110568-92-8Relevant academic research and scientific papers
Novel Spirosuccinimides with Incorporated Isoindolone and Benzisothiazole 1,1-Dioxide Moieties as Aldose Reductase Inhibitors and Antihyperglycemic Agents
Wrobel, Jay,Dietrich, Arlene,Woolson, Shiela A.,Millen, Jane,McCaleb, Michael,et al.
, p. 4613 - 4627 (2007/10/02)
Compounds from two novel series of spirosuccinimides were prepared.Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group.These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats.Many members from the isoindolone series 2,particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency.The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer.Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg).Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone.However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.
NOVEL SPIROSUCCINIMIDES AS ALDOSE REDUCTASE INHIBITORS AND ANTIHYPERGLYCEMIC AGENTS
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, (2008/06/13)
This invention relates to novel spirosuccinimide derivatives, to the processes for their preparation, to methods for using the compounds, and to pharmaceutical preparations thereof. The compounds have pharmaceutical properties which render them beneficial
Studies on the Chemistry of Isoindoles and Isoindolenines, XXVIII. - 3-Alkoxy-1H-isoindoles, Syntheses and Properties
Hennige, Hans,Kreher, Richard P.,Konrad, Michael,Jelitto, Frank
, p. 243 - 252 (2007/10/02)
3-Alkoxy-1H-isoindoles 1 bearing substituents at the carboxylic moiety have been synthesized from substituted 2,3-dihydro-1H-isoindol-1-ones 4 by regiospecific O-alkylation to 5 with trialkyloxonium tetrafluoroborates or methyl trifluoroborates or methyl trifluoromethanesulfonate and subsequent NH deprotonation.According to the spectroscopic properties the semicyclic alkyl imidates 1 exist exclusively in the benzoid 1H structure; the tautomeric o-quinonoid 2H structure 2 cannot be detected by spectroscopic means.
