Anti-inflammatory Properties of New Adamantane Derivatives. Design, Synthesis, and Biological Evaluation

• Published in: Archiv der Pharmazie (Weinheim) 1998-02, Vol.331 (2), p.72-78
• Main Authors: Antoniadou-Vyza, Ekaterini, Avramidis, Nikos, Kourounakis, Angeliki, Hadjipetrou, Lygeri
• Format: Article
• Language: English
• Subjects: Adamantane - analogs & derivatives; Adamantane derivatives; Animals; anti-inflammatory; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Drug Design; Female; Male; Medical sciences; Mice; Mice, Inbred BALB C; paw-edema; Pharmacology. Drug treatments; phlogistics; Structure-Activity Relationship
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/(SICI)1521-4184(199802)331:2<72::AID-ARDP72>3.0.CO;2-E

A series of adamantane‐containing molecules consisting of two lipophilic centers which are linked by different bridges (oxime esters, oxime ethers, amides, and symmetric alcohols), were designed and synthesized as anti‐inflammatory agents. Their anti‐inflammatory activity was evaluated as their ability to inhibit phlogistic‐induced mouse paw edema. Some of the tested compounds exhibited activity comparable to that of diclofenac, others had a weaker activity, while some oxime esters proved to enhance the inflammatory response. In all cases, activity was dose‐dependent. The deacylated compound 10 was found to be the most active of the series, inhibiting inflammation due to Baker’s yeast, the mechanism of which involves mainly the activation of lipoxy‐genase and/or complement systems, a property which is absent from most selective cyclooxygenase only inhibiting non‐steroidal anti‐inflammatory drugs (NSAIDs).