Alchilidene malonati e acetoacetati come intermedi per la preparazione di molecole bioattive

In this thesis we investigated the versatility and the potential applications of different kinds of alkylidene malonates, acetoacetates, malonamides and acetoacetoamides. Our research group devoted great attention to this kind of compounds since alkylidenes can be considered important intermediates in the synthesis of several scaffolds, to be inserted into molecules of potential biological and pharmaceutical interest. The increasing use of alkylidenes is due to their ability to react as unsaturated electrophiles and to the possibility to exploit them as intermediates for the introduction of different kind of functionalities.The preparation of alkylidene malonates, acetoacetates, malonamides and acetoacetoamides is presented in chapter 1. This section deals with different preparation methods of alkylidenes that we developed during the last few years and to the technologies involved for each synthetic protocol. The reactivity that allowed to use the alkylidenes as intermediates in the synthesis of scaffolds for biologically active compounds is shown in chapter 2. In particular, we will discuss the most important reactions used to obtain the desired molecules, and we will focus on the most interesting aspects of these latter ones. Finally, chapter 3 will illustrate the potential applications and the related syntheses of potential bioactive compounds. The synthesized molecules find application in several fields and for this reason we considered each class of compounds in its related branch of interest

A procedure to evaluate the indoor global quality by a sub objective-objective procedure

This paper proposes two complementary procedures for assessing the indoor global comfort: the first one, prevalently objective, is based on the acquisition of microclimate measured data and computed subjective values; the second one, that is purely subjective, uses a questionnaire drawn from the ISO/DP 10551 Recommendation. An application to some lecture-halls is here showe

A case study to the Evaluation of Global Environmental Quality, concerning thermal, acoustic and atmospheric conditions of urban areas

In this paper we propose an operative procedure aimed at assessing and check the global environmental quality in the urban areas. This methodology is set up by using an ergonomic approach that analyses the interaction man-environment in terms of cause-effect and uses information and data from various sources contributing to the formation of discomfort degrees.[1-2] The representation technique by normo-grams is used for showing some applications executed along the urban territory of Palermo and allows to evaluate very simply all the parameters involved in human comfort. This paper is divided in 5 sections, after the introduction in section 2 a review of the principal simple and complex indexes is presented, in section 3 the methodology used to assess the air quality is presented and in section 4 some experimental results on some areas of Palermo are presented, finally in section 5 some conclusions are drawn.[3-4

Wavelike Structures in the Turbulent Layer During the Morning Development of Convection at Dome C, Antarctica

n/

Development of freeze-drying cycle for a peptide-based drug in trays

Freeze-drying of a peptide solution is here presented, from the early identification of critical product temperature to the design of an appropriate cycle. Synergy between experimental characterisation techniques, mathematical modelling and process simulation has been implemented to develop a robust lyophilisation process and guarantee the removal of solvents impurities. Process has been carried out in bulk using a tray equipped with an anisotropic membrane, enabling unidirectional vapour flow

Copper(II) Lysinate and Pseudoproline Assistance in the Convergent Synthesis of the GLP-1 Receptor Agonists Liraglutide and Semaglutide

A growing interest in peptides as active pharmaceutical ingredients (APIs) requires the development of efficient strategies for their preparation. This is particularly challenging in the case of long peptides with a strong tendency for aggregation and folding. Here, we describe the pseudoproline-assisted convergent synthesis of GLP-1 receptor agonist lipopeptides liraglutide and semaglutide, which involves the stepwise condensation of three fragments in the solid phase. The insertion of a pseudoproline residue at the site of fragment coupling prevents aggregation and allows obtaining these peptides with excellent purity and high yield. In addition, for the synthesis of lipidated side chains, we developed a novel approach that involves copper(II) lysinate intermediates and can be particularly suitable for the industrial preparation of both liraglutide and semaglutide and other peptides with a similar branched structure.A growing interest in peptides as active pharmaceutical ingredients (APIs) requires the development of efficient strategies for their preparation. This is particularly challenging in the case of long peptides with a strong tendency for aggregation and folding. Here, we describe the pseudoproline-assisted convergent synthesis of GLP-1 receptor agonist lipopeptides liraglutide and semaglutide, which involves the stepwise condensation of three fragments in the solid phase. The insertion of a pseudoproline residue at the site of fragment coupling prevents aggregation and allows obtaining these peptides with excellent purity and high yield. In addition, for the synthesis of lipidated side chains, we developed a novel approach that involves copper(II) lysinate intermediates and can be particularly suitable for the industrial preparation of both liraglutide and semaglutide and other peptides with a similar branched structure

Agreement between physicians and parents in rating functional ability of children with juvenile idiopathic arthritis

<p>Abstract</p> <p>Objective</p> <p>To investigate concordance between physicians and parents in rating the degree of functional ability of children with juvenile idiopathic arthritis (JIA).</p> <p>Methods</p> <p>The attending physician and a parent were asked to rate independently the level of physical functioning of 155 patients with disease duration ≥ 5 years on a 6-point scale ranging from 1 = no disability (i.e. the child can do without difficulty all activities that children of his/her age can do) to 6 = severe disability (i.e. all activities are difficult for the child). At study visit, measures of JIA activity and damage were assessed. Agreement was evaluated with weighted kappa (<0.40 = poor agreement; 0.41–0.60 = moderate agreement; 0.61–0.80 = substantial agreement; >0.80 excellent agreement). Physician/parent evaluations were divided in 3 groups: 1) concordance; 2) parent over-rating = parent assessment over-rated relative to physician assessment; 3) physician over-rating = physician assessment over-rated relative to parent assessment. Factors affecting concordance/discordance were evaluated by means of Kruskal-Wallis or Chi-square/Fisher exact test.</p> <p>Results</p> <p>Concordance, parent over-rating and physician over-rating were observed in 107 (69%), 29 (18.7%) and 19 (12.3%) evaluations, respectively. Kappa value was 0.69. Parent over-rating was associated with greater intensity of pain (p = 0.01) and higher Childhood Health Assessment Questionnaire (C-HAQ) score (p = 0.004), whereas physician over-rating was associated with more severe joint disease (p = 0.04 to <0.001), higher C-reactive protein (p = 0.03) higher frequency of Steinbrocker functional class = II (p < 0.001), and greater articular damage, as measured with the Juvenile Arthritis Damage Index (p < 0.001).</p> <p>Conclusion</p> <p>Physicians and parents revealed fair concordance in rating functional ability of children with JIA. Parent over-rating was associated with greater child's pain and worse C-HAQ score, whereas physician over-rating was associated with greater severity of joint inflammation and damage.</p

Development and validation of a composite disease activity score for juvenile idiopathic arthritis

Objective. To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS). Methods. The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on &gt;4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0 \u2013101), 27-joint (range 0 \u201357), or 10-joint (range 0 \u2013 40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI). Results. The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change. Conclusion. The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials