A5102907949- Carbohydrate Chemistry and Synthesis
- HIV/AIDS drug development and treatment
- Peptidase Inhibition and Analysis
- Synthesis and Characterization of Heterocyclic Compounds
- Biochemical and Molecular Research
- Cellular transport and secretion
- Polyamine Metabolism and Applications
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Electrochemical sensors and biosensors
- Organophosphorus compounds synthesis
- Helminth infection and control
- Network Traffic and Congestion Control
- Chemical Synthesis and Analysis
- Distributed systems and fault tolerance
- Parasitic Infections and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Cholinesterase and Neurodegenerative Diseases
- Adenosine and Purinergic Signaling
- DNA and Nucleic Acid Chemistry
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Optimization and Search Problems
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2010-2019
Czech Academy of Sciences
2007-2019
Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy an anticancer agent. The use of MBZ for cancer, however, is challenging due to its poor solubility leading bioavailability. Herein, we prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt improve these characteristics. Compound 12, containing (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl...
2-Phosphonomethylpentanedioic acid (1, 2-PMPA) is a potent inhibitor of glutamate carboxypeptidase II which has demonstrated robust neuroprotective efficacy in many neurological disease models. However, 1 highly polar containing phosphonate and two carboxylates, severely limiting its oral bioavailability. We strategized to mask the groups via prodrug approach, increasing likelihood passive absorption. Our initial strategy was cover with hydrophobic moieties such as pivaloyloxymethyl (POM)...
We consider the following buffer management problem arising in QoS networks: Packets with specified weights and deadlines arrive at a network switch need to be forwarded so that total weight of packets is maximized. not before their are lost. The main result article an online 64/33 ≈ 1.939-competitive algorithm, first deterministic algorithm for this competitive ratio below 2. For 2-uniform case we give 1.377 matching lower bound.
4-Carboxy-α-[3-(hydroxyamino)-3-oxopropyl]-benzenepropanoic acid 1 is a potent hydroxamate-based inhibitor of glutamate carboxypeptidase II. In an attempt to improve its poor oral pharmacokinetics, we synthesized series prodrugs by masking hydrophilic hydroxamate group. Prodrugs were evaluated for availability in mice and showed varying degree plasma exposure 1. Of these, para-acetoxybenzyl-based, 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-carboxy-5-oxopentyl)benzoic acid, 12, provided 5-fold...
2-(Phosphonomethyl)-pentanedioic acid (2-PMPA) is a potent (IC50 = 300 pM) and selective inhibitor of glutamate carboxypeptidase II (GCPII) with efficacy in multiple neurological psychiatric disease preclinical models more recently inflammatory bowel (IBD) cancer. 2-PMPA (1), however, has not been clinically developed due to its poor oral bioavailability (<1%) imparted by four acidic functionalities (c Log P -1.14). In an attempt improve the 2-PMPA, we explored prodrug approach using...
One of the most potent and selective inhibitors Glutamate Carboxypeptidase II is 2-phoshonomethyl-pentanedioic acid (2-PMPA), a compound that has demonstrated robust neuroprotective efficacy in many neurological disease models. However, 2-PMPA highly polar containing phosphonate two carboxylates, severely limiting its oral bioavailability. We strategized to mask groups via prodrug approach, thereby increasing likelihood passive absorption. Our initial strategy was cover with hydrophobic...