Topical nonsteroidal antipsoriatic agents. 2. 2,3-(Alkylidenedioxy)naphthalene analogues of lonapalene.

Abstract

A series of 2,3-(alkylidenedioxy)naphthalene (5a-p) analogues of lonapalene (RS-43179, 1), a 5-lipoxygenase inhibitor currently under clinical investigation for the treatment of psoriasis, has been prepared and evaluated for topical inhibitory activity against arachidonic acid induced mouse ear edema. The results of these studies demonstrate that introduction of the fused 2,3-alkylidenedioxy ring, in place of the acyclic 2,3-dialkoxy substituent pattern characteristic of the previous series, caused a modest dimunition in overall potency within the series. These results suggest a potential steric intolerance for these extended planar analogues, in comparison with their 2,3-dialkoxy predecessors.

• Authors: M C Venuti, B E Loe, G H Jones, J M Young
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 31 Issue 11 Pg. 2132-6 (Nov 1988) ISSN: 0022-2623 [Print] United States
• PMID: 3141623 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Arachidonic Acids
• Naphthalenes
• Arachidonic Acid
• RS 43179

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, therapeutic use)
• Arachidonic Acid
• Arachidonic Acids (metabolism)
• Edema (chemically induced, prevention & control)
• Mice
• Naphthalenes (therapeutic use)
• Psoriasis (drug therapy)
• Structure-Activity Relationship