Derivatives of 3-sec-butyl-1-oxo-2,3-dihydroisoquinoline as inhibitors of μ-calpain

5 pages, 3 figures, 1 table.-- PMID: 16902923 [PubMed].-- Taken in part from the ongoing PhD thesis of R.C. and the MSc thesis of M.T.M. Patents ES-P200402995 and PCT-ES2005-070171 have been filed.The calpains (E.C. 3.4.22.17) are a family of cysteine proteases and consist of about 20 isoenzymes. Although most of these isoenzymes are present in only particular tissues or species, two isoenzymes, calpain I (or μ-calpain) and calpain II (or m-calpain), are ubiquitous. A distinctive mechanistic feature of calpain is that the enzyme is activated by Ca2+; the in vitro Ca2+ concentration required for half-maximal activity of μ-calpain is 2–75 μM and for m-calpain, 200–1000 μM. As these concentrations are exceptionally high for in vivo activity, several alternative mechanisms for calpain activation have been proposed.This work was financially supported by MCyT (BQU2001-2270), MEyC (CTQ2004-01978), Fundación "la Caixa" (02/162-02), and CAM (GR/SAL/0652/2004). M.A. thanks MEyC for a scholarship.Peer reviewe