Synthesis and antibacterial activity of novel lincomycin derivatives. III. Optimization of a phenyl thiadiazole moiety.

Lincomycin derivatives that have a 5-(2-nitrophenyl)-1,3,4-thiadiazol-2-yl thio moiety at the 7-position were synthesized. 5-Substituted 2-nitrophenyl derivatives showed potent antibacterial activities against Streptococcus pneumoniae and Streptococcus pyogenes with erm gene. Antibacterial activities of the 4,5-di-substituted 2-nitrophenyl derivatives were generally comparable to those of telithromycin (TEL) against S.

Synthesis and antibacterial activity of novel lincomycin derivatives. II. Exploring (7S)-7-(5-aryl-1,3,4-thiadiazol-2-yl-thio)-7-deoxylincomycin derivatives.

The synthesis and antibacterial activity of (7S)-7-(5-aryl-1,3,4-thiadiazol-2-yl-thio)-7-deoxylincomycin derivatives are described. These derivatives were mainly prepared by the Mitsunobu reaction of 2,3,4-tris-O-(trimethylsilyl)lincomycin and the corresponding thiols. Exploring structure-activity relationships of the substituent at the 5 position of a thiadiazole ring revealed that compounds with the ortho substituted phenyl group showed improved antibacterial activities against Streptococcus pneumoniae and Streptococcus pyogenes with erm gene compared with the reported compound (1) that had an unsubstituted benzene ring.

Synthesis and antibacterial activity of novel lincomycin derivatives. I. Enhancement of antibacterial activities by introduction of substituted azetidines.

The synthesis and antibacterial activity of (7S)-7-sulfur-azetidin-3-yl lincomycin derivatives are described. Modification was achieved by a simple reaction of (7R)-7-O-methanesulfonyllincomycin and the corresponding substituted azetidine-2-thiol. Several compounds first showed moderate antibacterial activity against Streptococcus pneumoniae and Streptococcus pyogenes with erm gene as lincomycin derivatives.

Novel azalides derived from 16-membered macrolides. III. Azalides modified at the C-15 and 4'' positions: Improved antibacterial activities.

The design and synthesis of 16-membered azalides modified at the C-15 and 4'' positions are described. The compounds we report here are characterized by an arylpropenyl group attached to the C-15 position of macrolactone and a carbamoyl group at the C-4'' position in a neutral sugar. Introduction of alkylcarbamoyl groups to the C-4'' position was regioselectively achieved by unique and convenient methods via acyl migration.

Novel azalides derived from 16-membered macrolides. Part II: Isolation of the linear 9-formylcarboxylic acid and its sequential macrocyclization with an amino alcohol or an azidoamine.

The design and synthesis of novel 14- to 16-membered 11-azalides starting from 16-membered macrolides are reported. A linear 9-formylcarboxylic acid was isolated via a mobile dialdehyde previously reported. Sequential macrocyclization of the formylcarboxylic acid with amino alcohol followed by deprotection afforded corresponding 14- to 16-membered azalides.

Clinical, radiographic, and histologic evaluation of localized ridge augmentation using a mandibular bone block.

This clinical case report presents a new technique for reconstructing the vertical and horizontal dimensions of the alveolar ridge using a mandibular bone block at sites planned for single implants. Augmentation was eased with the use of a mandibular bone block, which was shaped after placement with a round bur to passively fit the dimensions of the defect, at the recipient site. After treatment, approximately 7 mm of horizontal and 3 mm of vertical augmentation were gained.

Design and synthesis of novel leucomycin analogues modified at the C-3 position. Part II: 3-O-(3-Aryl-2-propenyl)leucomycin analogues.

The design and synthesis of 16-membered macrolides modified at the C-3 position are described. Starting from fully protected intermediate (5), appropriate modifications including Heck reaction were performed to furnish 3-O-(3-aryl-2-propenyl)leucomycin A(7) analogues (9a-9m). These leucomycin A(7) derivatives showed improved in vitro antibacterial activities against clinically important pathogens including erythromycin-resistant Streptococcus pneumoniae (ERSP).

Novel 16-membered macrolides modified at C-12 and C-13 positions of midecamycin A1 and miokamycin. Part 1: Synthesis and evaluation of 12,13-carbamate and 12-arylalkylamino-13-hydroxy analogues.

Design and synthesis of 16-membered macrolides modified at the C-12 and 13 positions are described. The compounds we report here have an arylalkylamino group attached to the C-12 position of the macrolactone. Both types of derivatives, 12,13-cyclic carbamates and non-carbamate analogues, were synthesized via 12-amino-13-hydroxy intermediates derived from 12,13-epoxide that was prepared by selective epoxidation at the C-12 and C-13 positions.

Novel azalides derived from sixteen-membered macrolides.

The design and synthesis of novel 15-membered 11-azalides and 16-membered 11,12-diazalide starting from 16-membered macrolides are reported. A mobile linear dialdehyde was isolated via a cyclic tetraol which was prepared by osmium oxidation of a conjugated diene. One-pot macrocyclization of this dialdehyde with an amine or a diamine afforded corresponding 15-membered azalides or 11,12-diazalide.

Discovery of 4-Pyridone derivatives as specific inhibitors of enoyl-acyl carrier protein reductase (FabI) with antibacterial activity against Staphylococcus aureus.

4-Pyridone derivatives were identified as potent inhibitors of FabI, the enoyl-acyl carrier protein reductase in Escherichia coli and Staphylococcus aureus. 1-Substituted derivatives of a hit compound exhibited potent antibacterial activities against S. aureus.

Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae.

The molecular mechanisms of reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae, particularly amino acid substitutions in mosaic penicillin-binding protein 2 (PBP2), were examined. The complete sequence of ponA, penA, and por genes, encoding, respectively, PBP1, PBP2, and porin, were determined for 58 strains isolated in 2002 from Japan. Replacement of leucine 421 by proline in PBP1 and the mosaic-like structure of PBP2 were detected in 48 strains (82.

AG205, a novel agent directed against FabK of Streptococcus pneumoniae.

AG205 was identified from high-throughput screening as a potent inhibitor of FabK, the enoyl-ACP reductase in Streptococcus pneumoniae. Specific inhibition of lipid biosynthesis in a macromolecular biosynthesis assay and identification of an Ala141Ser substitution in FabK from spontaneous AG205-resistant mutants indicated that AG205 exerts antibacterial activity against S. pneumoniae through the specific inhibition of FabK.

End-tidal carbon dioxide monitoring indicates recovery from cardiogenic shock in patients receiving percutaneous cardiopulmonary support.

The aim of this study was to examine the prognostic value of monitoring end-tidal carbon dioxide (ETCO(2)) levels for patients in cardiogenic shock undergoing percutaneous cardiopulmonary support (PCPS). Fifteen patients in whom PCPS was used to treat cardiogenic shock were enrolled in this study. For hemodynamic measurements, a thermodilution catheter was inserted into the pulmonary artery and an infrared absorption sensor was placed in the main stream of exhaled air between the respiration tube and the respirator to measure ETCO(2) levels.

Fifteen to twenty-eight years' follow-up results of high tibial valgus osteotomy for osteoarthritic knee.

A long-term follow-up study was performed on 75 knees of 53 patients after high tibial valgus osteotomy. The earlier results have previously been reported. There were 15 knees in 11 men and 60 knees in 42 women.

Synthesis and biological evaluation of novel leucomycin analogues modified at the C-3 position. I. Epimerization and methylation of the 3-hydroxyl group.

The synthesis and biological evaluation of sixteen-membered macrolides modified at the C-3 position are described. 3-Epi-leucomycin A7 (9), 3-O-acyl-3-epi-leucomycin A7 analogues (11a-11e), 3-O-acylleucomycin A7 analogues (13b-13e) and 3-O-methylleucomycin analogues (16a, 16b and 22) were synthesized via fully protected intermediates (7, 5a, 5b and 20). After appropriate modification, subsequent deprotections were performed to furnish a variety of leucomycin analogues.

Synthesis of granulatimide positional analogues.

The Stille coupling reaction of the stannylindole 13 with the 5-iodoimidazole derivative 14 (or 27) in the presence of PdCl(2)(PPh(3))(2) gave the corresponding indole-imidazole coupling product 15 (or 28), thereby affording a synthetic approach to 10-methylgranulatimide (7), 15-methylgranulatimide (11), and 10, 15-dimethylgranulatimide (12), as well as 10-methylisogranulatimide B (5).

Underestimation of varus angulation in knees with flexion deformity.

In order to investigate the change in limb alignment in cases of knee flexion deformity, 17 male volunteers aged from 25 to 35 years with no complaints and no knee disorders were selected. The femorotibial angle (FTA), which is the lateral angle at the intersection between the femoral axis and the tibial axis in an anteroposterior radiograph, was employed as an index of limb alignment. FTA in standing on one leg with and without knee flexion was measured.

Use of joint fluid analysis for determining cartilage damage in osteonecrosis of the knee.

Objective: To assess the value of joint fluid analysis for determining cartilage degradation and prognosis in spontaneous osteonecrosis (ON) of the knee.

Methods: Synovial fluid was obtained from 30 knees with spontaneous ON (26 medial femoral condyles, 4 medial tibial plateaus) as well as from 50 knees with medial compartmental osteoarthritis (OA) as a control. Levels of chondroitin 6-sulfate (C6S), C4S, and hyaluronic acid were measured with high-performance liquid chromatography.

Slow-releasing potential of vancomycin-loaded porous hydroxyapatite blocks implanted into MRSA osteomyelitis.

Although antibiotic-loaded hydroxyapatite blocks have been used for the treatment of chronic osteomyelitis, their long-term potential for releasing antibiotic into human bones is not well known. Five patients with chronic osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) infection were effectively treated with local implantation of vancomycin-loaded hydroxyapatite blocks. Blocks were removed during the following reconstructive surgeries when the releasing capability of the blocks, and the bacteriocidal activity of the remaining vancomycin in these blocks could be evaluated.

New synthetic route to granulatimide and its structural analogues.

The Stille coupling reaction of stannylindole 12 with 4-iodoimidazole 13 (or 24) in the presence of PdCl(2)(PPh(3))(2) gave the corresponding indole-imidazole coupling product 14 (or 25), thereby affording a new synthetic approach to the alkaloid granulatimide (7), isolated from the Brazilian ascidian Didemnum granulatum, as well as its structural analogues, 10-methylgranulatimide (23), 17-methylgranulatimide (30), 10,17-dimethylgranulatimide (31).

High tibial osteotomy with anterior advancement of distal fragment for medial and patellofemoral compartmental osteoarthritis of the knee.

High tibial osteotomy was performed in 73 knees of 50 patients with medial and patellofemoral compartmental osteoarthritis of the knee, which was combined with anterior advancement of the distal fragment. At the operation, parapatellar release of the retinaculum and subperiosteal elevation of contracted medial soft tissue were also adjoined. The average age of the patients at the time of surgery was 64 years.