Saudi Manal N S, Rostom Sherif A F, Fahmy Hesham T Y, El Ashmawy Ibrahim M
Department of Pharmaceutical Chemistry, Faculty of Veterinary Medicine, Alexandria University, Egypt.
Arch Pharm (Weinheim). 2003 Jun;336(3):165-74. doi: 10.1002/ardp.200390016.
The 2-phenylquinoline-4-carboxamide 1 (Chart[TH]1) has been found to possess moderate affinity for human neurokinin-3 (hNK-3) receptor. In the present work, and in a trial to investigate the effect of the lipophilic moiety at C-2 of the quinoline ring on the antagonistic activity, an enlargement of the aromatic area at this position was suggested. In this respect, two series of 2-(4-biphenylyl)quinoline-4-carboxylates and carboxamides have been synthesized with certain modifications at the quinoline-2 and 4-position in order to study their effect on the anticipated hNK-3 receptor antagonistic activity. Fifteen compounds were screened for such activity using guinea-pig isolated ileum longitudinal muscle preparation and senktide as selective hNK-3 receptor agonist. Some compounds showed considerable antagonistic effect. Compound 7b, 6-bromo-2-(4-biphenylyl)quinoline-4-carboxylic acid, was the most prominent hNK-3 receptor antagonist in this study. Unexpectedly, some compounds were agonists.
已发现2-苯基喹啉-4-甲酰胺1（图1）对人神经激肽-3（hNK-3）受体具有中等亲和力。在本研究中，为了研究喹啉环C-2位亲脂性部分对拮抗活性的影响，建议扩大该位置的芳香区域。在这方面，合成了两个系列的2-（4-联苯基）喹啉-4-羧酸酯和羧酰胺，并在喹啉-2和4位进行了某些修饰，以研究它们对预期的hNK-3受体拮抗活性的影响。使用豚鼠离体回肠纵肌制备物和senktide作为选择性hNK-3受体激动剂，对15种化合物进行了这种活性筛选。一些化合物表现出相当大的拮抗作用。化合物7b，6-溴-2-（4-联苯基）喹啉-4-羧酸，是本研究中最突出的hNK-3受体拮抗剂。出乎意料的是，一些化合物是激动剂。
