Contemporary Drug Synthesis

Abstract

1993, has achieved with great commercial success. Like its predecessor ticlopidine (I),clopidogrel (2) is an ADP-dependent platelet aggregation inhibitor. The mechanisms ofaction for both ticlopidine (1) and clopidogrel (2) are the same - through the antagonismof the P2Y12 purinergic receptor and prevention of binding of ADP to the P2Y12receptor. However, both ticlopidine (1) and clopidogrel (2) are not active in vitro, but areactivated in vivo by cytochrome P450-mediated hepatic metabolism. Remarkably, theidentity of the active metabolite 5 of clopidogrel (2) was unknown until 1999: when itwas isolated after exposure of clopidogrel (2) or 2-0x0-clopidogrel (4) to human hepaticmicrosomes. It is noteworthy that ticlopidine (1) and clopidogrel (2) do not share acommon active metabolite