title: Synthesis of 2-(4-biphenylyl)quinoline-4-carboxylate and carboxamide analogs. New human neurokinin-3 (hNK-3) receptor antagonists.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Veterinary Medicine, Alexandria University, Egypt.
authors.forename: Manal N S
authors.initials: MN
authors.lastname: Saudi
authors.forename: Sherif A F
authors.initials: SA
authors.lastname: Rostom
authors.forename: Hesham T Y
authors.initials: HT
authors.lastname: Fahmy
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El Ashmawy
mesh_terms: D000818:Animals; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009119:Muscle Contraction; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D011804:Quinolines; D018042:Receptors, Neurokinin-3