Azabicyclic indole esters as potent 5-HT4 receptor antagonists.
The synthesis of a series of azabicyclic indole esters is described and their potency reported as 5-HT4 receptor antagonists. Optimization of the most potent compound (19) by preparing the corresponding oxazino[3,2-a]indole ester afforded 34, which had a pIC50 of 9.5 in the guinea pig distal colon longitudinal muscle myenteric plexus preparation.
Wyman
P A
PA
SmithKline Beecham Pharmaceuticals, Harlow, Essex, U.K.
Gaster
L M
LM
King
F D
FD
Sutton
J M
JM
Ellis
E S
ES
Wardle
K A
KA
Young
T J
TJ
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4