Synthesis of novel quinolone and quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)amides: a late-stage diversification approach to potent 5HT1B antagonists.
Multiparallel amenable syntheses of 6-methoxy-8-amino-4-oxo-1,4-dihydroquinoline-2-carboxylic acid-(4-morpholin-4-yl-phenyl)amides (I) and 4-amino-6-methoxy-8-(4-methyl-piperazin-1-yl)-quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)amides (II) which facilitate late-stage diversification at the 8-position of (I) and at the 4- and 8-positions of (II) are described. The resulting novel series were determined to contain potent 5HT(1B) antagonists. Preliminary SAR data are presented.
Horchler
Carey L
CL
CNS Chemistry and Neuroscience, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, Wilmington, DE 19850, USA. carey.horchler@astrazeneca.com
McCauley
John P
JP
Hall
James E
JE
Snyder
Dean H
DH
Craig Moore
W
W
Hudzik
Thomas J
TJ
Chapdelaine
Marc J
MJ
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000577:Amides; D007202:Indicators and Reagents; D009025:Morpholines; D015363:Quinolones; D044302:Receptor, Serotonin, 5-HT1B; D012702:Serotonin Antagonists; C037574:morpholine