New acetylene based histamine H3 receptor antagonists derived from the marine natural product verongamine.
New histamine H3 receptor antagonists were developed using an acetylene moiety as a replacement for the amide-oxime functionality of verongamine 5. Optimization of receptor binding was performed by following aliphatic Topliss tree guidelines. These new H3 ligands demonstrate excellent blood-brain barrier penetration.
Ali
S M
SM
Gliatech Inc., Cleveland, Ohio 44122, USA.
Tedford
C E
CE
Gregory
R
R
Yates
S L
SL
Phillips
J G
JG
D000114:Acetylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D015195:Drug Design; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D006633:Histamine Antagonists; D010091:Oximes; D018100:Receptors, Histamine H3; C086787:verongamine; D014443:Tyrosine; D000114:Acetylene