Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo

N Y Shih; R Aslanian; A T Lupo Jr; S Orlando; J J Piwinski; M J Green; A K Ganguly; R West; S Tozzi; W Kreutner; J A Hey

doi:10.1016/s0960-894x(98)00020-1

Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo

Bioorg Med Chem Lett. 1998 Feb 3;8(3):243-8. doi: 10.1016/s0960-894x(98)00020-1.

Authors

N Y Shih¹, R Aslanian, A T Lupo Jr, S Orlando, J J Piwinski, M J Green, A K Ganguly, R West, S Tozzi, W Kreutner, J A Hey

Affiliation

¹ Department of Chemical Research, Schering-Plough Research Institute, Kenilworth, New Jersy 07033-0539, USA.

PMID: 9871662
DOI: 10.1016/s0960-894x(98)00020-1

Abstract

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.

MeSH terms

Animals
Guinea Pigs
Ileum / drug effects
Ileum / physiology
Imidazoles / chemistry
Imidazoles / pharmacology*
In Vitro Techniques
Muscle Contraction / drug effects
Pyrrolidines / chemistry
Pyrrolidines / pharmacology*
Receptors, Histamine H3 / drug effects*
Stereoisomerism
Structure-Activity Relationship

Substances

4-methyl-3-imidazoylpyrrolidine
Imidazoles
Pyrrolidines
Receptors, Histamine H3