ABSTRACT
The structure-activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. The SAR of the acetic acid amides was explored and the effect of substitution on enzyme inhibition as well as mechanism-based cell activity was studied. Additionally, several of the more potent inhibitors were screened for their off-target kinase selectivity.
Subject(s)
Imidazoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Pyrazines/pharmacology , Aurora Kinases , Crystallography, X-Ray , Models, Molecular , Structure-Activity RelationshipABSTRACT
The goal of this paper is to review the evaluation of mentors with a focus on training new investigators in clinical translational science. These scholars include physicians and Ph.D. scientists who are generally assistant professors in clinical departments. This white paper is one of a series of articles focused on the programmatic elements of effective mentoring practices and the "current state of the art." Evaluating mentor performance and providing formative feedback can lead to stronger mentoring and ultimately lead to increased success of new clinical and translational investigators. While there is general agreement that mentor evaluation can be helpful, the process is difficult. Trainees are reluctant to share negative experiences and to rate their mentors. Mentors are not sure they want to be evaluated. Program leaders are not sure how to effectively use the information. This white paper provides mentees, mentors, and program leaders with new perspectives on mentor evaluation and ideas for future research.
Subject(s)
Evaluation Studies as Topic , Mentors/education , Translational Research, Biomedical/education , Humans , Models, EducationalABSTRACT
Alcohol use disorders are common, but are often not discussed with patients. Through NIAAA funding, SIMmersion LLC and the University of Wisconsin are producing an interactive, immersive computer-based simulation that will allow learners to conduct an alcohol screening and brief intervention with a virtual standardized patient. The validity of this simulation will be evaluated through a study involving 100 clinicians.
Subject(s)
Alcoholism/diagnosis , Computer Simulation , Health Personnel/education , Physician-Patient Relations , Humans , WisconsinABSTRACT
Polyalkyl pyran-4-ones 1a-c were irradiated in methanol or ethanol. Although the expected solvent trapping products 3 could be observed, extended irradiation times allowed exclusive formation of secondary photoproducts 4 and 5 in combined yields of 37-64%. These bicyclic compounds are believed to arise from gamma-hydrogen abstraction by the excited enone chromophore of 3, followed by closure of the resulting biradical through one of two possible pathways. Moderate stereoselectivity was observed in the radical coupling to produce 4, whereas the analogous closure to 5 was completely diastereoselective. Tautomerization of the enol precursors to 5 also occurred with complete selectivity for protonation from the exo face. Overall, this process converts simple, planar heterocycles and alkanols into complex products in a single transformation.
