SSR69071 是一种有效的，具有口服活性的选择性中性粒细胞弹性蛋白酶 (neutrophil elastase) 抑制剂。SSR69071 对人弹性蛋白酶 (Ki=0.0168 nM) 的亲和力高于对大鼠 (Ki=3 nM)、小鼠 (Ki=1.8 nM) 和兔 (Ki=58 nM) 弹性蛋白酶。SSR69071 减少缺血再灌注损伤后的心肌梗死面积。SSR69071 还具有治疗慢性阻塞性肺病、哮喘、肺气肿、囊性纤维化和多种炎症性疾病的潜力。

SSR69071 is a potent, orally active, and selective inhibitor of neutrophil elastase. SSR69071 displays a higher affinity for human elastase (Ki =0.0168 nM) than for rat (Ki =3 nM), mouse (Ki =1.8 nM), and rabbit (Ki = 58 nM) elastases [2]. SSR69071 reduces myocardial infarct size following ischemia-reperfusion injury [1]. SSR69071 also has the potential for the treatment of chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis, and several inflammatory diseases.

SSR69071 is a potent inhibitor of human leukocyte elastase (HLE), with the inhibition constant (K i ) and the inactivation process constant (k on ) of 0.0168±0.0014 nM and 0.183±0.013 10 6 /mol sr, respectively [2]. SSR69071 is a potent, competitive and slow tight binding inhibitor of HLE in vitro with a Ki value of 16.8 pM [3].

SSR69071 (3 mg/kg i.v.) reduces cardiac infarct size when administered before ischemia or just prior to reperfusion (–37%, P<0.05)[1]. Treatment with SSR69071 (3 mg/kg i.v.) just prior to reperfusion significantly reduces cardiac elastase activity [1]. Bronchoalveolar lavage fluid from mice orally treated with SSR69071 inhibits HLE (ex vivo), and in this model, SSR69071 has a dose-dependent efficacy with an ED 50 =10.5 mg/kg p.o. SSR69071 decreases significantly the acute lung hemorrhage induced by HLE (ED 50 =2.8 mg/kg p.o.) in mice [2]. SSR69071 prevents carrageenan- (ED 30 =2.2 mg/kg) and HLE-induced (ED 30 =2.7 mg/kg) paw edema in rats after p.o. administration [2]. Animal Model: Male New Zealand white rabbits weighing 2-3 kg [1] Dosage: 3 mg/kg (dissolved in methane sulphonic acid before being diluted in 0.9% saline) Administration: Administered i.v. Result: Treatment just prior to reperfusion significantly reduced cardiac elastase activity.

344930-95-6

C27H32N4O7S

556.63

SSR 69071

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years