52377-28-3Relevant academic research and scientific papers
Synthesis and inverse virtual screening of new bi-cyclic structures towards cancer-relevant cellular targets
Bhogal, Amrit,Biancalani, Claudio,Cesari, Nicoletta,Cilibrizzi, Agostino,Crocetti, Letizia,Floresta, Giuseppe,Giovannoni, Maria Paola,Nazir, Shabnam,Vergelli, Claudia
, (2022/02/21)
We report here synthetic approaches to access new classes of small molecules based on three heterocyclic scaffolds, i.e. 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione, 1,8-naphthyridin-4(1H)-one and 4H-pyrido[1,2-a]pyrimidin-4-one. The bi-cyclic structure 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione is a new heterocycle, described here for the first time. In silico methodologies of inverse virtual screening have been used to preliminary analyse the molecules, in order to explore their potential as hits for chemical biology investigations. Our computational study has been conducted with 43 synthetically accessible small molecules towards 31 cellular proteins involved in cancer pathogenesis. Binding energies were quantified using molecular docking calculations, allowing to define the relative affinities of the ligands for the cellular targets. Through this methodology, 16 proteins displayed effective interactions with distinct small molecules within the matrix. In addition, 23 ligands have demonstrated high affinity for at least one cellular protein, using as reference the co-crystallised ligand in the X-ray structure. The evaluation of ADME and drug score for selected hits also highlights that these new molecular series can serve as sources of lead candidates for further structure optimisation and biological studies.
Catalytic syntheses of N-heterocyclic ynones and ynediones by in situ activation of carboxylic acids with oxalyl chloride
Boersch, Christina,Merkul, Eugen,Mueller, Thomas J. J.
supporting information; experimental part, p. 10448 - 10452 (2011/12/05)
Breaking the bottleneck: α-Keto carboxylic acids and N-heterocyclic carboxylic acids are activated in situ with oxalyl chloride then catalytically alkynylated to give ynediones and N-heterocyclic ynones efficiently in a one-pot fashion. 5-Acylpyrazoles and 2-phenylaminopyrimidines, potentially interesting for pharmaceutical applications, are readily synthesized in concise one-pot, three-component syntheses. Copyright
Design, synthesis, and antitubercular evaluation of novel series of 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1- pyrazolylcarbonyl-4-oxo-naphthyridin analogs
Manna, Kuntal,Agrawal, Yadvendra K.
experimental part, p. 3831 - 3839 (2010/09/11)
Twenty-eight newer 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin analogs were synthesized by microwave irradiation method and evaluated for in-vitro and in-vivo antitubercular activity agai
Synthesis and evaluation of new quinazolone derivatives of nalidixic acid as potential antibacterial and antifungal agents
Grover, Gaurav,Kini, Suvarna G.
, p. 256 - 262 (2007/10/03)
In continuation of our work on synthesis of biheterocycles carrying the biodynamic heterocyclic systems at position 3, a series of new nalidixic acid derivatives having quinazolones moiety were synthesised to achieve enhanced biological activity and wide spectrum of activity. Nalidixic Acid was first converted into its acid chloride using thionyl chloride as an acylating agent at laboratory temperature. Later it was converted to methyl ester. Nalidixoyl chloride formed vigorously reacts with methanol to give a methyl ester of nalidixic acid. The ester on addition of hydrazine hydrate furnished nalidixic acid hydrazide. Appropriate anthranilic acid was refluxed with acetic anhydride to form Benzoxazine/Acetanthranil. 5-iodo-derivative of anthranilic acid was prepared and also utilised to obtain 6-iodo-Benzoxazine/Acetanthranil. Also, 6-nitro-Benzoxazine/Acetanthranil was obtained by nitration of acetanthranil using conc. H2SO4 and fuming HNO3. Equimolar proportions of the appropriate synthesised acetanthranils and nalidixic acid hydrazide in the presence of ethanol were refluxed to synthesise quinazolones. Elemental analysis and IR spectra confirmed nalidixic acid hydrazide formation. The structures of the compounds obtained have been established on the basis of Spectral (IR, 1H NMR and mass) data. The current study also involves in vitro antimicrobial screening (using Agar dilution and Punch well diffusion method) of synthesised quinazolone derivatives bearing nalidixic acid moiety on randomly collected microbial strains. The derivatives Ga (NAH), Gb (QN) and Gd (NiQNA) showed marked inhibitory activity against enteric pathogen like Aeromonas hydrophila, a causative agent of diarrhoea in both children as well as adults. Among the respiratory pathogens included in study, derivative Gd (NiQNA) was found to be active against Streptococcus pyogenes. No significant inhibitory activity was seen by any of synthesised derivatives against Coagulase negative Staphylococcus. Derivative Ga (NAH) was found to show very high activity against the Candida colonies and derivative Gd (NiQNA) was also found to exhibit inhibitory activity against Candida albicans; a normal flora of the human body which plays an important role in causing opportunistic infections in immunocompromised hosts. Proteus vulgaris, a gram-negative bacteria included in our study was found to be inhibited by derivative Gb (QN).
