A5007471278- Neuroscience and Neuropharmacology Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Neurotransmitter Receptor Influence on Behavior
- Memory and Neural Mechanisms
- Pharmacological Receptor Mechanisms and Effects
- Alkaloids: synthesis and pharmacology
- Crystallography and molecular interactions
- Chemical synthesis and alkaloids
- Epilepsy research and treatment
- Synthesis and bioactivity of alkaloids
- Synthesis and Biological Evaluation
- Parasite Biology and Host Interactions
- Coordination Chemistry and Organometallics
- Chemical Synthesis and Analysis
- Helminth infection and control
- Neuropeptides and Animal Physiology
- Catalytic Cross-Coupling Reactions
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Phenothiazines and Benzothiazines Synthesis and Activities
- Parasites and Host Interactions
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Marine Sponges and Natural Products
University of Wisconsin–Milwaukee
2015-2024
Medical University of Vienna
2018
Alzheimer’s Research UK
2018
University of Mississippi Medical Center
2018
Warneford Hospital
2018
University of Oxford
2018
New England Biolabs (United States)
2018
Harvard University
2018
Cardiff University
2018
Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability largely unknown. In this study, maternal separation (MS) stress, restricted to pre-weaning period, was used as a model study mechanisms of protracted effects childhood stress/traumatic experiences on binge drinking impulsivity. Using an operant self-administration delay discounting assay measure impulsive-like behavior, we report early life...
Abstract A highly enantio‐ and diastereoselective strategy to access any member of the sarpagine/macroline family oxindole alkaloids via internal asymmetric induction was developed from readily available d ‐(+)‐tryptophan. At center this approach diastereospecific generation spiro[pyrrolidine‐3,3′‐oxindole] moiety at an early stage a tert ‐butyl hypochlorite‐promoted oxidative rearrangement chiral tetrahydro‐β‐carboline derivative. This key branching point determined spatial configuration...
In nonhuman primates we tested a new set of behavioral categories for observable sedative effects using pediatric anesthesiology classifications as basis. Using quantitative observation techniques in rhesus monkeys, examined the alprazolam and diazepam (nonselective benzodiazepines), zolpidem (preferential binding to
To provide back-up compounds to support the development of GABA<sub>A</sub> receptor (GABAAR) potentiator KRM-II-81, three novel analogs were designed: replacing pyridinyl with 29-Cl-phenyl (FR-II-60), changing positions N and O atoms in oxazole ring addition an ethyl group (KPP-III-34 KPP-III-51), or substituting a Br atom for ethynyl KRM-II-81 (KPP-III-34). The bound brain GABAARs. Intraperitoneal administration FR-II-60 KPP-III-34 produced anticonvulsant activity mice [maximal...
A series of novel imidazobenzodiazepine analogs the lead chiral ligand SH-053-2'F-
The need for improved medications the treatment of epilepsy and chronic pain is essential. Epileptic patients typically take multiple antiseizure drugs without complete seizure freedom, not fully managed with current medications. A positive allosteric modulator (PAM) α2/3-containing GABAA receptors (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole or KRM-II-81 (8) a lead compound in series imidazodiazepines. We previously reported that produces broad-based...
The stereospecific synthesis of aryloxy and amino substituted E- Z-ethyl-3-acrylates is interest because their potential in the polymer industry medicinal chemistry. During work on a copper-catalyzed cross-coupling reaction ethyl (E)- (Z)-3-iodoacrylates with phenols N-heterocycles, we discovered very simple (nonmetallic) method for acrylates. To study this long-standing problem stereoselectivity acrylates, series O- N-substituted nucleophiles was allowed to react (Z)-3-iodoacrylates....
Abstract Approximately 30% of current drinkers in the United States drink excessively, and are referred to as problem/hazardous drinkers. These individuals, who may not meet criteria for alcohol abuse or dependence, comprise binge, heavy drinkers, both. Given their high prevalence, interventions that reduce risk binge drinking have important public health implications. Impulsivity has been repeatedly associated with excessive clinical literature. As impulsivity is correlated with, play a...
A novel two step protocol was developed to gain regiospecific access 3-substituted β- and aza-β-carbolines, 3-PBC (<bold>1</bold>), 3-ISOPBC (<bold>2</bold>), βCCt (<bold>3</bold>), 6-aza-3-PBC (<bold>4</bold>) 6-aza-3-ISOPBC (<bold>5</bold>).
Parasitic flatworm infections (e.g. tapeworms and fluke worms) are treated by a limited number of drugs. In most cases, control is reliant upon praziquantel (PZQ) monotherapy. However, PZQ ineffective against sexually immature parasites, there have also been several concerning reports on cestode trematode with poor cure-rates, emphasizing the need for alternative therapies to treat these infections. We revisited series benzodiazepines given anti-schistosomal activity meclonazepam (MCLZ)....
GABAergic modulation involved in cognitive processing appears to be substantially changed Alzheimer's disease (AD). In a widely used 5xFAD model of AD, we aimed assess if negative and positive allosteric modulators α5 GABA
Abstract The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy animal models a human clinical trial benzodiazepine meclonazepam, discovered by Roche 1970’s. Meclonazepam was not brought to market because dose-limiting sedative side...
Recent studies suggest that among the gamma-aminobutyric acid type A (GABA
ABSTRACT The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad-spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy animal models a human clinical trial benzodiazepine meclonazepam, discovered by Roche 1970s. Meclonazepam was not brought to market because dose-limiting sedative side effects....
Imidazodiazepine (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole or KRM-II-81) is a potentiator of GABAA receptors (a GABAkine) undergoing preparation for clinical development. KRM-II-81 active against many seizure and pain models in rodents, where it exhibits improved pharmacological properties over standard-of-care agents. Since salts can be utilized to create opportunities increased solubility, enhanced absorption, distribution, as well efficient...
Antinociceptive ligand HZ-166 is a GABA