Amine-constrained pyridazinone histamine H₃ receptor antagonists

Babu G Sundar; Thomas Bailey; Edward Bacon; Lisa Aimone; Zeqi Huang; Jacquelyn Lyons; Rita Raddatz; Robert Hudkins

doi:10.1016/j.bmcl.2011.06.094

Amine-constrained pyridazinone histamine H₃ receptor antagonists

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5543-6. doi: 10.1016/j.bmcl.2011.06.094. Epub 2011 Jul 22.

Authors

Babu G Sundar¹, Thomas Bailey, Edward Bacon, Lisa Aimone, Zeqi Huang, Jacquelyn Lyons, Rita Raddatz, Robert Hudkins

Affiliation

¹ Discovery Research, Cephalon Inc., 145 Brandywine Parkway, West Chester, PA 19380, United States. bsundar@cephalon.com

PMID: 21824776
DOI: 10.1016/j.bmcl.2011.06.094

Abstract

Pyridazinone 1 was recently reported as a potent H(3)R antagonist with good drug-like properties and in vivo activity. A series of constrained amine analogs of 1 was synthesized to identify compounds with improved pharmacokinetic profiles. From these efforts, a new class of (S)-2-pyrrolidin-1-ylmethyl-1-pyrrolidinyl amides was identified.

MeSH terms

Amines / chemistry*
Animals
Dose-Response Relationship, Drug
Histamine H3 Antagonists / chemical synthesis
Histamine H3 Antagonists / chemistry
Histamine H3 Antagonists / pharmacology*
Humans
Molecular Structure
Pyridazines / chemical synthesis
Pyridazines / chemistry
Pyridazines / pharmacology*
Rats
Receptors, Histamine H3 / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

Amines
Histamine H3 Antagonists
Pyridazines
Receptors, Histamine H3