Synthesis and Evaluation of Novel 2,2-Dimethylthiochromanones as Anti-Leishmanial Agents.

Within this work, we describe the design and synthesis of a range of novel thiochromanones based on natural products reported to possess anti-leishmanial action, and their synthetic derivatives. All compounds were elaborated via the key intermediate 2,2,6-trimethoxythiochromanone, which was modified at the benzylic position to afford various ester, amine and amide analogues, substituted by chains of varying lipophilicity. Upon testing in Leishmania, IC50 values revealed the most potent compounds to be phenylalkenyl and haloalkyl amides 11a and 11e, with IC50 values of 10.5 and 7.2 µM, respectively.

Hospital initiation of benzodiazepines and Z-drugs in older adults and discontinuation in primary care.

OBJECTIVE: To examine factors associated with continuation of hospital-initiated benzodiazepine receptor agonists (BZRAs) among adults aged ≥65 years, specifically instructions on hospital discharge summaries. METHODS: This retrospective cohort study involved anonymised electronic record data on prescribing and hospitalisations for 38,229 patients aged ≥65 from forty-four GP practices in Ireland 2011-2016. BZRA initiations were identified among patients with no BZRA prescription in the previous 12 months. Multivariate regression examined whether instructions on discharge messages for hospital-initiated BZRA prescriptions was associated with continuation after discharge in primary care and time to discontinuation. RESULTS: In total, 418 hospital-initiated BZRAs were identified, 48.8% being to males and mean patient age was 79.0 (SD 8.3) years. Almost 60% of these discharge summarieshad some BZRA instructions (e.g. duration). Approximately 40% (n = 166) were continued in primary care. Lower age, being prescribed a Z-drug or great number of medicines were associated with higher risk of continuation. Of those continued in primary care, in 98 cases (59.6%) the BZRA was discontinued during follow-up (after a mean 184 days). Presence of instructions was associated with higher likelihood of discontinuation (hazard ratio 1.71, 95%CI 1.11-2.62). CONCLUSIONS: Improved communication to GPs after hospital discharge may be important in avoiding long-term BZRA use.