Watch case (1) with a part of the cover (7) containing a case lid (2), with a part of the base (8) containing a case base (3) and a circumferential wall of the box (4) between the lid of the box (2) and the base of the box (3), being surrounded in at least part of its circumference, by at least one decorative element (11), characterized in that the part of the Cover (7) is connected to the base part (8) by at least two connecting bridges (12) distributed over the entire perimeter of the decorative element (11). ** Formula ** in which, when Ar is an optionally substituted five-membered aromatic heterocycle or an optionally substituted five-membered aromatic carbocycle, Ar is optionally substituted with one or more R2 groups and / or one or more optional substituents; when Ar is an optionally substituted six-membered aromatic heterocycle, Ar is optionally substituted with M, one or more R2 groups and / or one or more optional substituents; when Ar is a substituted phenyl, optionally further substituted, Ar is substituted with M and optionally substituted with one or more R2 groups and / or one or more optional substituents; wherein M is selected from the group consisting of H, OH, SH, NO2, CN, NR "2 and an optionally substituted moiety selected from -L7-alkyl, -L7-alkenyl, -L7-alkynyl, -L7- cycloalkyl, -L7-cycloalkenyl, -L7-cycloalkynyl, -L7-heteroalkyl, -L7-heteroalkenyl, -L7-heteroalkynyl, -L7-haloalkyl, -L7-haloalkenyl, -L15 7- haloalkynyl, -L7-aryl, -L7 -heterocycloalkenyl, -L7-heterocycloalkynyl, -L7-heterocycloalkyl and -L7-heteroaryl; in which L7 is selected from a bond, -O-, -NH-, -S-, -C (O) -, -C ( S) -, -C (O) O-, -C (O) NH-, -S (O) -, -S (O) 2-, -OC (O) -, -C (O) NR "( CR "2) 1-6C (O) O-, -CR" 2NR "CR" 2C (O) O-, -C (O) NR "Y1C (O) O-, -C (O) NR" NR " C (O) O-, - S (O) NH-, -C (O) NR "CR" 2C (O) W-, -CR "2NR" WO-, -CR "2NR" Y1C (O) O- and -C (O) NR "O-; W is C1-6 alkylene; Y1 20 is optionally substituted arylene or optionally substituted heteroarylene; wherein said optional substituents are selected from halogen, OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkyl, C2-6 haloalkenyl, C2-6 haloalkynyl and C1 haloalkoxy -6; with the proviso that M is not H in Formula (2); each R "is independently H, OH, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, substituted C1-6 alkyl, substituted C2-6 alkenyl, substituted C2-6 alkynyl, C1-6 alkoxy, haloalkyl C1-6, C2-625 haloalkenyl, C2-6 haloalkynyl, C1-6 haloalkoxy, aryl, haloaryl or heteroaryl; R2 is independently selected from the group consisting of H, OH, halogen and an optionally substituted moiety selected from -L2- alkyl, -L2-alkenyl, -L2-alkynyl, -L2-cycloalkyl, -L2- cycloalkenyl, -L2-cycloalkynyl, -L2-heteroalkyl, -L2-heteroalkenyl, -L2-heteroalkynyl, -L2-haloalkyl, -L2- haloalkenyl, -L2-haloalkynyl, -L2-aryl, -L2-heterocycloalkyl, -L2-heterocycloalkenyl, -L2- heterocycloalkynyl and -L2-heteroaryl; wherein L2 is selected from a bond, -O-, -NH-, -S-, -C (O) -, -C (S) -, -C (O) O-, -C (O) NH-, -S (O) -, -S (O) 2-, - C (O) NR "(CR" 2) 1-6C (O) O-, -OC (O) -, -CR "2NR" CR "2C (O) O-, - C (O) NR" NR " C (O) O- and -S (O) NH-; wherein said optional substituents are selected from halogen, OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkyl, C2-6 haloalkenyl, C2-6 haloalkynyl and C1 haloalkoxy -6; or any two adjacent R2 groups may together form an optionally substituted 5 to 8 membered aryl, cycloalkynyl, cycloalkenyl, cycloalkyl or heterocyclic ring; or Ar is selected from the group consisting of and in which said optional substituents are selected from unsubstituted alkenyl, alkyl, alkoxy, alkylamine, alkylthio, alkynyl, amide, amino, aryl, aryloxy, arylthio, carbocyclic, cyano, cycloalkyl, halogen, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl, heterocyclic, hydroxy, isocyanate, isothiocyanate, mercapto, nitro, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, S-sulfonamido, C-carboxy, perhaloalkyl, perfluoroalkyl, thiocyanate and trihalomethanesulfonyl; and wherein the term "aromatic" or "aryl" refers to a closed ring structure having at least one ring having a conjugated pi electron system; or a pharmaceutically acceptable salt, pharmaceutically acceptable N-oxide or pharmaceutically acceptable solvate thereof.

New antibiotics with new mechanisms of action are desperately needed, as clinically significant bacterial pathogens have not only acquired resistance to nearly all existing antibiotics, but also increasingly exhibit multi-drug resistance. Peptide deformylase (PDF), a highly conserved metalloproteinase, is an essential enzyme in the bacterial life cycle. It catalyses the removal of the terminal formyl group from the N-terminal methionine residue of the nascent bacterial polypeptide chain. Thus, inhibition of PDF, by interfering with the bacterial protein maturation process, is providing a promising new and exciting target for antibiotic therapeutic intervention without interfering with eukaryotic metabolism. Antibiotics based on PDF inhibition have the potential to provide the much needed antibacterial activity against most of the major drug-resistant pathogens and could play a significant role in the treatment of community-acquired upper respiratory tract infections. This review covers all the patenting activity in this field of research up to, and including, March 2005, and will focus on the more significant patents and patent applications.

Heterocyclic scaffolds represent the central framework of many biologically active compounds. The goal of this review is to present advances in the field of microwave-assisted synthesis of heterocyclic compounds that have been described in the literature since 1994. In particular, it focuses on reactions in which a heteroatom is directly participating in the bond forming process that gives rise to a heterocyclic core. The review is divided into two sections, cycloaddition and cyclization reactions, which are further classified according to ring type. These reactions are discussed from a synthetic standpoint with emphasis on comparison between microwave and conventional techniques.

Screening of our compound collection using Staphylococcus aureus Ni-Peptide deformylase (PDF) afforded a very potent PDF inhibitor with an IC(50) in the low nanomolar range but with poor antibacterial activity (MIC). Three-dimensional structural information obtained from Pseudomonas aeruginosa Ni-PDF complexed with the inhibitor suggested the synthesis of a variety of analogues that would maintain high binding affinity while attempting to improve antibacterial activity. Many of the compounds synthesized proved to be excellent PDF-Ni inhibitors and some showed increased antibacterial activity in selected strains.

Microwave irradiation promotes the conversion of enaminoketones formed in situ into a variety of heterocycles by reaction with the appropriate bidentate nucleophile. The advantages of the method over previous approaches are short reaction times and facile purification by precipitation of the products in aqueous media. Moreover the convenient one-pot procedure makes these syntheses particularly suitable for library production. Organic reactions in aqueous media have become of great interest as water is not only more environmentally friendly, but also because organic reactions in water often display unique reactivity and selectivity.

BACKGROUND A mutation in the promoter of the uridine diphosphate glucuronosyltransferase gene has been described in patients with Gilbert's syndrome from Northern Europe. AIMS To assess the frequency of this mutation in Italian patients with Gilbert's syndrome and in normal controls, in order to establish the molecular basis and molecular epidemiology of the syndrome in Italy. PATIENTS Forty-six patients with a clinical diagnosis of Gilbert's syndrome and 44 individuals from the general population unselected for bilirubin levels. METHODS Polymerase chain reaction amplification of the TATA-box element in the promoter of uridine diphosphate glucuronosyltransferase and identification of wild-type and variant alleles by high-resolution polyacrylamide gel electrophoresis. RESULTS A TATA-box variant in the promoter of uridine diphosphate glucuronosyltransferase was found on 93% of chromosomes from patients with Gilbert's syndrome. The same variant was present on 44% of chromosomes from controls, unselected for bilirubin levels. Only 55% of controls homozygous for the TATA-box variant, however, had increased bilirubin levels. CONCLUSIONS The TATA-box variant in the promoter of uridine diphosphate glucuronosyltransferase is strongly associated with the phenotype of Gilbert's syndrome in Italy. The incomplete penetrance of the mutation observed in controls indicates that other acquired or inherited conditions affecting bilirubin production, uptake, cellular transport or excretion may contribute to the hyperbilirubinaemia of Gilbert's syndrome.

Objective: To define whether there is any relation between the iron status of patients with hepatitis C virus (HCV) chronic liver disease and their response to interferon therapy. Design: To evaluate the long-term response to 1 year of interferon therapy with addition of phlebotomies after 3 months of treatment if at that time alanine aminotransferase (ALT) had not normalized in a group of patients with HCV-positive chronic liver disease whose iron status had been characterized. Setting: A northern Italian hospital. Participants: Fifty-eight anti-HCV-positive patients (four HCV-RNA negative) with biopsy proven chronic hepatitis and no evidence of iron overload as indicated by normal transferrin saturation at the time of enrolment in the study. Intervention: Three times a week intramuscular injection of alpha interferon 3MU for 1 year with addition of phlebotomies (350ml/week) till iron depletion if after 3 months of interferon therapy ALT had not normalized. Results: A long-term response was observed in 19 of the 52 patients who completed the treatment, four HCV-RNA negative and 15 positive. The four RNA-negative and seven of the 15 RNA-positive long-term responders had been treated with interferon alone, and the other eight also with phlebotomies. At univariate analysis only HCV genotype, gammaglutamyltranspeptidase and liver iron concentration were significantly associated with response whereas sinusoidal iron deposition was of borderline significance. No association was found with sex, age, duration of disease, histology, Knodell score, transferrin saturation %, serum ferritin, hepatocytic iron score, and portal iron score. HCV-RNA serum levels, measured in 29 patients, did not correlate with response. At multivariate analysis liver iron concentration was still significant and one unit reduction of liver iron concentration (natural logarithm transformed) was associated with 2.95 odds ratio of response. Conclusion: These results indicate that iron in the liver is more closely related to response to interferon than the other variables considered, including HCV characteristics.

BACKGROUND:A strong association between sporadic porphyria cutanea tarda and chronic hepatitis C virus infection was recently described in Italy, France and Spain.AIMS:To explore whether hepatitis C virus genotype plays a role in porphyria cutanea tarda complicating chronic hepatitis C.PATIENTS:Forty-seven hepatitis C virus-positive porphyria cutanea tarda patients and a control group of 45 patients of similar age with hepatitis C virus-associated chronic liver disease.METHODS:Comparison of frequency of hepatitis C virus genotypes in the two groups and in relation to the age of patients, hepatic histopathology and with the presence of other factors potentially able to trigger porphyria cutanea tarda.RESULTS:A single genotype, hepatitis C virus 1b, was found to be present in nearly 90% of porphyria cutanea tarda-associated chronic liver disease, significantly exceeding the frequency of the same genotype in the control group (p = 0.0001). The presence of hepatitis C virus 1b was not related to the age of patients or disease severity as evaluated by hepatic histopathology.CONCLUSIONS:Hepatitis C virus-associated chronic hepatitis found in the majority of Italian patients with porphyria cutanea tarda is usually sustained by hepatitis C virus genotype 1b. This viral strain might have a direct pathogenic role in inducing porphyria cutanea tarda or could increase the susceptibility of patients of other triggering factors such as iron overload or alcohol abuse.