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Introdução: As quinolonocarboxamidas são substâncias orgânicas, derivadas das 4-oxoquinolinas, muito utilizadas na química medicinal. Com o desenvolvimento dos estudos frente aos derivados quinolonocarboxamídicos, observou-se que 25% dos medicamentos produzidos atualmente os têm inseridos, ampliando a necessidade de estudo. Sua importância está relacionada aos grupos farmacológicos presentes em sua estrutura e, consequentemente, as propriedades que eles acrescentam a essas substâncias. Dentre as aplicações desses derivados, tem-se potenciais: antivirais, antitumorais, antibacterianos e anti-HIV. Objetivo: O objetivo deste trabalho é estudar uma nova metodologia sintética para obtenção de derivados 3-carboxamida-4-oxoquinolínicos, a partir do p-cloroanilinoacrilato de dietila, em um único pote, ou seja, sem a necessidade de isolar o núcleo quinolonico obtido na reação. Material e métodos: Inicialmente adiciona-se o p-cloroanilinoacrilato de dietila em um balão volumétrico. A partir da ciclização térmica em difenil éter, obtém-se um derivado quinolônico. Posteriormente, adiciona-se a anilina de interesse e verifica-se através da cromatografia de camada fina (CCF) a eliminação do intermediário quinolônico, para que assim obtenha-se os derivados quinolonocarboxamídicos. Resultados: Obteve-se três derivados com rendimentos que variaram entre 43 e 75%. As substâncias obtidas foram caracterizadas por métodos físicos de análise. Conclusão: Devido a relevância dessas substâncias, destacou-se neste projeto a importância do estudo de novas metodologias para transformar sua síntese em um método mais econômico. A metodologia utilizada tem se mostrado viável e reprodutiva. Os derivados quinolonocarboxamídicos obtidos possuem rendimentos de 43 a 75%, algo favoravel já que que o rendimento global tem em média 32%. Por fim, pretende-se ampliar os estudos com a variação dos substituintes das anilinas e do anilinoacrilato de dietila.

4-quinolones derivatives can present fluorescent properties, depending on their substituents and on the chemical environment (e.g., acidic medium), allowing their application as ion sensors. We theoretically evaluated the photophysical properties of previously synthesized 3-acyl-4-quinolones to verify how different substituents (R1=H, NH2 and R2 = OEt, OH, NHPh) affect their absorption profiles and the emission profile of a reference compound, PB3. All DFT and TD-DFT calculations were performed at B3LYP-D3/6-311++G(d,p) level and continuum polarization model for simulated acetonitrile as solvent. For PB2 (R1 = H, R2 = OEt), we observed hypsochromic shift compared to PB3 due to the increase of the gap between HOMO/LUMO (absence of electron-donating group), in accordance with experimental data. For R1=NH2 and R2=OH, NHPh (PB6 and PB10, respectively), the gap between HOMO/LUMO increases, resulting in a soft bathochromic shift for the simulated absorption spectra. In addition, we evaluated the effect of acid addition on the absorption and emission profile of PB3 and the results were compared with experimental data. Our thermodynamic results suggest that protonation occurs on the endocyclic carbonyl of the quinolone moiety, probably due to an increased aromatic character, as suggested by our NICS calculations. Finally, we associate the increase of the fluorescence in the acidic medium to the establishment of an intramolecular hydrogen bond and, thus, increased rigidity.

Graphical abstract, Highlights • The repositioning of approved drugs is a promising approach for treating COVID-19. • Several approved drugs have shown anti-SARS-CoV-2 activity and are discussed herein. • In this review, the synthetic approaches toward such molecules was highlighted. • The mechanisms of action and pharmacological properties of such drugs is discussed., In December 2019, a new variant of SARS-CoV emerged, the so-called acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes the new coronavirus disease (COVID-19) and has been plaguing the world owing to its unprecedented spread efficiency, which has resulted in a huge death toll. In this sense, the repositioning of approved drugs is the fastest way to an effective response to a pandemic outbreak of this scale. Considering these facts, in this review we provide a comprehensive and critical discussion on the chemical aspects surrounding the drugs currently being studied as candidates for COVID-19 therapy. We intend to provide the general chemical community with an overview on the synthetic/biosynthetic pathways related to such molecules, as well as their mechanisms of action against the evaluated viruses and some insights on the pharmacological interactions involved in each case. Overall, the review aims to present the chemical aspects of the main bioactive molecules being considered to be repositioned for effective treatment of COVID-19 in all phases, from the mildest to the most severe.

Simple methodologies giving access to a new series of pophyrin/4-quinolone conjugates 6 and to the corresponding intra-cyclized derivatives 8 are described. The key steps to obtain 6 involved palladium-catalyzed amination reactions of 6-bromo-4-quinolones containing N-ethyl, N-pentyl and N-ribofuransyl substituents with (2-amino-5,10,15,20-tetraphenylporphyrinato)nickel(II) followed by demetallation. Compounds 8 were obtained from compounds 4, the nickel(II) complexes of 6, by an oxidative intracylization approach. The new conjugates were fully characterized and the evaluation of singlet oxygen production showed that these compounds possess good to high capability to generate singlet oxygen. The efficacy of these derivatives to photoinactivate Staphylococcus aureus, a Gram-positive bacteria, was evaluated and the best results were obtained with the N-ethyl derivatives 8a and 6a.

In the present article, we describe the synthesis, anti-HIV1 profile and molecular modeling evaluation of 11 oxoquinoline derivatives. The structure-activity relationship analysis revealed some stereoelectronic properties such as LUMO energy, dipole moment, number of rotatable bonds, and of hydrogen bond donors and acceptors correlated with the potency of compounds. We also describe the importance of substituents R(2) and R(3) for their biological activity. Compound 2j was identified as a lead compound for future investigation due to its: (i) high activity against HIV-1, (ii) low cytotoxicity in PBMC, (iii) low toxic risks based on in silico evaluation, (iv) a good theoretical oral bioavailability according to Lipinski 'rule of five', (v) higher druglikeness and drug-score values than current antivirals AZT and efavirenz.

In the title compound, C(18)H(16)N(4)O(2), the plane defined by the ethyl C atoms and the attached N atom is inclined to the adjacent pyridine ring at an angle of 67.87 (16)°. The dihedral angle between the two heterocyclic rings is 3.33 (16)°. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond and the crystal structure by inter-molecular C-H⋯O hydrogen bonds, forming a one-dimensional structure.