Lonapalene

Ultrasonic irradiation provides efficient promotion of the reactions between substituted buta-1,3-dienes with substituted 2,3-dimethoxycyclo-2,5-hexadiene-1,4-diones in Diels-Alder cycloadditions which afford a variety of bicyclo[4.4.0] fused-ring systems, e.g. I, in one step in high yields.Sonochem. provides an increase in yield over a much shorter period than conventional methodol. for reactions performed in benzene, toluene, and methylene chloride.It provides a convenient route to naphthaquinols and lonapalene, a 5-lipoxygenase inhibitor in the treatment of psoriasis.

Topical administration of lipoxygenase and cyclooxygenase inhibitors, antipsoriatic drugs and some immunomodulating drugs on adult mouse tail scales showed variable induction of of orthokeratosis. Dithranol and retinoic acid showed ED₅₀ concentrations of 0.5% and 0.23%, respectively. The lipoxygenase inhibitors catechol and octyl gallate showed ED₅₀ of 2.5 and 13.4%. 10% lonapalene showed 20% activity, curcumin, linoleic acid, primrose oil and AA673 10–15% activity, methyl and ethyl gallate 5% activity, nordihydroguaiaretic acid, diethylcarbamazine, ebselen, esculetin, quercetin, AA861, gallic acid, dodecyl gallate and 15-hydroxyeicosatetraenoic acid no activity. The cyclooxygenase inhibitors indomethacin, acetylsalicylic acid and bufexamac were inactive, benoxaprof-en showed 14% activity. The immunomodulating drugs fluo-rouracil and triamcinolone showed > 10% activity, cyclosporin A and thalidomide no activity. Fumaric acid showed 5% activity. The results show that this model could be proposed for screening antipsoriatic drugs.