Comparative action of carbocyclic thromboxane A(2) stereoisomers on platelets.
Stereospecific requirements for the interaction of the thromboxane A(2) carbocyclic mimetic CTA(2) 1 with the human platelet PGH(2)/TXA(2) receptor have been explored. The two pairs of trans-1,2 and cis-3,4 side chain diastereoisomers were synthesised and evaluated for agonist and antagonist activity in human platelet rich plasma. Interestingly, the natural and unnatural trans diastereoisomers, both possessed potent aggregatory activity and equipotently inhibited platelet responses to subsequent addition of agonists, whereas, the respective unnatural cis isomers proved only weakly active or inert.
Caton
M P
MP
The Research Laboratories, Rhone-Poulenc Rorer, Essex RMIO 7XS, Dagenham, UK.
Stuttle
K A
KA
Tuffin
D P
DP
Ansell
M F
MF
D001792:Blood Platelets / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects; D013237:Stereoisomerism; D013928:Thromboxane A2 / Q000737:chemistry / Q000494:pharmacology*
D013928:Thromboxane A2