Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
Extensive structural modification of immepyr (+)-2 led to the discovery of trans-4-methyl-3-imidazoyl pyrrolidine (+/-)-3a as a potent and highly selective H3 agonist. The pyrroline (+/-)-3a was resolved, and its (+) enantiomer, Sch 50971 [(+)-3a], showed a greater separation of H3 and H1 activities in vivo (H3/H1 ratio >> 330) than (R)-alpha-methylhistamine (+)-1 (H3/H1 ratio = 17), the standard H3 agonist.
Shih
N Y
NY
Department of Chemical Research, Schering-Plough Research Institute, Kenilworth, New Jersy 07033-0539, USA.
Aslanian
R
R
Lupo
A T
AT
Orlando
S
S
Piwinski
J J
JJ
Green
M J
MJ
Ganguly
A K
AK
West
R
R
Tozzi
S
S
Kreutner
W
W
Hey
J A
JA
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C116732:4-methyl-3-imidazoylpyrrolidine; D007093:Imidazoles; D011759:Pyrrolidines; D018100:Receptors, Histamine H3