Abd El-Salam O I, Abou El Ella D A, Ismail N S M, Abdullah M
Applied Organic Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
Pharmazie. 2009 Mar;64(3):147-55.
A series of 2-amino-5,6,7,8-tetrahydroquinoline-3-carbonitriles 4a-c has been synthesized and reacted with various reagents. Docking studies into the catalytic site of p38 mitogen activated protein kinase (MAPK) were used to identify potential anti-inflammatory lead compounds. The anticipated lead derivative 2-(pyridin-3-yl)-5-(4-methoxyphenyl)-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-4-amine 9b was endowed with good binding energy. Also, the obtained products were evaluated for their in vivo antiinflammatory activity as prostaglandin inhibitiors (% inhibition of edema and % inhibition of plasma PGE2 at the two dose levels were determined). The tested compounds exhibited significant anti-inflammatory activity and minor ulcerogenic effects, when compared to the reference standard indomethacin, with product 9b being of particular interest.
一系列2-氨基-5,6,7,8-四氢喹啉-3-腈4a - c已被合成并与各种试剂反应。通过对p38丝裂原活化蛋白激酶（MAPK）催化位点的对接研究来鉴定潜在的抗炎先导化合物。预期的先导衍生物2-(吡啶-3-基)-5-(4-甲氧基苯基)-6,7,8,9-四氢嘧啶并[4,5-b]喹啉-4-胺9b具有良好的结合能。此外，还对所得产物作为前列腺素抑制剂的体内抗炎活性进行了评估（测定了两个剂量水平下的水肿抑制率和血浆PGE2抑制率）。与参考标准吲哚美辛相比，测试的化合物表现出显著的抗炎活性和轻微的致溃疡作用，产物9b尤其令人关注。
