Design, Synthesis, and Evaluation of NO-Donor Containing Carbonic Anhydrase Inhibitors To Lower Intraocular Pressure
Design, Synthesis, and Evaluation of NO-Donor Containing Carbonic Anhydrase Inhibitors To Lower Intraocular Pressure
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DOI：
10.1021/acs.jmedchem.5b00043
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发表时间：
2015-03-26
影响因子：
7.3
通讯作者：
Edwards, Martin P.
中科院分区：
文献类型：
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作者：
Huang, Qinhua;Rui, Eugene Y.;Edwards, Martin P.
抗青光眼药物多唑胺(1)和布林唑胺(2)通过抑制碳酸酐酶(CA)减少房水产生来降低眼压(TOP)。在多唑胺(1)和布林唑胺(2)的烷基侧链上引入一氧化氮(NO)供体，导致了NO-多唑胺3a和NO-布林唑胺4a的发现，这可能通过两种机制降低顶端：CA抑制减少房水分泌(减少流入)和NO释放增加房水排出(增加流出)。与布林唑胺(2)相比，化合物3a和4a显示出更好的降低兔和猴子眼压的效果。
The antiglaucoma drugs dorzolamide (1) and brinzolamide (2) lower intraocular pressure (TOP) by inhibiting the carbonic anhydrase (CA) enzyme to reduce aqueous humor production. The introduction of a nitric oxide (NO) donor into the alkyl side chain of dorzolamide (1) and brinzolamide (2) has led to the discovery of NO-dorzolamide 3a and NO-brinzolamide 4a, which could lower TOP through two mechanisms: CA inhibition to decrease aqueous humor secretion (reduce inflow) and NO release to increase aqueous humor drainage (increase outflow). Compounds 3a and 4a have shown improved efficacy of lowering IOP in both rabbits and monkeys compared to brinzolamide (2).