29916-48-1Relevant articles and documents
Prodrugs of perzinfotel with improved oral bioavailability
Baudy, Reinhardt B.,Butera, John A.,Abou-Gharbia, Magid A.,Chen, Hong,Harrison, Boyd,Jain, Uday,Magolda, Ronald,Sze, Jean Y.,Brandt, Michael R.,Cummons, Terri A.,Kowal, Diane,Pangalos, Menelas N.,Zupan, Bojana,Hoffmann, Matthew,May, Michael,Mugford, Cheryl,Kennedy, Jeffrey,Childers Jr., Wayne E.
, p. 771 - 778 (2009)
Previous studies with perzinfotel (1), a potent, selective, competitive NMDA receptor antagonist, showed it to be efficacious in inflammatory and neuropathic pain models. To increase the low oral bioavailability of 1 (3-5%), prodrug derivatives (3a-h) were synthesized and evaluated. The oxymethylene-spaced diphenyl analogue 3a demonstrated good stability at acidic and neutral pH, as well as in simulated gastric fluid. In rat plasma, 3a was rapidly converted to 1 via 2a. Pharmacokinetic studies indicated that the amount of systemic exposure of 1 produced by a 10 mg/kg oral dose of 3a was 2.5-fold greater than that produced by a 30 mg/kg oral dose of 1. Consistent with these results, 3a was significantly more potent and had a longer duration of activity than 1 following oral administration in a rodent model of inflammatory pain. Taken together, these results demonstrate that an oxymethylene-spaced prodrug approach increased the bioavailability of 1.
GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 001309; 001310, (2021/01/22)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 001351; 001352; 001353, (2019/07/17)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
