[一氧化氮供体型色甘酸钠衍生物的设计、合成及抗哮喘活性]

[Design, synthesis and antiasthmatic activities of NO-donating seratrodast derivatives].

作者信息

Zhang Zhi-guo, Zhang Yi-hua, Ji Hui, Qiu Su-gan, Feng Xiao-chun

机构信息

Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Yao Xue Xue Bao. 2004 Sep;39(9):705-10.

PMID:15606018

Abstract

AIM

To search for novel antiasthmatic agents.

METHODS

Coupling seratrodast (SD), an antiasthmatic drug, with several different types of NO donors including oxatriazoles, N-hydroxyguanidines and furoxans; evaluating the antiasthmatic effects of coupled compounds by determining their inhibitory activity of guinea pig asthma induced by acetylcholine and histamine; and assessing NO releasing ability.

RESULTS

Nine novel target compounds (I1-9) were synthesized, and their structures were established by IR, NMR, MS and elemental analysis. Preliminary pharmacological test showed that most of the compounds showed high antiasthmatic activities (the latent period of induced asthma was prolonged from 10 s (SD) to 26-62 s), among which 3 compounds (I4, I6, I7) were more potent than SD (P < 0.05, P < 0.01) and released more NO than others. The maximum concentrations (Cmax) of NO-release in vitro were 0.1878, 0.1393 and 0.2473 mg x L(-1), respectively.

CONCLUSION

NO donating-SD derivatives are worthy to be futher investigated.

摘要

目的

寻找新型抗哮喘药物。

方法

将抗哮喘药物塞曲司特（SD）与几种不同类型的一氧化氮供体（包括恶二唑、N-羟基胍和呋咱）偶联；通过测定偶联化合物对乙酰胆碱和组胺诱导的豚鼠哮喘的抑制活性来评估其抗哮喘作用；并评估一氧化氮释放能力。

结果

合成了9种新型目标化合物（I1-9），并通过红外光谱、核磁共振、质谱和元素分析确定了它们的结构。初步药理试验表明，大多数化合物显示出高抗哮喘活性（诱导哮喘的潜伏期从10秒（SD）延长至26-62秒），其中3种化合物（I4、I6、I7）比SD更有效（P<0.05，P<0.01），且释放的一氧化氮比其他化合物更多。体外一氧化氮释放的最大浓度（Cmax）分别为0.1878、0.1393和0.2473毫克·升-1。