Doggrell Sheila A
Division of Health Practice, Auckland University of Technology-Akoranga Campus, Auckland, New Zealand.
Curr Opin Investig Drugs. 2005 Sep;6(9):874-8.
A major problem with using nitrates in the treatment of ischemic heart disease is that tolerance develops to their vasodilatory actions. YC-1 was used as the lead compound to synthesize further nitric oxide-independent soluble guanylate cyclase activators, including BAY-41-2272 and BAY-41-8543. A nitric oxide and heme-independent activator of soluble guanylate cyclase, BAY-58-2667, was subsequently discovered by high-throughput screening. Tolerance to the vasodilatory actions of BAY-41-8543 and BAY-58-2667 does not develop. Results from animal studies have suggested that these compounds may have potential in the treatment of ischemic heart disease, essential and pulmonary hypertension, congestive heart failure, glomerulonephritis and erectile dysfunction.
在缺血性心脏病治疗中使用硝酸盐的一个主要问题是会产生对其血管舒张作用的耐受性。YC - 1被用作先导化合物来进一步合成不依赖一氧化氮的可溶性鸟苷酸环化酶激活剂，包括BAY - 41 - 2272和BAY - 41 - 8543。随后通过高通量筛选发现了一种不依赖一氧化氮和血红素的可溶性鸟苷酸环化酶激活剂BAY - 58 - 2667。对BAY - 41 - 8543和BAY - 58 - 2667的血管舒张作用不会产生耐受性。动物研究结果表明，这些化合物在缺血性心脏病、原发性和肺动脉高压、充血性心力衰竭、肾小球肾炎及勃起功能障碍的治疗中可能具有潜力。
