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首页> 外文期刊>Drug design and discovery >Carbonic anhydrase inhibitors: topically acting antiglaucoma sulfonamides incorporating phthaloyl and phthalimido moieties.
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Carbonic anhydrase inhibitors: topically acting antiglaucoma sulfonamides incorporating phthaloyl and phthalimido moieties.

机译：碳酸酐酶抑制剂：结合有邻苯二甲酰基和邻苯二甲酰亚胺基的局部作用的抗青光眼磺酰胺。

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摘要

Sulfonamides incorporating 2-carboxy-benzenecarboxamido (phthaloyl) moieties in their molecules were prepared by reaction of phthalic anhydride with aromatic/heterocyclic sulfonamides in mild conditions. Another closely related series of derivatives was prepared by reaction of the same reagents in more energetic conditions, when the corresponding phthalimides were obtained. Some of these compounds showed very good in vitro carbonic anhydrase (CA) isozymes I, II and IV inhibitory properties, with affinities for the enzymes in the low nanomolar range for the best inhibitors. Some of the potent CA inhibitors reported here have been formulated as sodium salts, in aqueous solutions for topical administration as antiglaucoma agents, in normotensive/glaucomatous rabbits. Only the derivatives possessing good water solubility, showed effective and longer lasting topical intraocular pressure (IOP) lowering than dorzolamide and brinzolamide, two clinically used topical antiglaucoma drugs. All the in vivo effective new compounds belonged to the first series of derivatives, whereas the corresponding phthalimides, although stronger in vitro CA inhibitors were devoid of topical IOP lowering properties, probably due to their unproper physico-chemical properties.
机译：通过在温和的条件下使邻苯二甲酸酐与芳族/杂环磺酰胺反应，可以在分子中掺入2-羧基-苯甲酰胺基（邻苯二甲酰基）磺酰胺。当获得相应的邻苯二甲酰亚胺时，通过在更高能的条件下使相同的试剂反应来制备另一系列的密切相关的衍生物。这些化合物中的一些显示出非常好的体外碳酸酐酶（CA）同工酶I，II和IV抑制特性，并且对于最佳抑制剂而言，这些酶的亲和力在低纳摩尔范围内。在正常血压/青光眼兔中，此处报道的一些有效的CA抑制剂已制成钠盐，在水溶液中可作为抗青光眼剂局部给药。仅具有良好水溶性的衍生物显示出比两种临床使用的局部抗青光眼药物多佐胺和布林酰胺更有效，更持久的局部眼压降低。所有在体内有效的新化合物均属于第一系列衍生物，而相应的邻苯二甲酰亚胺，尽管更强的体外CA抑制剂没有局部降低IOP的特性，这可能是由于其理化特性不当造成的。

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