Relevance of flexibility versus radial force in rigid versus more flexible venous stents?

Introduction: Deep venous stenting has gained increasing interest. More flexible venous stents are thought to gain superior clinical outcomes. This research evaluated the patency and clinical outcomes between more rigid stents and more flexible stents.

Stent extension into a single inflow vessel is a valuable option after endophlebectomy.

Background Venous stenting with an endophlebectomy and arteriovenous fistula can be performed in patients with extensive post-thrombotic changes. However, these hybrid procedures can induce restenosis, sometimes requiring stent extension, into a single inflow vessel. This study investigates the effectiveness of stenting into a single inflow vessel.

The inability of venous occlusion air plethysmography to identify patients who will benefit from stenting of deep venous obstruction.

Background The aim of this study was to assess whether venous occlusion plethysmography can be used to identify venous obstruction and predict clinical success of stenting. Method Receiver operated characteristic curves were used to determine the ability of venous occlusion plethysmography to discriminate between the presence and absence of obstruction, measured by duplex ultrasound and magnetic resonance venography, and to discriminate between successful and non-successful stenting, measured by VEINES-QOL/Sym. Result Two hundred thirty-seven limbs in 196 patients were included.

Abdominal and pubic collateral veins as indicators of deep venous obstruction.

Objective: Chronic deep venous obstruction can cause a significant loss of quality of life, although it can be treated successfully by stenting. A clear referral pattern for additional imaging is warranted in patients with lower limb complaints. The aim of this study was to determine the value of clinically visible abdominal wall collateral veins in the diagnosis of a potentially treatable deep venous obstruction.

Synthesis and Biological Evaluation of N-((1-(4-(Sulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide Inhibitors of Glycine Transporter-1.

We previously disclosed the discovery of rationally designed N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues 10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics.

The value of hemodynamic measurements by air plethysmography in diagnosing venous obstruction of the lower limb.

Objective: Air plethysmography (APG) is a functional, noninvasive test that can assess volumetric changes in the lower limb and might therefore be used as a diagnostic tool in chronic deep venous disease. However, use of APG in chronic deep venous obstructive disease remains debatable. This study assessed the clinical value of APG in identifying chronic deep venous obstruction.

Risk factors of postthrombotic syndrome before and after deep venous thrombosis treatment.

Postthrombotic syndrome is the most common complication after deep venous thrombosis. Postthrombotic syndrome is a debilitating disease and associated with decreased quality of life and high healthcare costs. Postthrombotic syndrome is a chronic disease, and causative treatment options are limited.

Design, synthesis, and SAR of N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1.

The design, synthesis, and structure-activity relationships (SAR) of a series of N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1) are described. Optimization of the benzamide and central ring components of the core scaffold led to the identification of a GlyT-1 inhibitor that demonstrated in vivo activity in a rodent cerebral spinal fluid (CSF) glycine model.

4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.

Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.

5-Functionalized indazoles as glucocorticoid receptor agonists.

An indazole based series of glucocorticoid receptor agonists is reported. The SAR exploration of this scaffold yielded compounds with nanomolar affinity for the glucocorticoid receptor with indications of selectivity for the preferred transrepression mechanism; in vivo efficacy was observed in the mouse LPS induced TNFalpha model for compound 28.

Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides as potent gamma-secretase inhibitors.

We report the synthesis of benzoazepine-derived cyclic malonamides (2) and aminoamides (3) as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease. The in vitro structure-activity relationships of 2 and 3 along with dog pharmacokinetic results are described.

Synthetic Routes to Allenic Acids and Esters and Their Stereospecific Conversion to Butenolides.

The synthesis of allenic acids and esters and their conversion to butenolides has been examined in some detail. Racemic butenolides 10 are efficiently prepared from the esters 8 through treatment with BCl(3) and exposure of the derived acid 9 to catalytic AgNO(3) in acetone. Conversion of the enantioenriched allenylstannane (S)-17 to the acid 18 through lithiation and subsequent carboxylation with CO(2) afforded racemic product.