piperidines and Respiratory-Tract-Infections

Adults frequently develop eustachian tube dysfunction and middle ear pressure (MEP) abnormalities during natural and experimental influenza and human rhinovirus (HRV) infections. Oral rimantadine treatment did not reduce the otologic manifestations of experimental influenza in adults or natural influenza in children. However, intranasal zanamivir and oral oseltamivir significantly reduced MEP abnormalities during experimental influenza in adults, and oseltamivir treatment appears to reduce the likelihood of otitis media in children with acute influenza. Investigational anti-HRV agents, including intranasal tremacamra, intranasal AG7088, and oral pleconaril, warrant study in this regard. Depending on the virus, early antiviral therapy has the potential to impact the risk of otitis media following respiratory tract infections.

Topics: Acetamides; Adult; Anti-Bacterial Agents; Antiviral Agents; Child; Child, Preschool; Clinical Trials as Topic; Eustachian Tube; Guanidines; Humans; Infant; Influenza A virus; Influenza B virus; Influenza, Human; Interferon-beta; Oseltamivir; Otitis Media; Otitis Media with Effusion; Picornaviridae Infections; Piperidines; Pressure; Pyrans; Pyridazines; Respiratory Tract Infections; Rhinovirus; Rimantadine; Sialic Acids; Superinfection; Virus Replication; Zanamivir

This study evaluated the efficacy and safety of 26 weeks of twice-daily (BID) alogliptin + metformin fixed-dose combination (FDC) therapy in Asian patients with type 2 diabetes. Patients aged 18 to 75 years with hemoglobin A1c (HbA1c) of 7.5% to 10.0% after ≥2 months of diet and exercise and a 4-week placebo run-in were enrolled. Eligible patients were randomized (1:1:1:1) to placebo, alogliptin 12.5 mg BID, metformin 500 mg BID or alogliptin 12.5 mg plus metformin 500 mg FDC BID. The primary endpoint was change in HbA1c from baseline to end of treatment (Week 26). In total, 647 patients were randomized. The least-squares mean change in HbA1c from baseline to Week 26 was -0.19% with placebo, -0.86% with alogliptin, -1.04% with metformin and -1.53% with alogliptin + metformin FDC. Alogliptin + metformin FDC was significantly more effective ( P  < .0001) in lowering HbA1c than either alogliptin or metformin alone. The safety profile of alogliptin + metformin FDC was similar to that of the individual components alogliptin and metformin. The study demonstrated that treatment with alogliptin + metformin FDC BID resulted in better glycaemic control than either monotherapy and was well tolerated in Asian patients with type 2 diabetes.

Topics: China; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Diabetic; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Exercise; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Immunity, Mucosal; Incidence; Malaysia; Metformin; Middle Aged; Piperidines; Republic of Korea; Respiratory Tract Infections; Taiwan; Uracil

Novel antibacterial agents needed constantly to counter the ever emergent resistance development to commercially available drugs; one of the effective synthetic antibacterial classes is fluoroquinolone (FQ). This study includes structure activity relationship based design and synthesis of novel fluoroquinolone molecules active against resistant pathogens bearing mutations of DNA gyrase and/or topoisomerase IV which also express efflux pumps. Here, series of compounds were prepared by treating 1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid as a core with various 4-substituted-3,3-dialkyl piperidines as side chains, through conventional synthetic approaches. Subsequently, antibacterial activities of these fluoroquinolones were examined against Streptococcus pneumoniae, SPN 5844 (Moxi resistant DNA gyrase and topo IV mutant) and SPN 706 (FQ efflux positive). The current manuscript covers >50 examples of fluoroquinolone NCEs, amongst 20 NCEs have shown MIC in the range of (0.4 to >6.25 μg/ml) for SPN 5844 and (0.1-12.5 μg/ml) for SPN 706 strains. During the course of this study; WCK 919, comprising two chiral isomers; WCK 1152 and WCK 1153 were emerged as lead among the different series synthesized. Advance studies suggested either WCK 1152 or WCK 1153 are the worthy candidates for further clinical developments for respiratory infections caused by resistant pneumococci and staphylococci. However, on the basis of in house preclinical work, WCK 1152 had been selected for phase-1 domestic clinical trials.

Topics: Anti-Bacterial Agents; DNA Gyrase; DNA Topoisomerase IV; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Piperidines; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus; Streptococcus pneumoniae; Structure-Activity Relationship