Synthesis of novel quinolone and quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)amides: a late-stage diversification approach to potent 5HT1B antagonists

Carey L Horchler; John P McCauley Jr; James E Hall; Dean H Snyder; W Craig Moore; Thomas J Hudzik; Marc J Chapdelaine

doi:10.1016/j.bmc.2006.10.037

Synthesis of novel quinolone and quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)amides: a late-stage diversification approach to potent 5HT1B antagonists

Bioorg Med Chem. 2007 Jan 15;15(2):939-50. doi: 10.1016/j.bmc.2006.10.037. Epub 2006 Oct 20.

Authors

Carey L Horchler¹, John P McCauley Jr, James E Hall, Dean H Snyder, W Craig Moore, Thomas J Hudzik, Marc J Chapdelaine

Affiliation

¹ CNS Chemistry and Neuroscience, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, Wilmington, DE 19850, USA. carey.horchler@astrazeneca.com

PMID: 17126021
DOI: 10.1016/j.bmc.2006.10.037

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemical synthesis*
Amides / pharmacology*
Chromatography, High Pressure Liquid
Indicators and Reagents
Morpholines / chemical synthesis*
Morpholines / pharmacology*
Quinolones / chemical synthesis*
Quinolones / pharmacology*
Receptor, Serotonin, 5-HT1B / drug effects*
Serotonin Antagonists / chemical synthesis*
Serotonin Antagonists / pharmacology*
Structure-Activity Relationship

Substances

Amides
Indicators and Reagents
Morpholines
Quinolones
Receptor, Serotonin, 5-HT1B
Serotonin Antagonists
morpholine