SB-656104-A: a novel 5-HT(7) receptor antagonist with improved in vivo properties.
A focused SAR study around the previously reported selective 5-HT(7) receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A.
Forbes
Ian T
IT
GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK. ian_t_forbes@gsk.com
Douglas
Sara
S
Gribble
Andrew D
AD
Ife
Robert J
RJ
Lightfoot
Andrew P
AP
Garner
Ashley E
AE
Riley
Graham J
GJ
Jeffrey
Phillip
P
Stevens
Alexander J
AJ
Stean
Tania O
TO
Thomas
David R
DR
D000818:Animals; D001812:Blood-Brain Barrier; D006571:Heterocyclic Compounds; D007211:Indoles; D010636:Phenols / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000737:chemistry*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000493:pharmacokinetics
D006571:Heterocyclic Compounds; D007211:Indoles; D010636:Phenols; D011759:Pyrrolidines; D011985:Receptors, Serotonin; C404922:SB 269970; C475591:SB-656104-A; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor