Antiproteases and retinoids for treatment of chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a common, severe inflammatory condition of the respiratory tract for which there is an enormous worldwide pharmaceutical potential. Despite this, current pharmacotherapy for COPD is suboptimal. Consequently, there are legitimate reasons for seeking alternative therapies for COPD. Proteases may contribute to the pathophysiology of COPD, whilst retinoids may be involved in lung repair. Recent patent applications from a variety of pharmaceutical companies disclose an array of different structural classes of protease inhibitors and retinoid compounds that may be of benefit in COPD. The antiprotease compounds comprise inhibitors of matrix metalloproteinases, including hydroxamic and carboxylic acid derivatives, lactams, β-amino acid derivatives and piperidine and piperazine derivatives, inhibitors of serine proteases, including guanidine derivatives, polypeptides and oxadiazole derivatives and inhibitors of cysteine proteases, including amide derivatives and nitrile derivatives. The retinoid compounds comprise retinoid agonists, including retinoic acid isomers and selective retinoic acid receptor (RAR)-γ agonists and RAR antagonists, in particular RAR-α antagonists.

• airway(s)
• all-trans-retinoic acid (ATRA)
• cathepsin
• chronic obstructive pulmonary disease (COPD)
• elastase
• emphysema
• matrix metalloproteinase (MMP)
• mucus hypersecretion
• protease
• retinoid