Primofiore G, Da Settimo F, La Motta C, Simorini F, Minutolo A, Boldrini E
Dipartimento di Scienze farmaceutiche dell'Università di Pisa, Italy.
Farmaco. 1997 Oct;52(10):583-8.
Derivatives of 4-substituted 1,2-benzisothiazole-1,1-dioxide alkanoic acids were prepared and their in vitro aldose reductase inhibitory activity was tested in rat lens enzyme. The acetic derivatives 10, 12, and 16a-d proved to be much more potent inhibitors than the propionic derivatives 11, 13, and 17a-d. The presence of an acyl moiety on the amino group in position 4 of the acetic derivatives 16a-d led to a significant increase in activity with respect to the parent compound 14. One of the most active compounds in vitro, 10, was also evaluated in vivo as an inhibitor of glutathione lens depletion in galactosemic rats, but it did not show any activity in maintaining the rat lens glutathione level, probably due to problems of ocular bioavailability or metabolism.
制备了4-取代的1,2-苯并异噻唑-1,1-二氧化物链烷酸的衍生物，并在大鼠晶状体酶中测试了它们的体外醛糖还原酶抑制活性。乙酸衍生物10、12和16a-d被证明是比丙酸衍生物11、13和17a-d更有效的抑制剂。乙酸衍生物16a-d的4位氨基上存在酰基部分，导致相对于母体化合物14活性显著增加。体外活性最高的化合物之一10，也在体内作为半乳糖血症大鼠晶状体谷胱甘肽消耗的抑制剂进行了评估，但它在维持大鼠晶状体谷胱甘肽水平方面没有显示出任何活性，这可能是由于眼部生物利用度或代谢问题。
