scholarly journals A Concise Route to MK-4482 (EIDD-2801)

2020 ◽  
Author(s):  
Natarajan Vasudevan ◽  
Grace P. Ahlqvist ◽  
Catherine P. McGeough ◽  
Dinesh J. Paymode ◽  
Flavio S. P. Cardoso ◽  
...  
Keyword(s):  
Primary Alcohol ◽  
Step Count ◽  
Selective Esterification ◽  
Amine Coupling

A two-step route to MK-4482 (EIDD-2801, <b>1</b>) was developed consisting of an esterification and hydroxamination of cytidine. The reactions can be conducted in either order with overall yields of 67% (first step—esterification) and 37% (first step—hydroxamination). Selective esterification of the nucleoside’s primary alcohol by enzymatic means eliminated the need for diol protection/deprotection, and direct transamination with hydroxylamine precluded the necessity of activating the nucleobase for amine coupling. This results in a significant advancement over the reported synthesis which is formed in at best 17% yield. The step count is reduced from five transformation to two, and the more expensive uridine is replaced with the more available cytidine.

scholarly journals A Concise Route to MK-4482 (EIDD-2801)

2020 ◽  
Author(s):  
Natarajan Vasudevan ◽  
Grace P. Ahlqvist ◽  
Catherine P. McGeough ◽  
Dinesh J. Paymode ◽  
Flavio S. P. Cardoso ◽  
...  
Keyword(s):  
Primary Alcohol ◽  
Step Count ◽  
Selective Esterification ◽  
Amine Coupling

A two-step route to MK-4482 (EIDD-2801, <b>1</b>) was developed consisting of an esterification and hydroxamination of cytidine. The reactions can be conducted in either order with overall yields of 67% (first step—esterification) and 37% (first step—hydroxamination). Selective esterification of the nucleoside’s primary alcohol by enzymatic means eliminated the need for diol protection/deprotection, and direct transamination with hydroxylamine precluded the necessity of activating the nucleobase for amine coupling. This results in a significant advancement over the reported synthesis which is formed in at best 17% yield. The step count is reduced from five transformation to two, and the more expensive uridine is replaced with the more available cytidine.

scholarly journals Assessing Surface Coverage of Aminophenyl Bonding Sites on Diazotised Glassy Carbon Electrodes for Optimised Electrochemical Biosensor Performance

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 416
Author(s):  
Zari Tehrani ◽  
Hina Yaqub Abbasi ◽  
Anitha Devadoss ◽  
Jonathan Edward Evans ◽  
Owen James Guy
Keyword(s):  
Carboxylic Acid ◽  
Surface Coverage ◽  
Electrochemical Biosensor ◽  
Electrochemical Techniques ◽  
Differential Pulse ◽  
Second Step ◽  
Glassy Carbon Electrodes ◽  
Potential Marker ◽  
Pulse Voltammetry ◽  
Amine Coupling

Electrochemical biosensors using carbon-based electrodes are being widely developed for the detection of a range of different diseases. Since their sensitivity depends on the surface coverage of bioreceptor moieties, it necessarily depends on the surface coverage of amine precursors. Electrochemical techniques, using ferrocene carboxylic acid as a rapid and cheap assay, were used to assess the surface coverage of amino-phenyl groups attached to the carbon electrode. While the number of electrons transferred in the first step of diazotisation indicated a surface coverage of 8.02 ± 0.2 × l0−10 (mol/cm2), and those transferred in the second step, a reduction of nitrophenyl to amino-phenyl, indicated an amine surface coverage of 4–5 × l0−10 (mol/cm2), the number of electrons transferred during attachment of the amine coupling assay compound, ferrocene carboxylic acid, indicated a much lower available amine coverage of only 2.2 × l0−11 (mol/cm2). Furthermore, the available amine coverage was critically dependent upon the number of cyclic voltammetry cycles used in the reduction, and thus the procedures used in this step influenced the sensitivity of any subsequent sensor. Amine coupling of a carboxyl terminated anti-beta amyloid antibody specific to Aβ(1-42) peptide, a potential marker for Alzheimer’s disease, followed the same pattern of coverage as that observed with ferrocene carboxylic acid, and at optimum amine coverage, the sensitivity of the differential pulse voltammetry sensor was in the range 0–200 ng/mL with the slope of 5.07 µA/ng·mL−1 and R2 = 0.98.

scholarly journals Acceptability, Feasibility and Preliminary Evaluation of a Novel, Personalised, Home-Based Physical Activity Intervention for Chronic Heart Failure (Active-at-Home-HF): a Pilot Study

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Nduka C. Okwose ◽  
Leah Avery ◽  
Nicola O’Brien ◽  
Sophie Cassidy ◽  
Sarah J. Charman ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Heart Failure ◽  
Pilot Study ◽  
Chronic Heart Failure ◽  
Physical Activity Intervention ◽  
Step Count ◽  
Home Based ◽  
At Home

Abstract Purpose Less than 10% of heart failure patients in the UK participate in cardiac rehabilitation programmes. The present pilot study evaluated feasibility, acceptability and physiological effects of a novel, personalised, home-based physical activity intervention in chronic heart failure. Methods Twenty patients (68 ± 7 years old, 20% females) with stable chronic heart failure due to reduced left ventricular ejection fraction (31 ± 8 %) participated in a single-group, pilot study assessing the feasibility and acceptability of a 12-week personalised home-based physical activity intervention aiming to increase daily number of steps by 2000 from baseline (Active-at-Home-HF). Patients completed cardiopulmonary exercise testing with non-invasive gas exchange and haemodynamic measurements and quality of life questionnaire pre- and post-intervention. Patients were supported weekly via telephone and average weekly step count data collected using pedometers. Results Forty-three patients were screened and 20 recruited into the study. Seventeen patients (85%) completed the intervention, and 15 (75%) achieved the target step count. Average step count per day increased significantly from baseline to 3 weeks by 2546 (5108 ± 3064 to 7654 ± 3849, P = 0.03, n = 17) and was maintained until week 12 (9022 ± 3942). Following completion of the intervention, no adverse events were recorded and quality of life improved by 4 points (26 ± 18 vs. 22 ± 19). Peak exercise stroke volume increased by 19% (127 ± 34 vs. 151 ± 34 m/beat, P = 0.05), while cardiac index increased by 12% (6.8 ± 1.5 vs. 7.6 ± 2.0 L/min/m2, P = 0.19). Workload and oxygen consumption at anaerobic threshold also increased by 16% (49 ± 16 vs. 59 ± 14 watts, P = 0.01) and 10% (11.5 ± 2.9 vs. 12.8 ± 2.2 ml/kg/min, P = 0.39). Conclusion The Active-at-Home-HF intervention is feasible, acceptable and effective for increasing physical activity in CHF. It may lead to improvements in quality of life, exercise tolerance and haemodynamic function. Trial Registration www.clinicaltrials.gov NCT0367727. Retrospectively registered on 17 September 2018.

Alcohol and Primary Prevention in Scotland and Sweden

1995 ◽  
Vol 12 (1_suppl) ◽  
pp. 31-60
Author(s):  
Håkan Leifman
Keyword(s):  
Alcohol Consumption ◽  
Primary Alcohol ◽  
Control Policy ◽  
Alcohol Prevention ◽  
Upward Trend ◽  
Alcohol Control ◽  
Preventive Actions ◽  
Private Profit ◽  
Temperance Movements ◽  
Restrictive Legislation

This study compares primary alcohol prevention in Scotland and Sweden and the effectiveness of preventive actions with special reference to developments from the mid- or late 1970s when alcohol consumption peaked in both countries and when changes were made in their alcohol policies. A short historical overview shows many similarities between the countries, e.g. strong prohibition-oriented temperance movements, a history of alcohol (spirits) abuse and restrictive legislation. A major difference is the much more dominating role of private profit motives in Scottish alcohol trade. During the last 15-20 years, the two countries have chosen different strategies to prevent alcohol-related problems. Sweden has put heavy emphasis on restricting the availability of alcohol but also invested substantially in information, whereas Scotland has concentrated on the latter. A comparison of the trends during the last 15-20 years suggests that whereas Swedish alcohol control reduced the level of alcohol consumption and related problems in the late 1970s and early 1980s, the Scottish did not, even though the upward trend was broken for most indicators. The drinking sensible message has not been powerful enough to reduce the number of non-sensible drinkers. In fact, a continuing upward trend of liver cirrhosis deaths in Scotland, especially for women, may suggest the opposite. The study also shows that, despite rather stable overall consumption for the last 10 years, the specific alcohol-related problem of drinking and driving has been decreasing in both countries. This indicates that even if consumption increases in the future, as is likely in Sweden due to current changes in alcohol control policy, drinking in specific contexts may still be preventable.

Chirality Transfer from a Chiral Primary Alcohol Equivalent Through Allyl Cyanate-to-Isocyanate Rearrangement: Synthesis of (+)-Geranyllinaloisocyanide

Synthesis ◽  
2019 ◽  
Vol 51 (15) ◽  
pp. 2959-2964 ◽  
Author(s):  
Yoshiyasu Ichikawa ◽  
Hirofumi Morimoto ◽  
Toshiya Masuda
Keyword(s):  
Natural Product ◽  
Primary Alcohol ◽  
Marine Natural Product ◽  
Chirality Transfer ◽  
New Approach ◽  
Stereogenic Centers ◽  
Quaternary Stereogenic Centers

A new approach was developed to construct quaternary stereogenic centers bearing nitrogen substituents in an enantioselective manner. The strategy takes advantage of [1,3]-chirality transfer from a chiral primary alcohol equivalent through an allyl cyanate-to-isocyanate rearrangement. This approach was employed in an efficient eight-step synthesis of the marine natural product, (+)-geranyllinaloisocyanide, in 43% overall yield.

The translation of preschoolers’ physical activity guidelines into a daily step count target

2014 ◽  
Vol 33 (10) ◽  
pp. 1051-1057 ◽  
Author(s):  
Marieke De Craemer ◽  
Ellen De Decker ◽  
Ilse De Bourdeaudhuij ◽  
Maïté Verloigne ◽  
Yannis Manios ◽  
...  
Keyword(s):  
Physical Activity ◽  
Step Count ◽  
Daily Step ◽  
Physical Activity Guidelines ◽  
Daily Step Count
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