Synthesis of Hexahydrocyclopentimidazol-2-(1H)-one derivatives displaying selective DP-receptor agonist properties.
The rationale for investigating conformationally restricted analogues of BW245C as DP-receptor ligands and the syntheses of three such racemic bicyclic imidazolidinone analogues are described. Compounds 7 (BW587C), 8 (BW480C85), and 9 (BW572C85) were found to be potent inhibitors of human platelet aggregation and selective DP-receptor agonists in washed platelet and jugular vein isolated tissue assays.
Barraclough
P
P
Department of Medicinal Chemistry, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Bolofo
M L
ML
Giles
H
H
Gillam
J
J
Harris
C J
CJ
Kelly
M G
MG
Leff
P
P
McNeill
A
A
Robertson
A D
AD
Stepney
R J
RJ
Whittle
B J
BJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002087:Butyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D006827:Hydantoins / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007601:Jugular Veins / Q000187:drug effects / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011982:Receptors, Prostaglandin / Q000819:agonists*; D013329:Structure-Activity Relationship
C100557:BW 480C85; C100558:BW 572C85; C100556:BW 587C; D002087:Butyrates; D006827:Hydantoins; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D011982:Receptors, Prostaglandin; C030669:BW 245C