Structure-based discovery of (S)-2-amino-6-(4-fluorobenzyl)-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione as low nanomolar, orally bioavailable autotaxin inhibitor.

Inhibition of extracellular secreted enzyme autotaxin (ATX) represents an attractive strategy for the development of new therapeutics to treat various diseases and a few inhibitors entered in clinical trials. We herein describe structure-based design, synthesis, and biological investigations revealing a potent and orally bioavailable ATX inhibitor 1. During the molecular docking and scoring studies within the ATX enzyme (PDB-ID: 4ZGA), the S-enantiomer (Gscore = -13.

Palladium-catalyzed directed synthesis of -deuterated phenylacetic acid and analogues.

The synthesis of deuterium-labeled organic compounds is of increased interest, especially after the approval of deutetrabenazine by the Food and Drug Administration in 2014. The selective incorporation of deuterium in the place of hydrogen not only represents uniqueness in terms of a novel chemical class, but it also can improve the pharmacokinetic profiles of drug molecules while retaining potency and other parameters; thus, hydrogen-deuterium (H/D) exchange methods have been proven to be powerful additions in different areas of chemical science. In that regard, metal-catalyzed deuterium labeling via C-H activation mediated by a unique inbuilt directing group (DG) can play a significant role in the synthesis of novel deuterated chemical entities.

Arterial injuries after penetrating brain injury in civilians: risk factors on admission head computed tomography.

Object: The object of this study was to determine the specific CT findings of the injury profile in penetrating brain injury (PBI) that are risk factors related to intracranial arterial injuries.

Methods: The authors retrospectively evaluated admission head CTs and accompanying digital subtraction angiography (DSA) studies from patients with penetrating trauma to the head in the period between January 2005 and December 2012. Two authors reviewed the CT images to determine the presence or absence of 30 injury profile variables and quantified selected variables.

Vascular complications of penetrating brain injury: comparison of helical CT angiography and conventional angiography.

Object: The authors conducted a study to compare the sensitivity and specificity of helical CT angiography (CTA) and digital subtraction angiography (DSA) in detecting intracranial arterial injuries after penetrating traumatic brain injury (PTBI).

Methods: In a retrospective evaluation of 48 sets of angiograms from 45 consecutive patients with PTBI, 3 readers unaware of the DSA findings reviewed the CTA images to determine the presence or absence of arterial injuries. A fourth reader reviewed all the disagreements and decided among the 3 interpretations.