| Description | Tirofiban was launched as Aggrastat in Switzerland and the US for
patients with unstable angina or non-Q-wave myocardial infarction to prevent
cardiac ischemic events. Tirofiban is synthesized from (S)-tyrosine by a fourstep
process. Tirofiban is a novel highly potent antiplatelet agent that inhibits the
interaction of fibrinogen with GPⅡb/Ⅲa, an activated platelet membrane-bound
glycoprotein complex. It prevents arterial thrombus formation in a dosedependent
manner. Clinical efficacy was highly significant with an absolute and
relative risk reduction. In these studies, treatment with tirofiban was well
tolerated, without significant adverse effects. |
| Originator | Sibutramine (Sibutramine) |
| Uses | Aggrastat (Millot
Laboratories, France). |
| Uses | Tirofiban Hydrochloride is a selective nonpeptide platelet glycoprotein IIb/IIIa antagonist. |
| Manufacturing Process | The synthesis of tirofiban starts by reaction of tyrosine with bis-trimethylsilyl
trifluoraceramide to give a derivative in which both functions -OH and COOH_x0002_are protected. Treatment of this intermediate with butylsulfonyl chloride gives
the corresponding sulfonamide derivative; the quite labile silyl groups are then
removed under mildly acidic conditions to give N-butylsulfonyl-tyrosine. In a
parallel scheme, 4-picoline is converted to its anion by means of butyl lithium;
this gives 4-(4-chlorobutyl)-pyridine on alkylation with 1-bromo-3-
chloropropane. The reaction of this compound with N-butylsulfonyl-tyrosine in
presence of NaOH gives the ether 2-butylsulfonyaminol-3-[4-pyridin-4-ylbutoxy-phenyl]propionic acid. Hydrogenation over palladium on charcoal then
reduce the pyridine ring to a piperidine to afford the fibrinogen receptor
antagonist tirofiban. |
| Brand name | Tirofiban is INN and BAN. |
| Therapeutic Function | Fibrinogen receptor antagonist |
