Shepard K L, Graham S L, Hudcosky R J, Michelson S R, Scholz T H, Schwam H, Smith A M, Sondey J M, Strohmaier K M, Smith R L
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
J Med Chem. 1991 Oct;34(10):3098-105. doi: 10.1021/jm00114a020.
For several decades a tantalizing goal for the treatment of primary open-angle glaucoma has been the development of a topically active carbonic anhydrase inhibitor. Recent results from several research groups indicate that considerable progress has been made toward this objective. In this report, we present the design and synthesis of (hydroxyalkyl)sulfonyl-substituted benzene- and thiophenesulfonamides. These compounds exhibit inhibition of carbonic anhydrase II in the nanomolar range and lower intraocular pressure in the alpha-chymotrypsinized rabbit model of ocular hypertension after topical instillation.
几十年来，开发一种局部活性碳酸酐酶抑制剂一直是原发性开角型青光眼治疗中一个诱人的目标。几个研究小组最近的结果表明，在这一目标上已经取得了相当大的进展。在本报告中，我们介绍了（羟烷基）磺酰基取代的苯磺酰胺和噻吩磺酰胺的设计与合成。这些化合物在纳摩尔范围内表现出对碳酸酐酶II的抑制作用，并且在局部滴注后，在α-胰凝乳蛋白酶处理的兔高眼压模型中能降低眼压。
