A non-peptide NK1 receptor agonist showing subpicomolar affinity.
3-Quinolinecarboxamides have been synthesized and evaluated for their binding to the human NK(1) receptor. Several secondary amide derivatives show NK(1) receptor affinity in the picomolar range. The most active compound, hydroxymethylcarboxamide 3h showing an IC(50) value in the subpicomolar range, behaved as an agonist of NK(1) receptor in endothelial cell proliferation, inositol phosphate turnover, and NO-mediated cyclic GMP accumulation, thus proving it to be the first non-peptide NK(1) receptor agonist showing very high potency.
Cappelli
Andrea
A
Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy. cappelli@unisi.it
Giuliani
Germano
G
Pericot Mohr Gl
Gal la
Gl
Gallelli
Andrea
A
Anzini
Maurizio
M
Vomero
Salvatore
S
Cupello
Aroldo
A
Scarrone
Simona
S
Matarrese
Mario
M
Moresco
Rosa Maria
RM
Fazio
Ferruccio
F
Finetti
Federica
F
Morbidelli
Lucia
L
Ziche
Marina
M
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D006152:Cyclic GMP / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000819:agonists*; D013329:Structure-Activity Relationship
D000577:Amides; D007295:Inositol Phosphates; D011804:Quinolines; D018040:Receptors, Neurokinin-1; D009569:Nitric Oxide; D006152:Cyclic GMP