84446-04-8Relevant academic research and scientific papers
Acetic acid aldose reductase inhibitors bearing a five-membered heterocyclic core with potent topical activity in a visual impairment rat model
La Motta, Concettina,Sartini, Stefania,Salerno, Silvia,Simorini, Francesca,Taliani, Sabrina,Marini, Anna Maria,Da Settimo, Federico,Marinelli, Luciana,Limongelli, Vittorio,Novellino, Ettore
supporting information; experimental part, p. 3182 - 3193 (2009/04/06)
A number of 1,2,4-oxadiazol-5-yl-acetic acids and oxazol-4-yl-acetic acids were synthesized and tested for their ability to inhibit aldose reductase (ALR2). The oxadiazole derivatives, 7c, 7f, 7i, and 8h, 8i, proved to be the most active compounds, exhibiting inhibitory levels in the submicromolar range. In this series, the phenyl group turned out to be the preferred substitution pattern, as its lengthening to a benzyl moiety determined a general reduction of the inhibitory potency. The lead compound, 2-[3-(4-methoxyphenyl)-1,2,4- oxadiazol-5-yl]acetic acid, 7c, showed an excellent in vivo activity, proving to prevent cataract development in severely galactosemic rats when administered as an eye-drop solution in the precorneal region of the animals. Computational studies on the ALR2 inhibitors were performed to rationalize the structure-activity relationships observed and to provide the basis for further structure-guided design of novel ALR2 inhibitors.
Ring-transformation of 1,2,4-Oxadiazines. Raney Nickel Hydrogenation of Z-3-Aryl-5,6-dihydro-5-(substituted)methylene-4H-1,2,4-oxadiazine Derivatives
Tabei, Katsumi,Kawashima, Etsuko,Takada, Toyozo,Kato, Tetsuzo
, p. 569 - 574 (2007/10/02)
Raney nickel hydrogenation of Z-3-aryl-5-(ethoxycarbonyl)methylene-5,6-dihydro-4H-1,2,4-oxadiazine (1a-c) affords 2-aryl-6-hydroxymethyl-4-pyrimidinone (2) and ethyl (2-aryl-4-oxazolyl)acetate (3).A similar hydrogenation of Z-5-(arylcarbamoyl)methylene-5,
RING-TRANSFORMATION OF 1,2,4-OXADIAZINE DERIVATIVES INTO 4-HYDROXYPYRIMIDINE DERIVATIVES: CATALYTIC HYDROGENATION OF 3-ARYL-5-ETHOXYCARBONYLMETHYLENE-5,6-DIHYDRO-4H-1,2,4-OXADIAZINE DERIVATIVES
Tabei, Katsumi,Kawashima, Etsuko,Takada, Toyozo,Kato, Tetsuzo
, p. 2061 - 2066 (2007/10/02)
Catalytic hydrogenation of 3-aryl-5-ethoxycarbonylmethylene-5,6-dihydro-4H-1,2,4-oxadiazine derivatives (1) is described.The method leads to new synthesis of 2-aryl-4-hydroxypyrimidine derivatives (3) involving cyclization of ethyl 3-benzimidoylimino-4-hydroxybutanoate derivatives (2) by the elimination of ethanol.Nickel catalyzed hydrogenation of 1 gave ethyl 2-aryl-4-oxazoylacetate (4) as a by-product besides product 3.
