Synthesis and physicochemical properties of thiadiazolo[3,2-a]pyrimidinesulfonamides and thiadiazolo[3,2-a]triazinesulfonamides as candidates for topically effective carbonic anhydrase inhibitors.
Synthesis and physicochemical properties of thiadiazolo[3,2-a]pyrimidinesulfonamides and thiadiazolo[3,2-a]triazinesulfonamides as candidates for topically effective carbonic anhydrase inhibitors.
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作为局部有效碳酸酐酶抑制剂候选物的噻二唑并[3,2-a]嘧啶磺酰胺和噻二唑并[3,2-a]三嗪磺酰胺的合成和理化性质。
DOI：
10.1021/jm00394a021
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发表时间：
1987
影响因子：
7.3
通讯作者：
Bar-Ilan,A
中科院分区：
文献类型：
--
作者：
Katritzky,AR;Caster,KC;Maren,TH;Conroy,CW;Bar-Ilan,A
以5-氨基-1，3，4-噻二唑-2-磺酰胺为原料，合成了一系列双环1，3，4-噻二唑并[3，2-o]嘧啶-7-磺酰胺和1，3，4-噻二唑并[3，2-a]三嗪-7-磺酰胺类化合物。测试化合物的磺酰胺pK&、游离酸水溶性、CHCl 3/缓冲液分配和经角膜渗透（fein）的物理化学性质，以及针对碳酸酐酶（f50）的活性。这些化合物中的许多化合物与乙酰唑胺（1）和醋甲唑胺（2）相比，具有较低的磺胺pKE和较高的水溶解度，其中一种化合物（12）可使正常兔眼的IOP小幅降低。与青光眼相关的异常高眼内压（IOP）的重要治疗方法是通过抑制睫状突碳酸酐酶（CA）来抑制房水形成。1，3，4-噻二唑-2-磺酰胺类是最有效的CA抑制剂之一，具有酶抑制剂结合常数（/50）。
A series of bicyclic l, 3, 4-thiadiazolo [3, 2-o] pyrimidine-and l, 3, 4-thiadiazolo [3, 2-a] triazine-7-sulfonamides were synthesized from 5-amino-l, 3, 4-thiadiazole-2-sulfonamide and evaluated for topical efficacy as ocular hypotensive agents. The compounds were tested for the physicochemical properties of sulfonamide pK&, freeacid water solubility, CHCl3/buffer partition, and transcorneal penetration (fein), as well as for activity against carbonic anhydrase (/50). A number of these compounds exhibited lower sulfonamide pKE and higher water solubility than those of acetazolamide (1) and methazolamide (2), and one, 12, brought about a small reduction in IOP in the normal rabbit eye.An important treatment of the abnormally high intraocular pressure (IOP) associated with glaucoma is by the suppression of aqueous humor formation via inhibition of ciliary process carbonic anhydrase (CA). 1, 3, 4-Thia-diazole-2-sulfonamides are among the most potent CA inhibitors with enzyme-inhibitor binding constants (/50)