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A series of cyano- and amidino-substituted imidazo[4,5

Interleukin 17 (IL-17) cytokines promote inflammatory pathophysiology in many autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Such broad involvement of IL-17 in various autoimmune diseases makes it an ideal target for drug discovery. Psoriasis is a chronic inflammatory disease characterized by numerous defective components of the immune system. Significantly higher levels of IL-17A have been noticed in lesions of psoriatic patients, if compared to non-lesion parts. Therefore, this paper is focused on the macrolide inspired macrocycles as potential IL-17A/IL-17RA modulators and covers the molecular design, synthesis, and in vitro profiling. Macrocycles are designed to diversify and enrich chemical space through different ring sizes and a variety of three-dimensional shapes. Inhibitors in the nM range were identified in both target-based and phenotypic assays. In vitro ADME as well as in vivo PK properties are reported.

Within this work we describe the synthesis of versatile substituted 2-phenyl benzothiazole 3–10 and 2-phenylbenzimidazole 12–19 derivatives bearing amidino groups. Furthermore, the synthesized compounds were explored for their antiproliferative activity in vitro on three cancer cell lines. Tested compounds showed moderate to strong antiproliferative activity. Furthermore, the type of the attached amidino group on benzazole nuclei has the significant impact on the antiproliferative activity only within benzimidazole derivatives with 2-imidazolinyl substituted derivatives being more active in comparison to amidino substituted analogues. All obtained results revealed that this type of benzothiazole derivatives have a great potential for further optimization and development of more efficient potential antiproliferative agents. This work is licensed under a Creative Commons Attribution 4.0 International License.

New cis- and trans-3-aryl-4-[2-(2-vinylphenyl)ethenyl]sydnones 2 , aryl = phenyl, p-tolyl were prepared and transformed on irradiation in the presence of acrolein to a pyrazoline derivative that aromatized during isolation to trans-1-tolyl-3-[2-(2-vinylphenyl)ethenyl]pyrazole 7 and trans-5-formyl-1-tolyl-3-[2-(2-vinylphenyl)ethenyl]pyrazole 8 .

1H and 13C NMR spectra of cis- and trans-3-(2-[2-(4-methylphenyl)ethenyl]phenyl])sydnones, the first stilbene-substituted mezoionic oxadiazolium rings, were fully assigned combining the information in various solvents, such as deuterated benzene, acetone and chloroform, using 2D NMR techniques.