Kv7 K +通道代表了用于治疗包括癫痫在内的各种神经系统疾病的有吸引力的药理靶标。在本文中,已合成了42个原型Kv7激活剂瑞替加滨构象受限的类似物,并通过电生理膜片钳实验作为Kv7激动剂进行了测试。与瑞替加滨(0.93±0.43μM)相比,化合物23a增强Kv7.2电流的EC50(0.08±0.04μM)较低,而24a(0.63±0.07μM)的效力未见变化。此外,与瑞替加滨相比,23a和24a在激活异聚Kv7.2 / Kv7.3和同聚Kv7.4通道方面也显示出更高的效力。分子模型研究为结合位点的最佳相互作用所需的化学特征提供了新的见解。稳定性研究表明,与瑞替加滨相比,化学稳定性提高了23a和24a。总体而言,本发明结果突出了N5-烷基酰胺基吲哚部分为设计化学稳定的,高效的和选择性的Kv7激动剂提供了合适的药效学支架。
The present invention relates to compounds that are inhibitors of c-jun N-terminal kinase 1, 2, or 3 (JNK1, JNK2, or JNK3), compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders regulated by the activation of JNK1, JNK2 and JNK3.
Compounds of formula I:
1
are useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
Substituted imidazole derivatives, compositions, and methods of use as PTPase inhibitors
申请人:Mjalli M.M. Adnan
公开号:US20070191385A1
公开(公告)日:2007-08-16
The present invention provides imidazole derivatives of Formula (I-IV), methods of their preparation, pharmaceutical compositions comprising the compounds of Formula (I-IV), and their use in treating human or animal disorders. The compounds of the invention inhibit protein tyrosine phosphatase 1B and thus can be useful for the management, treatment, control, or the adjunct treatment of diseases mediated by PTPase activity. Such diseases include Type I diabetes and Type II diabetes.
Compounds of formula (I)
1
may be useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
Pyrimidine derivatives as ghrelin receptor modulators
申请人:Kosogof Christi
公开号:US20050070712A1
公开(公告)日:2005-03-31
The present invention is related to compounds of formula (I),
or a therapeutically suitable salt or prodrug thereof, the preparation of the compounds, compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders regulated by ghrelin including anorexia, cancer cachexia, eating disorders, age-related decline in body composition, weight gain, obesity, and diabetes mellitus.