Abstract:
:Structure-activity studies on a series of analogues of N-(3-methyl-S-(1-pyrrolidinyl carbonyl) butyl)-D-alanine ethyl ester hydrochloride (SC42619) have defined the features of this dipeptide analogue required for observation of thrombin receptor antagonist activity on the human platelet. The affinity for SC42619, and for its structural analogue SC43583 is enhanced by pretreatment of the platelets with chymotrypsin. Endothelial cell prostacyclin (PGI2) synthesis induced by thrombin and trypsin is selectively inhibited by SC42619 provided that prolonged exposure to this antagonist is avoided. However inhibition of PGI2 synthesis by SC42619 is not overcome by increasing the thrombin concentration. The data provide further support for identification of SC42619 and certain of its analogues as selective antagonists at the platelet thrombin receptor but suggest that these compounds may have more complex, and possibly non-selective effects on the endothelial cell.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Ruda EM,Scrutton MC,Manley PW,Tuffin DPdoi
10.1016/0006-2952(90)90037-lsubject
Has Abstractpub_date
1990-01-15 00:00:00pages
373-81issue
2eissn
0006-2952issn
1873-2968pii
0006-2952(90)90037-Ljournal_volume
39pub_type
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