The present work describes the synthesis of 22 new imidazopyridine analogues arising from medicinal chemistry optimization at different sites on the molecule. Seven and 12 compounds exhibited an in vitro EC ≤ 1 μM against () and () parasites, respectively. Based on promising results of activity (EC < 100 nM), cytotoxicity, metabolic stability, protein binding, and pharmacokinetics (PK) properties, compound was selected as a candidate for efficacy studies. This compound was screened in an acute mouse model against ( strain). After established infection, mice were dosed twice a day for 5 days, and then monitored for 6 weeks using an imaging system (IVIS). Compound demonstrated parasite inhibition comparable to the benznidazole treatment group. Compound represents a potential lead for the development of drugs to treat trypanosomiasis.

Aldehyde peptide like compounds display a bivalent reactive profile and improved antichagasic potency.

The Front Cover shows efforts among Brazilian, American, and European researchers to combat neglected tropical diseases. New heterocyclic compounds based on imidazopyridine/pyrimidine and furopyridine cores originating from Brazil travel to the USA and Europe to be developed as anti‐infective agents against Trypanosomiases. By exploring the chemical diversity at eight different positions of the central core, we obtained various heterocyclic compounds having significant potential for anti‐trypanosomiases drug discovery. More information can be found in the Full Paper by Daniel G. Silva, Flavio S. Emery et al. Cover design by Daniel Gedder Silva.

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Computer-assisted techniques and the strategy of combining chemical substructures were used to derive small modified peptides as potent angiotensin-converting enzyme (ACE) inhibitors. In addition to high potency, some of the predicted compounds are also shown to exhibit satisfactory pharmacokinetic parameters.

Herein we report the design and synthesis of a series of highly selective CCR2 antagonists as 18F‐labeled PET tracers. The derivatives were evaluated extensively for their off‐target profile at 48 different targets. The most potent and selective candidate was applied in vivo in a biodistribution study, demonstrating a promising profile for further preclinical development. This compound represents the first potential nonpeptidic PET tracer for the imaging of CCR2 receptors.

Natural products (NPs) are an excellent source of biologically active molecules that provide many biologically biased features that enable innovative designing of synthetic compounds. NPs are characterized by high content of sp 3-hybridized carbon atoms; oxygen; spiro, bridged, and linked systems; and stereogenic centers, with high structural diversity. To date, several approaches have been implemented for mapping and navigating into the chemical space of NPs to explore the different aspects of chemical space. The approaches providing novel opportunities to synthesize NP-inspired compound libraries involve NP-based fragments and ring distortion strategies. These methodologies allow access to areas of chemical space that are less explored, and consequently help to overcome the limitations in the use of NPs in drug discovery, such as lack of accessibility and synthetic intractability. In this review, we describe how NPs have recently been used as a platform for the development of diverse compounds with high structural and stereochemical complexity. In addition, we show developed strategies aiming to reengineer NPs toward the expansion of NP-based chemical space by fragment-based approaches and chemical degradation to yield novel compounds to enable drug discovery.