169808-27-9

Upstream product

• 25508-19-4 N-benzyloxycarbonyl-S-methyl-isothiourea 
• 169808-26-8 [4-(R,S)-(4-amino-phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl]acetic acid methyl ester 
• 100-19-6 (4-nitrophenyl)ethanone 
• 64464-22-8 (R,S)-5-methyl-5-(4-nitro-phenyl)-imidazolidine-2,4-dione 
• 169808-25-7 (R,S)-[4-methyl-4-(4-nitro-phenyl)-2,5-dioxo-imidazolidin-1-yl]acetic acid methyl ester 

Downstream Products

• 169808-28-0 [4-(R,S)-(4-benzyloxycarbonylguanidino-phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl]acetic acid 
• 169808-24-6 {2-[4-(R,S)-(4-benzyloxycarbonyl-guanidino-phenyl)-4-methyl-2,5-dioxo-imidazolidin-1-yl]acetyl}-Asp(O-t-Bu)-(S)-phenylglycine-O-t-Bu 

Relevant academic research and scientific papers

Discovery of an orally active non-peptide fibrinogen receptor antagonist based on the hydantoin scaffold

Antagonists of the platelet fibrinogen receptor (GP IIb/IIIa receptor) are expected to be a promising new class of antithrombotic agents. The binding of fibrinogen to the fibrinogen receptor depends on an Arg-Gly-Asp-Ser (RGDS) tetrapeptide recognition motif. Structural modifications of the RGDS lead have led to the discovery of a non-peptide RGD mimetic GP IIb/IIIa antagonist 44 (S 1197). Compound 44 inhibited, in a dose dependent and reversible manner, human and dog platelet aggregation as well as 125I-fibrinogen binding to ADP-activated human gel filtered platelets and isolated GP IIb/IIIa with Ki values of 9 nM and 0.17 nM, respectively. A pharmacophore mapping procedure with QXP and a 3D-QSAR analysis applying the GRID/GOLPE methodology yielded a stable, rather predictive model and revealed structural features which are important for binding. Hydrophobic substitutions both at the hydantoin nucleus and at the C-terminus increase the affinity toward the fibrinogen receptor. The crystalline ethyl ester prodrug 48 (HMR 1794) is an orally active antithrombotic agent which is a promising drug candidate for the treatment of thrombotic diseases in humans.