Quinazoline

A novel polycyclic quinazoline alkaloid ( 1 ) along with one new natural quinoline alkaloid ( 2 ) and two known quinoline alkaloids ( 3 , 4 ) were isolated from the marine-derived fungus Trichoderma longibrachiatum QD01. Structural determinations of those isolates were established by comprehensive spectroscopic analyses and literature comparison. Single-crystal X-ray diffraction analysis of novel compound verified its structure and stereochemistry, representing the first characterised crystal structure of a trimeric-type of tetrahydroquinazoline...

A highly efficient and straightforward one-pot synthesis of diversely substituted 3,4-dihydroquinazolines and quinazolin-4(3 H )-ones has been achieved through a domino three-component assembly reaction of arenediazonium salts, nitriles, and bifunctional aniline derivatives. This new protocol involves three C-N bond formations through the initial formation of N -arylnitrilium intermediates from arenediazonium salts and nitriles, followed by the sequential nucleophilic addition and cyclization reactions with bifunctional anilines, leading to such N -heterocyclic compounds of biological and pharmacological importance...

A novel series of trifluoromethyl-containing quinazoline derivatives with a variety of functional groups was designed, synthesized, and tested for their antitumor activity by following a pharmacophore hybridization strategy. Most of the 20 compounds displayed moderate to excellent antiproliferative activity against five different cell lines (PC3, LNCaP, K562, HeLa, and A549). After three rounds of screening and structural optimization, compound 10 b was identified as the most potent one, with IC50 values of 3...

A series of nine 2,3-disubstituted-quinazolin-4(3 H )-one derived Schiff bases and their three Cu(II) complexes was prepared and tested for their antimicrobial activities against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the substances were tested in vitro against Mycobacterium tuberculosis H37 Ra ATCC 25177, M. kansasii DSM 44162 and M. smegmatis ATCC 700084...

Quinazoline compounds have gained significant attention in the fields of agriculture and chemistry due to their diverse activities. In this study, we focused on a series of quinazoline derivatives ( 4a-l ). The objectives involved multiple aspects, including preparation, evaluation of their agricultural bioactivity against the maize aphid ( Rhopalosiphum maidis ), estimation of the structure-activity relationships (SAR), and conducting molecular docking analysis. The results of the agricultural bioactivities revealed that compound ( 4b ) possesses the highest insecticidal activity, and the other compounds have good potential as insecticidal agents...

In pursuit of enhancing the anti-resistance efficacy and solubility of our previously identified NNRTI 1, a series of biphenyl-quinazoline derivatives were synthesized employing a structure-based drug design strategy. Noteworthy advancements in anti-resistance efficacy were discerned among some of these analogs, prominently exemplified by compound 7ag, which exhibited a remarkable 1.37 to 602.41-fold increase in potency against mutant strains (Y181C, L100I, Y188L, F227L + V106A, and K103N + Y181C) in comparison to compound 1...

Novel triazoloquinazolines carrying the 2-[thio]acetamide entity (4 and 5a-d) and triazoloquinazoline/chalcone hybrids incorporating the 2-[thio]acetamide linker (8a-b and 9a-f) were developed as anticancer candidates. NCI screening of the synthesized compounds at 10 μM concentration displayed growth inhibition not only up to 99.74% as observed for 9a but also a lethal effect could be achieved as stated for compounds 9c (RPMI-8226 and HCT-116) and 8b, 9a, and 9e on the HCT-116 cell line. The antiproliferative activity was determined for the chalcone series on three cell lines: RPMI-8226, HCT-116, and MCF-7...

An efficient electrochemical dual C(sp3 )-H amination was developed under metal-free and chemical oxidant-free conditions. A series of imidazo[1,5- a ]quinazolin-5(4 H )-ones and 5-oxo-4,5-dihydroimidazo[1,5- a ]quinazoline-3-carbonitriles can be obtained in high yields and the product distribution can be modulated by virtue of this method. The reaction mechanism was investigated and the corresponding intermediates were studied. The reaction features a broad substrate scope, regulation of the product distribution, mild conditions and scalable preparation...

2-Chloro-4-sulfonylquinazolines undergo functional group swap when treated with an azide nucleophile: 1) the azide replaces the sulfonyl group at the C4 position; 2) the intrinsic azide-tetrazole tautomeric equilibrium directs the nucleofugal sulfinate from the first step to replace chloride at the C2 position. This transformation is effective with quinazolines bearing electron-rich substituents. Therefore, the title transformations are demonstrated on the 6,7-dimethoxyquinazoline core, which is present in pharmaceutically active substances...

Non-small cell Lung cancer (NSCLC) is the most common type of lung cancer, which is caused by high consumption of tobacco and smoking. It is an epithelial lung cancer that affects about 2.2 million people across the globe, according to International Agency for Research on Cancer (IARC). Non-small cell lung cancer is a malignant tumor caused by EGFR mutation that occurs in the in-frame deletion of exon 19 and L858R point mutation in exon 21. Presently, clinically available inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc...

A switch of reaction medium from organic solvents to water can improve the safety and lower the cost of production processes. Hydrochloric acid-promoted amination of fused pyrimidines has been studied using 4-chloro-7 H -pyrrolo[2,3- d ]pyrimidine and aniline as model compounds. Higher rate was observed in water than in four alcoholic solvents and DMF. An important aspect is that the amount of acid should be kept low to minimize the competing solvolysis. The substrate scope for the amination in water was evaluated by reacting 4-chloro-7 H -pyrrolo[2,3- d] pyrimidine with 20 aniline derivatives with variance in steric and electronic properties...

The synthesis, characterization, and catalytic application of a new phosphine-free, well-defined, water-soluble, and air-stable Mn(II)-catalyst [Mn(L)(H2 O)2 Cl](Cl) ([ 1 ]Cl) featuring a 1,10-phenanthroline based tridentate pincer ligand, 2-(1 H -pyrazol-1-yl)-1,10-phenanthroline ( L ), in dehydrogenative functionalization of alcohols to various N -heterocycles such as quinazolin-4(3 H )-ones, quinolines, and quinoxalines are reported here. A wide array of multisubstituted quinazolin-4(3 H )-ones were prepared in water under air following two pathways via the dehydrogenative coupling of alcohols with 2-aminobenzamides and 2-aminobenzonitriles, respectively...

An efficient methodology for the synthesis of highly diverse tetrahydroquinazoline scaffolds from 2-aminobenzonitriles and alkylidene malonates via 1,4-conjugate addition followed by an unprecedented rearrangement has been demonstrated. The methodology is further applicable for the synthesis of quinazolines and tetracyclic compounds. Some of the synthesized compounds exhibit photophysical properties.

This work reports an efficient synthesis of novel benzo[7,8]indolizino[2,3,4,5- ija ]quinazoline derivatives between 2-(2-ethynylaryl)acetonitriles 1 and anthranils 2. The synthetic approach involves the initial formation of 7-formylindole intermediates that can be implemented by DBU to activate a novel indole-nitrile-aldehyde cyclization.

The total synthesis of cyclotripeptidic natural products possessing a central piperazino[2,1- b ]quinazolin-3,6-dione core is described through an original strategy involving the pivotal cyclocondensation of an electrophilic homoserine lactone intermediate. The alkylidene group was spontaneously installed by autoxidation during the cyclocondensation process, while the propionamide side chain was introduced through the nickel-catalyzed aminocarbonylation of a bromoethyl intermediate. This last reaction is unprecedented on such highly functionalized intermediates...

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors and the development of effective therapeutics against HCC is urgently needed. A novel quinazoline derivative 04NB-03 (Qd04) has been proved to be highly effective against HCC without obvious toxic side-effects. However, the poor water solubility and low bioavailability in vivo severely limit its clinical application. In addition, Qd04 kills tumor cells by inducing an accumulation of endogenous reactive oxygen species (ROS), which is highly impeded by the overexpression of glutathione (GSH) in tumor cells...

Amidst the Zn2+ -dependant isoforms of the HDAC family, HDAC6 has emerged as a potential target associated with an array of diseases, especially cancer and neuronal disorders like Rett's Syndrome, Alzheimer's disease, Huntington's disease, etc. Also, despite the availability of a handful of HDAC inhibitors in the market, their non-selective nature has restricted their use in different disease conditions. In this situation, the development of selective and potent HDAC6 inhibitors will provide efficacious therapeutic agents to treat different diseases...

HER2 mutations were seen in 4% of non-small-cell lung cancer (NSCLC) patients. Most of these mutations (90%) occur as an insertion mutation within the exon 20 frame, leading to the downstream activation of the PI3K-AKT and RAS/MAPK pathways. However, no targeted therapies have yet been approved worldwide. Here a novel series of highly potent HER2 inhibitors with a pyrido[2,3,4- de ]quinazoline core were designed and developed. The derivatives with the pyrido[2,3,4- de ]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib...

Antimicrobial resistance has emerged as a covert global health crisis, posing a significant threat to humanity. If left unaddressed, it is poised to become the foremost cause of mortality worldwide. Among the multitude of resistant bacterial pathogens, Pseudomonas aeruginosa, a Gram-negative, facultative bacterium, has been responsible for mild to deadly infections. It is now enlisted as a global critical priority pathogen by WHO. Urgent measures are required to combat this formidable pathogen, necessitating the development of novel anti-pseudomonal drugs...

Tryptanthrin, an alkaloid applied in traditional Chinese medicine, exhibits a variety of pharmacological activities. This study aimed to investigate the anti-tumor activity of the tryptanthrin derivative (8-cyanoindolo[2,1-b]quinazoline-6,12-dione [CIQ]) in breast cancer cells. In both MDA-MB-231 and MCF-7 breast cancer cells, CIQ inhibited cell viability and promoted caspase-dependent apoptosis. At the concentration- and time-dependent ways, CIQ increased the levels of p-ERK, p-JNK, and p-p38 in breast cancer cells...