Title compds. I [X1 = S(O)q; R1 and R2 independently = H, (un)substituted alkyl, aryl, etc., or R1 and R2 are linked to form carbocyclic or heterocyclic ring; X = O or S, or divalent group selected from disulfide, disulfoxide, sulfone, amino, etc.; E = alkyl, alkenyl, alkynyl or (un)substituted carbocyclic or heterocyclic ring, optionally benzocondensed; Z = chelating moiety; m = 0 or 1; n = 0 or 1; q = 0-2], and their pharmaceutically acceptable salts thereof, are prepd. and disclosed as inhibitors of zinc metalloproteinases. Thus, e.g., II was prepd. by substitution of o-iodobenzoic acid with 4- methoxythiophenol. Data for inhibition activity of representative compds. towards select proteases were provided, e.g., 2-(2-biphenyl-4-ylthio)phenylacetic acid possessed IC50 values of 334±5.7, 0.33±0.026, and 6.7±0.3 (mM) toward MMP- 1, MMP-2, and MMP-9, resp.
INHIBITORS OF ZINC PROTEASES THIOARYL SUBSTITUTED AND THEIR USE
ROSSELLO, ARMANDO;NUTI, ELISA;ORLANDINI, ELISABETTA;
2008-01-01
Abstract
Title compds. I [X1 = S(O)q; R1 and R2 independently = H, (un)substituted alkyl, aryl, etc., or R1 and R2 are linked to form carbocyclic or heterocyclic ring; X = O or S, or divalent group selected from disulfide, disulfoxide, sulfone, amino, etc.; E = alkyl, alkenyl, alkynyl or (un)substituted carbocyclic or heterocyclic ring, optionally benzocondensed; Z = chelating moiety; m = 0 or 1; n = 0 or 1; q = 0-2], and their pharmaceutically acceptable salts thereof, are prepd. and disclosed as inhibitors of zinc metalloproteinases. Thus, e.g., II was prepd. by substitution of o-iodobenzoic acid with 4- methoxythiophenol. Data for inhibition activity of representative compds. towards select proteases were provided, e.g., 2-(2-biphenyl-4-ylthio)phenylacetic acid possessed IC50 values of 334±5.7, 0.33±0.026, and 6.7±0.3 (mM) toward MMP- 1, MMP-2, and MMP-9, resp.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
