Výsledky vyhledávání - "James B. Coutcher"

A Novel Series of Non-Carboxylic Acid, Non-Hydantoin Inhibitors of Aldose Reductase with Potent Oral Activity in Diabetic Rat Models: 6-(5-Chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and Congeners

Autor: William H. Martin, Banavara L. Mylari, Peter J. Oates, James B. Coutcher, Michael C. Linhares, David A. Tess, Michael S. Dina, David A. Beebe, Gregory J. Withbroe, Sandra J Armento, Melissa O'Gorman, William James Zembrowski, Edward L. Conn

Publikováno v: Journal of Medicinal Chemistry. 48:6326-6339

Discovery of a highly selective, potent, and safe non-carboxylic acid, non-hydantoin inhibitor of aldose reductase (AR) capable of potently blocking the excess glucose flux through the polyol pathway that prevails under diabetic conditions has been a

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d4950c5594f211c33eec4b7093b58b81
https://doi.org/10.1021/jm050462t

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SAR and species/stereo-selective metabolism of the sorbitol dehydrogenase inhibitor, CP-470,711

Autor: Peter J. Oates, Jian-Cheng Li, David A. Beebe, R. Matthew Weekly, Day Wesley Warren, Margaret Y. Chu-Moyer, William E. Ballinger, James B. Coutcher

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 12:1477-1480

SAR studies on the stereoisomers of CP-470,711 suggested that in vivo epimerization was taking place in rats. Further metabolism studies revealed that no epimerization was occurring in dogs, and that no epimerization was expected in humans. A mechani

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6551e784a1de915bb77401a612c70ed0
https://doi.org/10.1016/s0960-894x(02)00208-1

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ChemInform Abstract: Sorbitol Dehydrogenase Inhibitors (SDIs): A New Potent, Enantiomeric SDI, 4-[2-(1R-Hydroxy-ethyl)-pyrimidin-4-yl]-piperazine-1-sulfonic Acid Dimethylamide

Autor: Michael S. Dina, Nathaniel S. Brackett, Peter J. Oates, James B. Coutcher, William James Zembrowski, Banavara L. Mylari, David A. Beebe

Publikováno v: ChemInform. 32

We report here on our medicinal chemistry and pharmacology efforts to provide a potent sorbitol dehydrogenase inhibitor (SDI) as a tool to probe a recently disclosed hypothesis centered on the role of sorbitol dehydrogenase (SDH) in the second step o

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::42a97a560394336e88e2157646e4f2fb
https://doi.org/10.1002/chin.200149121

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A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy

Autor: James B. Coutcher, Chiara Gerhardinger, Peter J. Oates, Mara Lorenzi, Wei Sun

Publikováno v: Diabetes. 55(10)

Previously studied inhibitors of aldose reductase were largely from two chemical classes, spirosuccinamide/hydantoins and carboxylic acids. Each class has its own drawbacks regarding selectivity, in vivo potency, and human safety; as a result, the pa

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::346fb94673910c9d005428580b330ec3
https://pubmed.ncbi.nlm.nih.gov/17003340

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Design and synthesis of a novel family of triazine-based inhibitors of sorbitol dehydrogenase with oral activity: 1-[4-[3R,5S-dimethyl-4-(4-methyl-[1,3,5]triazin-2-yl)-piperazin-1-yl]-[1,3,5]triazin-2-yl]-(R) ethanol

Autor: David A. Beebe, James B. Coutcher, William James Zembrowski, Banavara L. Mylari, Peter J. Oates, Gregory J. Withbroe, Edward L. Conn, Nathaniel S. Brackett

Publikováno v: Bioorganicmedicinal chemistry. 11(19)

Two new templates, (R) 2-hydroxyethyl-pyridine and (R) 2-hydroxyethyl-triazine, were used to design novel sorbitol dehydrogenase inhibitors (SDIs). The design concept included spawning of these templates to function as effective ligands to the cataly

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::362bad9374e7958ccde32d601b5ae785
https://pubmed.ncbi.nlm.nih.gov/12951149

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A highly selective, non-hydantoin, non-carboxylic acid inhibitor of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran- 2-sulfonyl)-2-H-pyridazin-3-one

Autor: James B. Coutcher, Gregory J. Withbroe, Peter J. Oates, Melissa O'Gorman, Michael S. Dina, Edward L. Conn, William H. Martin, Banavara L. Mylari, William James Zembrowski, David A. Tess, David A. Beebe, Sandra J Armento, Michael C. Linhares

Publikováno v: Journal of medicinal chemistry. 46(12)

We report here on the discovery path that led to a structurally unprecedented non-hydantoin, non-carboxylic acid aldose reductase inhibitor, 24, which shows remarkably potent oral activity in normalizing elevated sorbitol levels and, more significant

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48a28c635fafc7155bc0c769f30e1bba
https://pubmed.ncbi.nlm.nih.gov/12773033

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A sorbitol dehydrogenase inhibitor of exceptional in vivo potency with a long duration of action: 1-(R)-[4-[4-(4,6-dimethyl[1,3,5]triazin-2-yl)- 2R,6S-dimethylpiperazin-1-yl]pyrimidin-2- yl]ethanol

Autor: Peter J. Oates, Michael C. Linhares, Gregory J. Withbroe, James B. Coutcher, Edward L. Conn, William James Zembrowski, Melissa O'Gorman, Banavara L. Mylari, David A. Beebe

Publikováno v: Journal of medicinal chemistry. 45(20)

We report here a novel sorbitol dehydrogenase inhibitor, 16, that shows very high oral potency (50 microg/kg) in normalizing elevated fructose levels in the sciatic nerve of chronically diabetic rats and sustained duration of action (24 h). Furthermo

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09607f6a1fc5ec3ce9cd426c31c991df
https://pubmed.ncbi.nlm.nih.gov/12238919

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Orally-effective, long-acting sorbitol dehydrogenase inhibitors: synthesis, structure-activity relationships, and in vivo evaluations of novel heterocycle-substituted piperazino-pyrimidines

Autor: Day Wesley Warren, David A. Beebe, Margaret Y. Chu-Moyer, William E. Ballinger, Peter J. Oates, Banavara L. Mylari, Jiancheng Li, James B. Coutcher, Richard Berger, R. Matthew Weekly

Publikováno v: Journal of medicinal chemistry. 45(2)

Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this eff

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c5caee518d28eff47eac6a0fcdf74b41
https://pubmed.ncbi.nlm.nih.gov/11784155

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