The invention relates to aryl-sulfonamido compds. endowed with affinity against metallo proteases MMP, having formula (I) below wherein R, R1, R2, R3, G and n have the meanings reported in the specification, properly labeled with diagnostic imaging moieties or even radiotherapeutic moieties. The invention also refers to the process for their prepn., to pharmaceutical compns. comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents. The invention relates to arylsulfonamido compds. of formula I, which endowed with affinity against metalloproteases MMP and are useful as diagnostic imaging agents. The invention also refers to the process for their prepn., to pharmaceutical compns. comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents. Compds. of formula I wherein R is -Ar-X-Ar1; Ar is (un)substituted (hetero)arylene and (un)substituted (hetero)aryl; Ar1 is (un)substituted (hetero)aryl and H; 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 H, OH, Ra and ORa; Ra is (un)branched C1-4 alkyl, C2-4 alkenyl and - (CH2)0-4-Z-(CH2)0-4-W; Z is a single bond, O, NH and derivs., NHCO and derivs., and CONH and derivs.; W is (un)substituted Ph and (un)substituted 5- to 6-membered heterocycle; R2 and R3 are independently H, (un)substituted (un)branched C1-4 alkyl and a zinc binding group; G is (un)branched C1-6 alkyl, (hetero)aryl, arylalkyl and -(CH2)1-6- NH2 and derivs.; and their pharmaceutically acceptable salts thereof, are claimed. Example compd. II·2CF3COOH was prepd. via hydroxyamidation of the corresponding acid with O-(tert-butyldimethylsilyl)hydroxylamine. All the invention compds. were evaluated for their metalloprotease inhibitory activity. From the assay, it was detd. that II exhibited the IC50 value of 0.3 ± 0.03 nM and 0.2 ± 0.01 nM against MMP2 and MMP13, resp.

Diagnostic Agents Selective agains Metalloproteinases

ROSSELLO, ARMANDO;NUTI, ELISA;
2010-01-01

Abstract

The invention relates to aryl-sulfonamido compds. endowed with affinity against metallo proteases MMP, having formula (I) below wherein R, R1, R2, R3, G and n have the meanings reported in the specification, properly labeled with diagnostic imaging moieties or even radiotherapeutic moieties. The invention also refers to the process for their prepn., to pharmaceutical compns. comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents. The invention relates to arylsulfonamido compds. of formula I, which endowed with affinity against metalloproteases MMP and are useful as diagnostic imaging agents. The invention also refers to the process for their prepn., to pharmaceutical compns. comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents. Compds. of formula I wherein R is -Ar-X-Ar1; Ar is (un)substituted (hetero)arylene and (un)substituted (hetero)aryl; Ar1 is (un)substituted (hetero)aryl and H; 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 H, OH, Ra and ORa; Ra is (un)branched C1-4 alkyl, C2-4 alkenyl and - (CH2)0-4-Z-(CH2)0-4-W; Z is a single bond, O, NH and derivs., NHCO and derivs., and CONH and derivs.; W is (un)substituted Ph and (un)substituted 5- to 6-membered heterocycle; R2 and R3 are independently H, (un)substituted (un)branched C1-4 alkyl and a zinc binding group; G is (un)branched C1-6 alkyl, (hetero)aryl, arylalkyl and -(CH2)1-6- NH2 and derivs.; and their pharmaceutically acceptable salts thereof, are claimed. Example compd. II·2CF3COOH was prepd. via hydroxyamidation of the corresponding acid with O-(tert-butyldimethylsilyl)hydroxylamine. All the invention compds. were evaluated for their metalloprotease inhibitory activity. From the assay, it was detd. that II exhibited the IC50 value of 0.3 ± 0.03 nM and 0.2 ± 0.01 nM against MMP2 and MMP13, resp.
2010
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/126177
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