508210-05-7Relevant articles and documents
Axially chiral 1,7-naphthyridine-6-carboxamide derivatives as orally active tachykinin NK1 receptor antagonists: Synthesis, antagonistic activity, and effects on bladder functions
Natsugari, Hideaki,Ikeura, Yoshinori,Kamo, Izumi,Ishimaru, Takenori,Ishichi, Yuji,Fujishima, Akira,Tanaka, Toshimasa,Kasahara, Fumiko,Kawada, Mitsuru,Doi, Takayuki
, p. 3982 - 3993 (2007/10/03)
Cyclic analogues of N-[3,5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N,7- dimethyl-5-(4-methylphenyl)-8-oxo-1,7-naphthyridine-6-carboxamide (1) having a 6-9-membered ring (6-9) were synthesized and evaluated for NK1 antagonistic activities. The 8
Novel, Potent, and Orally Active Substance P Antagonists: Synthesis and Antagonist Activity of N-Benzylcarboxamide Derivatives of Pyridopyridine
Natsugari, Hideaki,Ikeura, Yoshinori,Kiyota, Yutaka,Ishichi, Yuji,Ishimaru, Takenori,et al.
, p. 3106 - 3120 (2007/10/02)
A series of 4-phenylisoquinolone derivatives were synthesized and evaluated for NK1 (substance P) antagonist activity.Highly potent antagonists, 4-phenyl-3-isoquinolone-N-benzylcarboxamides (11), were discovered from the structure-activity relationship studies on the isoquinolone-urea lead 1a.Optimization of the activity in this series resulted in the development of 5-phenyl-6-pyridopyridine-N-benzylcarboxamides (30) which are highly potent orally active NK1 antagonists.Among the compounds synthesized, N--7,8-dihydro-N,7-dimethyl-8-oxo-5-(substituted phenyl)-6-pyridopyridinecarboxamides (30a,f,g) showed excellent antagonist activities with IC50 values (in vitro inhibition of 125I>BH-SP binding in human IM-9-cells) of 0.21-0.34 nM and ED50 values (in vivo inhibition of capsaicin-induced plasma extravasation in guinea-pig trachea, iv) of 0.017-0.030 mg/kg.These compounds exhibited significantly potent activity upon oral adiministration with ED50 values of 0.068-0.17 mg/kg.Conformational studies on 30g indicated that the two stable conformers of 30g are quite similar to those of CP-99,994.
