Identification of Selective Imidazopyridine CSF1R Inhibitors.

Colony stimulating factor-1 receptor (CSF1R or c-FMS), a class III receptor tyrosine kinase expressed on members of the mononuclear phagocyte system (MPS), plays a key role in the proper functioning of macrophages, microglia, and related cells. Aberrant signaling through CSF1R has been associated with a variety of disease states, including cancer, inflammation, and neurodegeneration. In this Letter, we detail our efforts to develop novel CSF1R inhibitors. Drawing on previously described compounds, including GW2580 (4), we have discovered a novel series of compounds based on the imidazo[4,5-b]pyridine scaffold. Initial structure-activity relationship studies culminated in the identification of 36, a lead compound with potent CSF1R biochemical and cellular activity, acceptable in vitro ADME properties, and oral exposure in rat.

Management of postoperative urinary retention: a randomized trial of in-out versus overnight catheterization.

BACKGROUND: There has been no consensus on the best catheterization strategy for the management of postoperative urinary retention. A prospective randomized trial was undertaken to establish the best practice guidelines for the management of postoperative urinary retention. The authors also evaluated the contemporary incidence of urinary retention following different categories of general surgery and examined risk factors associated with its occurrence. METHODS: All patients who underwent elective inpatient surgery between January 2002 and June 2003 were recruited into the study. Patients who developed postoperative urinary retention were randomized to either having in-out catheterization or placement of an indwelling catheter for 24 h after surgery. RESULTS: A total of 1448 patients was recruited. The overall incidence of urinary retention was 4.1% (n = 60). Significant risk factors associated with postoperative urinary retention included old age, anorectal procedures and use of spinal anaesthesia. Comparison of re-catheterization and urinary tract infection rates between patients who were treated with in-out versus overnight catheterization found no significant differences. CONCLUSIONS: Postoperative urinary retention should be managed by in-out catheterization. Indwelling catheterization for 24 h appeared to bestow no additional benefits. The incidence of urinary retention increases with age, anorectal procedures and the use of spinal anaesthesia.