5-Naphthoylsalicylanilides as improved anti-acne agents

DESCRIPTION (provided by applicant): The goal of our anti-acne drug discovery and development program is to produce a novel therapeutic for acne that adresses both the bacterial and inflammatory component of this disease. Our approach to accomplish this goal involves evaluating a focused series of patented 5-naphthoylsalicylanildes in biological systems predictive of clinical anti-acne activity (this Phase 1), and choosing the best compound from these studies for progression to pre-clinical pharmaceutical development (Phase 2) and clinical trials in humans (Phase 3). The combined biological and physico-chemcial properties of the 5-naphtholysalicylanilides gives them a unique advantage over several other drugs and formulations currently used in the treatment of this disorder. These include: 1) a broad spectrum of antibacterial activity, with exceptional activity against Propionibacterium acnes (a significant factor in the progression of acne) as well as other dermal pathogens such as Staphylococcus aureus and other Staphylococcus species that may play a secondary role in this condition; 2) potent dermal anti-inflammatory activity, 3) inhibition of cyclooxygenases and PgE2 production, 4) inhibitory activity against certain tissue destructive enzymes such as the matrix-metalloproteases 2 and 9 and neutrophil elastase which are activated in response to infection; 5) high lipophilicy which makes them suitable for use in topically administered treatments for conditions where they can partition and act in lipid rich components of affected sites and 5) a high level of both topical and oral safety These qualities, plus the patent status of the technology, make an optimized 5-naphthoylsalicylanilide an excellent candidate for development as an active anti-acne agent. In Phase 1 we chose an optimized compound for progression (Naphthafluor). In Phase 2 we are requesting support for several preclinical pharmaceutical development and safety studies required before evaluation in humans can commence. We expect the success of these studies will entice a major pharmaceutical partner to pursue the continued development and clinical evaluation of Naphthafluor (Phase 3) as an anti-acne treatment.