Reaction of 4-(2-amino-pyrimidin-4-yl-amino)-benzenesulfonamide with alkyl/aryl-sulfonyl halides, acyl halides or arysulfonyl isocyanates afforded a series of derivatives which were tested for inhibition of three carbonic anhydrase (CA) isozymes. These compounds were designed in such a way as to (i) strongly inhibit several CA isozymes involved in aqueous humor secretion within the eye (such as CA II and CA IV), and (ii) to possess a pharmacological profile that allows easy penetration through the cornea, when administered as eye drops in solution or suspension, constituting thus a valuable therapeutic approach for glaucoma. Several of the obtained inhibitors showed low nanomolar affinities for the two isozymes involved in aqueous humor secretion, CA II and CA IV. Furthermore, in normotensive and hypertensive rabbits, some of them showed an effective and prolonged intraocular pressure (IOP) lowering when administered topically, as 2% suspensions/solutions.

中文翻译：

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具有强大的局部抗青光眼特性的碳酸酐酶抑制剂，并带有4-（2-氨基嘧啶-4-基-氨基）-苯磺酰胺支架。

4-（2-氨基-嘧啶-4-基-氨基）苯磺酰胺与烷基/芳基-磺酰卤，酰基卤或芳磺酰基异氰酸酯的反应提供了一系列衍生物，经测试可抑制三种碳酸酐酶（CA）同工酶。 。这些化合物的设计方式是（i）强烈抑制与眼内房水分泌有关的几种CA同工酶（例如CA II和CA IV），以及（ii）具有易于渗透的药理特性当以溶液或悬浮液中的滴眼剂的形式给药时，角膜构成了一种有价值的青光眼治疗方法。几种获得的抑制剂对房水分泌中涉及的两种同功酶CA II和CA IV表现出较低的纳摩尔亲和力。此外，在血压正常和高血压的兔子中，