Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, pre-viously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan\u2013Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontin-uation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 \ub1 13.8 years and with an ETA duration of 4.1 \ub1 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients

Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors

In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kγ inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kγ inhibitor with ADME properties suitable for oral administration. Compound 15 was advanced into in vivo studies showing dose-dependent inhibition of LPS-induced airway neutrophilia in rats when administered orally

REGIOSELECTIVE AND STEREOSELECTIVE SYNTHESIS OF BETA-HALOHYDRINS FROM 1,2-EPOXIDES WITH AMMONIUM HALIDES IN THE PRESENCE OF METAL-SALTS

A simple efficient, stereoselective, and regioselective method for the synthesis of beta-chlorohydrins, beta-bromohydrins, and beta-iodohydrins by the direct opening of 1,2-epoxides with the corresponding ammonium halide in acetonitrile, in the presence of metal salts. is described. This new method appears to be of general use and competitive with the other methods previously reported

REGIOCHEMICAL CONTROL OF THE RING-OPENING OF 1,2-EPOXIDES BY MEANS OF CHELATING PROCESSES .7. SYNTHESIS AND RING-OPENING REACTIONS OF CIS-OXIDE AND TRANS-OXIDE DERIVED FROM 2-(BENZYLOXY)-3,6-DIHYDRO-2H-PYRAN

The regiochemical outcome of the ring opening of 1,2-epoxides bearing polar remote functionalities through chelation processes assisted by metal ions was verified in a conformationally semirigid cyclic oxirane system in which the polar functionality is both directly inserted into the cyclic system and present on the cyclic system itself. Diastereoisomeric cis 4 and trans epoxide 5, derived from 2-(benzyloxy)-3,6-dihydro-2H-pyran, were prepared and some of their opening reactions (azidolysis, aminolysis, Cl- addition, and LiAlH4 reduction) were studied. The regioselectivity observed is largely dependent for both 4 and 5 on the opening (standard or metal-assisted) reaction conditions, and a regioalternating process is almost obtained

METAL SALT-PROMOTED ALCOHOLYSIS OF 1,2-EPOXIDES

A simple, efficient, stereoselective, and regioselective method for the synthesis of beta-alkoxy alcohols by the direct opening of 1,2-epoxides with alcohols (primary, secondary, and tertiary) in a nonprotic solvent or with the alcohol itself as the solvent, in the presence of a metal salt, is described. This new method appears to be competitive with and/or alternative to the other methods previously reported

Morphodynamics of nearshore rhythmic forms: An energy-based classification

The present paper describes the bar system at Lido di Dante (Ravenna, Italy), a 3 Km beach facing the northern Adriatic Sea. The system shows a twofold behavior. A visual classification of the bar plan shape is presented in order to find a relation between the state of the system and the forcing conditions. If the total energy of storms exceeds a certain threshold, the changes between morphodynamics states are controlled by the forcing parameters (storms). However, under calm conditions the system returns to equilibrium, independently from the forcing signal, following a self-organization behavior. The area is strongly influenced by the room available for the bars. The available space is controlled by the position of the Bevano river mouth that represents the southern boundary of the study site. © 2007 World Scientific Publishing Co. Pte. Ltd

REGIOCHEMICAL CONTROL OF THE RING-OPENING OF 1,2-EPOXIDES BY MEANS OF CHELATING PROCESSES .8. SYNTHESIS AND RING-OPENING REACTIONS OF CIS-OXIDES AND TRANS-OXIDES DERIVED FROM 3-BENZYLOXYCYCLOHEXENE AND 2-BENZYLOXY-5,6-DIHYDRO-2H-PYRAN

The regiochemical outcome of the ring opening of 1,2-epoxides bearing polar remote functionalization through chelation processes assisted by metal ions, was verified in cyclic oxirane systems having the polar functionality in an allylic position to the oxirane ring. The diastereoisomeric cis/trans epoxide pairs 5,6 and 7,8 derived from 3-benzyloxycyclohexene, and 2-benzyloxy-5,6-dihydro-2H-pyran, respectively, were prepared and several of their opening reactions were studied. The regioselectivity observed largely depends on the reaction conditions (standard or metal-assisted) and, interestingly, on the nature of the nucleophile used