JNJ-39758979

Introduction: Atopic dermatitis (AD) is a chronic, inflammatory skin disease. Conventional treatments include topical emollients, corticosteroids, calcineurin inhibitors, phototherapy, and systemic immunomodulatory agents, however, these medications have limitations in the treatment of moderate to severe AD. Current literature demonstrates that oral small molecules may be an effective modality to treat AD. Method: Using PubMed/MEDLINE, Embase, Cochrane Skin databases and clinicaltrials.gov a search with terms 'atopic dermatitis or atopic eczema' and 'name of the oral small molecule' was conducted resulting in 1197 articles. Inclusion criteria were studies involving human subjects treated with oral small molecule medication for AD and written in English. Randomized clinical trials, open-label prospective trials, and case reports/series were reviewed. Results: Seven articles, with a total of 250 patients, were included for review. Oral small molecules studied include: apremilast, baricitinib, JNJ-39758979, and tofacitinib. Small molecules demonstrate improvement in AD disease scores, patient-reported outcomes, and quality of life. Conclusion: Preliminary results demonstrate that oral small molecules are an effective treatment option in AD with minimal side effects. Additional randomized studies with larger sample sizes are needed to determine the efficacy and long-term side effects of these novel therapies.

This study focuses on the design, synthesis, molecular modeling and biological evaluation of a novel group of alkyl-1,3,5-triazinyl-methylpiperazines. New compounds were synthesized and their affinities for human histamine H₄ receptor (hH₄R) were evaluated. Among them, 4-(cyclohexylmethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (14) exhibited hH₄R affinity with a K_i of 160 nM and behaved as antagonist in functional assays: the cellular aequorin-based assay (IC₅₀ = 32 nM) and [³⁵S]GTPγS binding assay (pK_b = 6.67). In addition, antinociceptive activity of 14in vivo was observed in Formalin test (in mice) and in Carrageenan-induced acute inflammation test (in rats).