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Your search keyword '"Thomas Richard Belliotti"' showing total 2 results
Start Over "Thomas Richard Belliotti" Journal bioorganicmedicinal chemistry letters
2 results on '"Thomas Richard Belliotti"'

1. Oxadiazolone bioisosteres of pregabalin and gabapentin

Author

Thomas Richard Belliotti, Susan M. Lotarski, Justin Stephen Bryans, Dic Williams, Jack J. Kinsora, Clare O. Kneen, Andrew John Thorpe, David J. Wustrow, Jacob Bradley Schwarz, Ayman El-Kattan, Charles Taylor, Sean D. Donevan, Lisa Buchholz, Thomas Capiris, Mark G. Vartanian, and Mark J. Field

Subjects
Gabapentin, Cyclohexanecarboxylic Acids, Protein subunit, Clinical Biochemistry, Pregabalin, Pharmaceutical Science, Organic Anion Transporters, Pharmacology, Biochemistry, Drug Discovery, Osteoarthritis, medicine, Potency, Animals, Drug Interactions, Cimetidine, Amines, Molecular Biology, gamma-Aminobutyric Acid, Oxadiazoles, Voltage-dependent calcium channel, Chemistry, Organic Chemistry, Brain, Rats, Probenecid, Molecular Medicine, Octamer Transcription Factors, Drug Therapy, Combination, Efflux, medicine.drug
Abstract

A series of oxadiazolone bioisosteres of pregabalin 1 and gabapentin 2 were prepared, and several were found to exhibit similar potency for the α 2 -δ subunit of voltage-gated calcium channels. Oxadiazolone 9 derived from 2 achieved low brain uptake but was nevertheless active in models of osteoarthritis. The high clearance associated with compound 9 was postulated to be a consequence of efflux by OAT and/or OCT, and was attenuated on co-administration with cimetidine or probenecid.

Published
2008

2. Discovery of 6-ethyl-2,4-diaminopyrimidine-based small molecule renin inhibitors

Author

Jeremy J. Edmunds, Suzie Ferreira, Mehran Jalaie, Rajendra Subedi, Daniel D. Holsworth, Erli Zhang, Samarendra N. Maiti, Patrick I. McConnell, John W. Bryant, Tingsheng Li, Noel A. Powell, Thomas Richard Belliotti, Cuiman Cai, Michael J. Ryan, Igor Mochalkin, Michael Stier, Aparna Kasani, and Wendy Collard

Subjects
Models, Molecular, Stereochemistry, High-throughput screening, Chemistry, Pharmaceutical, Clinical Biochemistry, Molecular Conformation, Pharmaceutical Science, Ring (chemistry), Crystallography, X-Ray, Biochemistry, Rats, Sprague-Dawley, chemistry.chemical_compound, Inhibitory Concentration 50, Structure-Activity Relationship, Drug Discovery, Renin–angiotensin system, Renin, Potency, Animals, Molecular Biology, Chemistry, Organic Chemistry, Small molecule, Rats, Diaminopyrimidine, Pyrimidines, Models, Chemical, Drug Design, Molecular Medicine, Structure based
Abstract

Novel 2,4-diaminopyrimidine-based small molecule renin inhibitors are disclosed. Through high throughput screening, parallel synthesis, X-ray crystallography, and structure based drug design, we have developed the first non-chiral, non-peptidic, small molecular template to possess moderate potency against renin. The designed compounds consist of a novel 6-ethyl-5-(1,2,3,4-tetrahydroquinolin-7-yl)pyrimidine-2,4-diamine ring system that exhibit moderate potency (IC(50): 91-650 nM) against renin while remaining 'Rule-of-five' compliant.

Published
2007

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