299397-03-8Relevant articles and documents
2- (PIPERIDIN-1-YL) -4-HETEROCYCLYL-THIAZOLE-5-CARBOXYLIC ACID DERIVATIVES AGAINST BACTERIAL INFECTIONS
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Page/Page column 186, (2010/07/02)
Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described. Ring A is selected from formula (a), (b) or (b'):
Sorbitol dehydrogenase inhibitors (SDIs): A new potent, enantiomeric SDI, 4-[2-1R-hydroxy-ethyl)-pyrimidin-4-yl]-piperazine-1-sulfonic acid dimethylamide
Mylari,Oates,Beebe,Brackett,Coutcher,Dina,Zembrowski
, p. 2695 - 2700 (2007/10/03)
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 of the polyol pathway, under conditions of high glucose flux. Starting from a weak literature lead, 2, and through newly developed structure-activity relationships, we have designed and executed an unambiguous synthesis of enantiomeric SDI, 6, which is at least 10 × more potent than 2. Also, 6 potently inhibits SDH in streptozotocin-diabetic rat sciatic nerve. We have described an expedient synthesis of a key building template, 33, for future research in the SDI area that may facilitate the discovery of even more potent SDIs with longer duration of action in vivo.
