公开(公告)号：US07041785B1

公开(公告)日：2006-05-09

申请号：US09242751

申请日：1997-08-14

申请人： Domenico Recoli ,  Gerard E. Plante ,  Fernand Gobeil ,  Witold A. Neugebauer ,  Adriana Zucollo ,  Orlando L. Catanzaro

发明人： Domenico Recoli ,  Gerard E. Plante ,  Fernand Gobeil ,  Witold A. Neugebauer ,  Adriana Zucollo ,  Orlando L. Catanzaro

IPC分类号： A61K38/00 ,  A61K49/00

CPC分类号： A61K38/04

摘要： The present invention relates to novel antagonists to a B1-bradykinin (B1-BK) receptor which have a good affinity and selectivity therefor, some of which being at least partially resistant to enzymatic degradation. The synthesis of the B1 receptors is induced during inflammation. Symptoms associated with inflammation (elevated hydrostatic pressure and plasma leakage or extravasation) have been observed in diabetic animal models (streptozotocin-induced diabetes (STZ)) as well as in spontaneously hypertensive rats (SHR). The present inventors confirm the presence of B1-BK receptors in these two models. B1-BK antagonists abolished the vasocontraction induced by B1-BK in SHR and STZ, and reduced the glycemia of diabetic animals to normal levels. The present B1-antagonists are useful for treating any condition wherein B1-receptor is expressed, particularly during inflammation, and more particularly wherein B1-receptor expression results in diabetic vasculopathy, other diabetic symptoms associated with an insulitis and a post-capillary resistance building as a consequence of the presence of a B1-receptor.

摘要翻译： 本发明涉及对其具有良好亲和性和选择性的B 1 - 半激动素（B 1 -BK）受体的新型拮抗剂，其中一些至少部分地 耐酶降解。 在炎症期间诱导B 1受体的合成。 在糖尿病动物模型（链脲霉素诱发的糖尿病（STZ））以及自发性高血压大鼠（SHR）中观察到与炎症相关的症状（升高的静水压力和血浆渗漏或外渗）。 本发明人证实在这两种模型中存在B 1 -KK受体。 B 1 BK拮抗剂消除了SHR和STZ中B 1 -BK引起的血管收缩，并将糖尿病动物的血糖降低至正常水平。 本发明的B 1 - 拮抗剂可用于治疗其中B 1 - 受体表达的任何情况，特别是在炎症期间，更具体地，其中B 1