Conformationally restricted indolopiperidine derivatives as potent CCR2B receptor antagonists.
The preparation and biological evaluation of a series of indolopiperidine CCR2B receptor antagonists possessing a conformationally restricted C-5 linker chain in combination with a restricted piperidine ring are described. Compared to the parent compound 1, analogue 8 shows a dramatic improvement in selectivity against a range of 5-HT and dopaminergic receptors.
Witherington
J
J
Department of Discovery Chemistry, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AD, Essex, UK. jason_withering@sbphrd.com
Bordas
V
V
Cooper
D G
DG
Forbes
I T
IT
Gribble
A D
AD
Ife
R J
RJ
Berkhout
T
T
Gohil
J
J
Groot
P H
PH
D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D018492:Dopamine Antagonists; D007211:Indoles; D010880:Piperidines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D012702:Serotonin Antagonists; C435666:indolopiperidine