Optimization of isoxazoline amide benzoxaboroles for identification of a development candidate as an oral long acting animal ectoparasiticide.

Novel isoxazoline amide benzoxaboroles were designed and synthesized to optimize the ectoparasiticide activity of this chemistry series against ticks and fleas. The study identified an orally bioavailable molecule, (S)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide (23), with a favorable pharmacodynamics profile in dogs (Cmax=7.42ng/mL; Tmax=26.

Discovery of an orally bioavailable isoxazoline benzoxaborole (AN8030) as a long acting animal ectoparasiticide.

A novel series of isoxazoline benzoxaborole small molecules was designed and synthesized for a structure-activity relationship (SAR) investigation to assess the ectoparasiticide activity against ticks and fleas. The study identified an orally bioavailable molecule, (S)-3,3-dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol (38, AN8030), which was long lasting in dogs (t1/2=22 days). Compound 38 demonstrated 97.

[Unexplained right-sided heart failure following open heart surgery: mind the pericardium].

Three men, aged 67 years, 80 years and 53 years, respectively, developed signs and symptoms of progressive right-sided heart failure following open heart surgery. They were diagnosed with constrictive pericarditis based on echocardiography, cardiac magnetic resonance and cardiac catheterisation. Following pericardiectomy, two of the patients fully recovered, while one, the 80-year-old man, died during convalescence.

Myocardial perforation by a guidewire crossing a stenotic aortic valve during cardiac catheterization.

Myocardial perforation by a guidewire after retrograde crossing of a stenotic aortic valve during cardiac catheterization is rare. We present a patient with calcific aortic stenosis who suffered this potentially life-threatening complication and in whom conservative treatment was successful. Early recognition of this complication is important for the operator performing cardiac catheterizations in patients with calcific aortic stenosis.