Synthesis and structure-activity relationships of 4,5-fused pyridazinones as histamine H(3) receptor antagonists.
Summary of "Synthesis and structure-activity relationships of 4,5-fused pyridazinones as histamine H(3) receptor antagonists."
Three series of novel 4,5-fused pyridazinones were synthesized as histamine H(3) receptor antagonists. The 2,5,6,7-tetrahydrocyclopenta[d]pyridazin-1-one 5q and 5,6,7,8-tetrahydro-2H-phthalazin-1-one 5u displayed high affinity at both rat and human H(3) receptors, and showed potent antagonist and full inverse agonist activity in functional assays.
Affiliation
Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA.
Journal Details
This article was published in the following journal.
Name: Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Pages: 6126-30
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21906941
- DOI: http://dx.doi.org/10.1016/j.bmcl.2011.08.045
Medical and Biotech [MESH] Definitions
Dimaprit
A histamine H2 receptor agonist that is often used to study the activity of histamine and its receptors.
Histamine Antagonists
Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.
Cimetidine
A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRINS output. It also blocks the activity of CYTOCHROME P-450 which might explain proposals for use in NEOADJUVANT THERAPY.
Quantitative Structure-activity Relationship
A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds.
Cinnarizine
A piperazine derivative having histamine H1-receptor and calcium-channel blocking activity with vasodilating and antiemetic properties but it induces PARKINSONIAN DISORDERS.
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