The synthesis of a novel thromboxane receptor antagonist 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid ICI 192605.
The synthesis and summary pharmacology of a novel thromboxane receptor antagonist 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1, 3-dioxan-cis-5-yl) hexenoic acid (3) is reported. Compound 3 was competitive and selective with pA2 values of 8.0 +/- 0.1 (rabbit) and 8.4 +/- 0.05 (rat) on smooth muscle preparations and 8.16 +/- 0.01 on human platelets. In vivo activity of 3 was demonstrated in a Konzett Rossler guinea pig model at 0.01 mg/kg p.o.
Brewster
A G
AG
Research Department 2, ICI Pharmaceuticals, Macclesfield, Cheshire, England.
Brown
G R
GR
Foubister
A J
AJ
Jessup
R
R
Smithers
M J
MJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D004146:Dioxanes / Q000138:chemical synthesis*; D004147:Dioxins / Q000138:chemical synthesis*; D006801:Humans; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D017482:Receptors, Thromboxane
D004146:Dioxanes; D004147:Dioxins; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C057498:ICI 192605; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid