Synthesis of Tetracyclic systems and (Thio)Ureas from Aminodi(Hetero)Arylamines in the Thieno[3,2-b]Pyridine series

Foundation for the Science and Technology (FCT–Portugal) for financial support through the Portuguese NMR network (Bruker 400 Avance III-Univ Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE/QREN/EU for financial support through the research centre PEst-C/QUI/UI686/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-doctoral grant of R.C.C. SFRH/BPD/68344/2010

Multi-site clinical assessment of Complete Revitalens MPDS in 2981 contact lens wearers across Europe and USA

(MPDS), Complete Revitalens (RevitaLens OcuTec in the US Market), for soft contact lens care in a large “real practice” setting. Method: This is an international multi-center, open-label assessment carried out in 10 countries across Europe and in the USA. Up to 10 subjects who were currently wearing soft contact lenses for at least 1 year and using a MPS as a lens care system were included at each investigational site. Results: Data were collected from 996 European and 1985 American wearers, 75% of those patients wore silicone hydrogel contact lenses. Approximately 94% found the new MPDS “somewhat more effective” to “much more effective” in keeping contact lenses feeling clean and 88% found the new MPDS to be somewhat more effective to much more effective in keeping their lenses feeling comfortable in the evening. Over 93% reported an improvement in vision clearness in the evening after approximately 1 month while using the new MPDS. Wearers with grade 2, 3 or 4 of severity decreased by 11.3, 6.4 and 9.8% over 1 month period for redness, burning and irritation, respectively. After approximately 1 month 83% of wearers declared that they would prefer to use the new MPDS. Conclusions: Over 88% felt their lenses were somewhat to much more comfortable at the end-of-day and 94% found the new MPDS to be somewhat to much more effective in keeping their lenses feeling clean compared to their previous care system.The authors wish to thank the eye care practitioners participating in this study across Europe and USA. The D'Ellis Group for the statistical support and Rafael Guerrero and Will Heydorn from Abbott Medical Optics, Inc. for their contributions in planning and coordinating the European and American branches of the study, respectively. The authors declare no proprietary or financial interest in any of the materials mentioned in this article. This study has been sponsored by Abbott Medical Optics Inc. These results were presented to the American Academy of Optometry Boston, 12-15th, 2011

Thieno[3,2-b]pyridine arylethers: synthesis and growth inhibitory activity on human tumor cell lines

Thienopyridine skeleton has been reported as havi ng inte resting biological activity, namely antitumorlll and antiangiogenic121 activities. Herein, we describe the synth esis of thienopyridine arylethers la-f in moderate to good yields by a copper-cata lyzed C- 0 coupling, using N,N-dimethylglycine as a ligand, of the 7-bromothieno[3,2-b]pyridine, also prepared with substituted phenols (see scheme)

Synthesis of novel 1-Aryl-3-[2-,3- Or 4-(Thieno[3,2-b]Pyridin-7-Ylthio)Phenyl]Ureas and evaluation as VEGFR2 Tyrosine kinase inhibitors

Vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase is involved in cancer and in angiogenesis. Herein, we report the synthesis of novel1-aryl-3-[2-, 3- or 4-{thieno[3,2-b ]pyridin-7-ylthio) phenyl]ureas as VEGFR2 inhibitors by promoting the regioselective attack of the thiol group of the 4-aminothiophenol in the chlorine nucleophilic displacement on 7-chlorothieno[3,2-b]pyridine 1, obtaining the aminated compounds Za- c. These were reacted with arylisocyanates to give the corresponding 1,3-diarylureas 3a-c, 4a-c and Sa-c (see scheme).Foundation for the Science and Technology (FCT–Portugal) for financial support through the NMR Portuguese network (Bruker 400 Avance III-Univ Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE/QREN/EU for financial support through the research unities PEst-C/QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI- QUI/111060/2009 and the post-Doctoral grant attributed to R.C.C. (SFRH/BPD/68344/2010

Fluorescence studies on new potential antitumoral 1,3-diarylurea derivatives of thieno[3,2-b]pyridines in solution and in nanoliposomes

This work was supported by Fundação para a Ciência e a Tecnologia (Portugal), QREN and FEDER through CFUM, CQ/UM and Project PTDC/QUI/81238/2006 cofinanced by FCT and program FEDER/COMPETE (FCOMP-01-0124-FEDER-007467)

Ocular dominance and visual function testing

To show the distribution of ocular dominance as measured with sensory and eye sighting methods and its potential relationship with high and low contrast LogMAR visual acuity in presbyopic subjects. Method. Forty-four presbyopes (48.5 ± 3.5 years) participated in this study. Ocular dominance was determined by eye sighting (hole-in-card) and sensorial (+1.50 D lens induced blur) methods. According to the dominance detected with each method (RE: right eye or LE: left eye), patients were classified in dominance type 1 (RE/RE), type 2 (RE/LE), type 3 (LE/RE) and type 4 (LE/LE). Results. Baseline refractive error (MSE) was RE:−0.36 ± 1.67 D and LE:−0.35 ± 1.85 D (P= 0.930). RE was the dominant eye in 61.4% and 70.5% of times as obtained from sensorial and sighting methods, respectively. Most frequent dominance was of type 1 (52.3%), in this case the RE showed statistically significant better distance low contrast LogMAR VA (0.04 LogMAR units) compared to the LE (P < 0.05 ). Conclusions. The dominance was more frequent in RE in this sample. The eye sighting and sensorial methods to define ocular dominance agreed in more than half of cases. Amount of MSE was not significantly different between dominant and non-dominant eye. But in case of right dominance, the RE presented better distance low contrast VA compared to the LE.Purpose. To show the distribution of ocular dominance as measured with sensory and eye sighting methods and its potential relationship with high and low contrast LogMAR visual acuity in presbyopic subjects. Method. Forty-four presbyopes (48.5 +/- 3.5 years) participated in this study. Ocular dominance was determined by eye sighting (hole-in-card) and sensorial (+1.50D lens induced blur) methods. According to the dominance detected with each method (RE: right eye or LE: left eye), patients were classified in dominance type 1 (RE/RE), type 2 (RE/LE), type 3 (LE/RE) and type 4 (LE/LE). Results. Baseline refractive error (MSE) was RE:-0.36 +/- 1.67D and LE:-0.35 +/- 1.85D (P = 0.930). RE was the dominant eye in 61.4% and 70.5% of times as obtained from sensorial and sighting methods, respectively. Most frequent dominance was of type 1 (52.3%), in this case the RE showed statistically significant better distance low contrast LogMAR VA (0.04 LogMAR units) compared to the LE (P < 0.05). Conclusions. The dominance was more frequent in RE in this sample. The eye sighting and sensorial methods to define ocular dominance agreed in more than half of cases. Amount of MSE was not significantly different between dominant and non-dominant eye. But in case of right dominance, the RE presented better distance low contrast VA compared to the LE.Present study has been supported by Fundacao para a Ciencia e Tecnologia (FCT) under Contract PTDC/SAU-BEB/098392/2008. The authors declare that they do not have any proprietary or financial interests in any of the materials mentioned in this paper. The present work has been presented in part at the 8th International Conference of Optometry (CIOCV'2011) at University of Minho (9-10 April, Braga, Portugal)

A UML Reuse Framework and Tool for Requirements Engineering

Requirement Engineering (RE) activities are critical by nature and mostly manual. Some automated support for tasks helps requirements engineers to reduce manual labor and, consequently, reduce defects rates and increase reuse and motivation. In this paper, we introduce a UML framework and tool support which automates part of the RE process. Using UML stereotypes as the core of this solution, we created a set of integrated tools composed by: (1) a reusable framework that models RE behavior patterns that are typically present in information system projects; (2) a function that allows the reuse of information provided by entity modeling; (3) a tool that automates the generation of application prototypes; (4) a tool for counting IFPUG Function Points; and (5)a tool that analyzes specific types of defects. Our findings indicate that the framework and the automated support are effective at RE modeling and review.  In addition, they increase motivation and promote team engagement, through elimination of repetitive activities.Sociedad Argentina de Informática e Investigación Operativ

Radiometric characterization of a novel LED array system for visual assessment

Light that enters the eye can be distorted due to several factors leading to a poor visual performance. The purpose of this paper is to describe and characterize the light-emitting diode (LED) display system to be used in a new device to assess visual quality under high glare conditions. The device has a central white LED and surrounding white LEDs distributed in a radial manner. Each LED is controlled independently using special designed software. The spectral power distribution and color of the LEDs were assessed at different voltage intensities to test the response in terms of output luminance and spectral distribution. It was found that the typical maximum luminance was about 2800 cd/m2 and 6 cd/m2 for the central and surrounding LEDs, respectively. Their color was found to be within the ΔE⁄ ab range of 2.6 and 0.23, respectively, if the minimum and maximum intensities are considered. The characterization of this device was proved successfully, which might indicate its usefulness in future visual assessments.This study has been funded by FEDER through the COMPTETE Program and by the Portuguese Foundation for Science and Technology (FCT) in the framework of projects PTDC/SAU-BEB/098391/2008, PTDC/SAU-BEB/098392/2008 and the Strategic Project PEST-C/FIS/UI607/2011

Synthesis, molecular Docking and biological evaluation of new 1-Aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenylureas as Potent Type II VEGFR-2 Tyrosine Kinase inhibitors

The vascular endothelial growth factor receptor 2 (VEGFR-2) is a tyrosine kinase receptor, expressed primarily in endothelial cells, and is activated by the specific binding of VEGF to the VEGFR-2 extracellular regulatory domain. Once activated, VEGFR-2 undergoes autophosphorylation, triggering signaling pathways leading to endothelial cell proliferation and subsequent angiogenesisY1 Small molecules may act as inhibitors by competing for the ATP-binding s'1te of the VEGFR-2 intracellular tyrosine kinase domain, thereby preventing the intracellular signa ling that leads to angiogenesis. [ZJ Here, we present the synthesis of new 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas la-c, as potent type 11 VEGFR-2 inhibitors based on molecular docking (Figure A) and biological evaluation including enzymatic assays using the VEGFR-2 tyrosine kinase domain (ICso=l0-28 nM) and studies in human umbilical vein endothelial cells (HUVECs). The latter included cell viability (MTS), proliferation (BrdU) and Western blot for total and phosphorylated VEGFR-2 (Figure B). The predicted docked poses were analyzed in detail and a plausible explanation for compounds 1 potency was obtained base9 on the simultaneous presence of a S-linker and the arylurea moiety in the meta position as a new substitution pattern for the type 11 VEGFR-2 inhibitors. These chemical features place the thieno[3,2-b]pyridine and the terminal aryl ring in close superimposition to a pyrrolo[3,2-d]pyrimidine derivative. The presence of hydrofobic substituents (F and Me) in the terminal aryl ring is also important. For these compounds a significant inhibition in HUVECs proliferation upon VEGF stimulation was observed at low concentrations (0.5-1.0 IJ.M) without affecting cell viability. Westernblot analysis demonstrated that compounds 1 significantly the inhibited VEGFR-2 phosphorylation at 1.0 jlM, thus confirming their anti-angiogenic potential

New 1,3-diarylureas linked by C-C Suzuki coupling to the methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate moiety: synthesis and fluorescence studies in solution and in lipid membranes

New six fluorescent 1,3-diarylureas linked by C-C Suzuki coupling to the 6-position of the methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate moiety were prepared by reaction of the amino groups on the ortho or meta positions relative to the C-C bond of the Suzuki coupling products, with different para-substituted arylisocyanates (H, OMe, CN), in high to excellent yields. The fluorescence properties of the 1,3-diarylureas in solution and in lipid membranes of egg-yolk phosphatidylcholine (Egg-PC), dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG) or dioctadecyldimethylammonium bromide (DODAB), with or without cholesterol (Ch), were studied. The six 1,3-diarylureas have reasonable fluorescence quantum yields in several solvents (between 0.02 and 0.69) and present a moderately solvent sensitive emission, but are not fluorescent in alcohols and water. The compounds bearing the arylurea moiety in the meta position relative to the C-C bond, especially with the OMe and CN substituents, present the better solvatochromic properties. Incorporation of the six compounds in lipid membranes indicates that all the compounds are deeply located in the hydrophobic region of the lipid bilayers, feeling the transition between the rigid gel phase and fluid phases.To the Foundation for the Science and Technology (FCT, Portugal) for inancial support to the NMR portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho). To the FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support to the Research Centres, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)] and CFUM [PEst-C/FIS/UI0607/2011 (F-COMP-01-0124-FEDER-022711)], and to the research projects PTDC/QUI/81238/2006 (FCOMP-01-0124-FEDER-007467) (photophysical studies) and PTDC/QUI-QUI/111060/2009 (F-COMP-01-0124-FEDER-015603) (organic synthesis)