177563-40-5

Usage

InChI:InChI=1/C24H27N5O5/c1-3-34-20(31)13-18(15-7-5-4-6-8-15)27-19(30)14-29-22(32)24(2,28-23(29)33)17-11-9-16(10-12-17)21(25)26/h4-12,18H,3,13-14H2,1-2H3,(H3,25,26)(H,27,30)(H,28,33)/t18-,24-/m0/s1

Upstream product

• 340188-50-3 (R)-3-amino-3-phenylpropionic acid ethyl ester hydrochloride 
• 6320-50-9 (R,S)-4-(4-bromophenyl)-4-methyl-2,5-dioxoimidazolidine 
• 72408-57-2 (R,S)-2-amino-2-(4-bromophenyl)-propionic acid 
• 99-90-1 para-bromoacetophenone 
• 340188-50-3 ethyl (S)-3-amino-3-phenyl-propionate hydrochloride 
• 184426-82-2 [4-(R)-(cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid 
• 340188-51-4 (R)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 
• 184427-33-6 (R,S)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 
• 184427-37-0 N-((S)-1-(4-bromophenyl)-1-(ethoxycarbonyl)ethyl)-N'-(ethoxy-carbonylmethyl)urea 
• 184426-81-1 2-((S)-4-(4-Cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid 
• 184427-38-1 2-((S)-4-(4-bromophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid 
• 184427-34-7 (S)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 

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.