Pyrazoles as novel protein tyrosine phosphatase 1B (PTP1B) inhibitors: An in vitro and in silico study.

Type 2 diabetes mellitus (DM) is a complex chronic disorder and a major global health problem. Insulin resistance is the primary detectable abnormality and the main characteristic feature in individuals with type 2 DM. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathway, which dephosphorylates insulin receptor and insulin receptor substrates, suppressing the insulin signaling cascade. Therefore, the inhibition of PTP1B has become a potential strategy in the management of type 2 DM. In this study, a library of 22 pyrazoles was evaluated here for the first time against human PTP1B activity, using a microanalysis screening system. The results showed that 5-(2-hydroxyphenyl)-3-{2-[3-(4-nitrophenyl)-1,2,3,4-tetrahydronaphthyl]}-1-phenylpyrazole 20 and 3-(2-hydroxyphenyl)-5-{2-[3-(4-methoxyphenyl)]naphthyl}pyrazole 22 excelled as the most potent inhibitors of PTP1B, through noncompetitive inhibition mechanism. These findings suggest that the presence of additional benzene rings as functional groups in the pyrazole moiety increases the ability of pyrazoles to inhibit PTP1B. The most active compounds showed selectivity over the homologous T-cell protein tyrosine phosphatase (TCPTP). Molecular docking analyses were performed and revealed a particular contact signature involving residues like TYR46, ASP48, PHE182, TYR46, ALA217 and ILE219. This study represents a significant beginning for the design of novel PTP1B inhibitors.

Styrylpyrazoles: Properties, Synthesis and Transformations.

The pyrazole nucleus and its reduced forms, pyrazolines and pyrazolidine, are privileged scaffolds in medicinal chemistry due to their remarkable biological activities. A huge number of pyrazole derivatives have been studied and reported over time. This review article gives an overview of pyrazole derivatives that contain a styryl (2-arylvinyl) group linked in different positions of the pyrazole backbone. Although there are studies on the synthesis of styrylpyrazoles dating back to the 1970s and even earlier, this type of compound has rarely been studied. This timely review intends to summarize the properties, biological activity, methods of synthesis and transformation of styrylpyrazoles; thus, highlighting the interest and huge potential for application of this kind of compound.

Pyrazoles as Key Scaffolds for the Development of Fluorine-18-Labeled Radiotracers for Positron Emission Tomography (PET).

The need for increasingly personalized medicine solutions (precision medicine) and quality medical treatments, has led to a growing demand and research for image-guided therapeutic solutions. Positron emission tomography (PET) is a powerful imaging technique that can be established using complementary imaging systems and selective imaging agents-chemical probes or radiotracers-which are drugs labeled with a radionuclide, also called radiopharmaceuticals. PET has two complementary purposes: selective imaging for diagnosis and monitoring of disease progression and response to treatment. The development of selective imaging agents is a growing research area, with a high number of diverse drugs, labeled with different radionuclides, being reported nowadays. This review article is focused on the use of pyrazoles as suitable scaffolds for the development of 18F-labeled radiotracers for PET imaging. A brief introduction to PET and pyrazoles, as key scaffolds in medicinal chemistry, is presented, followed by a description of the most important [18F]pyrazole-derived radiotracers (PET tracers) that have been developed in the last 20 years for selective PET imaging, grouped according to their specific targets.