Ludmila Alexandrova

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R1481 is a sub-type selective muscarinic receptor antagonist with the potential treatment of overactive bladder. R1481 presents two challenges for drug development. The first is the viscous semi-solid nature of the active pharmaceutical ingredient (API). The second challenge is the poor oral bioavailability of this water soluble, metabolically stable(More)
A series of novel 3,4-dihydro-2H-benzo[1,4]oxazine derivatives has been designed and synthesized as 5-HT(6) receptor antagonists. Many of the compounds displayed subnanomolar affinities for the 5-HT(6) receptor and good brain penetration in rats. The relationship of structure and lipophilicity to hERG inhibition of this series of compounds is discussed.
A series of benzo[d]isothiazole-1,1-dioxides were designed and evaluated as inhibitors of HCV polymerase NS5B. Structure-based design led to the incorporation of a high affinity methyl sulfonamide group. Structure-activity relationship (SAR) studies of this series revealed analogues with submicromolar potencies in the HCV replicon assay and moderate(More)
Measurement of neopterin in biological fluids is a sensitive and specific tool for detecting activation of the T cell/macrophage system. Serum neopterin level, detected by radioimmunoassay, and data from morphological investigations of myocardium were compared in 29 patients with a clinical diagnosis of dilated heart muscle disease. According to the results(More)
Antisperm antibodies (ASA) are a cause of male infertility. ASA are often found in varicocele patients. The study objective was to assess the ASA role in fertility recovery after varicocelectomy. The longitudinal study involved 99 patients with varicocele. Patients were examined according to the WHO recommendations; ASA level was measured using the direct(More)
A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on(More)
Benzothiazine-substituted tetramic acids were discovered as highly potent non-nucleoside inhibitors of HCV NS5B polymerase. X-ray crystallography studies confirmed the binding mode of these inhibitors with HCV NS5B polymerase. Rational optimization of time dependent inactivation of CYP 3A4 and clearance was accomplished by incorporation of(More)
Polarity switching mass spectrometry is an efficient way to collect structural data on drug metabolites. The value of this approach is illustrated with the in vitro metabolism of RO9237. Metabolites are identified by positive and negative electrospray ionization (ESI) full scan mass spectrometry, MS/MS and MS(3) using unlabelled and (14)C-radiolabelled(More)
Pulmonary arterial hypertension is a complication of methamphetamine use (METH-PAH), but the pathogenic mechanisms are unknown. Given that cytochrome P450 2D6 (CYP2D6) and carboxylesterase 1 (CES1) are involved in metabolism of METH and other amphetamine-like compounds, we postulated that loss of function variants could contribute to METH-PAH. Although no(More)
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