Naphthalenylsulfonyl-hydantoins as aldose reductase inhibitors
摘要:
Accumulation of intracellular sorbitol, formed from glucose by aldose reductase, is believed to play an important role in the development of certain chronic complications of diabetes mellitus. Several 1-(naphthalenylsulfonyl)hydantoins inhibit aldose reductase isolated from bovine lens in vitro, and decrease galactitol formation in sciatic nerves of galactosemic rats in vivo. The 5-bromo analogue (entry 12, table I) was found to be the most orally active aldose reductase inhibitor of this series with an ED50 value of 8.1 mg/kg po. The 1-(naphthalenylsulfonyl)-2-thiohydantoin analogues with the exception of entry 11 (table I) which showed good in vivo activity, were either inactive or had only marginal activity.
(EN) Radiolabeled amine compounds, methods for preparing these compounds, diagnostic compositions containing the radiolabeled amine compounds and methods for using these compositions in conducting radiodiagnostic examinations for determining the location and extent of an occurring blood clot in the body of a warm-blooded animal such as a human. The radiolabeled amine compounds of the present invention have the general formula; (FORMULA) wherein X is selected from the group consisting of oxygen; sulfur; lower alkylene, radioactive selenium; and radioactive tellurium, Y is a hydrocarbyl amino group, and when X is oxygen, sulfur or lower alkylene, Y is a radioactive iodine-substituted hydrocarbyl amino group. Also disclosed are pharmaceutically-acceptable, acid addition salts of the above radiolabeled amine compounds. (FR) Composes amines marques radioactivement, procedes de preparation desdits composes, compositions de diagnostic contenant ces composes amines marques radioactivement et methodes pour l"utilisation de ces compositions dans la conduite d"examens de radio diagnostic pour la determination de l"etendue et de l"emplacement d"un caillot sanguin qui peut se produire dans le corps d"un animal a sang chaud tel qu"un humain. Les composes amines marques radioactivement ont la formule suivante: (FORMULE) dans laquelle X est choisi parmi le groupe consistant en oxygene, soufre, alkylene inferieur, selenium radioactif et tellure radioactif; Y represente un groupe hydrocarbyl amino, et lorsque X represente un atome d"oxygene ou de soufre ou un alkylene inferieur, Y est alors un groupe hydrocarbyl amino substitue par un atome d"iode radioactif. Sont egalement decrits des sels d"addition acide, pharmaceutiquement acceptables, desdits composes amines marques radioactivement.