Inhibitor platelet aggregation

Recently, Picciola et al. (81FES1037) prepared some 2iT-indazole derivatives containing a phenylalkanoic acid residue with potential antiinflammatory activity (693). M.G. 18755 (R = CHMeC02H, R = R = R = H) and its lysine salt, M.G. 18334, showed greater activity than ibuprofen, and the homologous butyric acid derivative M.G. 18860 showed good activity as a platelet aggregation inhibitor. 

Therapeutic Function Blood platelet aggregation inhibitor... 

Therapeutic Function Vasodilator and platelet aggregation inhibitor Chemical Name Papaverine adenosine 5-monophosphate Common Name Papaverine adenylate... 

Therapeutic Function Hypolipidemic platelet aggregation inhibitor Chemical Name 2,6-Pyridinemethanol-bis(3,4,5-trimethoxybenzoate) Common Name —... 

Platelet-activating Factor Platelet Aggregation Inhibitors Platelet-derived Growth Factor Receptor Platelet Inhibitors Platelets... 

A recent patent of invention describes 3,4-bis(furazan-3-yl)furoxan, with general formula 53 and 54 (Fig. 14), able to generate NO and inhibit platelet aggregation [167]. Another invention has claimed Bfx with dual action as platelet aggregation inhibitors and antianginals, being compoimd 55 (Fig. 14) one of the presented example [168]. 

The patent literature covers many pyridazine derivatives claimed as blood platelet aggregation inhibitors and antithrombotic agents. The interest has been focused mainly on 6-aryl-4,5-dihydro-3(2//)-pyridazinones. In these compounds the aryl substituent has been varied within a wide range. Thus, dihydro-pyridazinones bearing a substituted or heterocycle-fused phenyl group at C-6 (60, R R2,R3 = H, alkyl Ar = substituted Ph) [34, 110-112,205-233] as well as various heteroaryl substituted congeners (61, R1, R2, R3 = H, alkyl Ar = pyridyl, thienyl, pyrrolyl, pyrazolyl) [234-241] have been prepared in search of novel antithrombotics. 

We now examine the metabolic fate of lactam bonds located in rings containing an additional heteroatom, designated here as complex lactams. Our first example is DN-9893 (5.73) a platelet-aggregation inhibitor [177]. Its ring-opened metabolite 5.74 was detected in rat urine after intravenous administration of DN-9893. However, insufficient evidence exists to determine whether hydrolysis of the lactam ring was enzymatic or nonenzymatic. 

M. Tanaka, F. Ishikawa, H. Hakusui, Isolation and Identification of Seven Metabolites of a Water-Soluble Platelet Aggregation Inhibitor in Rat Urine , Xenobiotica 1995, 25, 1247-1257. 

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