Importance of quinazoline and quinazolinone derivatives in medicinal chemistry

Bhat, Mahesh P.; Belagali, S. L.; Mamatha, S; Sagar, Belakavadi K.; Sekhar, E. Vijaya

doi:10.1016/b978-0-323-91095-8.00005-2

Cited by 16 publications

(7 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly Hit1, Hit2, and Hit3 are observed to have a quinazoline ring, and surprisingly Hit4 was observed to have a benzofuran ring ( Table S4 ). Numerous reports suggest that both scaffolds have strong anticancer, antimicrobial, and antiviral effects; therefore, it can be hypothesized that these compounds may show good inhibitory potential in experimental studies ( Nevagi et al., 2015 ; Bhat et al., 2021 ). The detailed molecular interactions of identified hit compounds are exposed in Figure 8 .…”

Section: Resultsmentioning

confidence: 99%

3D-QSAR-Based Pharmacophore Modeling, Virtual Screening, and Molecular Dynamics Simulations for the Identification of Spleen Tyrosine Kinase Inhibitors

Kumar

Parate

Danishuddin

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Spleen tyrosine kinase (SYK) is an essential mediator of immune cell signaling and has been anticipated as a therapeutic target for autoimmune diseases, notably rheumatoid arthritis, allergic rhinitis, asthma, and cancers. Significant attempts have been undertaken in recent years to develop SYK inhibitors; however, limited success has been achieved due to poor pharmacokinetics and adverse effects of inhibitors. The primary goal of this research was to identify potential inhibitors having high affinity, selectivity based on key molecular interactions, and good drug-like properties than the available inhibitor, fostamatinib. In this study, a 3D-QSAR model was built for SYK based on known inhibitor IC50 values. The best pharmacophore model was then used as a 3D query to screen a drug-like database to retrieve hits with novel chemical scaffolds. The obtained compounds were subjected to binding affinity prediction using the molecular docking approach, and the results were subsequently validated using molecular dynamics (MD) simulations. The simulated compounds were ranked according to binding free energy (ΔG), and the binding affinity was compared with fostamatinib. The binding mode analysis of selected compounds revealed that the hit compounds form hydrogen bond interactions with hinge region residue Ala451, glycine-rich loop residue Lys375, Ser379, and DFG motif Asp512. Identified hits were also observed to form a desirable interaction with Pro455 and Asn457, the rare feature observed in SYK inhibitors. Therefore, we argue that identified hit compounds ZINC98363745, ZINC98365358, ZINC98364133, and ZINC08789982 may help in drug design against SYK.

show abstract

Section: Resultsmentioning

confidence: 99%

3D-QSAR-Based Pharmacophore Modeling, Virtual Screening, and Molecular Dynamics Simulations for the Identification of Spleen Tyrosine Kinase Inhibitors

Kumar

Parate

Danishuddin

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…The privileged scaffold feature of the quinazolin‐4(3 H )‐one [9] and the possibility of easily decorating it in different ways prompted us to investigate it as a starting point for developing BRD9 ligands.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, due to the high interest of medicinal chemistry [9] for the quinazolin‐4(3 H )‐one nucleus related to the multiple biological functions, many synthetic methods are already reported for these compounds. However, most methods involve prolonged reaction times, high catalyst loading and less suitable to optimization procedures [12] .…”

Section: Resultsmentioning

confidence: 99%

6‐Methylquinazolin‐4(3H)‐one Based Compounds as BRD9 Epigenetic Reader Binders: A Rational Combination of in silico Studies and Chemical Synthesis

et al. 2022

View full text Add to dashboard Cite

Dedicated to Professor Cesare Gennari on the occasion of his 70th birthday 6-methylquinazolin-4(3H)-one-based compounds were here identified and synthesized as novel binders of bromodomaincontaining protein 9 (BRD9) epigenetic reader. Accounting a fast and efficient synthetic route aimed to easily obtain differently 2-and 8-disubstituted 6-methylquinazolin-4(3H)-one derivatives, a virtual library of synthesizable items was built and submitted to molecular docking experiments. Based on two 3D structure-based pharmacophore models recently developed by us on BRD9, 16 compounds were selected and synthesized, using mild conditions with good yields in relatively short reaction times. Among them, 14, 16, 18, 22, and 26 emerged as the most potent compounds of these series, able to bind BRD9 at the low micromolar range of concentrations. These molecules also showed a promising selective behavior when tested against BRD4 bromodomain. These results highlighted the quinazolin-4(3H)-one chemical core as a valuable scaffold for developing promising BRD9 binders.

show abstract

“…The bicyclic heterocycles, possessing a pyrimidine ring fused at veand sixpositions with a benzene moiety, commonly known as quinazolinones, belonging to a promising class of nitrogenheterocycles, are ubiquitously distributed in the core structure of numerous natural products [165][166][167] and medicinally privileged compounds. 168,169 Over the last decades, the design and development of efficient methods for the construction of this compound received ample attention [170][171][172][173] for their potential therapeutic applications, including antimicrobial, anti-HIV, antidepressant, anticancer, antidiabetic, anti-inammatory, and analgesic. [174][175][176][177] Given the properties mentioned above, Latip, Seo, and coworkers devised an atom-economical and practical one-pot multicomponent strategy to access a plethora of highly functionalized quinazolinones under ultrasound irradiation conditions (Scheme 35).…”

Section: Ultrasound Irradiation-promoted Transition-metal-free Synthe...mentioning

confidence: 99%

Ultrasound-assisted transition-metal-free catalysis: a sustainable route towards the synthesis of bioactive heterocycles

Borah

Chowhan

2022

RSC Adv.

View full text Add to dashboard Cite

show abstract

Importance of quinazoline and quinazolinone derivatives in medicinal chemistry

Cited by 16 publications

References 81 publications

3D-QSAR-Based Pharmacophore Modeling, Virtual Screening, and Molecular Dynamics Simulations for the Identification of Spleen Tyrosine Kinase Inhibitors

3D-QSAR-Based Pharmacophore Modeling, Virtual Screening, and Molecular Dynamics Simulations for the Identification of Spleen Tyrosine Kinase Inhibitors

6‐Methylquinazolin‐4(3H)‐one Based Compounds as BRD9 Epigenetic Reader Binders: A Rational Combination of in silico Studies and Chemical Synthesis

Ultrasound-assisted transition-metal-free catalysis: a sustainable route towards the synthesis of bioactive heterocycles

Contact Info

Product

Resources

About