111507-07-4Relevant academic research and scientific papers
NOVEL DRUGS FOR DEMENTIA
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Example 2, (2008/06/13)
The invention is directed to compounds that are prodrugs containing a chemical delivery system (CDS) moiety and a cysteine protease inhibitor moiety. The CDS moiety targets the prodrug to the brain or central nervous system. The cysteine protease inhibitor inhibits cysteine proteases upon release from the prodrug. Cysteine protease inhibitors are effective for treating dementia, Alzheimer's disease and vascular dementia. Targeting the brain or central nervous system offers significant advantages in treating these conditions and diseases. A preferred CDS prodrug is a dihydrotrigoneline CDS moiety coupled to an epoxysuccinyl peptide cysteine protease inhibitor moiety.
N-Haloacetyl-amino-acid amides as active-site-directed inhibitors of papain and cathepsin B
Girodano,Gallina,Ottaviano,Consalvi,Scandurra
, p. 865 - 873 (2007/10/02)
A series of N-haloacetyl-amino-acid amides were synthesized and tested as models of cysteine-protease inhibitors. They irreversibly inactivated papain and cathepsin B via a reversible enzyme-inhibitor intermediate. Apparent second-order rate constants of inactivation ranging from 65 to 16,700 M-1 s-1 were observed. Reactivity against papain, as compared to glutathione, was increased 16,400-fold for N-bromoacetyl-leucine isopentylamide and 25,700-fold for the corresponding iodoacetyl derivative; these increases are probably due to proximity effects. No inhibition of trypsin, chymotrypsin and porcine pancreatic elastase was observed. Haloacetamides represent an interesting class of easily synthesized, efficient, irreversible inhibitors of cysteine proteases, which have low non-specific alkylating properties.
