5 research outputs found
Arylsulfonamido compounds as metalloprotease inhibitors and their preparation, pharmaceutical compositions and use as diagnostic as well as radiotherapeutic agents
No full textThe invention relates to aryl-sulphonamido compounds endowed with affinity against metallo proteases MMP, having formula (I) below wherein R, R 1 , R 2 , R 3 , G and n have the meanings reported in the specification, properly labelled with diagnostic imaging moieties or even radiotherapeutic moieties. The invention also refers to the process for their preparation, to pharmaceutical compositions comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents
Diagnostic Agents Selective agains Metalloproteinases
No full textThe 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
Disegno, sintesi e valutazione biologica di nuovi inibitori selettivi della Metalloelastasi a struttura arilsolfonica
No full textLa MMP-12 o “metalloelastasi dei macrofagi” è una endopeptidasi zinco dipendente appartenente alla famiglia delle metalloproteasi della matrice extracellulare (MMPs). Essa gioca un ruolo importante nel rimodellamento e distruzione del tessuto polmonare, infatti, sono stati ritrovati alti livelli di MMP-12 nei tessuti polmonari dei malati di COPD (malattia polmonare cronica ostruttiva). Argomento del mio lavoro di Tesi è stato lo sviluppo e la sintesi di una nuova serie di derivati arilsolfonici capaci di inibire selettivamente la MMP-12. In particolare, il derivato morfolinico 2c ha dimostrato di essere un potente inibitore della MMP-12 e di avere una buona selettività verso le MMP -1, -9 e -14 nei saggi in vitro sugli enzimi isolati.
MMP-12 is a member of the matrix metalloproteinases family (MMPs), zinc dependent endoproteinases that participate in extracellular matrix degradation. MMP-12 plays a significant role in airway inflammation and remodeling. In fact, increased expression and production of MMP-12 has been found in the lung of human COPD (chronic obstructive pulmonary disease) patients. During my Thesis research work, a new series of arylsulfone compounds was synthesized as selective inhibitors of MMP-12. Particularly, the morpholine derivative 2c demonstrated to be a potent MMP-12 inhibitor and showed selectivity towards MMP -1, -9 and -14 in in vitro assays on purified enzymes
Adsorption Forms of CO<sub>2</sub> on MIL-53(Al) and NH<sub>2</sub>-MIL-53(Al) As Revealed by FTIR Spectroscopy
No full textAdsorption of CO2 on MIL-53(Al) and NH2-MIL-53(Al) has been studied by Fourier transform infrared (FTIR) spectroscopy at different temperatures and equilibrium pressures. For better interpretation of the spectra 13CO2 was also utilized. It is established that with both samples at low coverages CO2 forms O-bonded complexes with the structural OH groups (OH⋯O12CO). These species are characterized by μ3(12CO2) at 2337-2338 cm-1 and two μ2(12CO2) modes around 662 and 650 cm-1. Simultaneously, the μ(OH) modes of the hydroxyl groups are red-shifted, while the δ(OH) modes are blue-shifted. At higher coverages (OH⋯O12CO)2 dimeric species are formed and this leads to a decrease of the μ3(CO2) frequency by 2-4 cm-1. This change is due to vibrational interaction as proven by the observation that the frequency remains practically unaffected for (OH⋯O12CO) (OH⋯O13CO) dimeric species. Interaction between dimers leads to additional slight decrease of the value of μ3(CO2). In parallel with the CO2 adsorption a partial transformation of the material from large-pore to narrow-pore form occurs. Far before CO2 interacts with all hydroxyl groups, polymeric CO2 species are produced within the MIL-53(Al) sample. They are characterized by a split μ3(CO2) mode with a pronounced component at 2340 cm-1. The formation of these species involves some of the dimers and is accompanied by a reopening of the MIL-53 structure. Analysis of the shift of the OH modes led to the conclusion that the polymeric moiety interacts strongly with one OH group and more weakly with several other hydroxyls. No polymeric species were observed with the NH2-MIL-53(Al) sample which is associated with the more stable narrow-pore structure of this material. However, evidence of interaction between CO2 and the hydroxyls H-bonded to amino groups was found.ChemE/Catalysis Engineerin
