Using pentafluorophenyl as a Lewis acid to stabilize a cis secondary amide conformation.

[reaction: see text]. N-(pyrimidin-2-yl)pentafluorobenzamide adopts a cis amide bond in the solid state with a pyrimidyl nitrogen pointing toward the center of the perfluorophenyl ring. In solution, the compound is a mixture of cis and trans rotamers. The conformational equilibrium is strongly solvent dependent, and the cis rotamer is entropically favored. It is proposed that the entropic driving force is decreased solvation of the two aryl groups when in the cis conformation.

Hydrogen bonding isosteres: bimolecular carboxylic acid and amine-N-oxide interactions mediated via CH...O hydrogen bonds.

The X-ray structures of cocrystals between 2,2'-dipyridyl-N,N'-dioxide (1) with fumaric acid (2), itaconic acid (3), succinic acid (4), and oxalic acid (5) were solved to determine if concurrent CH...O interactions were capable of orienting the bimolecular association of the two molecules. Cocrystals 1.2, 1.3 and 1.4 produce cyclic hydrogen bonded motifs employing pair-wise OH...O and CH...O hydrogen bonds, whereas cocrystal 1.5 forms analogous OH...O hydrogen bonds with a different set of intermolecular CH...O hydrogen bonds. Evidence of cocrystal formation was also observed for these complexes by differential scanning calorimetry and FT-IR spectroscopy. The structures of 1.2, 1.3 and 1.4 demonstrate the potential of the pair-wise OH...O and CH...O hydrogen bonding interactions and serve to illustrate their use as hydrogen bonding isosteres in crystal engineering, molecular recognition, and drug design.

Design, synthesis, and activity of 2,6-diphenoxypyridine-derived factor Xa inhibitors.

A novel series of 2,6-diphenoxypyridines has been designed to inhibit factor Xa, a serine protease strategically located in the coagulation cascade. The evolution from the photochemically unstable bisamidine (Z,Z)-BABCH to potent bisamidine compounds with a pyridine heterocycle as the core scaffold has been achieved. The most potent compound in the series, 6h, has a Ki for human factor Xa of 12 nM. The selectivity of 6h against bovine trypsin and human thrombin was greater than 90- and 1000-fold, respectively. Two proposed modes of binding of 6h to factor Xa are made based on the crystal structures of 6h by itself and of 6h bound to bovine trypsin.

Relevance of oral intake and necessity to void as ambulatory surgical discharge criteria.

Discharge criteria used in the outpatient setting of a 500-bed academic medical center were evaluated by nursing staff in two ambulatory units to determine validity in identifying patient readiness for discharge. Criteria categories include temperature, circulation, activity and mental status, pain, bleeding, voiding, and oral intake. The hospital course and post-discharge course of a convenience sample of 248 ambulatory subjects was drawn from consecutive patients. Post-discharge recovery outcomes identified by the telephone assessment included recovery, complications, necessity of further medical treatment, and the need to return to a medical facility. The descriptive results showed the safety of the seven discharge criteria. Voiding and oral intake were related to prolonged stays in the ambulatory units. Approval was granted by the Hospital Policy Board to relax discharge criteria, and make voiding and oral intake optional for patients. A stage II follow-up study of 1,582 patient subjects was conducted using the new criteria of voluntary voiding and oral intake. The average ambulatory stay was reduced 50 minutes after voiding and oral intake were made optional.