Novel naphthyridines are histamine H3 antagonists and serotonin reuptake transporter inhibitors.
A series of novel tetrahydronaphthyridine-based histamine H(3) ligands that have serotonin reuptake transporter inhibitor activity is described. The 1,2,3,4-tetrahydro-2,6-naphthyridine scaffold is assembled via the addition of a nitrostyrene to a metalated pyridine followed by reduction and cyclization to form the naphthyridine. In vitro biological data for these novel compounds are discussed.
Letavic
Michael A
MA
Johnson & Johnson Pharmaceutical Research & Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121-1126, USA. mletavic@prdus.jnj.com
Keith
John M
JM
Ly
Kiev S
KS
Barbier
Ann J
AJ
Boggs
Jamin D
JD
Wilson
Sandy J
SJ
Lord
Brian
B
Lovenberg
Timothy W
TW
Carruthers
Nicholas I
NI
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006632:Histamine / Q000737:chemistry*; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000737:chemistry*; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
D006632:Histamine; D006633:Histamine Antagonists; D009287:Naphthyridines; D018100:Receptors, Histamine H3; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors