The invention relates to arylsulfonamide derivs. of formula I, which endowed with inhibitory activity against metalloproteases (MMP). The invention also refers to the process for their prepn., to pharmaceutical compns. comprising them and to their use as therapeutic agents, particularly in the treatment of degenerative disorders. Compds. of formula I wherein R is -Ar-X-Ar1; Ar is (un)substituted arylene and (un)substituted aryl; Ar1 is H, (un)substituted arylene and (un)substituted aryl; X is a single bond, (un)branched C1-4 alkylene, O, S, SO2, CO, NH and derivs., NHCO and derivs. and CONH and derivs.; R1 is OH and derivs.; R2 and R3 are independently H and (un)substituted (un)branched C1-4 alkyl; R4 is H, CORc, COORc, SO2Rc, CONHRc and SO2NHRc; Rc is C3-6 cycloalkyl, (un)branched alkyl, aryl, arylalkyl, alkylaryl, 5- to 6-membered heterocyclyl, etc.; R5 is H; R4R5 may taken together with nitrogen atom attached to form (un)substituted benzo(un)condensed 4- to 6-membered heterocyclyl; n is 1-2; A is (CH2)m; m is 1-6; provided that R is biphenyl-4-yl, R1 is iso-Pr, one of R2 and R3 is CONHOH and the other one of R2 and R3 is H, R5 is H, m and n are both 2, then R4 is not H and benzyloxycarbonyl; and their pharmaceutically acceptable salts thereof, are claimed. Example compd. II was prepd. by a multi-step procedure (procedure given). All the invention compds. were evaluated for their metalloproteases inhibitory activity. From the assay, it was detd. that II exhibited IC50 value of 0.13±0.03 nM against MMP-2.

Compounds having aryl-sulphonamidic structure useful as metalloproteases inhibitors

ROSSELLO, ARMANDO;NUTI, ELISA;ORLANDINI, ELISABETTA;TUCCINARDI, TIZIANO
2008-01-01

Abstract

The invention relates to arylsulfonamide derivs. of formula I, which endowed with inhibitory activity against metalloproteases (MMP). The invention also refers to the process for their prepn., to pharmaceutical compns. comprising them and to their use as therapeutic agents, particularly in the treatment of degenerative disorders. Compds. of formula I wherein R is -Ar-X-Ar1; Ar is (un)substituted arylene and (un)substituted aryl; Ar1 is H, (un)substituted arylene and (un)substituted aryl; X is a single bond, (un)branched C1-4 alkylene, O, S, SO2, CO, NH and derivs., NHCO and derivs. and CONH and derivs.; R1 is OH and derivs.; R2 and R3 are independently H and (un)substituted (un)branched C1-4 alkyl; R4 is H, CORc, COORc, SO2Rc, CONHRc and SO2NHRc; Rc is C3-6 cycloalkyl, (un)branched alkyl, aryl, arylalkyl, alkylaryl, 5- to 6-membered heterocyclyl, etc.; R5 is H; R4R5 may taken together with nitrogen atom attached to form (un)substituted benzo(un)condensed 4- to 6-membered heterocyclyl; n is 1-2; A is (CH2)m; m is 1-6; provided that R is biphenyl-4-yl, R1 is iso-Pr, one of R2 and R3 is CONHOH and the other one of R2 and R3 is H, R5 is H, m and n are both 2, then R4 is not H and benzyloxycarbonyl; and their pharmaceutically acceptable salts thereof, are claimed. Example compd. II was prepd. by a multi-step procedure (procedure given). All the invention compds. were evaluated for their metalloproteases inhibitory activity. From the assay, it was detd. that II exhibited IC50 value of 0.13±0.03 nM against MMP-2.
2008
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/111230
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