使用群体感应抑制剂靶向群体感应信号为已知抗生素的应用开辟了新途径。在这种情况下,合成了二十五个不对称嗪并作为群体感应抑制剂进行了评估。采用有效的一锅法,将3-甲基-2-(甲硫基)苯并[ d ]噻唑-3-盐,水合肼和取代的醛直接连接,得到所设计的化合物。初步测试了合成的化合物抑制紫薇色杆菌中基于CviR受体的QS信号的潜力。生物测定筛选结果表明,两种化合物对CviR受体均表现出强效的QS抑制活性,在200μM时显示出对紫丁香素的抑制作用(> 50%)。此外,使用铜绿假单胞菌的PlasB-gfp(ASV)生物监测菌株检查推定的阳性命中物抑制LasR受体基QS的潜力。发现这些化合物以剂量依赖性方式抑制QS介导的GFP信号。两种活性化合物在浓度为50μM时也表现出生物膜清除率。进行了对接研究,以检验其与铜绿假单胞菌LasR蛋白结合的潜力。
Carbocyclic hydrazino inhibitors of copper-containing amine oxidases
申请人:——
公开号:US20040236108A1
公开(公告)日:2004-11-25
The present invention is directed to carbocyclic hydrazino compounds that function as inhibitors of copper-containing amine oxidases commonly known as semicarbazide-sensitive amine oxidases (SSAO), including the human SSAO known as Vascular Adhesion Protein-1 (VAP-1). These SSAO inhibitors have therapeutic utility as drugs to treat conditions and diseases including, but not limited to, a number of inflammatory conditions and diseases (in particular chronic inflammatory conditions such as chronic arthritis, inflammatory bowel diseases, and chronic skin dermatoses), diseases related to carbohydrate metabolism and to aberrations in adipocyte differentiation or function and smooth muscle cell function, and vascular diseases. The novel compounds have the general formula:
1
or a pharmaceutically acceptable solvate, hydrate, or salt thereof, wherein R
1
to R
11
are as defined herein.