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Author: Daniel J Foley (21)


Oct
2017

The productive exploration of chemical space is an enduring challenge in chemical biology and medicinal chemistry. Natural products are biologically relevant, and their frameworks have facilitated chemical tool and drug discovery. A "top-down" synthetic approach is described that enabled a range of complex bridged intermediates to be converted with high step efficiency into 26 diverse sp-rich scaffolds.

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Oct
2016

Evaluating New Chemistry to Drive Molecular Discovery: Fit for Purpose?

Angew Chem Int Ed Engl 2016 Oct 30;55(44):13650-13657. Epub 2016 Aug 30.
Daniel J Foley, Adam Nelson, Stephen P Marsden
As our understanding of the impact of specific molecular properties on applications in discovery-based disciplines improves, the extent to which published synthetic methods meet (or do not meet) desirable criteria is ever clearer. Herein, we show how the application of simple (and in many cases freely available) computational tools can be used to develop a semiquantitative understanding of the potential of new methods to support molecular discovery. This analysis can, among other things, inform the design of improved substrate scoping studies; direct the prioritization of specific exemplar structures for synthesis; and substantiate claims of potential future applications for new methods.

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Jun
2015

A powerful strategy for the efficient lead-oriented synthesis of novel molecular scaffolds is demonstrated. Twenty two scaffolds were prepared from just four α-amino acid-derived building blocks and a toolkit of six connective reactions. Importantly, each individual scaffold has the ability to specifically target lead-like chemical space.

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Jan
2015

Controlling the properties of lead molecules is critical in drug discovery, but sourcing large numbers of lead-like compounds for screening collections is a major challenge. A unified synthetic approach is described that enabled the synthesis of 52 diverse lead-like molecular scaffolds from a minimal set of 13 precursors. The divergent approach exploited a suite of robust, functional group-tolerant transformations.

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May
2013

S-alkenyl-N-arylthiocarbamates are formed from allylic alcohols by sigmatropic rearrangement and isomerization or C═C bond cleavage. They undergo carbolithiation with a range of organolithium reagents, generating benzyllithium intermediates in a stereospecific manner which may undergo N to C aryl migration to yield thiocarbamates with tertiary substituents. A simple base-promoted alcoholysis reveals a series of hindered tertiary thiols with branched carbon skeletons.

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May
2009

Nocturnal urination (nocturia) is such a commonplace occurrence in the lives of many older adults that it is frequently overlooked as a potential cause of sleep disturbance.
We examined the prevalence of nocturia and examined its role in self-reported insomnia and poor sleep quality in a survey of 1424 elderly individuals, ages 55-84. Data were derived from a 2003 National Sleep Foundation telephone poll conducted in a representative sample of the United States population who underwent a 20-min structured telephone interview.

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Apr
2007

The objective of this study was to describe the prevalence and correlates of regular napping among older adults.
The National Sleep Foundation's "2003 Sleep in America Poll," a 20-minute telephone interview that focused on the topic of "sleep and aging" (N = 1,506 adults 55-84 years of age).
Overall, 15% of respondents reported regular napping, ranging in prevalence from 10% among those 55-64 years of age to 25% among those 75-84 years of age.

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Dec
1969

Although the clinical benefits of pharmacological treatments for insomnia have been studied, no systematic assessment of their economic value has been reported. This analysis assessed, from a broad payer and societal perspective, the cost effectiveness of long-term treatment with eszopiclone (LUNESTA, Sepracor Inc., [Marlborough, MA, USA]) for chronic primary insomnia in adults in the US.

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Oct
2005

Although driving by persons with Alzheimer's disease (AD) is an important public health concern, we know little about the attitudes and perceptions of key stakeholders regarding driving safety in these individuals or the factors that precipitate and influence driving assessment and cessation decisions.
We convened 10 focus groups composed of persons intimately involved in driving decisions for older adults to identify and compare beliefs and perceptions concerning AD and driving and to identify effective strategies to limit or cease unsafe driving. The 68 focus-group participants included health professionals, transportation and law-enforcement professionals, current and former drivers with AD, and family caregivers of current and former drivers with the disease.

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Mar
2005

Norms for cognitive measures used to assess dementia are scant for minority groups, in particular for older Japanese Americans. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery, we compared the baseline performance of demented and nondemented Japanese Americans. Participants came from two harmonized epidemiological studies of dementia which were examined separately: the Kame Project, Seattle (350 men and women; 201 nondemented), age 65 and older; Honolulu-Asia Aging Study (HAAS), Hawaii (418 men; 120 nondemented), age 71 and older.

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Jun
2004


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May
2004

Antioxidants have been hypothesized to protect against Alzheimer's disease, but studies conducted in late life have been inconsistent. Risk factors measured in midlife may better predict dementia in late life because they are less affected by the disease process. The authors examined the association of midlife dietary intake of antioxidants to late-life dementia and its subtypes.

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Aug
2003

To assess the association between sleep-disordered breathing and cognitive functioning in an elderly cohort of Japanese-American men.
Cross-sectional study.
The Honolulu-Asia Aging Study of Sleep Apnea, Oahu, Hawaii.

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May
2003

Clinicians have observed various patterns of functional decline at the end of life, but few empirical data have tested these patterns in large populations.
To determine if functional decline differs among 4 types of illness trajectories: sudden death, cancer death, death from organ failure, and frailty.
Cohort analysis of data from 4 US regions in the prospective, longitudinal Established Populations for Epidemiologic Studies of the Elderly (EPESE) study.

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May
2003

We studied the association between mid-life smoking and late-life dementia in the Honolulu Heart Program (1965-1971) and follow-up assessment for dementia (1991-1996) of 3734 Japanese-American men (80% of survivors). Neuropathologic data were available for 218 men. Adjusting for age, education and apolipoprotein E (APOE) genotype, the risk of Alzheimer's disease (AD) in smokers increased with pack-years of smoking at medium (odds ratio (OR)=2.

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Feb
2003

The National Center for Health Statistics conducted National Mortality Followback Surveys (NMFS) in 1986 and 1993. The next-of-kin's report of a physician's diagnosis of AD before death and a listing of AD or other dementia as the underlying cause increased significantly among women but remained stable among men. Currently, AD is among the top 10 leading causes of death in elderly white men and women in the United States.

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Aug
2002

We estimated total life expectancy and driving life expectancy of US drivers aged 70 years and older.
Life table methods were applied to 4699 elderly persons who were driving in 1993 and reassessed in a 1995 survey.
Drivers aged 70 to 74 years had a driving life expectancy of approximately 11 years.

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Jul
2002

This study determined the influence of depressive symptoms on subsequent mortality of all causes.
The Honolulu Heart Program, established in 1965, is a prospective, community-based cohort of Japanese American men living in Hawaii. The analysis was based on 3,196 Japanese American men aged 71-93 at the time of the fourth examination in 1991-1993.

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Jan
2002

Although white matter lesions (WMLs) on brain MRI in older persons are common, the mechanisms are unclear. Besides the associations with advanced age and high blood pressure (BP), variability in systolic BP (SBP) and the resulting changes in blood flow to the deep arteries of the brain may be contributing factors.
Japanese-American men in Hawaii have participated in a long-term study of cardiovascular disease, including midlife BP measurements at 3 clinical examinations in the period from 1965 to 1974.

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