Su, Ting; Naughton, Mary Ann H.; Smyth, Mark S.; Rose, Jack W.; Arfsten, Ann E.; McCowan, Jefferson R.; Jakubowski, Joseph A.; Wyss, Virginia L.; Ruterbories, Kenneth J.; Sall, Daniel J.; Scarborough, Robert M. published their research in Journal of Medicinal Chemistry on December 19 ,1997. The article was titled 《Fibrinogen Receptor (GPIIb-IIIa) Antagonists Derived from 5,6-Bicyclic Templates. Amidinoindoles, Amidinoindazoles, and Amidinobenzofurans Containing the N-α-Sulfonamide Carboxylic Acid Function as Potent Platelet Aggregation Inhibitors》.Synthetic Route of C10H6N2O The article contains the following contents:
A series of highly potent and specific fibrinogen receptor antagonists have been discovered and optimized through structural modification of novel amidinoindole and benzofuran compounds Systematic linker optimization afforded the amidinobenzofuran-containing inhibitor 3-[[3-(5-amidino-2-benzofurancarboxamido)propionyl]amino]-3-phenylpropionic acid (I), which displayed an IC50 value of 250 nM in platelet aggregation assays. Attempts to enhance activity by modifying the β-position of β-alaninate of inhibitor I had only a modest effect on inhibitory activity in aggregation assays. Analogs prepared to enhance the activity by conformational restriction were also found to be equally or less potent. In contrast, modification at the α-position of β-alaninate resulted in the identification of extremely potent and novel amidinobenzofuran-containing derivatives Reexamination of 5,6-bicyclic aromatic nucleus led to the further identification of amidinoindole- and amidinoindazole-containing derivatives These analogs exhibited potent in vitro activity with IC50 values of 25-65 nM in platelet aggregation assays and an IC50 value of 2 nM in fibrinogen binding assays and demonstrated a selectivity of >50,000-fold for GPIIb-IIIa vs. the most closely related integrin, the vitronectin receptor, αvβ3. In the experiment, the researchers used 3-Formyl-1H-indole-6-carbonitrile(cas: 83783-33-9Synthetic Route of C10H6N2O)
3-Formyl-1H-indole-6-carbonitrile(cas: 83783-33-9) is a member of nitriles. Nitriles have been reduced to amines by many methods, especially by catalytic hydrogenation and by metal hydrides. Aliphatic and aromatic nitriles have also been reduced to nitro derivatives using hydrazinium monoformate in the presence of Raney-nickel.Synthetic Route of C10H6N2O
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts