Nitroaromatic drugs represent an important class of therapeutic agents, endowed with different pharmacological properties such as antibacterial, antiprotozoal, anti-Parkinson, anticancer, etc. However, the nitroheterocycle and nitroarene fragments are considered potentially toxic, with reports of mutagenicity and genotoxicity. The bioreduction process of the nitro group plays a central role in the antimicrobial and toxicological mechanism of action of nitroaromatic drugs. This article will review the nitroaromatic drugs approved by the Food and Drug Administration (FDA) in the last 30 years, the mechanisms of bioactivation, metabolism and toxicity and, finally, it will revisit the main methodologies for obtaining the nitroaromatic fragment from aromatic nitration reaction and oxidation of arylamines and/or heteroarylamines. agents antibacterial antiprotozoal antiParkinson, antiParkinson anti Parkinson, Parkinson anti-Parkinson anticancer etc However toxic genotoxicity FDA (FDA 3 years bioactivation finally andor or heteroarylamines

ABSTRACT N-acylhydrazone is an interesting privileged structure that has been used in the molecular design of a myriad of bioactive compounds. In order to identify new antinociceptive drug candidates, we described herein the design, synthesis, X-ray diffraction study and the pharmacological evaluation of a series of 3-amino-4-methylthiophene-2-acylcarbohydrazone derivatives (8a-t). Compounds were prepared in good overall yields through divergent synthesis from a common key intermediate and were characterized by classical spectroscopy methods. X-ray diffraction study was employed for unequivocal determination of the imine double bond stereochemistry. 8a-t were evaluated in vivo through oral administration using the classical writhing test in mice. N-acylhydrazone derivatives 8j and 8l displayed relative potency similar to dipyrone, highlighting them as promising analgesic lead-candidates for further investigation.

Methodologies to obtain quinoxaline compounds regioselectively are rarely reported in literature, thus regioselective and multi-gram methodologies to obtain these derivatives are desirable to explore the entire potential of these scaffolds for academic and/or commercial application. A facile and multi-gram methodology is described to obtain compound 7-nitroquinoxalin-2-amine using o-phenylenediamine, a cheap and readily available reactant, as starting material in a five-step procedure in good yields and high purity without further purification such as crystallization or column chromatography.

The main aspects of the modern Medicinal Chemistry, among the classic and industrial paradigms, used in the drug discovery process will be treated. The contribution of the Brazilian science in the knowledge generation in Medicinal Chemistry will be demonstrated, with base in searches accomplished in the portal Web of Science® 7.10 and in the directory of groups of research of CNPq.

No âmbito de uma linha de pesquisas que trata da síntese e avaliação farmacológica de novos candidatos a protótipos de agentes antitrombóticos, explorando a hibridação molecular como estratégia de planejamento estrutural, descrevemos neste trabalho a síntese e avaliação farmacológica de novas sulfonilsemicarbazidas (10a-d), planejadas por analogia estrutural a antagonistas de receptores de TXA2, utilizando o safrol (9), produto natural brasileiro abundante, isolado do óleo de Sassafrás, como matéria-prima sintética. A avaliação das propriedades antiagregantes plaquetárias das sulfonilsemicarbazidas (10a-d) no modelo induzido por ADP, colágeno, ácido araquidônico e U46619, permitiu evidenciar um importante perfil antitrombótico ao nível da cascata do ácido araquidônico para o derivado 6-metil-3,4-metilenodioxifenil-sulfonil-N-feniltiosemicarbazida (10d), que representa um novo protótipo de agentes anti-trombóticos.

As part of a research program aiming at the synthesis and pharmacological evaluation of novel lead-compounds exploring Brazilian abundant natural products, we describe herein the synthesis and the antithrombotic profile of new aryl-sulfonylsemicarbazides and aryl-sulfonylthiosemicarbazides (10a-d). The new derivatives, designed with basis on the molecular hybridization concept, were prepared in good yields from natural safrole (9), isolated from sassafras oil. The anti-aggregating activity of these new derivatives (10a-d) on platelet aggregation induced by ADP, collagen, arachidonic acid and U-46619, indicates an important antithrombotic profile for the 6-methyl-3,4-methylenedioxyphenyl-sulfonyl-N-phenylthiosemicarbazide derivative (10d), acting at the arachidonic acid cascade and representing a new lead-compound with antithrombotic activity.