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Middle East respiratory syndrome coronavirus (MERS-CoV) poses a serious threat to human health, and currently there are no effective or specific therapies available to treat it. Herein a series of 1-phenyl-N-(benzothiazol-2-yl)methanimine derivatives with inhibitory activity against MERS-CoV are described. The compound 4f with a 50% inhibition concentration value of 0.09 μM is a promising inhibitor that warrants further evaluation, towards the development of potential anti-MERS-CoV drugs.

Middle East respiratory syndrome coronavirus (MERS-CoV) poses a serious threat to human health, and currently there are no effective or specific therapies available to treat it. Herein a series of 1-phenyl

Herein we reported a series of 14 novel derivatives based on the N-cyclobutylaminoethoxyisoxazole scaffold. In vitro binding studies of these compounds demonstrated their low nanomolar to subnanomolar potencies as σ1 receptor ligands, with moderate to excellent selectivity over the σ2 receptor as represented by compounds 17–30. The majority of the derivatives scored high (>4.7) in the CNS MPO appraisal system, indicating their high likelihood in penetrating the blood–brain barrier. A number of these compounds exhibited significant neurite outgrowth efficacy in N1E-115 neuronal cells and displayed excellent selectivity for σ1 receptors over the selected endogenous neurotransmitter transporters, such as DAT, NET and SERT. Among the mini-series, compound 28 (Ki σ1 = 0.2 nM, Ki σ2 = 198 nM, CNS MPO score = 5.4) emerged as a promising selective σ1 receptor ligand that warrants its further evaluation as a potential therapeutic for neurodegenerative diseases.

Herein we reported a series of 14 novel derivatives based on the

In our continued efforts to develop lithocholic acid (LCA) analogues as selective PTP1B inhibitors, 14 novel 2,3-pyrazole ring-substituted-4,4-dimethyl derivatives were synthesized and evaluated against PTP1B, as well as homologous protein tyrosine phosphatases (PTPs). All compounds were shown to be more potent and selective PTP1B inhibitors than LCA (IC50 = 12.74 μM) with IC50 values ranging between 0.42 to 4.49 μM. Moreover, treatment of CHO/hIR cells with 4,4-dimethyl-2′-(p-fluoro phenyl)-2′H-chola-2,5-dieno[3,2-c]pyrazol-24-oic acid (30) or 4,4-dimethyl-2′-(o-chloro phenyl)-2′H-chola-2,5-dieno[3,2-c]pyrazol-24-oic acid (34) increased the phosphorylation levels of IR and Akt in a dose dependent manner. The promising findings in this study suggest that further investigation of these compounds for the treatment of metabolic disorders is warranted.