From Carbohydrates to Complex Organofluorines: Synthesis, Conformation, and Lipophilicity of Multivicinal-Fluorine-Containing Hexitol Analogues.

There is growing interest in the preparation of fluorine-containing organic molecules. Multivicinal-fluorine analogues are among the most intriguing and promising compounds, but their physical and biological investigations are held back by challenging syntheses. Herein, we report on the synthesis of a large set of novel polyfluorohexitols. The dominant solution-state conformation of all trifluorohexitols was determined, and the solid-state conformations of some analogues were compared. Finally, the lipophilicity of a large set of polyfluorinated hexopyranose and hexitol analogues was attributed by using a log P determination method based on 19 F NMR spectroscopy.

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-ß-D-hexopyranose.

In this work, we have developed a simple synthetic approach using Et3N·3HF as an alternative to the DAST reagent. We controlled the stereochemistry of the nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-4-O-triflate-ß-ᴅ-talopyranose using Et3N·3HF or in situ generated Et3N·1HF. The influence of the fluorine atom at C2 on reactivity at C4 could contribute to a new fluorine effect in nucleophilic substitution. Finally, with the continuous objective of synthesizing novel multi-vicinal fluorosugars, we prepared one difluorinated and one trifluorinated alditol analogue.

Patterns of benzodiazepines use in primary care adults with anxiety disorders.

BACKGROUND: Benzodiazepines are among the most commonly prescribed drugs for anxiety disorders. While they are indicated as adjunctive treatment for short-term use according to clinical practice guidelines, previous studies have shown patterns of long-term use of benzodiazepines, which is problematic due to side effects, dependence and potential of abuse. The aims of this study were to examine among a large sample of primary care adults suffering from anxiety disorders: 1) benzodiazepine use patterns; and 2) correlates of long-term benzodiazepine use. METHODS: Data were drawn from the "Dialogue" project, a large primary care study conducted in 64 primary care clinics in the province of Quebec, Canada. Following a mental health screening in waiting rooms, patients at risk of anxiety or depression completed the Composite International Diagnostic Interview-Simplified (CIDIS). A sample of 740 adults meeting DSM-IV criteria for Generalized Anxiety Disorder, Panic Disorder or Social Anxiety Disorder in the past 12 months took part in this study. RESULTS: Benzodiazepines were used by 22.6% of participants with anxiety disorders in our primary care sample. A large majority of benzodiazepine users (88.4%) met our indicator of long-term use, as defined by utilization for more than 12 weeks including regular and as-needed use. Based on a logistic regression model, individual correlates associated with long-term benzodiazepine use included: being 30 years or older, having a comorbid physical illness, meeting criteria for comorbid agoraphobia, reporting the use of sleep-aids, and concurrent SSRI utilization. LIMITATION: Data collection with self-reported questionnaires may be subject to information bias. CONCLUSIONS: Despite knowledge of the risks of long-term use of benzodiazepines, this remains a pervasive problem. Clinicians need to be mindful of patterns and risk factors leading to long-term use of benzodiazepines in patients with anxiety disorders. Results of this study should raise awareness regarding appropriate prescription practices for benzodiazepines, including decision-making in initiation, duration of prescription, and use of strategies for discontinuation in current long-term benzodiazepine users.