) the ability to enter cells by passive diffusion results in highly potent (< 1 microM) cytotoxic agents.

Non‐Steroidal Antiinflammatory Agents, II1): Synthesis of Novel Pyrazole and Pyrazoline Derivatives of 4(3H)‐Quinazolinone Nicht‐steroidale Antiphlogistika, 2. Mitt.1): Synthese neuer Pyrazol‐ und Pyrazolin‐Derivate des 4(3H)‐Chinazolinons

Antiinflammatory and/or analgesic activities have been ascribed to compounds containing the 4(3H)-quinazolinone or pyrazole moiety. Continuation to the previous work in the field of the synthesis of non-steroidal antiinflammatory 4(3H)-quinazolinones, the present investigation deals with the synthesis of new compounds having the pyrazole or pyrazoline and 4(3H)-quinazolinone moieties in one molecule, hoping that such combination might improve their antiinflammatory activity. alpha,beta-unsaturated ketones when treated with hydrazine hydrate achieve cyclization to the corresponding pyrazoline derivatives, whereas, when arylhydrazines are used, pyrazole derivatives are formed.