Exploration of a new series of PAR1 antagonists.
Two series of new PAR1 antagonists have been identified. The first incorporates a cinnamoylpiperidine motif and the second a cinnamoylpyridine pattern. The synthesis, biological activity and structure-activity relationship of these compounds are presented. In each series, one analog showed potent in vivo antithrombotic activity in a rat AV shunt model, with up to 53% inhibition at 1.25mpk iv for compound 30.
Planty
Bruno
B
Department of Medicinal Chemistry 4, Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Castres Cedex, France.
Pujol
Chantal
C
Lamothe
Marie
M
Maraval
Catherine
C
Horn
Clemens
C
Le Grand
Bruno
B
Perez
Michel
M
D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D010455:Peptides / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D044463:Receptor, PAR-1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D010975:Platelet Aggregation Inhibitors
D005343:Fibrinolytic Agents; D010455:Peptides; D010880:Piperidines; D011725:Pyridines; D044463:Receptor, PAR-1; D010975:Platelet Aggregation Inhibitors