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Synthesis of 2‐(4‐Biphenylyl)quinoline‐4‐carboxylate and Carboxamide Analogs. New Human Neurokinin‐3 (hNK‐3) Receptor Antagonists
Author(s) -
Saudi Manal N. S.,
Rostom Sherif A. F.,
Fahmy Hesham T. Y.,
El Ashmawy Ibrahim M.
Publication year - 2003
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200390016
Subject(s) - quinoline , carboxamide , chemistry , agonist , stereochemistry , receptor , antagonist , carboxylic acid , moiety , chemical synthesis , pharmacology , in vitro , biochemistry , biology , organic chemistry
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.