567-03-3Relevant articles and documents
INHIBITORS OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE FOR TREATING CARDIOVASCULAR AND PULMONARY CONDITIONS
-
Page/Page column 41-42, (2018/06/06)
The present disclosure provides for methods of treating or preventing a cardiovascular disorder and/or a related pulmonary disorder in a subject. In certain embodiments, the method comprises administering a therapeutically effective amount of an inhibitor of Glucose-6-phosphate dehydrogenase (G6PD), or a pharmaceutically acceptable salt, non-salt amorphous form, solvate, poly-morph, tautomer or prodrug thereof.
Novel steroid inhibitors of glucose 6-phosphate dehydrogenase
Hamilton, Niall M.,Dawson, Martin,Fairweather, Emma E.,Hamilton, Nicola S.,Hitchin, James R.,James, Dominic I.,Jones, Stuart D.,Jordan, Allan M.,Lyons, Amanda J.,Small, Helen F.,Thomson, Graeme J.,Waddell, Ian D.,Ogilvie, Donald J.
supporting information; experimental part, p. 4431 - 4445 (2012/09/11)
Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially developed; the 3β-alcohol can be replaced with 3β-H-bond donors such as sulfamide, sulfonamide, urea, and carbamate. Improved potency was achieved by replacing the androstane nucleus with a pregnane nucleus, provided a ketone at C-20 is present. For pregnan-20-ones incorporation of a 21-hydroxyl group is often beneficial. The novel compounds generally have good physicochemical properties and satisfactory in vitro DMPK parameters. These derivatives may be useful for examining the role of G6PD inhibition in cells and will assist the future design of more potent steroid inhibitors with potential therapeutic utility.
Stereochemistry of hydrogen loss during C-21 dehydroxylation of tetrahydrodeoxycorticosterone by Eubacterium lentum
Holland, Herbert L.,Ninniss, Ronald W.,Brown, Frances M.
, p. 1590 - 1595 (2007/10/02)
The loss of hydrogen from the C-21 position of 5β-pregnane-3α,21-diol-20-one (tetrahydrodeoxycorticosterone, THDOC) during reductive removal of the 21-hydroxy group by the anaerobic bacterium Eubacterium lentum has been shown to be selective for the pro-S position by the use of THDOC labelled with deuterium at the C-21 pro-S and C-21 pro-R positions.The labelled substrates were obtained by using the bacterium Clostridium paraputrificum to reduce chemically prepared C-21 labelled samples of pregn-4-en-21-ol-3,20-dione (deoxycorticosterone, DOC) at C-3 and C-4 (5).The stereochemistry of deuterium label introduced by chemical means at C-21 of DOC was determined by comparison with a sample of 21-(R)-DOC-21-d1 produced by reduction of the corresponding aldehyde pregn-4-en-21-al-3,20-dione, 21-d by the enzyme 21-hydroxysteroid NAD oxidoreductase from beef liver. Key words: Eubacterium, Clostridium, steroids, tetrahydrodeoxycorticosteroids.
