Model For Glutamate Racemase inhibitors and Glutamate Racemase Antibacterial Agents
OwnerTarek M. Mahfouz, Kyle W. Skidmore +2inventors
InventorsTarek M. Mahfouz, Kyle W. Skidmore, Amy Stockert, Corey Scherer
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Abstract
Antibiotics that target the enzyme glutamate racemase are disclosed. Ligand based glutamate racemase inhibitors are developed using software to extract a pharmacophore model from a group of known glutamate racemase inhibitors. These compounds are assayed against S. pneumoniae and were shown to have antibacterial activity against the non-virulent strain R6 and against a multidrug resistant strain.
Claims30
A method of identifying antibacterial agents with enhanced pharmacokinetic properties comprising the steps of:
- a. Developing pharmacophore models based on known glutamate racemase inhibitors;
- and
- b. Either
- i. Excluding models with more than one charged element;
- or
- ii. Modifying elements in the pharmacophore models by replacing the negatively charged elements in the model with hydrogen-bond acceptor groups and the positively charged elements in the model with hydrogen-bond donor groups;
- To enhance pharmacokinetic properties of the models and obtain enhanced models;
- and
- c. Identifying compounds by searching chemical databases for compounds comprising a structure closest to the enhanced models.
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A pharmacophore model comprising the structure
- wherein N9 represents a negative ionizable site, D7 a hydrogen bond donor site, A1 a hydrogen bond acceptor site and both R11 and R12 are aromatic ring sites.
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A method of identifying antibacterial agents with enhanced pharmacokinetic properties comprising the steps of:
- a. Developing pharmacophore models based on known glutamate racemase inhibitors;
- and
- b. Either
- i. Excluding models with more than one charged element;
- or
- ii. Modifying elements in the pharmacophore models by replacing the negatively and positively charged elements in the model with neutral counterparts;
- To enhance pharmacokinetic properties of the models and obtain enhanced models;
- and
- c. Identifying compounds by searching chemical databases for compounds comprising a structure closest to the enhanced models.
Dependencies are inferred from the claim text.