Modeling of competitive phosphono amino acid NMDA receptor antagonists

• Published in: Journal of medicinal chemistry Vol. 35; no. 9; pp. 1509 - 1514
• Main Authors: Whitten, Jeffrey P, Harrison, Boyd L, Weintraub, Herschel J. R, McDonald, Ian A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-05-1992
• Subjects: Binding, Competitive; Biological and medical sciences; Computer Simulation; Electricity; Medical sciences; Miscellaneous; Models, Molecular; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Organophosphonates - pharmacology; Pharmacology. Drug treatments; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Competitive fixation; Structure activity relation; Molecular structure; Molecular competition; Organic phosphonate; Binding site; Antagonist; NMDA receptor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00087a002

A pharmacophore for the phosphono amino acid antagonists of the NMDA receptor has been developed using computer-based molecular modeling techniques. An important feature of this model is that a single binding site is proposed for the phosphonic acid moiety. All competitive antagonists we have examined incorporating amino acid and phosphonate groups in their structure fit the pharmacophore in energetically accessible conformations.