Department of Therapeutic Chemistry, National Research Centre, Dokki 12622, Giza, Egypt.
Arch Pharm Res. 2012 Jun;35(6):955-64. doi: 10.1007/s12272-012-0602-0. Epub 2012 Jun 30.
A series of fused pyranopyrazole and pyranoimidazole, namely 5-(3,6-diamino-4-aryl-5-carbonitrile-pyrano(2,3-c)pyrazol-2-yl)sulphonyl-8-hydroxyquinolines (5a-e), 5-(6-amino-4-aryl-5-carbonitrile-pyrano(2,3-c)pyrazol-3-yl)sulphonamido-8-hydroxyquinolines (6a-e), 5-(2-thioxo-4-aryl-5-carbonitrile-6-amino-pyrano(2,3-d)imidazol-2-yl)sulphonyl-8-hydroxyquinolines (10a-e), and 5-(2-oxo-4-aryl-5-carbonitrile-6-amino-pyrano(2,3-d)imidazol-2-yl) sulphonyl-8-hydroxyquinolines (11a-e), have been prepared via condensation of some arylidine malononitriles with 5-sulphonamido-8-hydroxyquinoline derivatives 3, 4, 8 and 9. All the synthesized compounds were screened for their antimicrobial activities, and most of the tested compounds showed potent inhibition growth activity towards Escherichia coli, Pseudomonas aeruginosa (Gramnegative bacteria). Furthermore, six selected compounds were tested for their antiviral activity against avian paramyxovirus type1 (APMV-1) and laryngotracheitis virus (LTV), and the results showed that a concentration range of 3-4 μg per mL of compounds 2, 3, and 4 showed marked viral inhibitory activity for APMV-1 of 5000 tissue culture infected dose fifty (TCID(50)) and LTV of 500 TCID(50) in Vero cell cultures based on their cytopathic effect. Chicken embryo experiments show that compounds 2, 3, and 4 possess high antiviral activity in vitro with an inhibitory concentration fifty (IC(50)) range of 3-4 μg per egg against avian APMV-1 and LTV and their toxic concentration fifty (CC(50)) of 200-300 μg per egg.
一系列融合的吡喃并吡唑和吡喃并咪唑，即 5-(3,6-二氨基-4-芳基-5-氰基-吡喃(2,3-c)吡唑-2-基)磺酰基-8-羟基喹啉(5a-e)、5-(6-氨基-4-芳基-5-氰基-吡喃(2,3-c)吡唑-3-基)磺酰胺基-8-羟基喹啉(6a-e)、5-(2-硫代-4-芳基-5-氰基-6-氨基-吡喃(2,3-d)咪唑-2-基)磺酰基-8-羟基喹啉(10a-e)和 5-(2-氧代-4-芳基-5-氰基-6-氨基-吡喃(2,3-d)咪唑-2-基)磺酰基-8-羟基喹啉(11a-e)，是通过一些芳基亚甲基丙二腈与 5-磺酰胺基-8-羟基喹啉衍生物 3、4、8 和 9 的缩合制备得到的。所有合成的化合物都进行了抗菌活性筛选，大多数测试化合物对大肠杆菌、铜绿假单胞菌(革兰氏阴性菌)的生长表现出强烈的抑制作用。此外，六种选定的化合物进行了抗禽副粘病毒 1 型(APMV-1)和喉气管炎病毒(LTV)的抗病毒活性测试，结果表明，化合物 2、3 和 4 在 Vero 细胞培养物中，浓度范围为 3-4μg/mL 时，对 APMV-1 的 5000 组织培养感染剂量五十(TCID(50))和 LTV 的 500TCID(50)表现出显著的病毒抑制活性。鸡胚实验表明，化合物 2、3 和 4 在体外具有很高的抗病毒活性，对禽 APMV-1 和 LTV 的抑制浓度五十(IC(50))范围为 3-4μg/个鸡蛋，其毒性浓度五十(CC(50))为 200-300μg/个鸡蛋。
