Synthesis of antiulcer drug esomeprazole.

Esomeprazole (Nexium®), the (S)-isomer of Omeprazole, is the first proton-pump inhibitor developed as a single isomer for the treatment of acid-related diseases. It is used for the treatment of peptic ulcers, gastroesophagal reflux disease, and erosive esophagitis. Herein, we report our synthetic study of esomeprazole sodium salt from the starting    2-mercapto-5-methoxybenzimidazole and 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine hydrochloride reagents. The Esomeprazole sodium salt was obtained from enantioselectivesulfoxidation reaction in moderate yield with high enantioselectivity

Eupolauridine alkaloids of Polyalthia nemoralis

Two eupolauridine alkaloids, eupolauridine (1) and 8-methoxyeupolauridine (2), together with a phenanthrene compound, 2,7-dihydroxy-3,6-dimethoxyphenanthrene (3), were isolated from the ethyl acetate extract of Polyalthia nemoralis barks. Their structures were elucidated on the basis of spectroscopic analysis and comparison with related known compounds. These compounds were evaluated the cytotoxicity on seven human cancer cell lines including KB, MCF7, LU-1, HepG2, LNCap, SW626 and SW480

Lignans isolated from the ethyl acetate extract of Knema pachycarpa fruit

Knema is a genus of tropical evergreen trees of the family Myristicaceae found in South East Asian countries such as Vietnam, Thailand, and Malaysia. In this paper, four lignans, (+)-pinoresinol (1),(+) epi-pinoresinol (2), piperitol (3), and pluviatilol (4), were isolated from the ethyl acetate extract of the fruit of Knema pachycarpa, an indigenus tree in Vietnam. The chemical structures were determined by spectroscopic data and comparison with the reported literature. These compounds were isolated from Knema genus for the first time. Keywords. Knema pachycarpa de Wilde, (+)-Pinoresinol, (+)-Epi-pinoresinol, Piperitol, Pluviatilol

A practical synthesis of fluoroquinolone antibiotic moxifloxacin

The fluoroquinoloneantibiotic has been used in clinical practice since the 1980s, primarily for the treatment infections caused by Gram-negative bacteria. Moxifloxacin, a fourth-generation fluoroquinolone antibiotic developed by pharmaceutical company Bayer AG, exhibit broad spectrum of activity against Gram-negative, Gram-positive bacteria as well as  anaerobia. Moxifloxacin is used for community-acquired respiratory tract infections, sinusitis, acute exacerbations of chronic bronchitis and pneumonia, and skin structure infections. We have described the synthesis of moxifloxacin using difluoroboron complex. In this paper, a practical synthesis of moxifloxacin using acetoxyboronate complexwas reported

PRESENT DAY DEFORMATION IN THE EAST VIETNAM SEA AND SURROUNDING REGIONS

This paper presents velocities of present-day tectonic movement and strain rate in the East Vietnam Sea (South China Sea) and surroundings determined from GPS campaigns between 2007 and 2010. We determine absolute velocities of GPS stations in the ITRF05 frame. The result indicates that GPS stations in the North of East Vietnam Sea move eastwards with the slip rate of 30 - 39 mm/yr, southwards at the velocities of 8 - 11 mm/yr. Song Tu Tay offshore moves eastwards at the rate of ~24 mm/yr and southwards at ~9 mm/yr. GPS stations in the South of East Vietnam Sea move to the east at the rate of ~22 mm/yr and to the south at the velocities of 7 - 11 mm/yr. The effect of relative movement shows that the Western Margin Fault Zone activates as left lateral fault zone at the slip rate less than 4 mm/year.In Western plateau, the first result from 2012 - 2013 GPS measurement shows that the velocities to the east vary from 21.5 mm/yr to 24.7 mm/year. The velocities to the south vary from 10.5 mm/yr to 14.6 mm/year. GPS solutions determined from our campaigns are combined with data from various authors and international projects to determine the strain rate in the East Vietnam Sea. Principal strain rate changes from 15 nanostrain/yr to 9 nanostrain/yr in the East Vietnam Sea. Principal strain rate and maximum shear strain rate along the Red River Fault Zone are in order of 10 nanostrain/year. East Vietnam Sea is considered to belong to the Sunda block

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2\ub75th percentile and 100 as the 97\ub75th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59\ub74 (IQR 35\ub74–67\ub73), ranging from a low of 11\ub76 (95% uncertainty interval 9\ub76–14\ub70) to a high of 84\ub79 (83\ub71–86\ub77). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of 'leaving no one behind', it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990-2017, projected indicators to 2030, and analysed global attainment. METHODS: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0-100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

© 2018 The Author(s). Background: Assessments of age-specifc mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Afairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specifc mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in diferent components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4-19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2-59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5-49·6) to 70·5 years (70·1-70·8) for men and from 52·9 years (51·7-54·0) to 75·6 years (75·3-75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5-51·7) for men in the Central African Republic to 87·6 years (86·9-88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3-238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6-42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2-5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specifc mortality shows that there are remarkably complex patterns in population mortality across countries. The fndings of this study highlight global successes, such as the large decline in under-5 mortality, which refects signifcant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Développement de nouvelles alcoxyamines libérant des radicaux libres contre les deux principales maladies parasitaires : le paludisme et la schistosomiase

Dans ce travail, nous avons développé des alkoxyamines destinées à devenir une nouvelle méthode pour le traitement simultané du paludisme et de la schistosomiase. Le mécanisme d'action est proposé sur le principe de la chimie radicalaire de même que pour l'artémésinine. Dans le cadre de cette étude, nous nous sommes intéressés aux nouveaux types d'alcoxyamines contenant différents cycles aromatiques tel que les terpyridines, les terphényles, les phénanthrolines et les quinoléines. Toutes les alcoxyamines synthétisées ont été étudiées pour leurs propriétés physiques et chimiques, en particulier l'homolyse qui était considéré comme le processus clé de la nouvelle méthode thérapeutique. Les essais biologiques initiaux sur des parasites anti-plasmodium et anti-schistosomes ont montré des résultats prometteurs. Trois composés présentent des bons résultats en termes d’activités anti-plasmodiales avec des valeurs de CI50 inférieures à 0,3 μM. Cependant, les indices de sélectivité de tous les composés sont assez faibles (inférieurs à 10). Aucune sélectivité n’a été observée quand à la destruction des parasites et des cellules normales. En outre, l’expérience initiale sur le mécanisme a confirmé que les alcoxyamines-terpyridine ne suivaient pas l’alkylation de l’hème comme l’artémisinine. Avec les activités anti-schistosomales, les alcoxyamines synthétisées peuvent réagir comme le Praziquantel à une concentration élevée (100 μg/mL) tandis qu’à une concentration faible (10 μg/mL), toutes les alcoxyamines testées deviennent inactivesIn this work, we have developed alkoxyamines aimed to become new therapy for the simultaneous treatment of Malaria and Schistosomiasis. The proposed mechanism of drug action was based on that of artemesinin, the radical chemistry. There are new types of alkoxyamines containing different aromatic rings: terpyridine, terphenyl, phenanthroline and quinoline. All the synthesized alkoxyamines were investigated the physical and chemical properties, especially the homolysis, which was the key process of the new therapeutic method. The initial bioassays in anti-plasmodium and anti-schistosoma parasites showed the promising results. There were three compounds having the good results in anti-plasmodial activities with the IC50 values below 0.3 μM. However, the selectivity indexes of all compounds were low (below 10), therefore there was no selection for the killing of parasites and normal cells. In addition, the initial of mechanism experiment confirmed that alkoxyamines-terpyridine did not follow the alkylation of the Heme like Artemisinin. With the anti-schistosomal activities, the alkoxyamines were active as well as the Praziquantel at the high concentration (100 μg/mL) but at low the concentration (10 μg/mL) the anti-schistosomal activities of all tested alkoxyamines were inactiv

How intramolecular coordination bonding (ICB) controls the homolysis of the C-ON bond in alkoxyamines

WOS:000481879400050Because the C-ON bond homolysis rate constant k(d) is an essential parameter of alkoxyamine reactivity, it is especially important to tune k(d) without a major alteration of the structure of the molecule. Recently, several approaches have become known, e.g., protonation of functional groups and formation of metal complexes. In this paper, coordination reactions of [Zn(hfac)(2)(H2O)(2)] with a series of new SG1-based alkoxyamines affording complexes with different structures are presented. The k(d) values of the complexed forms of the alkoxyamines were compared to those of free and protonated ones to reveal the contribution of the electron-withdrawing property and structure stabilization. Together with previously published data, this work provides clues to the design of alkoxyamines that can be effectively activated upon coordination with metal ions. Furthermore, our results provide insight into the mechanism underlying the influence of complexation on the reactivity of alkoxyamines. This led us to describe different types of coordination: intramolecular in nitroxyl fragment, intramolecular in alkyl fragment, intramolecular between alkyl and nitroxyl fragment, and intermolecular one. All of them exhibit different trends which are dramatically altered by changes in conformation