DSR-71167, a novel mineralocorticoid receptor antagonist with carbonic anhydrase inhibitory activity, separates urinary sodium excretion and serum potassium elevation in rats.

Mineralocorticoid receptor (MR) antagonists, such as spironolactone (SPI) and eplerenone (EPL), are useful for treating hypertension and heart failure. However, these two agents have the serious side effect of hyperkalemia. We hypothesized that adding the ability to inhibit carbonic anhydrase (CA) would reduce the risk of hyperkalemia associated with MR antagonists.

Safety and efficacy of carbon dioxide and intravascular ultrasound-guided stenting for renal artery stenosis in patients with chronic renal insufficiency.

We evaluated the feasibility, safety, and mid-term outcomes of renal artery stenting using carbon dioxide (CO₂) digital subtraction angiography and intravascular ultrasound (IVUS) for patients with renal insufficiency and significant atherosclerotic renal artery stenosis (RAS). Eighteen consecutive patients with chronic renal insufficiency underwent renal artery stenting under the guidance of CO₂ angiography and IVUS without contrast media. Renal function and blood pressure were assessed pre- and postintervention.

Effect of ecabet sodium treatment on urea breath test and stool antigen tests in volunteers with Helicobacter pylori infection.

Background And Aim: Ecabet sodium is reported to have a bactericidal effect on Helicobacter pylori and inhibit urease activity in vitro.

Methods: Seven male volunteers (mean age, 51.3 years; range, 45-55 years) with H.

Total synthesis of lactacystin and salinosporamide A.

Lactacystin and salinosporamide A are fascinating molecules with regard to both their chemical structures and biological activities. These naturally occurring compounds are potent and selective proteasome inhibitors. The molecular structures are characterized by their densely functionalized gamma-lactam cores.

Second generation catalytic asymmetric synthesis of Tamiflu: allylic substitution route.

Catalytic asymmetric synthesis of Tamiflu, an important antiinfluenza drug, was achieved. After the catalytic enantioselective desymmetrization of meso-aziridine 3 with TMSN3, using a Y catalyst (1 mol %) derived from ligand 2, an allylic oxygen function and C1 unit on the C=C double bond were introduced through cyanophosphorylation of enone and allylic substitution with an oxygen nucleophile. This second generation route of Tamiflu is more practical than our previously reported route.

De novo synthesis of Tamiflu via a catalytic asymmetric ring-opening of meso-aziridines with TMSN3.

An asymmetric ring-opening reaction of meso-aziridines with TMSN3 was developed using a catalyst prepared from Y(OiPr)3 and chiral ligand 2 in a 1:2 ratio. Excellent enantioselectivity was realized from a wide range of substrates with a practical catalyst loading. The products were efficiently converted to enantiomerically enriched 1,2-diamines, which are versatile chiral building blocks for pharmaceuticals and chiral ligands.

Catalytic asymmetric total synthesis of (+)-lactacystin.

Total synthesis of (+)-lactacystin, a potent and selective proteasome inhibitor, was accomplished using a catalytic enantioselective Strecker reaction of a ketoimine as the initial key step. An enone-derived N-phosphinoyl ketoimine 7 was selected as a stable masked alpha-hydroxy ketoimine analogue. Excellent enantioselectivity (98% ee) and practical catalyst activity were produced under the optimized catalyst preparation method using 2.

Asymmetric total synthesis of fredericamycin A: an intramolecular cycloaddition pathway.

The asymmetric total synthesis of the potent antitumor antibiotic fredericamycin A ((S)-1) was achieved by the intramolecular [4+2] cycloaddition of the silylene-protected styrene derivative (S)-7 followed by the aromatic Pummerer-type reaction of the sulfoxide (S)-5. Although we had already succeeded in the total synthesis of racemic 1 by the same approach, synthesis of its asymmetric version was more complicated than we had expected due to the difficulties involved in constructing the quaternary carbon center and the tendency of this center to undergo facile racemization. Racemization of this center during the installation of the acetylene moiety on the dione (R)-8 was the most serious aspect.